Podcasts about ezetimibe

In this podcast, Dr. Valentin Fuster discusses a pivotal study on the benefits of early acetamide initiation combined with statins after a myocardial infarction, showing improved cardiovascular outcomes. The study's findings suggest that early combination therapy reduces the risk of major cardiovascular events, urging healthcare pathways to adopt this approach as standard practice for better patient outcomes.

Welcome back to our weekend Cabral HouseCall shows! This is where we answer our community's wellness, weight loss, and anti-aging questions to help people get back on track! Check out today's questions:  Amy: Hi Dr. Cabral. First, thank you for all you do for the health community! You are my most trusted source of information. I'd love to get your thoughts on a red patch under my right eye. I've suffered through it flaring up and going away over half of this year. My dermatologist has tried 2 creams and we recently did a skin allergy test. While this was helpful, nothing has made it actually get better. I have a sneaking suspicion that it is more gut related than contact allergen related. Do you have any thoughts on ways to go about finding this root cause? Thanks!   Melissa: Hi! I just moved out of state and am in my mid 40s with menstrual irregularities. I'm feeling overwhelmed trying to find a new primary care and OBGYN that practices holistically with functional medicine therapies. How does one go about finding one. Or should I opt to doing a hormone therapy specialist?   Anonymous: Hi Dr. C, For several mornings now Ive been having a weird, somewhat sour chemical taste in my mouth. I believe this is due to my chronic constipation as my morning bowel movements are often incomplete, and any subsequent movements I have after my first one will smell more strongly of this sour chemical taste I wake up with in my mouth. My urine will have this smell as well. It does not smell of feces, just sort of chemically. I also have lots of pain in the area right below the sternum and seems to be chronic, and only reduces with the more bowel movements I have. Im already taking many magnesium supplements, motility activators, tudca, and miralax but I still find myself in these situations quite often. My stomach will often make high pitch, squealing sounds as if its straining   Lynne: Hello and thank you so much for all you do for all of us! I'm trying to understand why I tend to get benign growths such as lipomas. I also have a lump on my breast that has been there since I was 20. I am 52 and have gone through menopause and thought it would dissipate after the estrogen level dropped so dramatically. I also had hyperparathyroidism...another growth. Finally, I have a lymph node that feels like a tiny hard nodule on my neck (at the top near the ear). I have been taking proteolytic enzymes, am not overweight, exercise daily and eat a very clean diet. I would greatly appreciate any advice. Thank you!  Sorry, I forgot to mention that I listened to previous HouseCalls and have tried all of those things: massage, rebounder, sauna, dry brushing, castor oil, detoxes, etc. I have been doing these for a number of years.    Jill: Thanks for sharing your expertise and experience. I have a history of hyperlipidemia but through diet & lifestyle efforts have kept my cholesterol levels in check. Within the last few years, the levels have begun to climb and some of my inflammatory markers are worrisome. I am 53, post menopausal, and live an active lifestyle. I would like to avoid statins; however, I have been taking Icosapent Ethyl and Ezetimibe for the past 6 months and have seen a lowering of both my triglycerides and cholesterol to normal ranges again. My APOB is 139, LpA is 102 but my CT cardiac score is a zero. Where do I go from here? Is there any other testing I should consider to understand if need to continue on these medications, such as a CT angiogram?     Thank you for tuning into today's Cabral HouseCall and be sure to check back tomorrow where we answer more of our community's questions!    - - - Show Notes and Resources: StephenCabral.com/3263 - - - Get a FREE Copy of Dr. Cabral's Book: The Rain Barrel Effect - - - Join the Community & Get Your Questions Answered: CabralSupportGroup.com - - - Dr. Cabral's Most Popular At-Home Lab Tests: > Complete Minerals & Metals Test (Test for mineral imbalances & heavy metal toxicity) - - - > Complete Candida, Metabolic & Vitamins Test (Test for 75 biomarkers including yeast & bacterial gut overgrowth, as well as vitamin levels) - - - > Complete Stress, Mood & Metabolism Test (Discover your complete thyroid, adrenal, hormone, vitamin D & insulin levels) - - - > Complete Food Sensitivity Test (Find out your hidden food sensitivities) - - - > Complete Omega-3 & Inflammation Test (Discover your levels of inflammation related to your omega-6 to omega-3 levels) - - - Get Your Question Answered On An Upcoming HouseCall: StephenCabral.com/askcabral - - - Would You Take 30 Seconds To Rate & Review The Cabral Concept? The best way to help me spread our mission of true natural health is to pass on the good word, and I read and appreciate every review!  

Link to Buck's Results: https://drive.google.com/file/d/19BJaZNYwBxlPx4nR9695Q2NC3nNpgW6y/view?usp=sharing  https://drive.google.com/file/d/1br1ikAJKmgKev9X3jkS7nUPdXpAqMzYd/view?usp=sharing Section 1: Overview of Cholesterol Metabolism Cholesterol in the Body: Cholesterol is essential for cell membrane integrity, hormone synthesis, and bile acid production. It is produced endogenously in the liver and absorbed exogenously from dietary sources. Endogenous Production: Cholesterol is synthesized in the liver through the mevalonate pathway. Key intermediates: Lathosterol and Desmosterol, indicators of cholesterol production rate. Exogenous Absorption: Dietary cholesterol is absorbed in the intestines along with plant sterols like Beta-sitosterol and Campesterol. These sterols compete with cholesterol for absorption, reflecting dietary cholesterol absorption levels. Section 2: Detailed Analysis of the Test Components Production Markers: Lathosterol: Precursor in the cholesterol biosynthesis pathway. Elevated levels indicate increased hepatic cholesterol synthesis (overproduction). Example: Lathosterol level of 329 µmol x 100/mmol in my study indicates hyperactive cholesterol production. Desmosterol: Another precursor in the synthesis pathway, contributing to total cholesterol production. High levels reinforce the diagnosis of increased cholesterol production. Example: Desmosterol level of 74 µmol x 100/mmol in my study supports elevated production. Absorption Markers: Beta-sitosterol: Plant sterol absorbed in the intestines, competes with cholesterol. High levels suggest increased absorption of dietary cholesterol. Example: Beta-sitosterol level of 120 µmol x 100/mmol indicates borderline absorption. Campesterol: Similar to Beta-sitosterol, reflects cholesterol absorption efficiency. Elevated levels indicate increased absorption. Example: Campesterol level of 113 µmol x 100/mmol within normal limits but suggests absorption could be a factor. Cholesterol Balance Score: Ratio of production to absorption markers. A higher score indicates predominant cholesterol production; a lower score indicates absorption as the main issue. Example: Score of 2.4 suggests overproduction is the dominant issue. Section 3: Clinical Implications and Treatment Strategies (10 minutes) Frequency of Overproduction vs. Overabsorption: Common to see patients with either overproduction or overabsorption, but less commonly both. Overproducers: Significant portion of hypercholesterolemia patients, especially those with genetic conditions like Familial Hypercholesterolemia. Overabsorbers: Often have high-cholesterol diets or genetic predispositions. Treatment Implications: Overproducers: Statins are first-line treatment; they inhibit HMG-CoA reductase in cholesterol synthesis. Overabsorbers: Ezetimibe, which inhibits intestinal cholesterol absorption, can be effective. Combination Therapy: Considered for mixed dyslipidemia cases. Case Examples: Example of a patient with high production markers but borderline absorption: Statin therapy may be appropriate, with potential addition of Ezetimibe. Example of a patient who is a high absorber but not a high producer: Dietary changes and Ezetimibe might suffice without statins. Section 4: Physiological Mechanisms and Genetic Considerations Pathophysiology of Cholesterol Production: Overproduction may result from genetic mutations (LDL receptor or PCSK9) or conditions like insulin resistance. Pathophysiology of Cholesterol Absorption: Increased absorption could be due to genetic polymorphisms (NPC1L1 gene), leading to higher dietary cholesterol absorption. Section 5: Practical Application in Clinical Practice Incorporating the Test into Clinical Workflow: Integrate the Boston Heart Cholesterol Balance Test for patients with unexplained hypercholesterolemia or non-responders to standard therapy. Tailor treatment based on whether a patient is an overproducer, an overabsorber, or both. Patient Communication: Explain test results in an understandable way, emphasizing personalized treatment plans.

On this episode of the Real Life Pharmacology podcast, I continue my education on the top 200 drugs. Raloxifene, prednisone, phenytoin, fish oil, and ezetimibe are covered in this podcast episode. Prednisone is a corticosteroid that may cause hyperglycemia, insomnia, GI upset, osteoporosis, HPA suppression, and hypertension as primary adverse effects. Raloxifene is classified as a SERM and can be used for osteoporosis and breast cancer. DVT and hot flashes are significant adverse effect concerns. Fish oil (Lovaza) is used to reduce triglycerides. Elevated triglycerides can increase the risk of pancreatitis. Ezetimibe inhibits the absorption of cholesterol through the gut. It lowers LDL but not to the extent of statins. Phenytoin is a narrow therapeutic index medication (NTI) that is used as an anticonvulsant. Ataxia, confusion, GI upset, and vertical nystagmus are potential signs of toxicity.

Tratamento medicamentoso da dislipidemia: Ezetimibe, funciona mesmo? by Cardiopapers

This case report explores the intricacies of familial hypercholesterolemia (FH), delving into its genetic basis, atherosclerotic cascade, and early-onset cardiovascular complications. It examines established diagnostic criteria and emphasizes personalized management, including statins, novel therapies, and lifestyle modifications. CardioNerds cofounders (Drs. Amit Goyal and Danial Ambinder) join Dr. Irfan Shafi, Dr. Preeya Prakash, and Dr. Rebecca Theisen from the Wayne State University/DMC and Central Michigan University at Campus Martius in Downtown Detroit for some holiday ice-skating! They discuss an interesting pediatric case (see case synopsis below). Dr. Luis C Afonso provides the Expert CardioNerd Perspectives & Review segment for this episode. Audio editing by CardioNerds academy intern, Pace Wetstein. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Synopsis FH, a 9-year-old female with no previous medical history, recently moved back to the US from Iraq. She presented to establish care and discuss new-onset chest pain and dyspnea. A systolic ejection murmur was noted during her initial visit to the pediatrician, prompting cholesterol testing and a cardiology referral. Testing revealed, alarming cholesterol levels (Total Cholesterol: 802 mg/dL, LDL: 731 mg/dL, Triglycerides: 123 mg/dL) prompted concern for cardiac involvement. Due to persistent symptoms, FH was transferred to Children's Hospital of Michigan. Despite normal findings on EKG and chest x-ray, a 2/6 systolic murmur was noted. She was discharged with a cardiology clinic follow-up. However, two days later, FH experienced severe chest pain at rest, sweating, and difficulty breathing. She was transported to Children's Hospital again, and her troponin level measured 3000, and her total cholesterol was 695 mg/dL. An echocardiogram revealed valvar and supravalvar aortic stenosis, necessitating collaboration between Pediatric and Adult cardiology teams. CTA thorax revealed severe supravalvular stenosis, a hypoplastic right coronary artery, and significant coronary artery obstructions. Diagnostic cardiac catheterization confirmed severe aortic stenosis and coronary artery disease, leading to the decision for surgical intervention. FH underwent the Ross operation, left main coronary artery augmentation, and right coronary artery reimplantation. Intraoperatively, atherosclerotic plaques were observed in multiple cardiac structures. FH's recovery was uneventful, discharged on a regimen including Atorvastatin, Ezetimibe, evolocumab, and antiplatelet therapy. Persistent high LDL levels required regular plasmapheresis. Plans for evaluations in Genetics, Lipid Clinic, Endocrine, and Gastroenterology were made, potentially leading to a liver transplant assessment. Given the severity of her condition, a heart/liver transplant might be considered in the future. Conclusion: This case of FH highlights the complex presentation of severe aortic stenosis and coronary artery disease in a pediatric patient. Urgent diagnosis, interdisciplinary collaboration, and aggressive management were crucial. The case underscores the importance of comprehensive care for pediatric patients with rare cardiac conditions, emphasizing collaboration between specialties for optimal outcomes and long-term well-being. Case Media Pearls - Familial Hypercholesterolemia Mutations in LDLR, ApoB, or PCSK9 genes disrupt LDL-C clearance, leading to a cascade of events culminating in accelerated atherosclerosis and early-onset cardiovascular complications (e.g., CAD, aortic stenosis, PAD, stroke). Diagnosis of familial hypercholesterolemia relies on ...

