Podcasts about copenhagen city heart study

Parmi tous les sports que l'on peut pratiquer, le tennis ressort souvent comme l'un des plus bénéfiques pour la santé globale. Et ce n'est pas qu'une impression : plusieurs études scientifiques appuient cette idée.Prenons une étude marquante publiée en 2018 dans le British Journal of Sports Medicine. Menée dans le cadre de la Copenhagen City Heart Study, elle a suivi plus de 8 500 personnes pendant environ 25 ans, en comparant les effets de différents sports sur l'espérance de vie. Résultat : les joueurs réguliers de tennis vivent en moyenne 9,7 ans de plus que les personnes sédentaires. C'est plus que les nageurs (+3,4 ans), les coureurs (+3,2 ans) ou les cyclistes (+3,7 ans). Pourquoi un tel écart ? Parce que le tennis combine les bienfaits de l'activité physique intense avec ceux des interactions sociales. Or, la recherche montre que l'isolement social est un facteur de risque comparable au tabagisme ou à l'obésité.Sur le plan physiologique, le tennis fait appel à tout le corps. Il renforce le système cardiovasculaire en améliorant l'endurance et la capacité respiratoire. Lors d'un match, la fréquence cardiaque peut facilement atteindre 70 à 85 % de la fréquence maximale, ce qui correspond à une activité aérobique intense, excellente pour le cœur. Il stimule également les muscles, notamment ceux des jambes, des bras, du tronc et du dos, grâce aux mouvements de course, de frappe, de rotation et d'équilibre.Mais ce n'est pas tout. Le tennis améliore la coordination œil-main, la concentration, la rapidité de réaction et même la mémoire, notamment à travers l'anticipation et la stratégie de jeu. Ces aspects ont un effet protecteur sur les fonctions cognitives, en particulier chez les personnes âgées.Sur le plan mental, le tennis est aussi un excellent régulateur de stress. Une étude publiée dans PLoS One en 2020 a révélé que les sports de raquette, comme le tennis, étaient associés à une meilleure santé mentale que les sports individuels. Ils réduisent les symptômes d'anxiété, améliorent l'estime de soi et favorisent un meilleur sommeil.Enfin, le tennis est un sport qui peut se pratiquer à tout âge, avec des règles adaptables et une intensité modulable. Il offre ainsi une activité physique complète, durable et socialement engageante — autant d'éléments qui expliquent pourquoi, selon la science, le tennis est l'un des sports les plus sains au monde. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

Capital Investment Advisors' Chief Investment Officer Connor Miller joins Wes in the studio for today's episode. They delve into the latest information on the Tesla rental car situation. They contrast the state of the economy with public sentiment. They also share a strategy that often helps combat inflation. They cite the Copenhagen City Heart Study's findings about the sport of tennis and how it's been shown to increase human lifespan. Finally, Wes breaks down the wisdom of tennis champion Roger Federer's recent words and compares his winning rate to that of the stock market.

In this insightful episode we delve into the groundbreaking findings of the Copenhagen City Heart Study. We uncover the four main lessons from this pivotal research and explore how these lessons profoundly impacted our client, Michelle's, approach to exercise and longevity. Join us as we share how Michelle's journey towards a more informed and confident exercise regimen could inspire your path to a healthier, longer life.Key Points Discussed:Understanding the Copenhagen City Heart Study: We start by breaking down this influential study, explaining its significance in the realm of health and exercise.Four Main Lessons Learned: Our deep dive into the study reveals four crucial lessons about the types of exercise that can potentially enhance lifespan and overall well-being.Michelle's Story: Hear about our client, Michelle, whose exercise routine was transformed by applying these lessons. We discuss how the study's findings influenced her choices and the positive changes she experienced.Life-Enhancing Workout Strategies: We outline practical, life-enhancing workout strategies that you can incorporate into your routine, inspired by the study's findings.Confidence and Reassurance in Exercise Choices: Discover how Michelle left feeling more confident and reassured about her health and fitness journey. We discuss the importance of making informed exercise choices based on scientific research.Episode Highlights:Personal Impact: Real-life applications of the Copenhagen study on our client's exercise regimen.Scientific Insights: Understanding how specific types of exercise can contribute to a longer, healthier life.Empowered Decisions: How knowledge from research can empower us to make better choices for our health.Conclusion:This episode is not just about understanding a groundbreaking study; it's about translating scientific knowledge into practical, everyday decisions that can lead to a healthier, longer life. Whether you're a fitness enthusiast or just starting your health journey, there's something in this episode for you.Additional Resources:Link to the full Copenhagen City Heart Study for further reading.Youtube Video - 7 Most Life Extending Forms Of ExerciseConnect with Us:Join Our Online Health Membership - Direct message us via our facebook page. We love hearing from our listeners! Share your thoughts, questions, or personal stories at The Health and Sport Show. Join our community on social media for daily health tips and updates.

ORAL MINOXIDIL IN PEDIATRICS   Jerjen R et al (starts at 12:33). Low-dose oral minoxidil improves global hair density and length in children with loose anagen hair syndrome. Br J Dermatol. 2021;184(5):977-978. Nicolas-Ruanes et al (starts at 15:33). Low-dose oral minoxidil for treatment of androgenetic alopecia and telogen effluvium in a pediatric population: A descriptive study. J Am Acad Dermatol. 2022 Apr 26; John JM et al (starts at 17:24). Safety and tolerability of low-dose oral minoxidil in adolescents: A retrospective review. J Am Acad Dermatol . 2022 Jul 5;S0190-9622(22)02245-9.   HAIR FIBERS AND CAMOUFLAGE Ring and Keller (starts at 25:13). Effect of camouflaging agents on psychologic well-being: A cross-sectional survey of hair loss patients. J Am Acad Dermatol. 2017 Jun;76(6):1186-1189 Babadjouni A et al (starts at 28:15). Patient Satisfaction and Adverse Effects Following the use of Topical Hair Fiber Fillers. Int J Trichology. 2022 May-Jun; 14(3): 97–102   HYDROXYCHLOROQUINE IN PREGNANCY Reynolds JA et al (starts at 34:38). Outcomes of children born to mothers with systemic lupus erythematosus exposed to hydroxychloroquine or azathioprine. Rheumatology (Oxford). 2022 Jun 29: Sperber K et al (starts at 38:25). Systematic review of hydroxychloroquine use in pregnant patients with autoimmune diseases. Pediatr Rheumatol Online J 2009;7:9. Kaplan Y et al (starts at 39:17). Reproductive outcomes following hydroxychloroquine use for autoimmune diseases: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016 May;81(5):835-48. Clowse MEB et al (starts at 40:27). Hydroxychloroquine in the pregnancies of women with lupus: a meta-analysis of individual participant data. Lupus Sci Med. 2022 Mar;9(1):e000651. Huybrechts K et al (starts at 42:37). Hydroxychloroquine early in pregnancy and risk of birth defects. Am J Obstet Gynecol 2021 Mar;224(3):290.e1-290.e22 Huybrechts K et al (starts at 45:20). Hydroxychloroquine early in pregnancy and risk of birth defects: absence of evidence is not the same as evidence of absence. Am J Obstet Gynecol. 2021 May;224(5):549-550. Bérard et al (starts at 46:58). Chloroquine and Hydroxychloroquine Use During Pregnancy and the Risk of Adverse Pregnancy Outcomes Using Real-World Evidence. Front Pharmacol. 2021 Aug 2;12:722511. Howley et al (starts at 47:17). Maternal exposure to hydroxychloroquine and birth defects. Birth Defects Res. 2021 Oct 15;113(17):1245-1256. Andersson et al (starts at 47:34). Fetal safety of chloroquine and hydroxychloroquine use during pregnancy: a nationwide cohort study. Rheumatology (Oxford). 2021 May 14;60(5):2317-2326.   TERIFLUNOMIDE INDUCED HAIR LOSS IN MULTIPLE SCLEROSIS Travis LH et al (starts at 53:28). Real-World Observational Evaluation of Hair Thinning in Patients with Multiple Sclerosis Receiving Teriflunomide: Is It an Issue in Clinical Practice? Neurol Ther. 2018 Dec; 7(2): 341–347. Porwal MH et al (starts at 55:41). Alopecia in Multiple Sclerosis Patients Treated with Disease Modifying Therapies. J Cent Nerv Syst Dis. 2022 Jun 23;14:11795735221109674.   DO IT YOURSELF LOW-ALLERGEN PRODUCTS Xiong M and Warshaw EM. (starts at 1:05:45) Hair Care Product Hacks: Do It Yourself Alternatives. Dermatitis. 2022 Jun 29. Zirwas M and Moennich J (starts at 1:00:25). Shampoos. Dermatitis. 2009 Mar-Apr;20(2):106-10 Tawfik M, Rodriguez-Homs LG, Alexander T, et al (starts at 1:01:10). Allergen content of  best-selling ethnic versus nonethnic shampoos, conditioners, and styling products. Dermatitis 2021;32(2):101–110 https://donovanmedical.com/diy   PREMATURE GREYING (EARLY CANITIES) Anggraini et al (starts at 1:08:50). Risk Factors Associated with Premature Hair Greying of Young Adult. Open Access Maced J Med Sci . 2019 Nov 14;7(22):3762-3764. Dawber RP (starts at 1:09:12). Integumentary associations of pernicious anaemia. Br J Dermatol . 1970 Mar;82(3):221-3. Mosley JG and Gibbs AC (starts at 1:09:50). Premature grey hair and hair loss among smokers: a new opportunity for health education? British Medical Journal 1996; 313: 1616. Bhat RM et al (starts at 1:10:21). Epidemiological and investigative study of premature graying of hair in higher secondary and pre-university school children. Int J Trichology. 2013;5:17–21. Chang H-C and Sung C-W (starts at 1:10:35). Association between serum levels of minerals and premature hair graying: a systematic review and meta-analysis. Int J Dermatol. 2020 Oct;59(10):e378-e380. Schnohr P et al (starts at 1:12:35). Longevity and gray hair, baldness, facial wrinkles, and arcus senilis in 13,000 men and women: The Copenhagen city heart study. J Gerontol A Biol Sci Med Sci. 1998;53:M347–50. Schnohr P et al. Gray hair, baldness, and wrinkles in relation to myocardial infarction: the Copenhagen City Heart Study. Am Heart J  1995 Nov;130(5):1003-10.   Kocaman SA et al (starts at 1:14:10) . The degree of premature hair graying as an independent risk marker for coronary artery disease: A predictor of biological age rather than chronological age. Anadolu Kardiyol Derg 2012;12:457-63.  Paik S et al (starts at 1:14:25). Association Between Premature Hair Greying and Metabolic Risk Factors: A Cross-sectional Study. Acta Derm Venereo. 2018 Aug 29;98(8):748-752. Mahendiratta S et al (starts at 1:15:09). Premature graying of hair: Risk factors, co-morbid conditions, pharmacotherapy and reversal-A systematic review and meta-analysis. Dermatol Ther. 2020 Nov;33(6):e13990. Das S et al (starts at 1:15:51) Cardiovascular risk markers in premature canities. Indian J Dermatol Venereol Leprol. 2022 Jun 30;1-5.