N Engl J Med 2015;372:2387-2397Background: Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, effectively lower low-density lipoprotein (LDL) and improve cardiovascular outcomes across different populations. High-intensity statins exhibit greater efficacy in lowering LDL and decreasing non-fatal cardiac events compared to moderate-intensity statins. Nonetheless, due to the residual risk of cardiac events, and concerns about the safety and tolerability of high intensity statins, there is a growing demand for newer therapeutic options.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.Ezetimibe acts on the Niemann–Pick C1–like 1 (NPC1L1) protein, inhibiting cholesterol absorption from the intestine. When combined with statins, ezetimibe further decreases LDL levels by an average of 23 to 24%.The IMPROVE-IT trial sought to test the hypothesis that adding ezetimibe to simvastatin is superior to simvastatin alone in reducing cardiovascular events in patients with recent acute coronary syndrome.Patients: Patients were enrolled if they had acute coronary syndrome (STEMI, NSTEMI or high-risk unstable angina) in the preceding 10 days, and were at least 50 years old. LDL levels within 24 hours of the acute coronary syndrome (ACS) had to be at least 50 mg/dL but less than or equal to 125 mg/dL in lipid-therapy naïve patients or less than or equal to 100 mg/dL in patients receiving lipid lowering therapy. Patients were excluded if they had hemodynamic or electrical instability following the ACS event, planned CABG, active liver disease, creatinine clearance< 30 ml/min, or they had chronic lipid lowering therapy of simvastatin> 40mg, atorvastatin 40mg or more, any dose of rosuvastatin, or any ezetimibe/simvastatin combination.Baseline characteristics: The average age of patients was 64 years with 76% being men. The average weight was 83 kg. About 27% had diabetes, 61% had hypertension, 21% had prior myocardial infarction, 4% had congestive heart failure and 33% were current smokers. The median creatinine clearance was 85 ml/ min. The index event was STEMI in 29% of the patients, NSTEMI in 47% and unstable angina in the rest. Coronary angiogram was performed in 88% of the patients and percutaneous coronary intervention was performed in 70%. The mean LDL was 94 mg/dL and was similar in both groups.Procedures: Patients were randomized 1:1 in a double blinded fashion to receive simvastatin 40mg daily plus ezetimibe 10mg daily or simvastatin 40mg daily plus placebo. Patients had follow-up visits at 30 days, 4 months, and every 4 months thereafter.In both study groups, if LDL level was higher than 79 mg/dL on two consecutive measurements, the simvastatin dose was increased to 80 mg per day. This practice continued until June 2011, approximately one year after the study's randomization concluded, when the Food and Drug Administration advised limiting new prescriptions of simvastatin 80 mg daily. If LDL levels were higher than 100 mg/dL on the new regimen, the study drug could be discontinued, and more potent therapy could be initiated. Patients were followed for at least 2.5 years and for up to 7 years.Endpoints: The primary efficacy end point was a composite endpoint of death from cardiovascular disease, a major coronary event (defined as nonfatal myocardial infarction, unstable angina requiring hospital admission, or coronary revascularization occurring at least 30 days after randomization), or nonfatal stroke. The trial also reported death from any cause as part of one of the secondary composite endpoints. Safety variables included liver enzymes and creatine kinase levels, myopathy or rhabdomyolysis, gallbladder-related adverse events or cancer.Statistical analysis was performed based on the intention-to-treat principle. To achieve 90% power for detecting 9.375% lower relative risk for the primary end point with simvastatin–ezetimibe combination compared to simvastatin alone, an estimated sample size of 18,000 patients and 5,250 primary events was required.Results: The trial randomized 18,144 patients in 39 countries; 9067 randomized to the simvastatin–ezetimibe combination and 9077 to the simvastatin monotherapy group.The simvastatin–ezetimibe combination led to greater reduction in LDL. At 1 year, the mean LDL was 53 mg/dL in the simvastatin–ezetimibe combination group and 70 mg/dL in the simvastatin monotherapy group. The simvastatin dose was increased to 80mg per day in 6% of the patients in the simvastatin–ezetimibe group and 27% in the simvastatin monotherapy group.The use of simvastatin–ezetimibe led to greater reduction in the primary endpoint compared simvastatin monotherapy (32.7% vs 34.7%, HR: 0.94; 95% CI: 0.89 - 0.99; p= 0.016). This reduction in the composite primary endpoint was primarily driven by reduction in non-fatal myocardial infarction (12.8% vs 14.4%) as well as ischemic stroke (3.4% vs 4.1%). There was no significant difference in death from any cause (15.4% vs 15.3%) or death from cardiovascular causes (6.9% vs 6.8%).The benefits of simvastatin–ezetimibe were more pronounced in patients who were 75 years or older (39.0% vs 47.6%, HR 0.80, 95% CI: 0.70 - 0.90; p for interaction= 0.005) and in patients with diabetes (40.0% vs 45.5%, HR: 0.86, 95% CI: 0.78 - 0.94; p for interaction= 0.023).No significant differences in safety endpoints were observed between both groups. Elevation of liver enzymes 3 times or more the upper limited of normal occurred in 2.5% of the patients in the simvastatin–ezetimibe combination group and 2.3% in the simvastatin monotherapy group.Conclusion: In patients with recent acute coronary syndrome, the combination of simvastatin–ezetimibe as compared to simvastatin monotherapy improved the primary composite outcome of death from cardiovascular disease, major coronary events, or nonfatal stroke. This reduction was modest, about 6% relative reduction, and was primarily driven by reduction in non-fatal myocardial infarctions and ischemic strokes. The trial results supports the hypothesis that lower LDL levels improves outcomes regardless of how it's achieved. The trial has good interval validity but the external validity is limited in the current era because simvastatin is infrequently used nowadays with atorvastatin and rosuvastatin being the preferred agents. Patients taking atorvastatin 40mg or more and patients taken any dose of rosuvastatin at baseline were excluded from the trial. Furthermore, it's unclear why the trial did not permit the inclusion of patients whose LDL exceeded certain limits as only patients with mild elevation in LDL at baseline were permitted to be enrolled.This trial does not answer the question most physicians may encounter in their practice: What's the benefit of adding ezetimibe to high-intensity statins or prescribing it to patients with moderate or high elevation in LDL levels?Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

“Menopause is inevitable, but suffering through it is not," says Mary Claire Haver, M.D. Mary Claire, a board-certified OBGYN and certified menopause practitioner, joins us to discuss everything a woman needs to know during this hormonal transition and beyond, including: - Old vs. new menopause (~00:07) - Signs of peri menopause in 30s, 40s & 50s (~02:04) - Sleep deprivation during menopause (~05:09) - Menopause weight gain (~06:36) - How to enhance body composition as you age (~09:25) - Protein needs for women (~14:20) - The link between food & hot flashes (~16:09) - Pros & cons of hormone replacement therapy (~18:43) - How to know if you're a good candidate for HRT (~25:02) - Best questions to ask your doctor (~27:23) - Why we should have annual midlife wellness visits (~28:28) - The future of menopause care (~31:23) - A drug that can prolong estrogen production (~33:02) - How to measure estrogen swings (~35:10) - How to be your own menopause advocate (~39:35) Visit shop.mindbodygreen.com/whey20 to get 20% off whey protein isolate+. Cannot combine with gift cards or other discount codes. Referenced in the episode: - Mary Claire's book, The New Menopause - The Galveston Diet - Follow Mary Claire on Instagram - mbg Podcast episode #529, with Lisa Mosconi, Ph.D. - mbg Podcast episode #480, with Peter Attia, M.D. - Statins Peter mentions: PCSK9 inhibitors, Ezetimibe, and Bempedoic Acid - WHI study on frailty - A study on estrogen therapy & dementia - menopause.org - Mary Claire's Menopause Empowerment Guide - Tests to ask for at the doctor - Oviva Therapeutics We hope you enjoy this episode, and feel free to watch the full video on YouTube! Whether it's an article or podcast, we want to know what we can do to help here at mindbodygreen. Let us know at: podcast@mindbodygreen.com. Learn more about your ad choices. Visit megaphone.fm/adchoices

Dhineli Perera sits down with Adam Nelson to discuss updates in the management of hypercholesterolaemia. Adam explains how triglycerides, LDL cholesterol and HDL cholesterol differ in their links to cardiovascular disease. He provides useful tips for checking a lipid profile and highlights other tests that may be helpful when assessing a patient with hypercholesterolaemia. Adam also explains the latest in treatments for reducing LDL cholesterol concentrations and what this means for the role of statins. Read the full article by Adam Nelson and Stephen Nicholls in Australian Prescriber.

Found My Fitness - Rhonda Patrick Key Takeaways “The healthier an individual is, the more they can rely on their mitochondria for ATP generation under increasing demands of the cell. This is one of the hallmarks of health.” – Dr. Peter AttiaSpend good time training in Zone 2; this means a rate you can hold a conversation and form sentences at, but really don't want toFor many, rate of perceived exertion is an accurate measureMaffetone heart rate is a helpful target: take 180-age for target HRFour things are causal risk factors for atherosclerotic cardiovascular disease: (1) ApoB; (2) insulin resistance; (3) hypertension; (4) smokingStatin use is inexpensive, accessible, and effective but “If money were no issue, you'd probably just be on PCKS9 inhibitors, ezetimibe, and bempedoic acid.” – Dr. Peter AttiaTip: don't skip your eye exams! By looking at the retina and capillaries at the back of the eye, diabetes can be detected earlier“Exercise is probably the single most important thing we have at our disposal to increase insulin sensitivity.” – Dr. Peter AttiaSleep, energy balance, hormone balance are key as wellTo optimize cardiovascular health and mitochondrial efficiency: start with how much time you're willing to exercise – then divide that into 80/20 with 80% at zone 2 and 20% at VO2 max VO2 max sweet spot is 3-8 minutes with 1:1 ratio of rest to recovery – it takes some time to find how much effort you can put out in this time; it's slower than a Tabata (20 on/10 off x 8 rounds) but by no means endurance  “Exercise is probably the single most important thing we have at our disposal to increase insulin sensitivity.” – Dr. Peter AttiaThe difference between normal glucose and type 2 diabetes is just a teaspoon of blood glucose – muscle is the sink for glucose disposalSmoking and obesity are the greatest modifiable risk factors for cancer Why obesity? It's not actually the amount of fate cells; it's likely the inflammatory environment that comes with obesity –the excess fat that spills into areas where fat accumulation is harmful like around organs, in muscleTip: don't rely on mammograms exclusively, especially if you're high risk – combine with ultrasound or MRI“There has been no greater disservice brought by the medical community onto anyone, in particular in this case women, than the abject failure of the Women's Health Initiative.” – Dr. Peter AttiaHormone replacement therapy started at the onset of menopause will help most womenTestosterone replacement therapy in men should be based on bloodwork in combination with symptoms – but be conservative, there are side effects for individuals at risk (hair loss, slightly elevated risk of cardiovascular events, acne)Read the full notes @ podcastnotes.org Download the 9-Page "Cognitive Enhancement Blueprint" Discover my premium podcast The Aliquot Show notes are available by clicking here Peter Attia, MD is a highly respected expert in preventive medicine, focused on the crucial subject of longevity and cardiovascular health. He's also the author of the NY Times best selling book Outlive - which I highly recommend if you have not read it already. Peter's philosophy transcends the conventional goal of merely extending lifespan; it's about enriching the quality of every year, ensuring that each stage of life is lived with optimal health and vitality. In this episode, we discuss: (00:07:36) Defining cardiovascular disease (00:09:43) Coronary plaque and fatality risk (00:11:09) What is cholesterol? (00:13:34) How ApoB predicts heart disease (00:21:34) Factors elevating ApoB (00:25:24) ApoB reference range explained (00:27:23) Does high ApoB cause cardiovascular disease (00:37:01) ApoB thresholds for ASCVD prevention (00:40:27) Dietary factors raising ApoB (00:39:33) Genetics of ApoB and LDL (00:53:24) Does low LDL increase cancer? (00:56:19) Cholesterol-lowering drugs (00:59:59) Statins, uses, and side effects (01:03:12) Are statins toxic to mitochondria? (01:09:56) Ubiquinol for statin-induced muscle soreness (01:11:09) How to train in zone 2 (01:17:09) Statins and neurodegenerative disease risk (01:21:54) Cholesterol synthesis in the brain (desmosterol role) (01:25:58) Statin alternatives – pros and cons (01:27:30) Ezetimibe (01:31:01) Bempedoic acid (01:36:49) Berberine for CVD Risk Reduction? (01:39:36) Muscle as a glucose sink (01:45:58) Chronic glucose toxicity and vascular impact (01:51:38) Hemoglobin A1C Levels and Mortality Data (01:55:35) 80/20 Zone 2/VO2 Max Training Protocol (02:02:12) Insights from VO2 max testing data (02:12:17) How obesity increases cancer risk (02:15:03) Cancer screening benefits and risks (02:20:47) Dr. Attia's recommended cancer screening age (02:28:54) Liquid biopsies for detecting cancer (02:34:48) CT scans, mammograms and radiation concerns (02:40:32) Menopause – hormonal shifts and health effects (02:45:13) Hormone replacement therapy (HRT) (02:58:57) Perimenopause diagnosis with hormone levels (03:02:04) HRT's impact on dementia, cancer, and heart disease risk (03:04:49) Estrogen's role in bone density (03:07:42) Vitamin D (03:16:24) Testosterone replacement for women's sexual function (03:18:47) HRT safety 10 years post-menopause (03:23:05) Treating low testosterone in men (03:29:53) TRT side effects and risks (03:32:33) Ways to reduce blood pressure (03:39:33) How to measure blood pressure (03:45:30) Peter's longevity optimization routines Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/premium

Found My Fitness - Rhonda Patrick Key Takeaways “The healthier an individual is, the more they can rely on their mitochondria for ATP generation under increasing demands of the cell. This is one of the hallmarks of health.” – Dr. Peter AttiaSpend good time training in Zone 2; this means a rate you can hold a conversation and form sentences at, but really don't want toFor many, rate of perceived exertion is an accurate measureMaffetone heart rate is a helpful target: take 180-age for target HRFour things are causal risk factors for atherosclerotic cardiovascular disease: (1) ApoB; (2) insulin resistance; (3) hypertension; (4) smokingStatin use is inexpensive, accessible, and effective but “If money were no issue, you'd probably just be on PCKS9 inhibitors, ezetimibe, and bempedoic acid.” – Dr. Peter AttiaTip: don't skip your eye exams! By looking at the retina and capillaries at the back of the eye, diabetes can be detected earlier“Exercise is probably the single most important thing we have at our disposal to increase insulin sensitivity.” – Dr. Peter AttiaSleep, energy balance, hormone balance are key as wellTo optimize cardiovascular health and mitochondrial efficiency: start with how much time you're willing to exercise – then divide that into 80/20 with 80% at zone 2 and 20% at VO2 max VO2 max sweet spot is 3-8 minutes with 1:1 ratio of rest to recovery – it takes some time to find how much effort you can put out in this time; it's slower than a Tabata (20 on/10 off x 8 rounds) but by no means endurance  “Exercise is probably the single most important thing we have at our disposal to increase insulin sensitivity.” – Dr. Peter AttiaThe difference between normal glucose and type 2 diabetes is just a teaspoon of blood glucose – muscle is the sink for glucose disposalSmoking and obesity are the greatest modifiable risk factors for cancer Why obesity? It's not actually the amount of fate cells; it's likely the inflammatory environment that comes with obesity –the excess fat that spills into areas where fat accumulation is harmful like around organs, in muscleTip: don't rely on mammograms exclusively, especially if you're high risk – combine with ultrasound or MRI“There has been no greater disservice brought by the medical community onto anyone, in particular in this case women, than the abject failure of the Women's Health Initiative.” – Dr. Peter AttiaHormone replacement therapy started at the onset of menopause will help most womenTestosterone replacement therapy in men should be based on bloodwork in combination with symptoms – but be conservative, there are side effects for individuals at risk (hair loss, slightly elevated risk of cardiovascular events, acne)Read the full notes @ podcastnotes.org Download the 9-Page "Cognitive Enhancement Blueprint" Discover my premium podcast The Aliquot Show notes are available by clicking here Peter Attia, MD is a highly respected expert in preventive medicine, focused on the crucial subject of longevity and cardiovascular health. He's also the author of the NY Times best selling book Outlive - which I highly recommend if you have not read it already. Peter's philosophy transcends the conventional goal of merely extending lifespan; it's about enriching the quality of every year, ensuring that each stage of life is lived with optimal health and vitality. In this episode, we discuss: (00:07:36) Defining cardiovascular disease (00:09:43) Coronary plaque and fatality risk (00:11:09) What is cholesterol? (00:13:34) How ApoB predicts heart disease (00:21:34) Factors elevating ApoB (00:25:24) ApoB reference range explained (00:27:23) Does high ApoB cause cardiovascular disease (00:37:01) ApoB thresholds for ASCVD prevention (00:40:27) Dietary factors raising ApoB (00:39:33) Genetics of ApoB and LDL (00:53:24) Does low LDL increase cancer? (00:56:19) Cholesterol-lowering drugs (00:59:59) Statins, uses, and side effects (01:03:12) Are statins toxic to mitochondria? (01:09:56) Ubiquinol for statin-induced muscle soreness (01:11:09) How to train in zone 2 (01:17:09) Statins and neurodegenerative disease risk (01:21:54) Cholesterol synthesis in the brain (desmosterol role) (01:25:58) Statin alternatives – pros and cons (01:27:30) Ezetimibe (01:31:01) Bempedoic acid (01:36:49) Berberine for CVD Risk Reduction? (01:39:36) Muscle as a glucose sink (01:45:58) Chronic glucose toxicity and vascular impact (01:51:38) Hemoglobin A1C Levels and Mortality Data (01:55:35) 80/20 Zone 2/VO2 Max Training Protocol (02:02:12) Insights from VO2 max testing data (02:12:17) How obesity increases cancer risk (02:15:03) Cancer screening benefits and risks (02:20:47) Dr. Attia's recommended cancer screening age (02:28:54) Liquid biopsies for detecting cancer (02:34:48) CT scans, mammograms and radiation concerns (02:40:32) Menopause – hormonal shifts and health effects (02:45:13) Hormone replacement therapy (HRT) (02:58:57) Perimenopause diagnosis with hormone levels (03:02:04) HRT's impact on dementia, cancer, and heart disease risk (03:04:49) Estrogen's role in bone density (03:07:42) Vitamin D (03:16:24) Testosterone replacement for women's sexual function (03:18:47) HRT safety 10 years post-menopause (03:23:05) Treating low testosterone in men (03:29:53) TRT side effects and risks (03:32:33) Ways to reduce blood pressure (03:39:33) How to measure blood pressure (03:45:30) Peter's longevity optimization routines Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/premium

Download the 9-Page "Cognitive Enhancement Blueprint" Discover my premium podcast The Aliquot Show notes are available by clicking here Peter Attia, MD is a highly respected expert in preventive medicine, focused on the crucial subject of longevity and cardiovascular health. He's also the author of the NY Times best selling book Outlive - which I highly recommend if you have not read it already. Peter's philosophy transcends the conventional goal of merely extending lifespan; it's about enriching the quality of every year, ensuring that each stage of life is lived with optimal health and vitality. In this episode, we discuss: (00:07:36) Defining cardiovascular disease (00:09:43) Coronary plaque and fatality risk (00:11:09) What is cholesterol? (00:13:34) How ApoB predicts heart disease (00:21:34) Factors elevating ApoB (00:25:24) ApoB reference range explained (00:27:23) Does high ApoB cause cardiovascular disease (00:37:01) ApoB thresholds for ASCVD prevention (00:40:27) Dietary factors raising ApoB (00:39:33) Genetics of ApoB and LDL (00:53:24) Does low LDL increase cancer? (00:56:19) Cholesterol-lowering drugs (00:59:59) Statins, uses, and side effects (01:03:12) Are statins toxic to mitochondria? (01:09:56) Ubiquinol for statin-induced muscle soreness (01:11:09) How to train in zone 2 (01:17:09) Statins and neurodegenerative disease risk (01:21:54) Cholesterol synthesis in the brain (desmosterol role) (01:25:58) Statin alternatives – pros and cons (01:27:30) Ezetimibe (01:31:01) Bempedoic acid (01:36:49) Berberine for CVD Risk Reduction? (01:39:36) Muscle as a glucose sink (01:45:58) Chronic glucose toxicity and vascular impact (01:51:38) Hemoglobin A1C Levels and Mortality Data (01:55:35) 80/20 Zone 2/VO2 Max Training Protocol (02:02:12) Insights from VO2 max testing data (02:12:17) How obesity increases cancer risk (02:15:03) Cancer screening benefits and risks (02:20:47) Dr. Attia's recommended cancer screening age (02:28:54) Liquid biopsies for detecting cancer (02:34:48) CT scans, mammograms and radiation concerns (02:40:32) Menopause – hormonal shifts and health effects (02:45:13) Hormone replacement therapy (HRT) (02:58:57) Perimenopause diagnosis with hormone levels (03:02:04) HRT's impact on dementia, cancer, and heart disease risk (03:04:49) Estrogen's role in bone density (03:07:42) Vitamin D (03:16:24) Testosterone replacement for women's sexual function (03:18:47) HRT safety 10 years post-menopause (03:23:05) Treating low testosterone in men (03:29:53) TRT side effects and risks (03:32:33) Ways to reduce blood pressure (03:39:33) How to measure blood pressure (03:45:30) Peter's longevity optimization routines Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/premium

Elite Athletes and COVID-19; Statin and Ezetimibe in Acute Coronary Syndrome; Redo-TAVR; Chagas Disease Progression

Specialist hired by MPMD and host of the podcast Atlas Hour. Dr. Hotchkiss specializes in health and performance optimization and body composition and competes in powerlifting, bodybuilding, and CrossFit. In today's podcast, he covers a wide range of topics associated with hormone replacement therapy, cardiovascular disease, insulin resistance, PED's, anabolic steroids and more as well as a Q&A from the audience.  If you liked this episode, please share it with your friends or family. To support the podcast, the best cost-free way is to subscribe and please rate the podcast 5* on spotify and apple podcasts. Thanks for watching. Watch The Podcast: https://www.youtube.com/channel/UCqgN2kieCEHwZ9M-QFBxfCgPharma TRT, GH analogs, peptides, IGF-1, var troche, fat-loss/hair-loss treatments, etc | HRT Men's Health Optimization: https://transcendcompany.com/patient-intake-form/?ls=Nyle+NaygaHuge Elements Line (astragalus, citrus bergamot, etc): https://hugesupplements.com/collections/elementsCode 'NYLE' for 10% off - proceeds go towards upgrading content productionHuge Supplements (Protein, Pre, Utilize, Vital): https://hugesupplements.com/?aff=165Support code 'NYLE' 10% offYoungLA Clothes: https://www.youngla.com/discount/nyleYoungLA For Her: https://www.youngla.com/collections/all-products-1/For-HerCode ‘NYLE' to support the podcastLet's chat about the Podcast:Instagram: https://www.instagram.com/transparentpodcast/TikTok: https://www.tiktok.com/@transparentpodcastCoaching | Personalized program:  https://www.nylenaygafitness.com00:00:00 – 00:09:00 - Dr. Hotchkiss | Is Josh Manoi Natural?00:09:00 – 00:17:09 - Journey and PED's00:17:09 -  00:25:32    - Nandrolone00:25:32 -  00:31:03 - Tren, Hormones & Loyalty00:31:03 -  00:37:25 - Red Pill & Open Relationships00:37:25 - 00:43:51 - Cognitive Function, Cyclic Dextrin & more00:43:51 - 00:53:00 - Sleep Apnea, Kratom, Digestion00:53:00 - 00:58:35 - Insulin Resistance & more00:58:35 - 01:10:19 - Ezetimibe, Telemisartin, Cholesterol, Heart Disease, Blood Work, Food01:10:19 - 01:36:19 - Q&A Q 0101:36:19 - 01:43:43 - Q&A Q 02#podcast #mentalhealth #discipline #selfdevelopment #personaldevelopment #fitness #ifbbpro #npc #bodybuilder #bodybuilding #selfimprovement #workout #gym #nutrition #mensphysique #classicphysique #love #discipline #relationships #tren #workout #gym #trt #hormones #discipline #hardstyle #music #edm #zyzz #gear #steroids #bodybuilding #peptides fitness trt hormones personal development

Welcome to the 18th episode in my drug name pronunciation series!  We're talking about ezetimibe today.  In the first 4 minutes, I break ezetimibe down into syllables, explain which syllable has the emphasis, and reveal the source of the information. The last 4 minutes is a bonus.  My husband (Nathan) guest appears to say some drug names from this series.  Why? To share a fun memory!  When I was in pharmacy school, Nathan made me laugh/distracted me from the stress of studying by say drug names and medical terms badly.  It worked!  I laughed a lot, thanks to Nathan.  During this episode, Nathan shows that he can still make me laugh! Thank you for listening to episode 228 of The Pharmacist's Voice ® Podcast! Read the FULL show notes on https://www.thepharmacistsvoice.com/podcast.  Look for episode 228. Subscribe to or follow The Pharmacist's Voice ® Podcast to get each new episode delivered to your podcast player and YouTube every time a new one comes out.   Apple Podcasts   https://apple.co/42yqXOG  Google Podcasts  https://bit.ly/3J19bws  Spotify  https://spoti.fi/3qAk3uY  Amazon/Audible  https://adbl.co/43tM45P YouTube https://bit.ly/43Rnrjt Ezetimibe has four syllables. ezetimibe = e ZET i mibe e, which is a short “E” sound, like the “E” in “bed.” This sounds like a schwa “E.”  (Like the second “E” in the word “elephant.”) ZET, which rhymes with “pet” I, as in “illusion” (short “I” sound, almost like a schwa “I.”  Think of the “I” in the word “president.”) mibe, which rhymes with “vibe” (“I” has the long “I” sound, like “ice cream” or “eyeball.”) I found the pronunciation of ezetimibe in the USP Dictionary Online.  The pronunciation guide is especially important for the last syllable in ezetimibe.  Thank you to the USP Legal Dept for permission to publish your written pronunciations in my podcast show notes! 5 drug names from the bonus Ezetimibe (Episode 228) Metoprolol (Episode 177, 8th episode in this series) talimogene laherparepvec or T-VEC (Episode 159, 6th in this series) Eszopiclone (Episode 134, 1st episode in this series) Carisoprodol (Episode 198, 13th in the series)    Links from this episode USP Dictionary Online (aka USAN)   USP Dictionary's (USAN) pronunciation guide (Source:  American Medical Association's  website Alice and Jack Hike the Grand Canyon by RDML Pam Schweitzer, PharmD and her daughter Amy Graves (children's book) The Pharmacist's Voice ® Podcast episode 219, pronunciation episode 17 (semaglutide) The Pharmacist's Voice ® Podcast episode 215, pronunciation episode 16 (mifepristone and misoprostol) The Pharmacist's Voice ® Podcast episode 211, pronunciation episode 15 (Humira®) The Pharmacist's Voice ® Podcast episode 202, pronunciation episode 14 (SMZ-TMP) The Pharmacist's Voice ® Podcast episode 198, pronunciation episode 13 (carisoprodol) The Pharmacist's Voice ® Podcast episode 194, pronunciation episode 12 (tianeptine) The Pharmacist's Voice ® Podcast episode 188, pronunciation episode 11 (insulin icodec)  The Pharmacist's Voice ® Podcast episode 184, pronunciation episode 10 (phenytoin and isotretinoin) The Pharmacist's Voice ® Podcast episode 180, pronunciation episode 9 Apretude® (cabotegravir) The Pharmacist's Voice ® Podcast episode 177, pronunciation episode 8 (metoprolol)  The Pharmacist's Voice ® Podcast episode 164, pronunciation episode 7 (levetiracetam) The Pharmacist's Voice ® Podcast episode 159, pronunciation episode 6 (talimogene laherparepvec or T-VEC)  The Pharmacist's Voice ® Podcast episode 155, pronunciation episode 5 Trulicity® (dulaglutide)  The Pharmacist's Voice ® Podcast episode 148, pronunciation episode 4 Besponsa® (inotuzumab ozogamicin) The Pharmacist's Voice ® Podcast episode 142, pronunciation episode 3 Zolmitriptan and Zokinvy The Pharmacist's Voice ® Podcast episode 138, pronunciation episode 2 Molnupiravir and Taltz The Pharmacist's Voice ® Podcast episode 134, pronunciation episode 1 Eszopiclone and Qulipta 

Special guest Steven E. Nissen, MD, MACC, the Chief Academic Officer at the Heart and Vascular Institute, Lewis and Patricia Dickey Chair in Cardiovascular Medicine, and Professor of Medicine at the Cleveland Clinic Lerner School of Medicine at Case Western Reserve University joins us to talk about non-statins for LDL lowering.Listen in as they debate which non-statin to use for LDL lowering...due to recent headlines about bempedoic acid.You'll also hear practical advice from panelists on TRC's Editorial Advisory Board:Reid B. Blackwelder, MD, FAAFP, Associate Dean of Graduate and Continuing Medical Education at East Tennessee State UniversityAndrea Darby Stewart, MD, Associate Director, Family Medicine Residency at Honor HealthAnthony A. Donato, Jr., MD, MHPE, Associate Program Director, Internal Medicine from the Reading Health System, and Professor of Medicine at the Sidney Kimmel Medical College at Thomas Jefferson UniversityDouglas S. Paauw, MD, MACP, Professor of Medicine at the University of Washington School of MedicineCraig D. Williams, PharmD, FNLA, BCPS, Clinical Professor, Department of Pharmacy Practice at the Oregon Health and Science UniversityFor the purposes of disclosure, Dr. Steven Nissen reports relevant financial relationships [cardiology] with AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Medtronic, MyoKardia, New Amsterdam Pharma, Novartis, Pfizer, Silence Therapeutics (grants/research support). The other speakers have nothing to disclose. All relevant financial relationships have been mitigated.Pharmacist's Letter offers CE credit for this podcast. Log in to your Pharmacist's Letter account and look for the title of this podcast in the list of available CE courses.If you're not yet a Pharmacist's Letter subscriber, find out more about our product offerings at trchealthcare.com. Follow or subscribe, rate, and review this show in your favorite podcast app. You can also reach out to provide feedback or make suggestions by emailing us at ContactUs@trchealthcare.com.

This week I continued with my series on cardiovascular health. We explored how statin drugs work to lower cholesterol and how they cause detrimental side effects. We talked about another commonly used drug that also has side effects, ezetimibe. And there's the somewhat newer PCSK-9 inhibitors, which lower cholesterol by an alternate mechanism. For some […]

“We're clearly over-nourished, under-muscled, under-slept, and overstressed. All of those things dramatically impact our state of health," says Peter Attia, M.D. Peter, a Stanford, John Hopkins, and NIH-trained physician, joins us to discuss how we can actually eradicate cardiovascular disease, plus: - Peter's personal connection to healthspan & heart health (~00:58) - The four horsemen that lead to death (~03:25) - What's driving chronic disease? (~06:37) - What is ApoB & why is it important? (~11:26) - Does exercise play a role in lowering ApoB? (~17:37) - How pharmaceuticals can lower ApoB (~18:35) - Why aren't we talking about these heart disease treatments? (~22:36) - The best lab tests to measure cardiovascular health (~31:39) - The best lifestyle modifications for heart health (~36:36) - Labs you should demand at the doctor (~39:01) - Peter's personal nutrition philosophy (~43:34) - How to eat more protein every day (~46:48) - Why exercise is the ultimate elixir (~53:09) - What we still don't know about cardiovascular health (~01:00:52) - The power of grip strength for longevity (~01:03:24) - How Peter views the future of well-being (~01:06:10) Order a copy of my new book The Joy Of Well-Being at thejoyofwellbeing.com!  Referenced in the episode: - Peter's book, Outlive. - Peter's podcast, The Drive. - Research on PCSK9 inhibitors, Ezetimibe, and Bempedoic Acid. - National Lipid Association member finder. - SPRINT trial on blood pressure. - STOP-Bang questionnaire. - A study on exercise & mortality risk. - mbg Podcast episode #466, with Don Layman, Ph.D. - Maui Nui Venison Snacks & UCAN granola. - Sign up for The Long Game.  We hope you enjoy this episode, and feel free to watch the full video on YouTube! Whether it's an article or podcast, we want to know what we can do to help here at mindbodygreen. Let us know at: podcast@mindbodygreen.com.