This month on Episode 33 of Discover CircRes, host Cynthia St. Hilaire highlights two original research articles featured in the February 4 issue of Circulation Research. In addition, she previews Circulation Research's Compendium on Women and Cardiovascular Health, featured in the February 18th issue. This episode also features a conversation with Dr Alastair Poole and Dr Laura Corbin from the University of Bristol and Dr Stephen White from the Manchester Metropolitan University about their study, Epigenetic Regulation of F2RL3 Associates with Myocardial Infarction and Platelet Function.   Article highlights:   Samargandy, et al. Blood Pressure Trajectories and Menopause   Gilchrist, et al. Research Goes Red Registry   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's Journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh and today I'm going to be highlighting articles from our February issues of Circulation Research. I'm also going to speak with Dr Alastair Poole and Dr Laura Corbin from the University of Bristol and Dr Stephen White from the Manchester Metropolitan University about their study, Epigenetic Regulation of F2RL3 Associates with Myocardial Infarction and Platelet Function.   Cindy St. Hilaire:        The first article I want to share is titled Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter? The first author is Saad Samargandy, and the corresponding author is Samar El Khoudary from the University of Pittsburgh. Blood pressure increases with age, but after midlife, the rate of increase for women generally exceeds that for men. This observation has led to debate over whether menopause might influence the blood pressure trajectory.   Cindy St. Hilaire:        To find out, this group examined data on over 3300 women of diverse ethnicity enrolled in the Study of Women's Health Across the Nation, or SWAN study. The women began the study between 42 and 52 years old, and they had 17 follow-up visits at roughly one-year intervals. At these visits, blood pressure, hormone levels, weight and other health parameters were measured.   Cindy St. Hilaire:        Analysis of the data revealed women fell largely into three blood pressure trajectory groups. Those with low blood pressure before menopause and accelerated blood pressure after menopause, those with a linear increase linked to age, and those with high blood pressure before and a slower ascent afterwards. White, Chinese and Japanese women were more likely to be in the low to accelerated group, as were those with early menopause, while Latino and Black women were more likely to have high blood pressure in general. Together, the results indicate that for many women, menopause itself does not accelerate age-related blood pressure increase, and that women of menopausal age should be advised of this risk and have their blood pressure monitored regularly.   Cindy St. Hilaire:        The second article I want to highlight is titled Research Goes Red: Early Experience With a Participant-Centric Registry. The first author is Susan Gilchrist and the corresponding author is Jennifer Hall from the American Heart Association. Cardiovascular disease is a leading cause of death for men and women alike, but there are particular factors such as pregnancy and menopause that may specifically influence the genesis, presentation and management of the condition in women.   Cindy St. Hilaire:        With that in mind, for the past two decades, the AHA's Go Red for Women campaign has been raising awareness of and driving research into women's cardiovascular health issues. The latest Go Red initiative, an online platform called Research Goes Red, was launched in 2019 with the aim of empowering women to contribute to health research by, among other things, taking part in health surveys. In the last two years, the platform has garnered 15,000 registered individuals between the ages of 30 and 60. It has deployed six targeted health surveys and prompted two AHA-funded research studies based on participant responses: one on perimenopausal weight gain, and one on the use of social media to engage young women in cardiovascular disease awareness. While Research Goes Red has successfully amassed middle aged participants, the authors say that future goals should include increasing the number and the diversity of the registrants and encouraging researchers to use the registry not just for data, but for identifying potential trial participants.   Cindy St. Hilaire:        I want to now mention the 15 articles that are featured in our Compendium on Women and Cardiovascular Disease that is featured in our February 18th issue of Circulation Research. And this also happens to correspond with February being the American Heart Month. So Susan Cheng and colleagues present A Scientific Imperative As Seen Through a Sharpened Lens: Sex, Gender and the Cardiovascular Condition. Genetic, molecular and cellular determinants of sex-specific cardiovascular traits is discussed by Teemu Niiranen and colleagues. Bonnie Ky et al. describe sex-specific cardiovascular risks of cancer and its therapies. Sex differences and similarities in valvular heart disease is presented by Francis Delling and colleagues. Cecile Lahiri and colleagues wrote about the cardiovascular implications of immune disorders in women. Joshua Smith and colleagues discuss sex differences in cardiac rehabilitation outcomes.   Cindy St. Hilaire:        Pregnancy and reproductive risk factors of cardiovascular disease in women is reviewed by Michael Honigberg and colleagues. The impact of sex and gender on stroke is presented by Kathryn Rexrode and colleagues. Ersilia DeFilippis and colleagues cover heart failure subtypes and cardiomyopathies in women. Demilade Adedinsewo and colleagues wrote about cardiovascular disease screening in women, leveraging artificial intelligence, and digital tools. Sexual dimorphism in cardiovascular biomarkers, clinical research implications, is discussed by Jennifer Ho and colleagues. Connie Hess et al. review sex differences in peripheral artery disease. Janet Wei and colleagues provide an update on coronary arterial function and disease in women with non-obstructive coronary arteries. Sex differences in myocardial and vascular aging is presented by Hongwei Ji and colleagues. And lastly, arrhythmias in female patients, incidence, presentation and management, is reviewed by Andrea Russo and colleagues.   Cindy St. Hilaire:        Today I have with me Drs  Alastair Poole and Laura Corbin from the University of Bristol and Dr Stephen White from the Manchester Metropolitan University. And they're here with me to discuss their study, Epigenetic Regulation of F2RL3 Associates with Myocardial Infarction and Platelet Function. And this article is in our February 4th issue of Circ Res. Well, Drs Corbin, Poole and White, thank you so much for joining me today.   Laura Corbin:             Thank you very much.   Stephen White:            Thank you.   Alastair Poole:            Thanks.   Cindy St. Hilaire:        So this is a really neat study. It's bringing in a couple different fields. It's investigating what I'm calling a Venn diagram of these intersecting topics all related to cardiovascular disease: cigarette smoking, epigenetic modification and platelet activation. So can you maybe give us a little bit of background on the status of the field and how these three topics intersected at the start of your study?   Laura Corbin:             So yeah, our working hypothesis was based on existing literature and it was really to look at whether smoking-induced epigenetic DNA hypermethylation of F2RL3 could increase risk of myocardial infarction and whether the route to that could be through platelet function. So there's quite a lot of literature going back probably to around about 2015 that shown that there are changes to the methylome in response to smoking. And DNA methylation is a way of cells controlling gene expression, but without having to actually make changes in the DNA sequence itself. So this could be a really important way that we know that smoking increases the risk of a number of cardiovascular diseases, but we don't really know how that happens. And one way that that could happen is through changes to methylation.   Cindy St. Hilaire:        What is known about how cigarette smoke impacts the status of DNA methylation? How has that switched or changed? Maybe when someone is actively smoking, when someone quits, is it dynamic? What is known about that relationship?   Laura Corbin:            Okay. So yeah, going back to about 2015, there was a number of studies that looked at methylation across the whole genome. So in a hypothesis-free untargeted manner, developments and technology meant that we could look at many, many sites across the genome at the same time. And so studies were done to look at changes that were associated with smoking. And what was found was those changes, actually quite a lot of changes across the genome in a number of different genes, but not really anything much beyond that. So F2RL3 was one of the first sites to be identified as being associated, methylation at that site associated with smoking. And it was replicated in several studies.   Laura Corbin:            And it was also showing that there was a dose-response relationship. So the more a person smoked, the less methylated that site appeared to be. And then there's been some work done already, but we also did it in our paper to show that those methylation marks actually hang around for quite a long time once somebody quits smoking. But also that there's a lot of variation within an individual, so even if you smoke, it doesn't necessarily mean that you'll definitely have low methylation, there's still variation. So there's other factors that are involved in that.   Cindy St. Hilaire:        So you were looking at a specific population of patients, can you tell us a little bit about that group of patients you were looking at? And you mentioned the variability in the amount of smoke they were exposed to, do you know that information? And I guess one of the base questions I had is I'm in Pittsburgh, which back in the '80s and earlier was a steel mill town that had a lot of pollution. And so I'm wondering if you're able to clearly separate out a cigarette smoker from maybe someone who is a light cigarette smoker, but lives in a more polluted area?   Laura Corbin:             Okay. So there's two parts of the study that were looking at this in a human context, so in a whole person context. One of those was using data from the Copenhagen City Heart Study, and that's the one where we looked at the relationship between smoking and methylation and then between methylation and myocardial infarction. So that study is great because it's been tracking people over time and so we're able to use the samples that were collected before they had their cardiovascular event and look at methylation at that point. So we know that the event occurs after that point, which is important. And so we were able to verify in that population that we did see an association between smoking and methylation. We were able to show that it was a dose-dependent relationship. So if we look at something like in that dataset, we had things like the intensity of which people smoke, so pack years is one of the things that we looked at. And it did appear to correspond in an approximately linear fashion.   Laura Corbin:             So we don't really know, I don't think, at this point, what impact other environmental exposures would have on the methylome and how that would interact with the cigarette smoking. That's actually a really interesting point that we'll probably come onto later about whilst we were looking here at the smoking effect on this methylation site, in the second part of the work, we were able to show that even in non-smokers, there's variability in methylation at this site, and that can still have impacts on the biology downstream. So yeah, it's an interesting point.   Stephen White:            Just to maybe just jump in, there's very good amounts of literature now that show quite a good correlation between changes in air quality and cardiovascular events. So smogs, wildfires and so on, clearly correlate with an increase in cardiovascular events. But actually the opposite's also been observed in the more recent COVID lockdowns, where reduction in air pollution also mirrored a reduction in the number of cardiovascular events. So I think you raise a really interesting point about is it cigarette smoke alone or does air quality in general play an effect? And clearly it does play an effect, although we didn't correlate that within this current dataset.   Cindy St. Hilaire:        Your study looked at DNA methylation patterns at cytosine, phosphate, guanidine or CPG sites in the genome. Can you tell us a little bit more about what these islands are and how they change throughout maybe different cells in the body, but also maybe in the same cell, but throughout the course of life or the course of, in this case, cigarette exposure?   Stephen White:            So if we just want to focus in on our study, what we showed was that exposure to cigarette smoke changes endothelial cell methylation. It also changes megakaryocyte methylation patterns in the same way. And I think one of the surprising things was that only 48 hours of exposure to cigarette smoke significantly changes the methylation pattern of the F2RL3 locus. So it's quite a dynamic event, but it does show that these can be quite rapidly regulated. And Laura's really nice work shows that the methylation on cessation of smoking, that pattern does actually go down, but it's a 20-year process. So it looks like it can be rapidly induced, but may actually remain as a methylation mark for a considerable length of time.   Stephen White:            And I think one of the things we did in our study was actually to triangulate not only the observational data and the association data in patients, but actually start to look at a mechanism of how that might actually relate to changes in gene expression. So we showed that this particular CPG site is right next to a binding site for a transcription factor, and transcription factors are the cell's way of regulating how much of a particular gene is expressed. And we show that changes in methylation changed the binding of this transcription factor and therefore change the amount of this particular gene that was made.   Cindy St. Hilaire:        Yeah. Actually, I want to start to talk about that locus you were interested in. So what was known about the F3RL2 locus? How big is it, but also what genes are there and what did you start to investigate with your in vitro modeling?   Stephen White:            So I think when we started, we had the observation that a change in methylation at the F2RL3 locus was associated with the risk of cardiovascular events. And then it was a detective expedition into the gene using various in silico analyses that identified the methylation site that we are interested in, or most interested in, is right next to a transcription factor binding site.   Stephen White:            So we then went on to show that binding of that transcription factor is sensitive to methylation, that if we would just excise that piece of DNA, we can show that that has the ability to regulate F2RL3 expression or the expression of a reporter gene. And then if you knocked out the transcription factor binding site, you lose that regulation. So it was a series of detective work and experimental steps that allowed us to put a mechanism behind the observation that changes in methylation might truly affect the level of gene expression of the F2RL3, otherwise known as PAR4 to platelet biologists. So get that in there.   Alastair Poole:            I first came across it when another member of our team actually mentioned it to me over a casual conversation actually a few years ago that F2RL3 gene was regulated in this way. To me as a platelet biologist, F2RL3 didn't mean a lot, but when I was told then it was the gene that encodes PAR4, it meant everything. And so platelet biologists, we talk about PAR4, which is of course the protein product of the F2RL3 gene. And PAR4 is one of several really key receptors on a platelet surface that responds to, in this case, to changes in thrombin generation, thrombin activity, which is of course the major effectively end product of the coagulation cascade.   Alastair Poole:            So it's what couples coagulation and platelet biology together, thrombin. And there are two major receptors on platelets that operate in response to changes in thrombin and that's PAR1 and PAR4. And they're both very important genes, but yeah, really interestingly, you have this rather selective effect on PAR4 and the paper actually shows it is indeed a selective effect on PAR4 as opposed to PAR1 in terms of epigenetic regulation of its responsiveness to PAR4 activation.   Cindy St. Hilaire:        So I want to tap back onto something that Laura had mentioned briefly, and that is talking about your platelet assays where you isolated platelets from a specific subset of the patients. And I believe it was figure three, and you looked at patients who in adolescence had exhibited differences in the methylation pattern at the site in the F3RL2 locus. What do we know about that innate or early-age change? And then I would love to hear more about this actual experiment, how you looked at the patients earlier versus current and what the thinking was behind that.   Laura Corbin:            So yeah, this part of the work was done in a birth cohort study called the Avon Longitudinal Study of Parents and Children, which is based at the University of Bristol. And this is a really great study, a great resource that we have, and in fact, it's open to all researchers so anyone could use it, where mothers were recruited during pregnancy, which was in around 1991 to 1992. And then those children that were born from those pregnancies have then been followed up ever since.   