Commentary by Dr. Valentin Fuster

Episode #253. In Part Three of the blood lipids series, we take a deep dive into interventions to lower the risk of atherosclerotic cardiovascular disease (ASCVD). While nutrition is the most powerful lifestyle tool we have to dramatically decrease ApoB, there certainly remains a need for pharmacological interventions – and in this episode, Dr Thomas Dayspring and I walk through four main drug classes, discussing their mechanism of action, effectiveness, and safety profile. We discuss: Evolution of cardiovascular disease treatments (03:42) Are we becoming a drug-dependent society? (07:30) Bile acid sequestrants, statins, and more (13:54) Cholesterol-lowering drugs and cognition (35:12) Is Bempedoic acid a good statin alternative? (47:39) Ezetimibe and nuances you should know (55:46) PCSK9 inhibitors (1:03:32) Do statins increase the risk of diabetes? (1:14:58) Gene therapy targeting PCSK9 (1:19:20) Pelacarsen for lowering Lp(a) (1:23:48) Can we take drugs that raise HDL to lower cardiovascular disease risk? (1:26:38) HDL and atherosclerosis (1:34:59) Elevated triglycerides and atherosclerosis (1:46:48) Takeaways (2:05:12) Outro (2:08:31) The best place to connect with Dr Thomas Dayspring is on Twitter, @DrLipid. Learn more about Dr Dayspring's career and current work on LinkedIn. Head to The Proof website for the full show notes, including supporting studies and my key takeaways. To assist with the digestibility of this content, Dr Dayspring, my team, and I have included extensive illustrations and graphs in the video format of these episodes. If you are visually inclined, you can watch these episodes on The Proof YouTube channel. Even if you prefer listening through audio the first time, I highly recommend coming back for a second pass with the video versions. These episodes are investments into a healthier future. We are also currently working on a summary PDF highlighting the key learnings from each part of the series. To receive a copy of this simply submit your email at theproof.com/lipidseries. We are also working on transcripts for these episodes, with the release date to be advised soon. Enjoy, friends. Simon Want to support the show? The best way to support the show is to use the products and services offered by our sponsors. To check them out, and enjoy great savings, visit theproof.com/friends. You can also show your support by leaving a review on the Apple Podcast app and/or sharing your favourite episodes with your friends and family. Simon Hill, MSc, BSc (Hons) Creator of theproof.com and host of The Proof with Simon Hill Author of The Proof is in the Plants Watch the episodes on YouTube or listen on Apple/Spotify Connect with me on Instagram, Twitter, and Facebook Nourish your gut with my Plant-Based Ferments Guide Download my complimentary two-week meal plan and high-protein Plant Performance recipe book

Huberman Lab Podcast Notes Key Takeaways Prevention of atherosclerosis (the leading cause of death in the world): (1) maintain healthy blood pressure (120/80); (2) don't smoke anything; (3) measure ApoB and lipoproteins starting in the 20sApoB is far superior for predicting risk than LDL: LDLc measures the total concentration of cholesterol in LDL; APoB measures the number of them “There is no ambiguity that ApoB is causally related to atherosclerosis.” – Dr. Peter AttiaMost of the cholesterol you eat, you don't absorbUnequivocal truths for brain health: sleep matters, lower LDL cholesterol, and ApoB is better, not having type 2 diabetes matters, exercise matters (low-intensity cardio, strength, interval training) Avoiding head injuries is also important; research on the use of hyperbaric oxygen immediately following head injury is emerging (but don't consider hyperbaric oxygen as useful for anything else)“Some component of your training needs to be stressing type 2 fibers. You have to be doing strength training that taxes those fibers.” – Dr. Peter AttiaTo offset the probability of falls you have to be able to jump and land safely – after a fall at minimum your quality of life is impacted, on the far end risk of death increases by 15-30%The Hallmark of aging in muscle is the degradation of type 2 muscles (fast twitch) – we lose speed, then strength, then size; you have to train jumping and landing Pillars of longevity through physical health: (1) strength, (2) stability, (3) aerobic efficiency, (4) aerobic peak output/VO2 maxEmotional health is potentially the most important factor in health – an infinite lifespan if you're miserable is worthless; poor emotional health is a risk factor for every marker of health Redirect negative self-talk: communicating lovingly with yourself is critical for your ability to not beat up those around you as wellThe goal is not perfection – you will set yourself up for failure if your goal is to be perfect, instead focus on being the best at repairing damage when you cause it  Read the full notes @ podcastnotes.orgIn this episode, my guest is Peter Attia, M.D. He completed his medical and advanced training at Stanford University School of Medicine, Johns Hopkins School of Medicine and the National Institutes of Health (NIH). Dr. Attia is host of the health and medicine podcast, The Drive, and the author of a new book, “Outlive: The Science & Art of Longevity,” which examines disease prevention and healthy aging, including emotional health. He explains the leading causes of death worldwide and how to measure one's risk of death and mitigate each risk factor. Dr. Attia shares how, in addition to blood-based markers of lipids and hormones, there are behavioral measures and interventions, and key aspects of emotional health (i.e., relationships, emotional stability, purpose, etc.) that fundamentally impact our physical health and longevity, and how to assess and adjust our emotional health. This episode is rich with actionable information related to disease screening and biomarker testing, nutritional, exercise, behavior and prescription-based tools that area useful to all people regardless of age, male or female, and that can significantly improve vitality, health and lifespan. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman Eight Sleep: https://eightsleep.com/huberman LMNT: https://drinklmnt.com/huberman   HVMN: https://hvmn.com/huberman InsideTracker: https://www.insidetracker.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Timestamps (00:00:00) Dr. Peter Attia (00:03:22) Sponsors: Eight Sleep, LMNT, HVMN, Momentous (00:07:34) Lifespan vs. Healthspan (00:10:54) “4 Horseman of Death”, Diseases of Atherosclerosis (00:14:44) Tool: Hypertension & Stroke, Blood Pressure Testing  (00:23:14) Preventing Atherosclerosis, Smoking & Vaping, Pollution (00:32:24) Sponsor: AG1 (Athletic Greens) (00:33:29) Cholesterol, ApoB (00:42:21) Cholesterol Levels, LDL & ApoB Testing (00:49:29) ApoB Levels & Atherosclerosis, Causality (01:01:06) ApoB Reduction, Insulin Resistance, Statins, Ezetimibe, PCSK9 Inhibitors (01:12:30) Monitoring ApoB (01:17:12) Sponsor: InsideTracker (01:18:30) Reducing Blood Pressure, Exercise & Sleep (01:20:50) High Blood Pressure & Kidneys (01:23:11) Alcohol, Sleep & Disease Risk (01:31:21) Cancer & Cancer Risks: Genetics, Smoking & Obesity (01:39:47) Cancer Screening & Survival (01:44:17) Radiation Risks, CT & PET Scans (01:48:48) Environmental Carcinogens (01:52:11) Genetic & Whole-Body MRI Screening, Colonoscopy (01:58:47) Neurodegenerative Diseases, Alzheimer's Disease, ApoE (02:08:08) Alzheimer's Disease & Amyloid (02:13:58) Interventions for Brain Health, Traumatic Brain Injury (TBI) (02:21:26) Accidental Death, “Deaths of Despair”, Fentanyl Crisis (02:31:20) Fall Risk & Stability, 4 Pillars of Strength Training (02:41:05) Emotional Health (02:53:45) Mortality & Preserving Relationship Quality (03:02:20) Relationships vs. Outcomes, Deconstructing Emotions (03:09:34) Treatment Centers, Emotional Processing & Recovery (03:16:34) Tool: Inner Monologue & Anger, Redirecting Self-Talk (03:27:37) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Social Media, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

In this episode, my guest is Peter Attia, M.D. He completed his medical and advanced training at Stanford University School of Medicine, Johns Hopkins School of Medicine and the National Institutes of Health (NIH). Dr. Attia is host of the health and medicine podcast, The Drive, and the author of a new book, “Outlive: The Science & Art of Longevity,” which examines disease prevention and healthy aging, including emotional health. He explains the leading causes of death worldwide and how to measure one's risk of death and mitigate each risk factor. Dr. Attia shares how, in addition to blood-based markers of lipids and hormones, there are behavioral measures and interventions, and key aspects of emotional health (i.e., relationships, emotional stability, purpose, etc.) that fundamentally impact our physical health and longevity, and how to assess and adjust our emotional health. This episode is rich with actionable information related to disease screening and biomarker testing, nutritional, exercise, behavior and prescription-based tools that area useful to all people regardless of age, male or female, and that can significantly improve vitality, health and lifespan. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman Eight Sleep: https://eightsleep.com/huberman LMNT: https://drinklmnt.com/huberman   HVMN: https://hvmn.com/huberman InsideTracker: https://www.insidetracker.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Timestamps (00:00:00) Dr. Peter Attia (00:03:22) Sponsors: Eight Sleep, LMNT, HVMN, Momentous (00:07:34) Lifespan vs. Healthspan (00:10:54) “4 Horseman of Death”, Diseases of Atherosclerosis (00:14:44) Tool: Hypertension & Stroke, Blood Pressure Testing  (00:23:14) Preventing Atherosclerosis, Smoking & Vaping, Pollution (00:32:24) Sponsor: AG1 (Athletic Greens) (00:33:29) Cholesterol, ApoB (00:42:21) Cholesterol Levels, LDL & ApoB Testing (00:49:29) ApoB Levels & Atherosclerosis, Causality (01:01:06) ApoB Reduction, Insulin Resistance, Statins, Ezetimibe, PCSK9 Inhibitors (01:12:30) Monitoring ApoB (01:17:12) Sponsor: InsideTracker (01:18:30) Reducing Blood Pressure, Exercise & Sleep (01:20:50) High Blood Pressure & Kidneys (01:23:11) Alcohol, Sleep & Disease Risk (01:31:21) Cancer & Cancer Risks: Genetics, Smoking & Obesity (01:39:47) Cancer Screening & Survival (01:44:17) Radiation Risks, CT & PET Scans (01:48:48) Environmental Carcinogens (01:52:11) Genetic & Whole-Body MRI Screening, Colonoscopy (01:58:47) Neurodegenerative Diseases, Alzheimer's Disease, ApoE (02:08:08) Alzheimer's Disease & Amyloid (02:13:58) Interventions for Brain Health, Traumatic Brain Injury (TBI) (02:21:26) Accidental Death, “Deaths of Despair”, Fentanyl Crisis (02:31:20) Fall Risk & Stability, 4 Pillars of Strength Training (02:41:05) Emotional Health (02:53:45) Mortality & Preserving Relationship Quality (03:02:20) Relationships vs. Outcomes, Deconstructing Emotions (03:09:34) Treatment Centers, Emotional Processing & Recovery (03:16:34) Tool: Inner Monologue & Anger, Redirecting Self-Talk (03:27:37) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Social Media, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

#1123-Podcast Cardiopapers: Estatina + ezetimibe é uma boa opção para hipercolesterolemia? by Cardiopapers

Hyperlipidemia treatments are really about statins and then what to do if that doesn't work. This episode has a few mnemonics that will help you remember them.  Need more help; you can find many of my mnemonics books on Audible that you might be able to get your first for free if you've never had one before.  https://www.audible.com/pd/Memorizing-Pharmacology-Mnemonics-Audiobook/B07DLGC8MP?source_code=AUDFPWS0223189MWT-BK-ACX0-118296&ref=acx_bty_BK_ACX0_118296_rh_us

Lipids Update 2022: Cardiovascular Risk Reduction and New Medications on the Horizon with Erin Michos, MD Show description:  Ready to take the next step in management of your patient with hyperlipidemia? Dr. Erin Michos (@erinmichos) returns to give us a lesson in Advanced Lipidology. She updates us on what new medications we can use for those difficult to treat lipids and what medications are on the horizon. Unfortunately, this episode will not be available for CME. You can claim free CME for other episodes at curbsiders.vcuhealth.org! Episodes | Subscribe | Spotify | Swag! | Top Picks | Mailing List | askcurbsiders@gmail.com | Free CME! Show Segments Intro, Getting to know Dr. Erin Michos, Pick of the Week Patient Case, Digging into ASCVD Risk  Coronary artery calcium scoring - why it's important What are “Risk Enhancing Factors”? Biomarker testing, what is the significance of Lip a and how can we use it to drive management? Introduction to PCSK9 inhibitors More than just statins - other LDL-lowering medications siRNAs, ASOs - Pelacarsen and more Apollo Trial regarding Pelacarsen Importance of Family History What to do if maxed out on a statin or statin intolerance - Ezetimibe, PCSK9 inhibitors, MAB therapies, and more Bempedoic Acid discussion Medication side effects Homozygous FH - approach to treatment, ANGPTL3 inhibitors Triglycerides discussion, icosapent ethyl, the REDUCE-IT trial Wrap-up and Take home points, Outtro Credits Producer and written by: Christopher Chiu MD, FACP, FAAP Show Notes: James Antaki MD Infographic: Edison Jyang Cover Art: Kate Grant MBChB, DipGUMed Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP    Associate Editor: Leah Witt MD Showrunner: Matthew Watto MD, FACP Technical Production: PodPaste Guest: Erin Michos MD, MHS Sponsor: Birch Living Birch is giving $400 off all mattresses and 2 free eco-rest pillows at BirchLiving.com/curb. 

This week on Pharm5: LDL

High-Intensity Statins have been the treatment of choice for ASCVD. However, the recent non-inferiority RACING study evaluates the role of combination moderate-dose statin plus ezetimibe to high-dose statin in ASCVD. Host Geoff Wall breaks down another potential GameChanger in Pharmacotherapy.The GameChanger Combination moderate-dose statins plus ezetimibe may be non-inferior to high-dose statins – and have the benefit of better tolerability. Show Segments 00:00 – Introductions 01:55 – Long-Term Efficacy and Safety of Moderate Intensity Statins with Ezetimibe 02:55 – Statins and Ezetimibe in ASCVD  13:52 – The GameChanger 20:50 – Connecting to Practice  22:01 – Closing Remarks Host Geoff Wall, PharmD, BCPS, FCCP, CGP Professor of Pharmacy Practice, Drake University Internal Medicine/Critical Care, UnityPoint Health References and resources:Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trialRedeem your CPE or CME creditCPE (Pharmacist) CME (Physician) Get a membership & earn CE for GameChangers Podcast episodes (30 mins/episode) Pharmacists: Get a Membership Prescribers: Get a Membership Continuing Education Information:Learning Objectives:1. Discuss the RACING study results comparing moderate-dose statin plus ezetimibe to high-dose statins2. Describe the known ‘nocebo' effect of muscle-related statin adverse effects. 0.05 CEU | 0.5 HrsACPE UAN: 0107-0000-22-310-H01-PInitial release date: 09/05/22Expiration date: 09/05/2023Additional CPE & CME details can be found here 

Let's have a talk based on a very recent meta-analysis from the BMJ about PCSK9 and ezetimibe use in prevention of ASCVD/MACEvents.