Laura Corbin:             So that was the data that we were able to use for this part of the study. And what we wanted to do was to look at how this could work functionally, so look at the platelet function, but we really wanted at this point to step away from the smoking. Because obviously if you're going to look at platelet function in smokers versus non-smokers, it's incredibly difficult then to say that that's coming through a specific pathway, because we know that smoking induces lots and lots of changes in methylation, in proteins, all sorts of things going on. So we couldn't see a way of doing that part of the experiment with a comparison of smokers versus non-smokers. But what we know is that there's natural variation in methylation across all sites, including F2RL3.   Laura Corbin:             So we had historic data from earlier time points, so two earlier time points from when the children were under 20. And we looked at those measures for F2RL3 and then just simply ranked people according to whether they had high or low methylation, and then used those two ranks together to then work out who had a consistently high versus consistently low level. And then we invited participants back into the clinic to have samples taken from those up and lower ends of the distribution. At that point, we were just really hoping that that methylation pattern would continue because this was then, I think they aged about 24 by the time we did this work, so it was some time after. And we restricted our selection just to people who were non-smokers, so never smokers based on the information they provided, but also asking them when they came in for that clinic just to verify that they were non-smokers.   Laura Corbin:             And then we had a look at the methylation again. This time we looked across four sites in the region, which are the sites presented in the paper. And luckily for us, there was still that mean difference between the high group and the low group. But what we were able to then do is to compare people with high and low methylation, but without all of the trouble of isolating that pathway in amongst all the other smoking effects. And also not just the smoking effects, but the other confounding factors that come with smoking. So we know that smoking is correlated with a lot of other lifestyle factors. So if you ever do a smoking versus non-smoking comparison, it's really hard to work out exactly which bits are coming from smoking and which pathways it might be going down. So this was the idea behind this part of the study was to just really zoom in on F2RL3 methylation in the absence of all of the other noise in the other experimental designs.   Laura Corbin:             So yeah, the natural variation we see in the non-smoking healthy participants in this part of the study is actually quite a lot less than we see when we look at smokers compared to non-smokers, but it was still enough to then go on and look at the platelet function. And then the differences we saw in the platelet's responses, there is nothing pathological there. It was just very subtle changes in the response when stimulated in the lab.   Alastair Poole:            The only other thing I could add would be that platelets are very complicated cells. Every cell of the body is very complicated. Platelets are certainly very complicated. PAR4, F2RL3, is just one of very many components of the platelet that modulate its activity. So platelets are controlled by multiple forces sort of thing, at which F2RL3 and PAR4 is just one of them. So biology is very good at compensating for one level going up in one part of a pathway and going down compensatory wise in another part of a pathway. There isn't necessarily a direct relationship between one pathway enhancement and an overall effect because of the compensation.   Cindy St. Hilaire:        Why would it be easy?   Alastair Poole:            Yeah. Yeah. It's just very complex, the biology. So yeah, I completely get what you're saying, Laura, that we obviously don't want to frighten people that maybe they've got a propensity to enhance thrombosis based upon a single gene methylation difference because it will be much more complex than that.   Cindy St. Hilaire:        Yeah. I think that's one of the beautiful things about your study is with the luck of having this sample population, you were able to ask these really precise questions that... You can't just start a study now and ask that sort of question. So it was really elegant in that sense.   Cindy St. Hilaire:        Do we know the mechanism of how cigarette smoke induces these methylation changes, or maybe even the specific components of the smoke? And I guess I'm thinking that in terms of vaping that's becoming more and more popular, obviously the company selling those products want to advertise them as safer, but it comes down to is it all of the mixture of the cigarette smoke or is it one component that we know impacts the methyltransferases and demethyltransferases in this process?   Alastair Poole:            Those are two follow-on routes of our study that I have to say that we discussed previously amongst ourselves and identified those as definitely very important follow-up areas. So do e-cigs have similar effects and that's a study that definitely needs to be done. We have done a little bit of work to try to investigate that initially, but I think that's a very important follow-on study. But yeah, you're also right that one of the key things that we want to understand and is, the missing piece in a way, is how is methylation at a molecular mechanistic level altered by smoking? Steve, I don't know whether you have any further details to add to that.   Stephen White:            I think one of the key molecular pathways seems to be the antioxidant response. And so that's largely controlled by another transcription factor called NRF2. And so if you think about smoking or poor air quality, all of those things do combine through this particular pathway that senses free radical damage, free radical stress. So as Alastair said, it's an area we are going to carry on to look at and it's a big area of my own lab's investigations. But oxygen stress is probably the mediating factor, but the actual nuts and bolts about how the demethylase is targeted to this particular locus is still an area of active investigation.   Cindy St. Hilaire:        All right, well, I will be on the lookout for those future studies because it's a really interesting topic, just the whole interplay of all of this. Are there any translational implications for these findings? Do you think potentially we could screen patients, say, to see their methylation status? I don't know if megakaryocytes are easy to isolate, but is it in a circulating cell, would this possibly be able to be turned into a screening tool or a diagnostic tool to predict thrombic events in patients?   Alastair Poole:            It is possible. I think it would not be possible to isolate megakaryocytes very easily. There are a small number in the peripheral circulation, but the majority are not in the peripheral circulation. But we and others have used other blood cells as proxy measures. So actually, the gene methylation changes that we identified here come from other leukocytes, white blood cells, and those effectively are a cell that are exposed to smoke in the same way, or the smoke products in the same way. So we'd use a proxy cell for that.   Alastair Poole:            Yes, I suppose it is possible. As you say, there's a natural variation in methylation status of that gene and there's, layered on top of that, a smoking induced. And I suppose that it would be an interesting further investigation to understand whether, effectively, your natural methylation status of that gene happened to give you an enhanced risk of a cardiovascular event. The work we've done seems to suggest that that may well be the case and therefore you could imagine possibly a personalized medicine approach that might include understanding the methylation status of F2RL3 as part of that.   Cindy St. Hilaire:        Well, it was a beautiful study. I love these studies that bring in lots of different fields or specialties to ask interesting questions. So Dr Corbin and Dr Poole from the University of Bristol and Dr White from Manchester Metropolitan University, thank you so much joining me today.   Stephen White:            Thank you. Our pleasure.   Alastair Poole:            Thank you.   Laura Corbin:             I'd also just like to acknowledge all of our co-authors as it really was a big team effort, especially the guys who are not represented on the call today, which is the folk from the Copenhagen City Heart Study, and also to all of the participants of that study and the Children of the '90s Study that contributed to the work. Thanks very much.   Cindy St. Hilaire:        That's it for the highlights from our February issues of Circulation Research. Thank you so much for listening. Please check out the CircRes Facebook page and follow us on Twitter and Instagram with the handle @CircRes and the hashtag #DiscoverCircRes. Thank you to our guests, Drs  Alastair Poole, Laura Corbin and Stephen White.   Cindy St. Hilaire:        This podcast is produced by Ashara Ratnayaka, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Some of the copy text for highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discoverer CircRes, your on-the-go source for the most exciting discoveries and basic cardiovascular research.   Cindy St. Hilaire:        This program is copyright of the American Heart Association 2022. The opinions expressed by speakers of this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, please visit ahajournals.org.    

👉🏽 https://www.adidas.es/running ---------------------------------------------------------------------- En los últimos años ha aumentado el número de accidentes cardiacos entre corredores. La prensa se ha echo eco de ello y la alarma social es evidente. En este episodio, el Dr. Joaquín Barjau nos presenta la evidencia científica que hay sobre este tema y nos cuenta cómo funciona el corazón cuando corremos, qué es lo que puede fallar e intentamos posibles soluciones a este problema que ya es una realidad. RRSS del Dr. Barjau: @dr.barjau Estudios a los que se refiere el doctor en este episodio: 1. Training for Longevity: The Reverse J-Curve for Exercise. Mo Med. Jul-Aug 2020;117(4):355-361 2. Dose of jogging and long-term mortality: the Copenhagen City Heart Study. J Am Coll Cardiol. 2015 Feb 10;65(5):411-9. 3. Various Leisure-Time Physical Activities Associated With Widely Divergent Life Expectancies: The Copenhagen City Heart Study. Mayo Clin Proc. 2018 Dec;93(12):1775-1785. 4. Exercise-Related Acute Cardiovascular Events and Potential Deleterious Adaptations Following Long-Term Exercise Training: Placing the Risks Into Perspective–An Update: A Scientific Statement From the American Heart Association. Circulation. 2020;141:e705–e736 5. Charla TED de James Okeefe https://youtu.be/Y6U728AZnV0 6. Charla de Iñigo San Millán https://youtu.be/DZfOvYiQtow

Learn about whether it’s better to be a big fish in a small pond or a small fish in a big pond, a mysterious, ancient city called Cahokia that’s, weirdly, just outside St. Louis, and how AI might be able to catch heart disease with a selfie. Curiosity Daily is a finalist in the 2020 Discover Pods Awards, and we need your vote to win! Please vote for Curiosity Daily for Best Technology & Science Podcast via the link below. It's free and only takes a minute. Thanks so much! https://awards.discoverpods.com/vote/ Is It Better to Be a Big Fish in a Small Pond or a Small Fish in a Big Pond? By Kelsey Donk Even When You’re A Member Of An Elite Group, It Can Be Demoralising To Rank Lower Than Your Peers. (2020, September 24). Research Digest; Research Digest. https://digest.bps.org.uk/2020/09/24/even-when-youre-a-member-of-an-elite-group-it-can-be-demoralising-to-rank-lower-than-your-peers/#more-40380  Zell, E., & Lesick, T. L. (2020). Taking Social Comparison to the Extremes: The Huge-Fish-Tiny-Pond Effect in Self-Evaluations. Social Psychological and Personality Science, 194855062095653. https://doi.org/10.1177/1948550620956535  Cahokia Was the Mysterious, Massive Ancient City in ... St. Louis? By Reuben Westmaas Newitz, A. (2016, December 13). Finding North America’s lost medieval city. Ars Technica; Ars Technica. https://arstechnica.com/science/2016/12/theres-a-1000-year-old-lost-city-beneath-the-st-louis-suburbs/  Mound 38 – Monks Mound – Cahokia Mounds. (2015, October 23). Cahokiamounds.Org. https://cahokiamounds.org/mound/mound-38-monks-mound/  Woodhenge - Cahokia Mounds, Illinois. (2020). Scienceviews.Com. https://scienceviews.com/indian/woodhenge.html  AI Might Be Able to Catch Heart Disease with a Selfie by Kelsey Donk “Selfies” could be used to detect heart disease. (2020). EurekAlert! https://www.eurekalert.org/pub_releases/2020-08/esoc-cb082120.php  Christoffersen, M., Frikke-Schmidt, R., Schnohr, P., Jensen, G. B., Nordestgaard, B. G., & Tybjærg-Hansen, A. (2014). Visible Age-Related Signs and Risk of Ischemic Heart Disease in the General Population. Circulation, 129(9), 990–998. https://doi.org/10.1161/circulationaha.113.001696  Lin, S., Li, Z., Fu, B., Chen, S., Li, X., Wang, Y., Wang, X., Lv, B., Xu, B., Song, X., Zhang, Y.-J., Cheng, X., Huang, W., Pu, J., Zhang, Q., Xia, Y., Du, B., Ji, X., & Zheng, Z. (2020). Feasibility of using deep learning to detect coronary artery disease based on facial photo. European Heart Journal. https://doi.org/10.1093/eurheartj/ehaa640  Schnohr, P., Lange, P., Nyboe, J., Appleyard, M., & Jensen, G. (1995). Gray hair, baldness, and wrinkles in relation to myocardial infarction: The Copenhagen City Heart Study. American Heart Journal, 130(5), 1003–1010. https://doi.org/10.1016/0002-8703(95)90201-5  Subscribe to Curiosity Daily to learn something new every day with Ashley Hamer and Natalia Reagan (filling in for Cody Gough). You can also listen to our podcast as part of your Alexa Flash Briefing; Amazon smart speakers users, click/tap “enable” here: https://www.amazon.com/Curiosity-com-Curiosity-Daily-from/dp/B07CP17DJY See omnystudio.com/listener for privacy information.

James O’Keefe is a preventative cardiologist and bestselling author of The Forever Young Diet and Lifestyle. In this episode, James discusses cardiac physiology and what makes the human heart susceptible to disease. He provides evidence for what supports his approach to exercise--elucidating both positive and negative kinds of exercise for heart health. He also discusses the role of nutrition, specific nutrients, and pharmacological interventions to support heart and brain longevity.   We discuss: James’ background and why he favors a preventative approach to cardiology [3:15]; Understanding atherosclerosis and the misconception that it’s a “plumbing problem” [10:15]; The danger in excessive exercise—a reverse J-shaped mortality curve [21:15]; The story of Micah True—A case study of excessive exercise [49:15]; The best kinds of exercise for longevity—The Copenhagen City Heart Study [53:00]; Being a more balanced athlete and finding the right exercise intensity [58:45]; Heart rate during exercise, resting heart rate, and other important metrics [1:04:00]; Nutrition for cardiovascular health [1:09:45]; Important nutrients: Magnesium, potassium, calcium, sodium, and collagen [1:19:30]; SGLT2 inhibition for diabetes, cardio-protection, and general longevity [1:24:15]; GLP-1 agonists for weight loss and reducing cardiovascular risk [1:34:15]; Statins—Mechanism of action, safety, and useful alternatives [1:37:25]; A 40-year view on cardiovascular risk, and the possibility of reversing arterial calcification [1:45:45]; Evidence for high dose EPA and DHA for the reduction of cardiovascular disease risk [1:53:30]; The impact of omega-3, curcumin, and other compounds on mental health and dementia [1:59:00]; James’ focus beyond cardiology [2:02:15]; and More. Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/JamesOKeefe  Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

High-density lipoprotein or HDL is one of the most important of the lipoproteins in most species and there is evidence that points towards a role of HDL in normal immune function.  A paper appearing in the May 2019 issue of Clinical Chemistry tested the hypothesis that concentrations of HLD cholesterol are associated with risk of autoimmune disease. That study from the Copenhagen General Population Study and the Copenhagen City Heart Study included over 100,000 individuals.  We are pleased to have the senior author of that paper with us today, Dr. Borge Nordestgaard. 