In the latest Hot Topics podcast from NB Medical Dr Neal Tucker discusses the latest research important in primary care and interviews two experts in improving asthma care and sustainable healthcare.In new research we examine: The role of self-monitoring of BP in women with hypertension or higher risk of pre-eclampsia - does it provide early detection?Do ezetimibe and PCSK9 inhibitor provide additional real-world benefits over statins alone? Which is best?Can an oral biological agent, baricitinib, provide some hope for patients with severe alopecia?We are also joined by Dr Aarti Bansal and Dr Veena Aggarwal to talk about improving asthma care with a new Asthma Toolkit from Greener Practice and healthcare sustainability in the UK. Why are our asthma outcomes poor? Can simple measures improve care? What is the NHS doing to help primary care reduce its carbon footprint?If you want more join us for our FREE NB Clinic on Tuesday 17th May, 8pm, for Improving Asthma Care and Thinking Green.ResourcesGreener Practice Asthma ToolkitJAMA Self-monitoring of BP in PregnancyBMJ Ezetimibe and PCSK9 inhibitors for Reducing CVD Risk: network meta-analysisBMJ Lipid-lowering medication Rapid Recommendations NEJM Baricitinib for AlopeciaFaculty of Medical Leadership and Management Fellowship webpageBMJ Open Cost of Switching Asthma Inhalers

The role of Ezetimibe in reducing CVD adverse outcomes

Commentary by Dr. Valentin Fuster

Leo's channel: https://www.youtube.com/c/LeoandLongevity Derek's channel: https://www.youtube.com/channel/UCoR7CHkMETs3ByOv74OAbFw Steve's channel: https://www.youtube.com/user/VigorousSteve TIMESTAMPS: 0:00 intro 0:29 Connor Murphy/ Ayahuasca and DMT 1:36 Kenny KO and Connor 2:10 Leo on psychedelics/ his friend 3:38 Steve on psychedelics 5:29 Marijuana and schizophrenia/ More on Connor 7:45 Man cutting his genitals off on drugs 9:30 Screen sharing on Zoom 9:58 Leo's manic Canadian friend 10:47 Derek will avoid psychedelics 12:13 Derek on being ambitious 13:29 Losing your ego 14:12 How Leo hurt his finger 16:42 Antoine's Vaillant bicep and Olympia placing 19:06 Derek's bodybuilding genetics 20:13 Why Derek stopped doing steroids/ Making money as a bodybuilder 23:16 GH15, Antoine, and Frank Mcgrath 24:44 Bodybuilding, dieting, and tren 26:25 Recovery from injury Beta-blockers either before or after a surgery Nebivolol, collagen and gelatin protein, Propranolol, 29:03 Angiogenesis BPC 157, TB500, erythropoietin 31:06 Growth factors and hair loss/ Icing and cooling injuries 32:06 MK677, ghrelin  and surgeries/ MK677, GH, and IGF1 34:05 MK677, Ghrelin, PTSD, and Insulin 39:22 Jujimufu and Greg Ducette/Canadian accents 43:34 People being hyper-critical of people in the fitness industry. 44:49 Jujimufu, arm wrestling, and stomach distension 47:53 Leo's GH experience 49:31 Jujimufu's genetics 51:06 Looking like you work out while wearing a shirt 52:25 Anabolic pathways 53:30 Dallas McCarver autopsy/ Anthony Roberts ban 58:20 Dallas McCarver organs 1:00:21 Leo's friend taking large sums of steroids/ Derek on the autopsy 1:07:00 Derek and Steve on blood and urine drug tests/ Tren cough 1:11:10 What steroids do to your heart Dislipidemia, HDL goes down, HDLC decreases by approx 50%, APO A1 decreases by 33-41%, increases LDLC by approx 36% Reduce lipoprotein [a] 1:12:41 Homocysteine blood tests/ Chris Masterjohn  Creatine, Choline, B vitamins 1:13:50 More on Lipoprotein [a] Niacin, Repatha, and steroids 1:15:01 Derek's client with strange test results 1:15:54 Hypercholesterolemia  Homozygous APOCIII, CETP, and APOE4 1:17:33 Steroids, left ventricular systolic function, left ventricular diastolic function, and heart hypertrophy. 1:19:15 Heart FMRI 1:20:28 Impaired tonic cardiac autonomic regulation, and Clenbuterol 1:22:32 Leo's list of tests and genetics 1:23:25 Statins, Ezetimibe, and cholesterol 1:25:00 Automated gene searches 1:26:09 Statins and natural status 1:27:24 Lowering LDL and extending life PCSK9 inhibitors, Bempedoic acid, Ezetimibe, and Statins 1:28:41 Steve on Ezetimibe 1:29:32 Leo on Statins (the good and the bad) Pitavastatin, Rosuvastatin crestor ,livalo, lipitor 1:33:56 Telmisartan, Valsartan, Azilsartan and Irbesartan 1:39:17 Diuretics, bloating, and Estrogen 1:41:28 Hyperkalemia, Potassium and drug interactions 1:43:20 Minoxidil as a potassium channel opener and microneedling 1:45:49 Steve doesn't like hair 1:47:40 Leo's hypothesis on hair loss/ Derek on hair loss 1:54:25 Topical dutasteride 1:55:35 70-year-old women and balding 1:56:45 Steve on being secure with hair loss 2:00:40 Men and size 2:02:04 Pre-workout androgens Anadrol, Dianabol, Superdrol and Anadrol 2:08:26 Taking short-acting compounds around your workout 2:10:00 How steroids cause liver cancer and why Anavar doesn't cause it 2:11:56 Dianabol back pumps 2:13:19 Egyptian bodybuilders 2:14:52 Steve's fasting protocols 2:18:15 Reasons to fast 2:20:44 Leo's reasons to fast/ Satchin Panda's book/Valter Longo's fasting-mimicking diet and Prolon 2:23:47 Proper fasts on PEDs Allopurinol 2:27:36 How Steve and Leo prepare salads 2:30:35 The discord group 2:34:19 Unhealthy relations to Youtubers 2:39:58 Epigenetics and children 2:43:14 IVF and metabolic profiles 2:45:35 Coming off of testosterone and getting back to baseline 2:46:37 Having kids at an older age (epigenetic damage over time to sperm) 2:49:42 Steve and Leo on TV 2:50:15 Past downloading services 2:54:06 Unusual pre workout supplements for more strength or a better pump 2:56:40 Why the hell are people taking Phenibut and Kratom pre workout 2:58:00 Low dose Naltrexone therapy 3:00:16 Getting over addiction 3:02:34 Gynecomastia 3:05:43 Removing your glands before you take steroids/ Problems with Nolvadex 3:08:02 Derek and Steve on their gyno experiences 3:10:45 How to deal with gyno if you don't want the surgery 3:11:56 Steve on growing your gyno, to get the surgery JOIN OUR COMMUNITY: Reddit ▶ https://www.reddit.com/r/TheLongLived/ FOR GENETIC ANALYSIS & COACHING: Website ▶ https://www.leoandlongevity.com TO READ MY ARTICLES: Blog ▶ https://www.leoandlongevity.com/blog TO FOLLOW ME ON SOCIAL MEDIA:  Instagram ▶ https://www.instagram.com/leoandlongevity Twitter ▶ https://www.twitter.com/leoandlongevity

Zetia (Ezetimibe) Antitrust v. Merck & Company, Inc.

En este episodio de Red Silanes: en aras de dar con un tratamiento efectivo que se adapte a las necesidades de cada uno de los pacientes, el doctor Miguel Angel Monribot explica que la elección de un tratamiento médico debe hacerse con base en los estudios científicos, por lo que desglosa las ventajas que representa la combinación Rosuvastatina-Ezetimibe por encima de cualquier otra opción; además de describir la diferencia entre la Simvastatina y la Rosuvastatina.

Commentary by Dr. Kathryn Ruddy

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: And I'm Dr Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, our feature article this week relates to an international multi-center evidence-based reappraisal of genes reported to cause congenital long QT syndrome. But, before we get to that, how about if we grab a cup of coffee and start on our other papers? Do you have one you'd like to discuss? Dr Carolyn Lam: Yes. My favorite part of the week. So this first paper really asks the question, "What's the association between HDL functional characteristics, as opposed to HDL cholesterol levels, and acute coronary syndrome?" The paper comes from Dr Hernáez from IDIBAPS in Barcelona, Spain and colleagues who conducted a case control study nested within the PREDIMED cohort. Originally a randomized trial where participants followed a Mediterranean or low-fat diet. Cases of incident acute coronary syndrome were individually matched one is to two to controls by sex, age, intervention group, body mass index, and follow-up time. The authors measure it the following functional characteristics, which were HDL cholesterol concentration, cholesterol efflux capacity, antioxidant ability, phospholipase A2 activity and sphingosine-1-phosphate, apolipoproteins A1 and A4, serum amyloid A and complement 3 protein. Dr Greg Hundley: Wow Carolyn, a detailed analysis. What did they find? Dr Carolyn Lam: They found that low values of cholesterol efflux capacity, and levels of sphingosine-1-phosphate and apolipoprotein A1 in HDL or all associated with a higher risk of acute coronary syndrome in high cardiovascular risk individuals, irrespective of HDL cholesterol levels and other cardiovascular risk factors. Low cholesterol efflux capacity values and sphingo-1-phosphate levels were particularly associated with an increased risk of myocardial infarction, whereas HDL antioxidant or anti-inflammatory capacity was inversely related to unstable angina. Now this is significant because it's the first longitudinal study to comprehensively examine the association of several HDL function related biomarkers with incident acute coronary syndrome beyond HDL cholesterol levels in a high-risk cardiovascular risk population. Greg Hundley: Very nice. Carolyn. It sounds like function over just the levels is important. Dr Carolyn Lam: Exactly, you summarized it well. Well Greg, I've got another paper and I want to pick your brain first. Is it your impression that type 2 myocardial infarction, the type that occurs due to acute imbalance in myocardial oxygen supply versus demand in the absence of atherothrombosis, do you think that this type of MI is on the rise? It seems more and more common in my country. Dr Greg Hundley: Do we want to say it's on the rise? Certainly by measuring all these high sensitivity troponins, et cetera, we're finding, I think, more evidence of type 2 MI. So, all in all, yeah it probably is on the rise, but likely related to some of our measurement techniques. Dr Carolyn Lam: Oh, you are so smart, Greg. Because this paper that I'm about to tell you about really addresses some of these issues and it's from corresponding author Dr Gulati from Mayo Clinic in Rochester, Minnesota. And they really start by acknowledging that despite being frequently encountered in clinical practice, the population base incidents and trends of type 2 myocardial infarction is unknown and long-term outcomes are incompletely characterized. So they prospectively recruited 5,640 residents of Olmsted County, Minnesota who experienced an event associated with cardiac troponin T greater than 99th percentile of a normal reference population, which is greater than or equal to 0.01 nanograms per milliliter. And this was between 2003 and 2012, so very careful to talk about which Troponin T assay exactly to the point you discussed earlier, Greg. The events were retrospectively classified into type 1 versus type 2 MI using the universal definition. Dr Greg Hundley: So Carolyn, what did they find? Dr Carolyn Lam: They found that there was an evolution in the types of MI occurring in the community over a decade with the incidence of type 2 MI now being similar to type 1 MI. Adjusted long-term mortality following type 2 MI is markedly higher than after type 1 MI and that's driven by early and non-cardiovascular deaths. Mortality of type 2 MI is associated with a provoking factor and is more favorable when the principle provoking mechanism was an arrhythmia compared with postoperative status, hypotension, anemia or hypoxia. And these findings really underscore the healthcare burden of type 2 MI and provide benchmarks for clinical trial design. Dr Greg Hundley: Very nice, Carolyn. Well, my paper comes from type 5 long QT syndromes and an analysis. And it's from Dr Jason Roberts from Western University. Through an international, multi-center collaboration, improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in long QT 5 was sought across 22 genetic arrhythmia clinics and four registries from nine countries that included 229 subjects with autosomal dominant long QT five. So there were 229 of those subjects. And then 19 individuals with the recessive type 2 Jervell and Lang-Nielsen syndrome. The authors compared the effects of clinical and genetic predictors on a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter defibrillators shocks, aborted cardiac arrest, and sudden cardiac death. Dr Carolyn Lam: Wow. What did they find? Dr Greg Hundley: Well, several things, Carolyn. First, rare loss of function KCNE1 variants are weakly penetrant and do not manifest with a long QT syndrome phenotype in a majority of individuals. That's a little bit of a surprise. Second, QT prolongation and arrhythmic risk associated with type 2 Jervell and Lang-Nielsen syndrome is mild in comparison with the more malignant phenotype observed for type 1 Jervell and Lang-Nielsen syndrome. And then number three, all individuals possessing a rare loss of function KCNE1 variant should be counseled to avoid QT prolonging medications and should undergo a meticulous clinical evaluation to screen for long QTS phenotype. And then finally, Carolyn, the last finding, in the absence of a long QTS phenotype, more intensive measures, such as beta blockade and exercise restriction, may not be merited. Dr Carolyn Lam: Oh, very interesting. Well, I've got one more original paper and in this, authors describe a new cellular mechanism linking ischemia-reperfusion injury to the development of donor specific antibody, a pathologic feature of chronic antibody-mediated rejection, which mediates late graph loss. This paper is from corresponding author Dr Jane Witt from Yale University School of Medicine and colleagues who use humanized models and patient specimens to show that ischemia-reperfusion injury promoted elaboration of interleukin 18 from endothelial cells to selectively expand alloreactive interleukin 18 receptor 1 positive T peripheral helper cells in allograph tissues and this promoted donor specific antibody formation. Dr Greg Hundley: Carolyn, here's the famous question. What does that mean clinically for us? Dr Carolyn Lam: Aha, I'm prepared. Therapies targeted against endothelial cell derived factors like interleukin 18 may therefore block late complications of ischemia-reperfusion injury. Dr Greg Hundley: Very nice. Sounds like more research to come. Well, how about other articles in the issue? Dr Carolyn Lam: Well, I'd love to talk about a white paper from Dr Al-Khatib, and it's about the research needs and priorities for catheter ablation of atrial fibrillation and this is a report from the National Heart, Lung, and Blood Institute Virtual Workshop. Dr Greg Hundley: Well, I've got another arrhythmia paper, so this is from Professor Michael Ackerman at the Mayo Clinic and its minor long QT gene disease associations by coupling the genome aggregation database. It's a harmonized database of 140,000 or more exomes and genome derived in part from population-based sequencing projects, with phenotypic insights gleaned from a large long QT syndrome registry to reassess the strength of these minor long QT syndrome gene disease associations. Next, Carolyn, in an on my mind piece, Professor Gerd Heusch from University of Essen Medical School discusses, how can the many positive preclinical and clinical proof of concept studies on reduced infarct size by ischemic conditioning interventions and cardioprotective drugs be reconciled with the mostly neutral results in regard to clinical outcomes. The author discusses the important differences between animal models that have been used a lot in this ischemia reperfusion and infarct size reduction science, and then the clinical scenarios of STEMI in humans as well as the many aspects of coronary reperfusion. How is that affecting the myocytes? How is that affecting the microcirculation, et cetera, that must be addressed? And then finally Carolyn, there is a series of letters, one from Professor Oliver Weingärtner from Universitätsklinikum Jena and another from Professor Yasuyoshi Ouchi from Toranomon Hospital. They're exchanging letters debating the utility of lipid lowering with Ezetimibe in individuals over the age of 75 years. Dr Carolyn Lam: Very nice, Greg. Thanks so much. Shall we now move to our future discussion. Dr Greg Hundley: You bet. Well, welcome everyone. This is our feature discussion and today we're going to hear more about long QT syndrome. We have Dr Michael Gollob from University of Toronto and our own associate editor, Dr Sami Viskin from Tel Aviv Medical Center. Good morning. Good afternoon, gentlemen. Before we get started with a discussion of some of the study findings and results, Michael, could you tell us a little bit about why you performed the study and what were some of the hypotheses you wanted to test? Dr Michael Gollob: As you know, long QT syndrome is probably the most recognized channelopathy associated with sudden cardiac death in young individuals and adults. And at the present time, there are 17 genes available for clinical genetic testing in cases of suspected long QT syndrome. We simply ask the question, "Is there sufficient scientific evidence to support that each of these genes are single gene causes of long QT syndrome based on our contemporary knowledge of genetics and the human genome? Dr Greg Hundley: Great, Michael. So, can you tell us a little bit about your study population? How did you go about this and what was your study design? Dr Michael Gollob: We designed a methods approach that would assure that any conclusions that were made from our working group were not based on the opinions of one or two individuals. We wanted to ensure that this was a consensus conclusion with multiple experts in the field including genomic scientists, genetic counselors, inherited arrhythmia experts, and researchers in the field. We created three independent teams of genetic experts to curate the genetic evidence reported in the medical literature for each of these 17 reported causes of long QT syndrome. This was essentially an evidence-based approach using a pre-specified evidence-based matrix or scoring system depending on the level of evidence, genetic primarily, in the reported literature for each gene. Each of these curation teams worked independently of each other and they were blinded to each other's work and they were tasked with concluding whether a gene, based on the medical literature and the resource methodologies, had sufficient evidence for disease causation. Their classifications would be one of disputed evidence, limited evidence, moderate evidence, strong or definitive evidence for claims towards disease causation. Remarkably, independently, all of these teams reached the same conclusion. In the end, their summary data was reviewed by a clinical domain expert panel with individuals with expertise, particularly in long QT syndrome and other channelopathies. So in total 19 individuals reviewed all of the literature and the data presented and came to unanimous conclusions for each gene. Dr Greg Hundley: Out of the 17, were there some that were more important than others or was it uniformly all 17 were relevant? Dr Michael Gollob: Well, I think the most relevant conclusions of our study are that nine of these genes, more than half of these genes, were felt not to have sufficient evidence to support their causation as a single gene cause for typical long QT syndrome. So nine genes that are currently tested by clinical genetic testing providers do not have enough evidence to support their testing in patients with suspected long QT. And to us, that is the most relevant observation because testing genes that do not have sufficient evidence for disease causation poses a significant risk to patient harm and family harm. We concluded that only three genes had very definitive evidence for causation of long QT syndrome. Those three genes were KCNQ1, KCNH2, and SCN5A. There were another four genes that were concluded to have strong or definitive evidence for unusual presentations of long QT syndrome. And by that, I mean presentations that typically occur in the neonatal period and are associated with heart block seizures or developmental delay or in the case of one of these genes, Triadin, an autosomal recessive form of the disease. Dr Greg Hundley: So helping us perhaps what types of genes to screen for when we have someone with this condition or suspected. So Sami, can you help us put this into perspective? How does this study help us in management of this clinical situation. Dr Sami Viskin: In Circulation, we immediately recognize the importance of the manuscript, the importance of the study because unfortunately, there are too many physicians all over who will accept the results of genetic testing essentially like gospel. Now it's in the DNA, it's in the genes, so whatever you find must be true. And too often, clinical decisions on treatment including ICD implantation have been undertaken based on results of genetic testing’s; thus are wrongly interpreted. So we recognize immediately the importance of this paper. We already had a different study by Dr Gollob and his associates. Again, reassessing the role of genes in Brugada syndrome. So we were familiar with this type of analysis. We recognize the importance and we moved ahead to accept this paper, it went fairly easily, I think only one revision. At the same time, we were getting additional paper by other groups. So in the same issue, we have two more papers, one from Jason Roberts with the International Long QT Registry of long QT 5, reaching similar conclusions that this is a gene with very limited penetrants and another study by the Mayo clinic also showing that many of the genes who are not the major genes are overrepresented in the healthy population. So we put all these three papers together with a very nice editorial by Chris Semsarian in the same issue. So everything is put in the right perspective of how we should be looking at all the genes of these disease in a different way. Dr Greg Hundley: So as a clinician quickly, how can I use this information in the issue, perhaps this paper and all three, in management of patients with either suspected or long QT syndrome? Dr Michael Gollob: First off, I would emphasize that the diagnosis of long QT syndrome or any genetic base disease for that matter, should be based on clinical phenotype and not the observation of a genetic change, particularly if genes are being tested that do not have strong evidence for disease causation, as is the case for the nine genes that we've pointed out in this manuscript. So I think clinicians need to be wary of the genetic testing panels that they are requesting be screened or used in the assessment of their patients and be knowledgeable that at this point in time, we really only have three genes with very strong evidence to support disease causation of the typical form of long QT syndrome. And that for the most part, these other genes should not be tested or should only remain in the realm of research. I think that responsibility extends further than just the clinician taking care of the patient, but also clinical genetic testing providers, companies that offer these genetic testing services. I think they should assume a responsibility to ensure that they are only offering services for genes that have strong evidence for disease causation because when they report results in genes that are not valid for the disease, that only confuses the care of the patient and that creates a risk of harm to them if that information is misinterpreted by a physician. As Dr Viskin or Sami pointed out, we do see patients who are inappropriately diagnosed. We remove the diagnosis of roughly 10 to 20% of cases in our own clinic. And unfortunately, many of these patients and their families have suffered undue anxiety. Some of them have ICDs in place that should not have been there. So I think overall, the field needs to be aware of what genes are relevant and what genes still are within the realm of research. Dr Greg Hundley: Can you tell us just quickly Michael and then also Sami, what do you see as the next study in this field? Dr Michael Gollob: We're taking a step back now. The first decade of this century saw an exponential growth in reported gene disease associations. And now in the last five or six years, we've learned a lot about human genetic variation, which has provided us an opportunity to reflect back on some of these previous and reported genes as causes for long QT and other diseases. So I think many individuals in our field may say, "Well, you know, this is disappointing. We believed in these genes. We really thought these genes were causes of long QT." And to that point I would say, we need more research. If you believe in some of these genes that have now been considered to have limited or disputed evidence, research should continue if these remain plausible candidates for the disease. So I think future research has to continue. There are probably still a few other genes that have not yet been discovered. I think we've got the vast majority. I think in most cases, at least in our experience, 90 to 95% of cases are explained by the top three genes. But there are probably other genes out there and it's always fascinating to learn or discover new genes, but those sorts of studies have to be done with the correct methodologies and rigid protocols. Lastly, I think in the future us clinicians and geneticists and genetic counselors need to work closely with genetic testing providers to ensure that they are offering responsible genetic testing services. Dr Greg Hundley: Sami, do you have anything to add? Dr Sami Viskin: Just congratulate the authors. I think they did a very great service to the medical community by pointing out the limitations of the genetic testing and the way we interpret the results, and they deserve to be applauded for reminding us that we have to be careful when we read papers about genetic results or when we get genetic testing results ourselves. Dr Greg Hundley: I want to thank Michael from University of Toronto and Sami from Tel Aviv Medical Center for participating. And on behalf of both Carolyn and myself, wish you all a great week and look forward to chatting with you next week. This program is copyright, the American Heart Association 2020.  

In this podcast, Robert Giugliano, MD, SM, discusses his latest analysis of IMPROVE-IT data, which compared simvastatin-ezetimibe combination therapy with simvastatin monotherapy among patients aged 75 years or older who had had acute coronary syndrome. He also explains which patient groups benefitted the most from ezetimibe add-on therapy. More at: www.consultant360.com/cardiology.

Commentary by Dr. Valentin Fuster

Interview with Richard G. Bach, MD, author of Effect of Simvastatin-Ezetimibe Compared With Simvastatin Monotherapy After Acute Coronary Syndrome Among Patients 75 Years or Older: A Secondary Analysis of a Randomized Clinical Trial, and Antonio M. Gotto, MD DPhil, author of Intensive Lipid Lowering in Elderly Patients

Interview with Richard G. Bach, MD, author of Effect of Simvastatin-Ezetimibe Compared With Simvastatin Monotherapy After Acute Coronary Syndrome Among Patients 75 Years or Older: A Secondary Analysis of a Randomized Clinical Trial, and Antonio M. Gotto, MD DPhil, author of Intensive Lipid Lowering in Elderly Patients

On this episode, I discuss ezetimibe pharmacology. Ezetimibe works by inhibiting Niemann-Pick C1-Like1 (NPC1L1) transporter. This transporter aids in cholesterol absorption so by blocking it, we can reduce cholesterol levels (and LDL) in the bloodstream. Ezetimibe is usually very well tolerated. Diarrhea, myopathy, and elevations in LFT's are adverse effects that have been reported but do not occur at high rates. Ezetimibe is dosed at 10 mg once daily. This is a nice advantage because this is a starting dose and the usual treatment dose. With the most recent cholesterol guideline updates, I do expect ezetimibe to be utilized a little more than it used to be. They place more emphasis on a target LDL and getting patients to goal. Statins are going to be used first line for cholesterol and ezetimibe will be an add on therapy to consider. They don't, unfortunately, lower cholesterol as much as high-intensity statins do.

This week, the FDA weighs in on concerning reports about paclitaxel-coated stents, and it approves a device to treat patent ductus arteriosus in infants weighing as little as 2 pounds. Also, a treat-to-target approach for CVD risk factors decreased atherosclerosis in rheumatoid arthritis patients, and ezetimibe was effective for primary prevention in elderly patients.