E ai Legião AF, será que álcool engorda? Como será que ele age no nosso corpo? O que o álcool faz no seu organismo? No episódio de hoje do nosso Podcast, vamos responder essas perguntas e dar 5 dicas para beber menos e melhor. Dá o play e descobre tudo sobre álcool! Compartilhe esse Podcast e um abraço Legião AF. Quer se juntar a nossa Legião? espaco.autoridadefitness.com/ Também estamos por aqui: Instagram > instagram.com/afnoinsta Youtube > www.youtube.com/c/AutoridadeFitnessOficial Facebook > www.facebook.com/autoridadefitness/ Fontes: How To Drink & NOT Get Drunk - Brit Lab https://www.youtube.com/watch?v=6dEZNZ8tKFA Glass shape influences speed at which we drink alcohol http://www.bristol.ac.uk/news/2015/april/glass-shape-and-alcohol-consumption.html Alcool, congénères et gueule de bois http://gueuledebois.info/aller-plus-loin/les-congeneres/ The doctor’s guide to healthy drinking https://www.onemedical.com/blog/live-well/healthy-drinking/ Is it Possible to Drink and Still be Healthy? https://www.nerdfitness.com/blog/alcohol/ Quick tips: Staying healthy with alcohol https://www.hsph.harvard.edu/nutritionsource/2013/12/18/5-quick-tips-staying-healthy-with-alcohol/ Does mixing alcoholic drinks cause hangovers? http://www.bbc.com/future/story/20140428-does-wine-beer-huge-hangover Waist circumference in relation to history of amount and type of alcohol: results from the Copenhagen City Heart Study. http://www.ncbi.nlm.nih.gov/pubmed/12587005 Beer consumption and the 'beer belly': scientific basis or common belief? http://www.ncbi.nlm.nih.gov/pubmed/19550430 Red Wine: Good or Bad? https://authoritynutrition.com/red-wine-good-or-bad/ Alcohol, body weight, and weight gain in middle-aged men http://ajcn.nutrition.org/content/77/5/1312.full.pdf+html Alcohol and Health: the Good, the Bad and the Ugly https://authoritynutrition.com/alcohol-good-or-bad/ Alcohol consumption, weight gain, and risk of becoming overweight in middle-aged and older women. https://www.ncbi.nlm.nih.gov/pubmed/20212182 Alcohol consumption and body weight: a systematic review. https://www.ncbi.nlm.nih.gov/pubmed/21790610 Metabolismo do Etanol http://www.jmcprl.net/PRESENTACIONES/files/ETANOL.pdf O impacto do consumo alcoólico no ganho de peso http://www.scielo.br/pdf/rpc/v35s1/a06v35s1.pdf Alcohol Consumption and Obesity: An Update https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338356/ What is an alcohol unit? https://www.drinkaware.co.uk/alcohol-facts/alcoholic-drinks-units/what-is-an-alcohol-unit/ Understanding standard drinks and drinking guidelines https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276704/ UK Chief Medical Officers’ Low Risk Drinking Guidelines https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/545937/UK_CMOs__report.pdf Governmental standard drink definitions and low‐risk alcohol consumption guidelines in 37 countries https://onlinelibrary.wiley.com/doi/full/10.1111/add.13341 Red wine with the noon meal lowers post-meal blood pressure: a randomized trial in centrally obese, hypertensive patients. https://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12033702 Alcohol's Effects on the Body https://www.niaaa.nih.gov/alcohol-health/alcohols-effects-body Type of alcoholic drink and risk of major coronary heart disease events and all-cause mortality. https://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=10224979 National Institute on Alcohol Abuse and Alcoholism - Are Women More Vulnerable to Alcohol's Effects? https://pubs.niaaa.nih.gov/publications/aa46.htm What happens when you get drunk http://news.bbc.co.uk/2/hi/health/1721987.stm EVERYTHING SCIENCE KNOWS ABOUT HANGOVERS—AND HOW TO CURE THEM https://www.wired.com/2014/05/hangover-cure/ Alcohol Hangover Research Group http://www.alcoholhangover.com/hangover.html Existem mais fontes que não couberam na descrição. Caso vocês queiram, podem nos pedir no Instagram.

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.                                                 Can proteomic biomarkers distinguish between subtypes of aortic stenosis even years before surgery? Well, to find out more, stay tuned. That's coming right up after these summaries.                                                 The first original paper this week adds to the evidence that smoke-free policies are associated with a lower risk of cardiovascular disease. First and corresponding author, Dr Mayne from Northwestern University Feinberg School of Medicine, and her colleagues linked smoke-free policies to participants of the Coronary Artery Risk Development in Young Adults, or CARDIA study, which has a follow-up of up to 20 years. They found that smoke-free policies in workplaces were associated with significantly lower risk of incident cardiovascular disease after controlling for a wide range of covariants. Results were weaker for bar and restaurant bans, but in the same direction.                                                 Preventive fractions range from an impressive 24 to 46%. Thus, smoke-free policies may improve cardiovascular health through reducing population exposure to tobacco smoke. However, we should remember that much of the US population remains unprotected by smoke-free policies. Thus, taken together with prior ecological work, these results support the continued expansion of smoke-free policies in indoor public places.                                                 Most phase-3 randomized control trials feature time-to-first event end points for their primary analysis. In chronic diseases, however, a clinical event can occur more than once and recurrent event methods have been proposed to more fully capture the disease burden, as well as to improve statistical precision and power.                                                 However, is this really the case? This question was examined by first author, Dr Brian Claggett, corresponding author, Dr Scott Solomon, from Brigham Women's Hospital in Boston, Massachusetts, and their colleagues, who sought to better characterize factors that influence the statistical properties of recurrent events and time-to-first event methods in the evaluation of randomized therapy.                                                 They performed repeated simulated trials with 1:1 randomization of 4000 patients to active versus control therapy. Through simulation, they varied the degree of between-patient heterogeneity of risk as well as the extent of treatment discontinuation. They then compared their findings with those from the actual randomized control trials.                                                 The authors found that the statistical power of both recurrent events and time-t- first event methods were reduced by increasing heterogeneity of patient risk, a parameter that's not usually included in conventional power and sample size formulae. Furthermore, data from real clinical trials were consistent with the simulation studies, confirming that the greatest statistical gains from the use of recurrent events methods occurred in the presence of high patient heterogeneity and low rates of study drug discontinuation.                                                 The next paper uncovers a novel biomarker and therapeutic target of pulmonary arterial hypertension, and that is selenoprotein P. First author Dr Kikuchi, corresponding author, Dr Shimokawa, from Takaoka University Graduate School of Medicine in Japan and their colleagues performed micro-array analyses using pulmonary arterial hypertension, pulmonary artery smooth muscle cells, and found a 32-fold up regulation of selenoprotein P compared with controls.                                                 Selenoprotein P promotes cell proliferation and apoptosis through increased oxidative stress and mitochondrial dysfunction. Using five strains of genetically modified mice, the authors demonstrated a pathogenic role of selenoprotein P in the development of hypoxia-induced pulmonary hypertension.                                                 Furthermore, sanguinarine, which is an orally active small molecule identified by throughput screening reduced selenoprotein P expression and pulmonary arterial smooth muscle cell proliferation and ameliorated pulmonary hypertension.                                                 In summary, this study shows that selenoprotein P plays a crucial role in the pathogenesis of pulmonary arterial hypertension and may be a useful and novel biomarker and therapeutic target in this disorder.                                                 Familial hypercholesterolemia is known to be associated with a high risk of ischemic heart disease, including myocardial infraction, but what about the risk of ischemic stroke? Well, first author, Dr Beheshti, corresponding author, Dr Nordestgaard, from Copenhagen University Hospital and their colleagues examined the associations of familial hypercholesterolemia and high LDL cholesterol with ischemic stroke in both causal, genetic, and observational analyses using more than 106000 individuals from the Copenhagen General Population Study, and more than 10000 individuals from the Copenhagen City Heart Study.                                                 They used a Mendelian randomization design to test whether high LDL per se had a causal effect on ischemic stroke risk using a combination of the familial hypercholesterolemia causative mutations and common genetic variants associated with high LDL.                                                 The authors found that there was no association between familial hypercholesterolemia mutations and ischemic stroke risk. In the Mendelian randomization analysis, also including common genetic variants, there was also no causal effect of high LDL on the risk of ischemic stroke.                                                 These findings imply that the predominant goal of targeting LDL lowering in those with and without familiar hypercholesterolemia is likely to reduce myocardial infractions, rather than ischemic stroke. Well, that wraps it up for our summaries. Now for our feature discussion.                                                 Circulation publishes numerous papers regarding circulating biomarkers. We talk about biomarkers in the diagnostic, prognostic sense, but what about in a pathophysiologic sense, and especially in a disease as important as aortic stenosis? Well, that's what our featured paper this week is all about and I'm so excited to have with us corresponding author, Dr Stefan Söderberg, from Umeå University in Sweden, as well as our associate editor, Dr Peipei Ping from UCLA. We will be discussing the paper entitled “Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement.” Stefan, could you tell us a bit about what made you look at this very interesting question, and perhaps the unique resources you had in Sweden to look at this? Dr Stefan Söderberg:      I'm a practicing cardiologist, and I have been working a lot with aortic stenosis over the years. It's frustrating that we can't do anything to stop the process. In many cases, the patients are old and frail, and if you could find the means to stop the process long before they need surgery, it will be of great benefit for the human and for the society.                                                 