Dr. Mike Miedema, a preventive cardiologist with the Minneapolis Heart Institute, discusses cardiovascular disease (CVD) prevention, including current uses of aspirin and diabetic agents for primary CVD prevention.  Dr. Miedema also discusses current changes in recent cholesterol guidelines. Objectives: Upon completion of this CME event, program participants will be able to: Describe current optimal use of aspirin for primary cardiovascular disease prevention. Express their understanding of novel diabetic agents used for CVD prevention. Explain changes in the recent cholesterol guidelines. CME credit is only offered to Ridgeview Providers for this podcast activity. Complete and submit the online evaluation form, after viewing the activity.  Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within 2 weeks.  You may contact the accredited provider with questions regarding this program at rmccredentialing@ridgeviewmedical.org. Click on the following link for your CME credit:  CME Evaluation: A 2018 Cardiovascular Prevention Update - CME Enduring Activity (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.)  The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition.”   FACULTY DISCLOSURE ANNOUNCEMENT  It is our intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker’s outside interest may reflect a possible bias, either the exposition or the conclusions presented. Planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event.     Show Notes:   We were fortunate to be joined by Dr. Michael Miedema on December 14, 2018 to discuss cardiology updates and how they are about to impact our practice, if not already. He is a board certified cardiologist, and senior consulting cardiologist and principal investigator with MHI. He trained in medical school at U of M, then went on to an internal medicine residency at Abbott Northwestern, with his cardiology fellowship to follow at the University of Minnesota.  He went on then to another fellowship in cardiovascular prevention at Harvard, in addition to earning his Masters in Public Health. He happens to also be on the committee for the ACC/AHA 2019 Guidelines for the primary prevention of cardiovascular disease. And despite the fact that he grew up in rural Minnesota, this midwesterner speaks as fast as any east-coaster I’ve ever met! So whether you’re in your car,  operating your snowblower or starting that crossfit New Year's resolution , enjoy the knowledge that’s about to be dropped by our very esteemed colleague, Dr. Mike Miedema.   Aspirin: should people take aspirin for primary prevention of heart attack and stroke? We used to say, probably yes!  In the ASCEND trial (New England Journal) in the fall of 2018, Low dose aspirin was looked at and in 7.5 years there was approximately a 12% reduction in major CV events, however serious bleeding was increased by 29%. Not a simple nose bleed, but hospitalization type bleeding.    Another trial, ASPREE in the NEJM also in the fall of 2018, looked at older patients without CV disease, above age 70, taking low dose aspirin for 5 years. It showed no benefit again in overall CV risk, but bleeding risk was increased signficantly, by 38%. In fact all cause mortality showed an increase in cancer in this group, which is interesting. At the very least, the study showed no improvement in cancer risk.   Another trial published in Lancet, the ARRIVE study, consisted of 12000 patients. They were kept on ASA low dose for 5 years, and once again no improvement in the aspirin group was shown. However, the calculated risk was about twice what their actual risk was. The bleeding risk once again was higher.  Rates of MI actually demonstrated no change in the aspirin group.    The Physicians Health Study looked at a primary outcome of MI. It showed that ASA prevented the outcome of MI. Later the investigators tried to expand the outcomes of the study to include CV deaths in general. Unfortunately this now diluted the effect of aspirin and in other words, aspirin’s effect on preventing all cause CV death, like aortic dissection, etc., which makes aspirin look less effective. In addition, there is the issue of these trials looking at “intention to treat” which relates to an inherent bias toward the intervention arm, which didn’t account for the people who had to pull out the trial.  The double edged sword is that many people do in fact pull out of the trials and are still included in the trial results, which skews the results as well.    To conclude, aspirin is likely not helpful if you’re over age 70.  Essentially, if you’re at low CV risk or increased bleeding risk, you probably also shouldn’t take it. Between the ages of 40 and 70, patients may benefit from aspirin therapy, although not without risk of bleeding.      Cholesterol: One month ago, ACC/AHA updated the cholesterol guidelines from the 2013 version. In 2013, statins were recommended for primary and secondary prevention.  Secondary prevention includes lifestyle modifications.  There has been a movement to stratify people into not high risk and higher risk.    With regard to secondary prevention, the Improve-It trial was reanalyzed. The initial trial looked at ezetimibe with and without a statin.  Over 7 years and 18000 patients, there was  a 2% reduction in risk for CV disease. Cholesterol went down by 20%. Risk scores were calculated when the study was reanalyzed. Only half the trial had zero to 1 of the usual risk factors, and there was no benefit in this group. And in this group over the 7 years, there was no benefit from ezetimibe. In 25% of the trial, there was a benefit, but these people had 3 or more risk factors. Consequently, this group saw the most improvement and benefit. Essentially, if you’re not at high risk, a statin is sufficient. Ezetimibe can be considered in this group if the statin does not get you below an LDL of 70.  Otherwise, if you decide not to add ezetimibe, a maximally tolerated statin is appropriate. Older than age 75?  A statin can be offered but not mandatory. The very high risk group, however, meaning a major CV event (ACS, MI, Stroke or symptomatic PAD) history, along with at least one other risk factor, the LDL goal must be less than 70.  Statin therapy, along with ezetamibe is warranted, and if this doesn’t work, a PCSK9 inhibitor is indicated as well. These are expensive meds, though. Ezetimibe is not very expensive and tolerated well, so if that LDL can’t get below 70, it should really be added in this group.   Regarding primary prevention, familial hypercholesterolemia should be screeened for.  An LDL > 190 should be on a statin. No other risk factors are needed. People with type2 DM should be on a statin as well. Greater than age 75? Risks must be weighed, but statin is optional. Age 0-20, lifestyle, FH screening. 20-39, if LDL > 160 and/or a calculated greater lifetime risk, a statin can be offered. Plaque is much more regressable in earlier rather than later stages. A trial is currently under way looking at this concept, attempting to treat people in their 30s. This is the Cure Athero trial which is ongoing.  For age 40-75 with ldl between 70-190, if risk is less than 5%, no intervention besides lifestyle is indicated. With a calculated risk of >20% they should be on a statin.  If somewhere between low and high risk, there are other risk enhancers that should be looked at, i.e. family hx, inflammatory diseases, ethinicity, etc. If the calculated risk is 7.5 to 20%, a statin should be offered, but if there is uncertainty about whether to treat, a calcium score should be obtained. In fact, this is one of the major guideline changes, in that calcium scoring should be looked at. If the score is 0, then no therapy should be used. Scores between 1-99, statin should be offered, but 100 or greater, statin is indicated.  This concept was from a paper published in JACC in 2015.  Again, Ca++ scoring is best used in the group with intermediate risk between 7.5 and 20%.  Following the cholesterol is also advised. In fact, fasting lipid panels are not required. The panel can now be done non-fasting. Trial data has also shown that statins are very safe. Over 20 years, cancer, dementia and other theorized health risks were debunked.  Coenzyme Q10 use, and monitoring CPK, ALT/AST on asymptomatic patients are not indicated.  To summarize, people with known CV disease should be on a high intensity statin with goal LDL < 70, ezetimibe and PCSK9 added if at high risk. Also, if FH, consider adding ezetimibe and PCSK9, goal < 100. DM? Moderate intensity statin, higher if at high risk. Primary prevention? Moderate intensity statin, high intensity if high risk. If risk is uncertain, do a Calcium score.  Another trial is ongoing looking at fish oil (EPA and DHA).  EPA (vasepia) the purified variety ("fish oil on steroids"), is implemented in the mildly elevated TG population. Over 5 years, this medication along with statin therapy showed a reduced risk 25% reduction and 5% absolute risk reduction. Strangely, if your TG are in the 1000s, you are not at higher CV risk, but when they are mildly elevated, there is more atherogenicity. Essentially, if you have mildly elevated TG, you may benefit from this treatment. Expense and dosing is an issue, but this must be a considered therapy.    Diabetes: Cardiologists are becoming more engaged in DM care once again. The vast majority of DM is type 2. 1/3 of adults in this country are pre-diabetic. The risk of MI and stroke is significantly greater in diabetics and lifestyle really matters most with diabetics as well.  A recent paper in JACC demonstrated the significant benefit in lifestyle improvement.  The UKPDS trial looked at lifestyle vs. insulin vs. metformin.  Metformin showed substantial benefit in diabetes related events and diabetes related death. If metformin is started before insulin, a significantly lower Hgb A1C and lower BMI is seen. Type 2 DM is a disease of insulin sensitivity, not deficiency. Insulin is a storage hormone and does lead to weight gain. Metformin is recommended therefore as first line for type 2 DM, based on studies in the 90s and early 2000s. They showed improvement in Hgb A1C, but CV risks really weren’t shown to improve.  Based on 3 large trials in 2010 (ADvance trial, a VA trial and the Accord trial) no significant reduction in CV events was shown. In fact a slight increase in all cause mortality was shown. This was in people with more intense glucose control. Weight gain was a significant issue in aggresive Hgb a1c treatment group.   There a two relatively new medications: sglt2 inhibitors and the glp1 agonists. The sglt2s basically block the  pulling of glucose from the urine back into the blood stream. This lowers the HgbA1C. It also has a natriuretic/diuretic effect as well. There is very little risk of hypoglycemia with this drug as well. It is also a natriuretic. In 2015, a trial looking at this class of med revealed a 14% reduction in MACE.  CV death showed a 38% reduction. Most of the benefit was in patients with risk of heart failure.  Another trial also showed a 33% reduction in heart failure hospitalizations.  The largest trial though of 17000 patients was a primary and secondary prevention trial. Similar benefts were noted, but also a renal benefit. Ultimately, our type 2 DM patients should have these medications considered for both primary and secondary prevention. GLP1 receptor agonists or glutides, are also an option. This medication class causes less glucose production by the liver, more uptake by the muscles and delayed gastric emptying. Weight loss may occur with this med. CV effects include decreased inflammation and decreased risk for clotting in the smaller vessels. Overall reduction in Hgb a1c, weight loss, improved LDL, decrease in BP and decreased inflammation. 13 to 14 % reduction in MACE was noted with this, especially in stroke and atherosclerosis. Not so much with CHF due to an anti-atherosclerotic mechanism.  Glutides are given once weekly. Yeast infections are more common with the SGLT2s due to increased glucose in the urine.  ACC constructed a pathway for use of these various medications:  Essentially, For your DM pts with CHF, an SGLT2 should be given, and a GLP1 for DM pts with previous CV events. Cost is also an issue with these meds; however they can be used together.   CV genetics considerations and screenings is an up and coming topic.  The Framingham study said CV disease is due to multiple-factorial processes and risk factors. Therefore it is hypothesized that mutliple genes may lead to higher risk.  If your lifestyle is good, even if you have increased genetic risk, you can substantially lower your risk. In about 2% of the population, an FH gene can be found.  If you have this gene, your risk is higher than others at a similar cholesterol level, and for a longer period of your life of course. Therefore it is important for these patients to address this with medication and lifestyle.  Adding the genetic risk score to your overall basic CV risk factors will help to predict your actual CV risk.  This risk calculation and stratification is still being studied and looked at.   ACC/AHA Risk calculator link: cvriskcalculator.com   In summary:    ASA for primary prevention probably shouldn’t be used. Select high risk patients are okay, but avoid in the elderly.  Cholesterol:  Statin plus ezetemibe and pcsk9 for higher risk, and Ca score for  those uncertain about their risk.  DM: use the new meds with type 2 DM at high CV risk.  Genetics: not quite ready for prime time, but we need to look into this more and get ready for patients desiring this in the future.  Again, a big thanks to Dr. Miedema for joining us and for providing this cardiology update. Ridgeview appreciates his expertise, his ongoing dedication to his patients and to the cardiology specialty.

In this five-part series, Thomas Dayspring, M.D., FACP, FNLA, a world-renowned expert in lipidology, and one of Peter's most important clinical mentors, shares his wealth of knowledge on the subject of lipids. In Part IV, Peter and Tom review the history and current use of drugs to prevent cardiovascular disease. They also discuss why some drugs appear to be more effective than others, an in-depth conversation about niacin, cholesterol and brain health, and the futility of using CKs (creatinine kinase) and liver function tests to identify adverse effects in statins, to name a few topics in this episode. We discuss: Bile acid sequestrants and statins [2:00]; Ezetimibe (Zetia) [15:00]; PCSK9 inhibitors [27:30]; Fibrates [41:00]; Fish oil, DHA, and EPA [1:01:00]; Niacin [1:05:15]; PCSK9 inhibitors [1:23:45]; Cholesterol, statins, and the brain [1:30:00]; Elevated creatine kinase (CK) and liver function tests (LFTs) on statins [1:50:30]; and More. Learn more at www.PeterAttiaMD.com Connect with Peter on Facebook | Twitter | Instagram.