Also, knowing that the interventions on the statins, for example, have been unsuccessful, we thought that there must be better ways or other biomarkers. Furthermore, that many of these studies, the phenotype of aortic stenosis has been very poorly described and there is probably much more behind just aortic stenosis than just, for example, calcium deposits in an X-ray, et cetera, et cetera. Dr Carolyn Lam:                You used some very unique resources in Sweden to therefore look at the proteomic signatures of aortic stenosis. Could you describe that and simplify perhaps the results so we can understand it? Dr Stefan Söderberg:      First of all, I got this idea from other studies done up in northern Sweden. If you have an absolutely unique setting, the combination of huge population-based studies in 30 years back, we have a huge biobank with examples of extraordinary good quality from each of these participants. For example, for each participant, the blood has been spun and put into freezer, deep freezer, within one hour for 30 years, and they are now, as I said, about 100000.                                                 Furthermore, I'm working as a cardiologist at a university, and up here, you do all of the aortic surgery for the whole northern Sweden. That is, we can combine the names of the person undergoing surgery together with these population-based surveys and we can get details from all those who have participated in the surveys long before they did the surgery, and they can go and retrieve samples from cases and match controls from the freezers. It's a unique setup. Then, when we were designing the study, we got the chance to get these analyses done by our friends at the university to get the proteomic analysis via a unique data technique. Dr Carolyn Lam:                Wow. Could you describe your results? Dr Stefan Söderberg:      The results that we found in the first set of 334 patients who underwent surgery is 10 years after their first sampling, we found six proteins. Then, we got the question back from Circulation to establish a validation cohort, and we were able to do so to include all those new cases in the last 2 years, and there we could replicate five of these proteins.                                                 The interesting thing that the pattern is completely different between those having coronary artery disease from those without. That kind of phenotyping has not been done throughout other aortic stenosis studies. Therefore, this study is unique. We have had two papers in the last year in the Journal of American Heart Association from the cohort, as well, showing the thing that happened.                                                 For example, lipoprotein little A is only associated with future aortic stenosis valve replacement only in those with concomitant coronary artery disease. There are many unique things, the prospective design, and the phenotype differentiating those with and without coronary artery disease. Dr Carolyn Lam:                Yeah, and if I may just reiterate that the population base that you work with is just enviable and just so that the audience realizes, these are biomarkers that were collected 11 years before the aortic stenosis surgery, isn't it? You really had a long follow-up.                                                 Also, just to let everyone know, it was a proximity extension assay that you used for the discovery, and the six proteins were growth differentiating factor 15, or GDF15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and PCSK9, so very interesting. Peipei, you have a way of putting things into context so beautifully. Could you tell us your thoughts when you saw this paper? Dr Peipei Ping:                   I thought this is a very high-quality study that actually benefited from the long-term established, well-controlled cohort in northern Sweden, as Dr Söderberg just shared with us. On the other end, it married a technology platform that's very well-established and -validated, and this situation targeted proteomics platforms using multi-proximity extension assays with carefully controlled markers and screened 92 cardiovascular candidate markers.                                                 This is the kind of approach that provides semi-quantitative as well as quantitative outputs and is capable to offer validated screens on large population clinical subsets. A study of such with a high value cohort combined with a validated and well-controlled technology platform offered results that clearly have clinical significance, as well as setting up examples for other studies to follow. The enthusiasm from the editorial boards, as well as the reviewers, have been substantially high and supportive. Dr Stefan Söderberg:      Fantastic. I'm very glad to hear this. Dr Carolyn Lam:                Stefan, you also mentioned that a very unique element was the separation of aortic stenosis with and within coronary artery disease, or at least established or visible coronary artery disease. Could you explain how that provided pathophysiologic insights? Dr Stefan Söderberg:      First, I should say we were very, very strict. Our routine is that everyone was 100% undergoing, aortic valve replacement, they undergo a coronary angiogram before. If we saw any sign of atheromatosis, it was not enough that they had the significant stenosis, but any signs, they were put into the group of coronary artery disease. Those without, we couldn't see anything there. Radiograph here reported absolutely clean coronary arteries. Of course, we cannot exclude if there were aortic changes within them all, of course.                                                 We believe that this is a very important message that in order to further study aortic stenosis, we should be very careful in phenotyping the disease. We hope the growing cohort will be able to do this further. For example, cuspid versus tricuspid valves, women versus men, et cetera.                                                 My answer in short is phenotype. Let me take one example which I found very, very exciting. That is the finding of PCSK9, which is closely related not only to cholesterol symptoms, but also to lipoprotein little A emphasis. As you know, the first strong finding in aortic stenosis was the LP little A. This is related to that genetic finding, and that was in the huge study from Canada. They did not have the same phenotyping, so we had information to his important findings. That's one example.                                                 Another example is the transferring receptor, where data has shown that bleeding acutely in the valvular tissue causes damage, and this relates iron metabolism to the formation of the aortic valve. Obviously, it seems that the process in the aortic valve is very much similar to the vessel arteriosclerosis. It seems to be different. This is the indication that when we formulate new studies or new drugs on aortic stenosis, we must be very careful to use the right drug for the right type of valvular disease. Dr Carolyn Lam:                Those are great points. Peipei, do you think that's the main clinical take-home message, beyond that great comment you made earlier that this paper's just a great example of the use of tools, modern tools, that we have in proteomic characterization like the proximity extension assay to provide pathophysiologic insights when you have a really well-phenotyped cohort? What's the critical take-home message, though? Is there one now? Dr Peipei Ping:                   The take-home message is marriage of amazing high value cohort's data sets with that of the well-controlled clinical study using target proteomics approaches. In this particular study, one main critical innovation is the study is capable of providing insights regarding molecular signatures that have predicted values. As stated in the manuscript, the circulating proteins that found critically important, their alterations took place years before the surgery were associated with aortic stenosis. That is of value, clinical value, to many other clinical studies to follow. Dr Carolyn Lam:                Wow. That's wonderful. Thank you so much for putting these findings in context for us. Thank you, listeners, for joining us today. Don't forget to tune in again next week.  

Are you a runner? If so, how well do you pace yourself? This is Judy Gaman and this is your Stay Young Medical Minute. There is a commonly held myth that runners are healthy people who will naturally live longer due to their strenuous exercise. The Copenhagen City Heart Study found quite the contrary. It turns out that joggers did live longer than those who didn't exercise at all, but intense runners who ran too much and too fast, didn't do themselves any favors and in some cases harmed their health putting their mortality equal to those who didn't exercise at all. Bottom line – you need to pace yourself. So how long and at what pace you ask? One to two and a half hours a week and a slow pace of jogging seems to be the sweet spot. At this point, the heart gets a good workout and so does the rest of the body. So break out those running shoes, but don't wear them out too soon. For more tips on how you can stay young and stay healthy, visit Stay Young America.com where you can find my book Stay Young: 10 Proven Steps to Ultimate Health. Stay Young America.com Thank you for listening to the Stay Young Medical Show! With all the mixed messages on health, you need information that you can use and that you can trust. Listen in as the experts discuss all topics health related. It's time to STAY YOUNG and stay healthy! Each week we tackle a topic and often with leading scientists, best-selling authors, and even your favorite celebrities! As a listener of our show, your input is important to us. Please take a moment to fill out this quick survey so we can serve you better - https://survey.libsyn.com/stayingyoung2 For more information on The Staying Young Show, please visit our website at www.StayYoungAmerica.com, and subscribe to the show in iTunes, Stitcher, or your favorite podcast app  You can also reach out to our host, Judy Gaman on www.judygaman.com for book purchasing, and speaking opportunities in your area!