Dr. Carolyn Lam:               Welcome to Circulation On The Run, your weekly podcast summary and backstage pass to the journal and its editors. I am Dr. Caroline Lam, Associate Editor from the National Heart Center and Duke National University of Singapore.                                                 Can we reverse the cardiac effects of sedentary aging? Well if you're curious, you have to read the feature paper in this week's journal, as well as listen to the upcoming discussion of a trial that addresses this issue. All coming right up, after these summaries.                                                 Desmond mutations are known to cause skeletal and cardiac muscle disease, and also recently has been described in patients with inherited arrhythmogenic right ventricular cardiomyopathy or dysplasia. In today's first original paper, however, authors identified a novel Desmond mutation in a large Spanish family with inherited left ventricular arrhythmogenic cardiomyopathy or dysplasia, and a high incidence of, at first, cardiac events.                                                 First in corresponding author, Dr. Bermudez Jimenez from Granada, Spain, describe for the first time the largest family to date with a single Desmond mutation with a phenotype of left dominant arrhythmogenic dysplasia in the absence of skeletal myopathy symptoms and atrioventricular conduction disorders and supported by strong clinical and functional data. In a series of elegant experiments using explanted cardiac tissues and mesenchymal stem cell derived cardio myocyte from the family members, the author showed that the pathogenic mechanism probably corresponds to alteration in Desmond dimer and oligomer assembly and its connection with membrane proteins within the intercalated discs, thus Desmond mutations should be suspected in patients presenting with a cardiomyopathy characterized by mild left ventricular systolic dysfunction and/or dilatation, fibrosis, ventricular arrhythmias and a family history of sudden death.                                                 The next study is the first large scale report examining the incremental risk of surgical aortic root enlargement in patients undergoing aortic valve replacement.                                                 First author Dr. Rocha, corresponding author Ouzounian from University of Toronto and their colleagues sought to evaluate the early outcomes of patients undergoing aortic valve replacement with or without surgical aortic root enlargement.                                                 Now aortic root enlargement allows for larger prosthesis implantation and maybe an important adjunct to surgical aortic valve replacement in the transcatheter valve in valve era.                                                 Among more than 7,000 patients undergoing aortic valve replacement at a single institution from 1990 to 2014, the authors observed no incremental risk in post-operative mortality or adverse events following surgical enlargement of the aortic root as compared to aortic valve replacement alone. They therefore concluded that surgical aortic root enlargement appears to be a safe adjunct to surgical aortic valve replacement in the modern era.                                                 The next study suggests that in patients with acute coronary syndrome and an LDL cholesterol above 50 milligrams per deciliters, health care providers should consider adding ezetimibe to statins, particularly in two patient subgroups.                                                 First in corresponding author Dr. Giugliano from the TIMI study group at Harvard Medical School in Boston, Massachusetts and his colleague explored outcomes stratified by diabetes in the "improve it" trial where patients with a recent acute coronary syndrome were randomized to ezetimibe versus placebo on top of backgrounds in the statin.                                                 They found that patients with diabetes derived significantly greater relative and absolute benefit with the addition of ezetimibe relative to patients without diabetes. This enhanced benefit was driven by reductions in acute ischemic events including myocardial infarction and ischemic stroke in diabetics, while non-diabetic patients who were more than 75 years of age or who had a high risk score also significantly benefited from the addition of Ezetimibe to Simvastatin.                                                 These benefits of Ezetimibe were achieved without an increase in safety events compared to placebo. Thus, the two patient subgroups of acute coronary system who are likely to achieve greater benefits with the addition of ezitimibe include: one, patients with diabetes, and two, patients without diabetes who have a high risk score.                                                 The final study provides insight into sudden cardiac arrests in the young and the potential contribution of standard cardiovascular risk factors to this risk, even in the young.                                                 First author, Dr. Reshmy Jayaraman, corresponding author Dr. Chugh from Cedars-Sinai Medical Center in California and their colleagues, prospectively ascertained 3,775 individuals who suffered sudden cardiac arrest between the ages of 5 and 34 years in the Portland, Oregon Metropolitan area and who were also followed up for 13 years. They found that 5% of cases occurred in young residents between the age of 5 and 34 years.                                                 Among the young, there was an unexpectedly high prevalence of classical cardiovascular risk factors, such as obesity, diabetes, hypertension, hyperlipidemia and smoking. In fact, one or more risk factor was observed in 58% of cases, with obesity being the most common.                                                 Less than a third had warning symptoms prior to their lethal event and sports activity was a trigger in only 14% of young cases. Thus, standard cardiovascular risk factors, especially obesity, may play a larger role in sudden cardiac arrests in the young than previously recognized. This suggests the potential role of public health approaches that screen for cardiovascular risk factors at earlier ages.                                                 And that wraps it up for our summaries, now for our feature discussion.                                                 Oh boy, today's featured discussion is gonna make everyone listening fall in love with exercise and seriously get off your chair right now as you listen to this discussion.                                                 It's about how exercising may reverse cardiac aging and I am so delighted to have with me none other than the corresponding author, Dr. Ben Levine from the institute of exercise and environmental medicine at Texas Health Presbyterian and UT Southwestern, as well as Dr. Jarett Berry, and he's our dear associate editor from UT Southwestern.                                                 Ben, I have been dying to have you on this show, so welcome and please, tell us what you did. Dr. Ben Levine:                 Thank you very much, it's a pleasure to be here Carolyn, thanks for inviting me to talk about it. As you know, our lab has been particularly interested in the components of aging that are related to senescent versus those that are related to senescence activity.                                                 Perhaps the most dramatic reason that we're interested in this, I'm just gonna give you a little bit of background, if you don't mind, comes from one of the most important studies ever done in our field, that was done in Dallas in the mid-1960s. It's called the Dallas Bedrest and Training Study.                                                 At that time, my mentors, G Blomqvist, Jerry Mitchell, Bengt Saltin, took five young men, put them to bed for three weeks and then trained them for two months and virtually everything we know about the adaptive capacity of the circulation to exercise starts without study.                                                 I was only ten years old, so I really had nothing to do with it, but 1996, 30 years later, we found those same five guys and brought them back to Dallas to study them again.                                                 Now, these are the most intensively studied humans probably in the history of the world. 78 pages of circulation in 1968. What we found was quite amazing. We found that not a single one of those five guys was in worse shape 30 years later, than they were after three weeks of bed rest when they were in their 20s.                                                 So, three weeks of bed rest was worse for the body's ability to physically work than 30 years of aging. And so, we sort of launched off that in a series of experiments, trying to figure out when in the aging process does the shrinking and stiffening of the heart develop, that is the sine qua non. if you will, of the cardiac aging. So, when does it start? How much exercise do you have to do to prevent that?                                                 We did one interesting study where we compared a group of very highly selected seniors, all aged around 70, who were healthy, but did no exercise, compared to a group of elite Masters Athletes. Amazingly, the healthy seniors, their hearts got smaller and it shrunk and they got stiffer and the athletes had hearts that were indistinguishable from healthy 30 year olds.                                                 So, a lifelong training at the level of being an elite athlete completely prevented that aging response, which is really interesting scientifically, but not a very good public health measure.                                                 So, we then asked how much exercise do you need to do over a lifetime to preserve the compliance, the youthfulness, if you will, of the circulation, and at times, they act like you need to do about 4 or 5 days a week over a lifetime. 2 to 3 days a week didn't do anything. 4 to 5 days a week did almost as much as being an elite competitive athlete. So, now we've got the dose. 4 to 5 days a week.                                                 We said, "okay, if we do that, can we reverse cardiac aging once it's occurred?" So, we took our healthy sedentary people and we also looked at a group of HFpEF patients and we trained them for a year, at the right dose, using high intensity exercises. We made them fitter, but we couldn't touch their cardiac or vascular stiffness. Quite disappointing actually.                                                 Last thing then, we said "okay, this leads up in to our current study maybe, just maybe, if we pick the right sweet spot in time, when the heart is just beginning to stiffen in that late middle age period and deal the right dose at the right time for a long enough period, we could reverse the effects. And, that's what we did. We took 60 people, healthy, middle aged, 45-64, mean age around 50. We randomly assigned them to two years of exercise training or two years of yoga, balance, flexibility, and we did 2 light heart caths. We measured their cardiac compliance directly invasively and we showed that our 2 year training program, which included high intensity intervals, reversed the effects of decades of sedentary aging. Dr. Carolyn Lam:               Wow, Ben, you know, no one tells the story like you and I have to tell you, I've been a fan of your work, citing it since I was 10. Thank you so much for this amazing contribution to the Journal this week. I just know everybody's asking questions like "So, you've given us when to start, you given us the dose, but we want to understand a bit better, what do you mean high intensity, how many minutes and what exactly." Could you give us an idea? Dr. Ben Levine:                 Sure. There are multiple different ways to go about doing HIIT or High Intensity Interval Training. And there's no magic to intervals. Intervals just allow you to do something for a shorter period of time and harder than you could do for a longer period of time. That is the strategy that athletes use to go faster and stronger and higher, because the body adapts to the load that's placed on it.                                                 Interval training, what I like, is based on an old Norwegian ski team workout. It's called the "4x4". What that means is 4 minutes at 95% of your maximum followed by 3 minutes of recovery, active recovery, repeated 4 times. So, basically, you go as hard as you can go for 4 minutes and at the end of those 4 minutes, you should be ready to stop. Typically, your heart rate will drift up towards 95% of maximum or so. Then, at the end of the 3 minutes of recovery, you should be ready to do the next interval.                                                 As it turns out, that's extremely effective training stimulus. Not just for healthy people or athletes, for the patients with hypertension and with heart failure. Dr. Carolyn Lam:               I noticed that you have to screen over 260 individuals to finally get your 60, so how doable is this and what was the compliance? Dr. Ben Levine:                 Right. You have to remember that out of those 260 individuals that we screened, the majority of them were excluded up front because they had hypertension or if they were obese or they already had heart disease. So, the first round of screening was making sure we're getting people of the right age and were healthy. And, then another fraction, say 40 of them or so, didn't wanna undergo two light heart catheterizations. And, I get that. We were pretty pleased that somebody volunteered to do it, but you know, it's an intense commitment. People have to be willing to be randomized. So, they couldn't say "Well, I wanna do your study, but only if I get randomized to exercise", that was not acceptable.                                                 So, everybody had to be prepared to be randomized to either yoga or the fitness training and the yoga, it makes people feel better, it's relaxing. I think it provided that clinical equipoise and it ensured that even the controlled patients had close contact with our research team.                                                 Then, what we had was, on average 88% of the prescribed sessions were followed by our exercisers and a fraction of them, 15 or 20%, actually did 100% of their prescribed sessions over two years, didn't miss a single one. Dr. Carolyn Lam:               So, Jarett, have you started doing that yourself now? Dr. J Berry:                          I tell you, I pried my kids out of bed last summer, to go do 4x4s and get them ready for cross country. I talked all about Ben Levine and told my kids that we were doing what Dr. Levine recommended. That didn't help too much, they found it rather challenging. It was interesting that the VO2 plateaus a little bit at that 10 month mark, when you guys backed off on that additional interval training. Do you think that the plateau is just a limitation of the training effect or do you think that something that has to do with the lower level of interval training at that time? Dr. Ben Levine:                 You know Jarett, I think that's a fascinating question and it's one of the things that really surprised me. So, Jarett pointing to the fact that at that 10 month mark, we measured VO2 max, we didn't cath them, but we did an Echo, and it showed that from 10 months to 2 years VO2 max didn't increase very much.                                                 There was a dramatic increase from baseline to 10 months. It took 3 months at that peak dose. But then, when we dropped one interval and did the same thing every week for 2 years, there wasn't an influence of time. The heart didn't continue to get bigger, the stroke volume didn't continue to enlarge.                                                 I think it highlights a critical part, an essential element, to that exercise training and that is, doing the same thing, over and over again doesn't get you fitter. If you wanna get fitter than you are, you have to change things around, you have to increase the load. So, I think that if we had wanted to make them even fitter than they were at 10 months, we'd have had to either kept that second interval or added another one or increase the duration of some of the base training sessions.                                                 It's really interesting to me, that they didn't continue to improve simply on the basis of time. That surprised me. Dr. Jarett Berry:                Yeah, cause you wonder. You think about, the guidelines suggest moderate intensity exercise, which is obviously much lower intensity than what you're talking about with this interval training, but very little guidance with regard to interval training.                                                 Your data here obviously suggests that it's not just getting off the couch and doing something, and not just doing a decent amount, it seems to suggest that the interval training component may be a secret ingredient that might be most helpful, at least for those patients who can tolerate that level of training. Dr. Ben Levine:                 Yeah, I think that maybe it's the secret sauce, Jarett, but I think, you do have to ask yourself, what is the goal of training and what is your objective outcome? What you want is to reduce cardiovascular mortality. I think we would all agree that you get the biggest bang for your buck by going from sedentary to active. And, the mechanism of that is uncertain, but could relate to autonomic function or clotting or improving stabilization of endothelium or other risk factors, inflammation, who knows, there's a lot of different candidates. So, I think that particularly for people who are at the highest risk for heart failure, either from their family history or other risk factors, like hypertension and diabetes, those are the ones who were likely to get in a special benefit on altering cardiac structure.                                                 That's why I think our data is still an important poll. We didn't really know why do you get the biggest bank for your buck with a little training, but if you really wanna prevent heart failure, you gotta do more.                                                 In our data that we did partnered with the Cooper Clinic and looked at people who had done the same number of exercise sessions over 25 years. None, 2-3, 4-5 or 6-7, over 25 years, we saw virtually no effect of 2-3 days a week of what we call casual training on anything we could measure, related to cardiac structure. Their vascular stiffness was the same as people who were sedentary, their cardiac stiffness was the same as people who were sedentary. They were a little fitter and perhaps there were other important differences that are related to just improving immortality, but you have to get past that low to moderate dose to have the structural effects on the circulation. Dr. Jarett Berry:                These are really great points here, Ben. I want for our listeners to hear you comment a little bit more on the primary outcome and how you guys measured stiffness, because I think in addition to the level of training, it's also the approach and the phenotype that you collected to measure this and I think it would be helpful for you to walk us through that a little bit and how you guys measured stiffness. Dr. Ben Levine:                 We used an old physiological technique called "Lower Body Negative Pressure". We first let the subject settle down, we measure a variety of cardiovascular variables, cardiac output, and we do an advanced ECHO imaging and some arterial stiffness measures and after about 40-45 minutes or so, we'll measure the pulmonary capillary wedge pressure, that's what we use as an index, and plus ventricular and diastolic pressure. We'll do 3D ECHO volumes and then we unload the heart by doing Lower Body Negative Pressure. We basically seal the subject in a box at the iliac crest and turn on a vacuum cleaner and suck blood into their venous capacitance. It's a very simple way to unload the heart.                                                 In contrast to people who do put in conductants or reflectant catheters and occlude the IVC and do pressure volume rudes, we have taken a little bit of a different approach. I do steady state and diastolic pressure volume curves. So that means, we look at the pressure and volume in the heart at baseline at two different unloading levels. So, let's say the baseline ledge is 10. The first level of LBNT of minus 15 will get it down to 6 or 7. The next level of minus 30 gets it down to 2 or 3. And, so we get a nice unloading of the heart and we're able to establish a steady state, which is probably more afunctional than a release of an IVC occlusion.                                                 Then, we let go of the suction, everything returns to normal. We repeat our baseline measures and then we give the rapid saline infusion. When I say rapid saline, I mean 15 and 30 mls per kilogram, that's at 200 mls a minute. That's a big volume infusion, but we'll give those doses and we'll raise the ceiling pressure from 10 at baseline to 15 and then 19, 18, 19. So, we get a large physiologic range of the diastolic pressure volume curve, and then we'll fit that to an extremely widely accepted exponential equation, which allows us to calculate the overall stiffness of the heart, the diastolic component, and then we'll do a few other things, we'll measure distensibility , which is the volume at any given pressure and DPDV, the change in pressure for a given volume, which is the hansen float to the exponential curve fitting. Dr. Jarett Berry:                Can you comment a little bit about what this means for how this is distinguished perhaps from maybe more conventional non invasive measurements of cardiac stiffness? Dr. Ben Levine:                 I think the most important thing to realize is that, cardiac compliance is dynamic. It depends on the volume at which you're making that measurement. So, as you unload the heart, any heart, even the stiff heart, it gets more compliant, and as you load the heart, even a compliant heart, it gets stiffer. Part of that is a function of pericardial constraint, as well as myocardial stiffness.                                                 The whole idea that there is a measure of diastolic function that you can measure by ECHO that is load independent is frankly an oxymoron, because, diastole is load dependent. I think the ECHO measurements are interesting and useful, depending on what you're trying to find out, because there are many different aspects of feeling and diastolic suction and diastolic stiffness. All of which influence how well the heart feels at rest and during exercise. Dr. Carolyn Lam:               I have to ask you one last question. I am so pleased that you included at least 52% women. Were there any differences by sex? Dr. Ben Levine:                 Of course, Carolyn, it's critical to include women, since they're 50% of the population. We've been very interested in their training responses in men and women at different age groups in many of our other studies. What's interesting is that in premenopausal women, there's a quite clear distinction in how women respond to training. They don't hypertrophy as much, even for the same stimulus, heart beats a heart beat, over a year, there's a much less hypertrophic response to premenopausal women than young men.                                                 We didn't see anywhere near that difference in our mostly postmenopausal middle aged men and women. We didn't have enough power to clearly be confident that there was no difference, but when we tried to test that hypothesis, whether there was a different response in men or women, we could not detect a difference. Dr. Carolyn Lam:               That is a good thing. So, women out there, you heard it from Dr. Levine. We got to exercise too. High intensity. All the time.                                                 Thank you audience, for listening today. Don't forget to tune in again next week.  

Familial hypercholesterolemia is a frequent genetic disorder encountered in clinical practice and is associated with high levels of serum LDL cholesterol known as the “bad cholesterol.” A diagnosis of familial hypercholesterolemia has important clinical implications with respect to risk of cardiovascular disease and a requirement for intensive pharmacological therapy. Often, the baseline LDL cholesterol before treatment is not available because the patient has initiated and continues on lipid lowering therapy, especially statins. Furthermore, the original baseline LDL cholesterol may predate the current status by many years and cannot be easily retrieved. The February 2018 issue of Clinical Chemistry published a paper describing a method to obtain an imputed, or estimated, baseline LDL cholesterol concentration in these patients who are already taking cholesterol lowering drugs. Both a computer program and a smartphone app are available from links in the paper. We are pleased to have the lead author of that paper as a guest on this podcast. Isabelle Ruel is a Clinical Biochemist at the Research Institute of the McGill University Health Center Royal Victoria Hospital in Montreal, Quebec, and is currently the national coordinator of the Canadian Registry on Familial Hypercholesterolemia.

Learn the latest in lipid lowering therapy in this extensive discussion with Dr. Paul S. Jellinger, MD, MACE, Professor of Medicine at the University of Miami and Chair of the writing committee for the American Association of Clinical Endocrinologists (AACE) 2017 Guidelines for the Management of Dyslipidemia and Prevention of Cardiovascular Disease (CVD). Topics include ezetimibe, PCSK9, FOURIER trial, statin myopathy, CoQ10, fish oil, fibrates and more. For a more basic discussion of dyslipidemia check out episode #10. Full show notes are available at http://thecurbsiders.com/podcast Join our newsletter mailing list. Rate us on iTunes, recommend a guest or topic and give feedback at thecurbsiders@gmail.com. Time Stamps 00:00 Intro 03:10 Rapid fire questions 08:15 Dyslipidemia defined 10:26 Classifying dyslipidemia 13:21 Diagnosing Familial Hypercholesterolemia 17:48 A difficult lipid case discussed 22:40 Lp (a), Apo B and LDL particle concentration 28:40 What labs to order 31:31 ACC/AHA versus other risk scores 38:21 IMPROVE-IT 41:35 Non-statin medications discussed 45:05 Hypertriglyceridemia fibrates and fish oil 48:25 How often to check the lipid panel 49:58 Statin Myopathy and CoQ10 54:17 FOURIER, PCSK9 and very low LDLs 59:43 Extreme risk category discussed 62:34 Is plaque regression possible? 64:12 Take home points 67:08 Outro Tags: assistant, care, cholesterol, doctor, education family, fish oil, foam, foamed, health, hospitalist, hospital, internal, internist, ldl, lipid, medicine, medical, myopathy, nurse, pcsk9, physician, practitioner, primary, statin, resident, student

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

Amol and Reena want you to understand the following: 1. When added to moderate dose statin, the IMPROVE-IT randomized trial showed that ezetimibe improved clinical outcomes in patients after acute coronary syndrome. 2. A network meta-analysis showed that no blood pressure lowering therapy improved mortality in patients with diabetes and chronic kidney disease. The combination of ACE-inhibitors and ... The post Summer Replay 4: Ezetimibe and clinical outcomes, BP lowering in diabetes and kidney disease appeared first on Healthy Debate.

Amol and Reena want you to understand the following: 1. When added to moderate dose statin, the IMPROVE-IT randomized trial showed that ezetimibe improved clinical outcomes in patients after acute coronary syndrome. 2. A network meta-analysis showed that no blood pressure lowering therapy improved mortality in patients with diabetes and chronic kidney disease. The combination of ACE-inhibitors and ...The post Summer Replay 4: Ezetimibe and clinical outcomes, BP lowering in diabetes and kidney disease appeared first on Healthy Debate.

Amol and Reena want you to understand the following: 1. When added to moderate dose statin, the IMPROVE-IT randomized trial showed that ezetimibe improved clinical outcomes in patients after acute coronary syndrome. 2. A network meta-analysis showed that no blood pressure lowering therapy improved mortality in patients with diabetes and chronic kidney disease. The combination of ACE-inhibitors and ... The post Debatable Landmarks: Ezetimibe and clinical outcomes, BP lowering in diabetes and kidney disease appeared first on Healthy Debate.

Amol and Reena want you to understand the following: 1. When added to moderate dose statin, the IMPROVE-IT randomized trial showed that ezetimibe improved clinical outcomes in patients after acute coronary syndrome. 2. A network meta-analysis showed that no blood pressure lowering therapy improved mortality in patients with diabetes and chronic kidney disease. The combination of ACE-inhibitors and ...The post Debatable Landmarks: Ezetimibe and clinical outcomes, BP lowering in diabetes and kidney disease appeared first on Healthy Debate.

Alistair Lindsey talks to Christopher Cannon, Havard Clinical Research Institute, about the results of his IMPROVE-IT trial, which examined clinical outcomes of adding ezetimibe to simvastatin. This podcast was recorded at the American Heart Association scientific sessions in Chicago.

A monthly audio round-up detailing the contents of the latest issue of DTB.Articles:How to misinform patients DTB 2009; 47: 85Management of carpal tunnel syndrome DTB 2009; 47: 86 - 89So, what exactly is a cytokine? DTB 2009; 47: 89 - 91Ezetimibe – an update DTB 2009; 47: 91 - 95Understanding statistical terms: 5 – systematic reviews and meta-analyses DTB 2009; 47: 95 - 96