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 Centre and Duke-National University of Singapore. Our featured discussion today relates to 20 year outcomes after mitral valve repair versus replacement for severe degenerative mitral regurgitation.                                                 But first, here's your summary of this week's issue. The first paper suggests that agonistic angiotensin receptor autoantibodies may be biomarkers of adverse outcomes. In this study from first author Dr. Abadir, corresponding author Dr. Fedarko, and colleagues from Johns Hopkins University School of Medicine in Baltimore, Maryland, authors developed a quantitative immunoassay for measuring agonistic angiotensin AT1 receptor autoantibodies in the serum.                                                 They then assessed its operating characteristics in a discovery group of 255 community dwelling adults from Baltimore and validated these findings in a second group of 60 individuals from Chicago. They found that AT1 receptor autoantibody levels were significantly associated with higher levels of inflammatory cytokines, weaker grip strength, slower walking speed, higher risk for frailty, more falls and increased mortality.                                                 Furthermore, chronic treatment with angiotensin receptor blockers, it attenuated the AT1 receptor autoantibody association with decline in grip strength and increased mortality. These results therefore suggest that followup studies and intervention trials in chronic inflammatory diseases should test whether AT1 receptor autoantibody levels can be used to stratify patient risk and whether they can be used to identify patients who may benefit from angiotensin receptor blocker treatment.                                                 The next paper suggests that baseline target mismatch on CT perfusion imaging may predict the response to tenecteplase in ischemic stroke. Dr. Bivard and colleagues from John Hunter Hospital University of Newcastle in Australia pooled two clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke.                                                 Baseline CT perfusion was analyzed to assess if patients met the diffused two target mismatch criteria. These criteria are absolute mismatch volume of more than 15 mL, mismatch ratio of more than 1.8, baseline ischemic core less than 70 mL and volume of severely hypoperfused tissue less than 100 mL.                                                 Among 146 pooled patients, 71 received received alteplase and 75 received tenecteplase. Overall tenecteplase treated patients had greater early clinical improvement by NIH Stroke Scale change and less parenchymal hematoma, but did not show a significant difference in three month patient outcome by the Modified Rankin Scale.                                                 74 of the 146 patients met target mismatch criteria. It was only among these patients with target mismatch that treatment with tenecteplase result in greater early clinical improvement and better late independent recovery than those treated with alteplase. In summary, tenecteplase may offer an improved efficacy and safety profile versus alteplase, benefits that are possibly exaggerated in patients with baseline CT perfusion defined target mismatch.                                                 The next study is the first to provide a comprehensive analysis of circulating metabolite levels and relate these to clinical outcomes in patients with pulmonary arterial hypertension. First author Dr. Rhodes, corresponding author Dr. Wilkins and colleagues from Imperial College London conducted a comprehensive study of plasma metabolites using ultra-performance liquid chromatography mass-spectrometry in 365 patients with idiopathic or heritable pulmonary arterial hypertension and 121 healthy controls.                                                 They found that increases in circulating modified nucleosides originating from transfer RNAs, energy metabolism intermediates, tryptophan and polyamine metabolites and decreased steroids, sphingomyelins and phosphatidylcholines independently discriminated pulmonary arterial hypertension from controls and predicted survival. Furthermore, correction of metabolite levels overtime was linked to better clinical outcomes and patients who responded well to calcium channel blocker therapy had metabolic profiles comparable with healthy controls, thus these findings suggest that monitoring plasma metabolites overtime could be useful to assess disease progression and response to therapy in pulmonary arterial hypertension. Therapeutic strategies targeted against metabolic disturbances, particularly translational regulation and energy metabolism, may merit further investigation in pulmonary arterial hypertension.                                                 The final study takes a contemporary look at age associated changes in left ventricular diastolic function. Dr. Shah and colleagues from Brigham and Women's Hospital in Boston, Massachusetts related diastolic measures including tissue Doppler E prime, E to e prime and left atrial size, to the risk of heart failure hospitalization or death in 5801 elderly participants in the ARIC study. They further defined sex-specific 10th percentile limits in 401 participants free of cardiovascular disease or risk factors. They found that each diastolic measure was robustly associated with incident heart failure hospitalization or death. Reference limits for E to e prime and LA size were generally in agreement with existing guidelines, whereas limits for tissue Doppler E prime were substantially lower at 4.6 for septal E prime and 5.2 for lateral E prime in the ARIC study compared to 7 and 10 respectively in international guidelines. Compared to the guideline cut points, the ARIC base limits improved risk discrimination and reclassified over one-third of the study population as having normal diastolic function. These findings were further replicated in the Copenhagen City Heart Study.                                                 In summary, this study suggests that a decline in left ventricular longitudinal relaxation velocity occurs maybe as part of healthy aging and is largely prognostically benign. This supports the use of age-based normative values when considering an elderly population.                                                 Well, that wraps it up for the summaries, now for our featured discussion.                                                 Today we are discussing the very important result of the mitral regurgitation international database and we have with us today no other than the corresponding author Dr. Jean-Louis Vanoverschelde, and he is from University of Louvain in Brussels. Welcome Jean-Louis, I made it. Dr Jean-Louis Vanoverschelde:  Hey, how are you? Dr Carolyn Lam:                Thank you so much for joining us. Also joining us today is Dr. Victoria Delgado, associate editor from Leiden University Medical Center in the Netherlands. Welcome Victoria. Dr Victoria Delgado:        Hello. Thank you very much for having me in this podcast. Dr Carolyn Lam:                So, severe degenerative mitral regurgitation with flail leaflets, a very important condition and your study, Jean-Louis, really provides important clinically applicable information. Could you please address our clinicians out there with a take home message from your paper. Dr Jean-Louis Vanoverschelde:  Well, the take home message is very easy, once this condition needs to be operated on, there are really two options, one which is to repair the valve and keep the native tissue and the other is to replace the valve and trash the native tissue if I can say so. The results of the study are really clear. There is a major survival advantage by repairing the valve as opposed to replacing it. So for everyone of those who have degenerative mitral regurgitation with flail leaflets, the best treatment option is mitral repair. Dr Carolyn Lam:                Now these results came from a multi-center registry of thousands of patients. I was really struck with the duration of the study. I think that's something that's really novel. You had a 20 year follow up but also patients were recruited from 1980 all the way to 2005, am I right? So could you expand a little bit about the possibility of techniques changing during that period? Dr Jean-Louis Vanoverschelde:  Although there has been subtle changes in the practice, the basic principle have remained the same. So we have not really accounted for these changes in the practice over time, with regard to what happened to mitral valve replacement, clearly the prostheses that were there 30 years ago are not the same as the ones that are currently implanted to the patients, but none the less when we performed an analysis, a sensitivity analysis to look at whether the results were different from 20 years ago compared to those that were more recent, we found exactly the same result. Dr Carolyn Lam:                Yes, I thought that was a very important sensitivity analysis. Tell us a bit more about the propensity score matching as well because another thing people will be thinking is, you know, this is a registry, huge numbers very important but obviously there would be differences in indication for repair versus surgery. Dr Jean-Louis Vanoverschelde:  For sure, the fact is that there are statistical means that allow you to mimic not to be the exactly the same as, but to mimic randomization and it is the propensity score matching. That means that you perform a prior analysis that will identify similar patients in the two cohorts and match them so that you are basically having the same kind of patients that are treated with two different ways. So it's not randomization but it's getting close to randomization when you use cohorts like the one from the MIDA registry. Dr Carolyn Lam:                Perfect. Victoria, did you take the same take home messages and are you applying this clinically? I noticed that you invited an editorial, a lovely editorial on this paper as well, so please share your thoughts. Dr Victoria Delgado:        Yeah, I share the same take home message that Dr. Vanoverschelde has outlined. I think that this is very important article, it's a landmark article highlighting one of the most important things that mitral valve repair should be probably the standard of care for patients with severe mitral regurgitation without degenerative cause with a flail and the article basically what it does is also endorsing the recommendations of current guidelines highlighting the value of mitral valve repair. Of course that mitral valve repair should be performed in centers with experience and with good durability of these repairs, so the centers need to have a good heart team where they can analyze their results in such a way like the MIDA registry has done demonstrating a good durability of the repair. Dr Carolyn Lam:                And do you have anything to add to that Jean-Louis? Dr Jean-Louis Vanoverschelde:  No, I think basically Victoria very well summarized the basic features not only of the paper itself but also of the condition and what currently is in the guidelines. In fact, the guidelines have already said that we should be preferring mitral valve repair over replacement, but the data on which this was based were probably not as conclusive as the one that are provided by this analysis of our registry, so I think it's really reinforcing the idea that we should go ahead and try to perform repair as much as possible, now with a caveat of course that the surgeons need to be skilled enough to perform that. But with the type of differences that we see in survival between the two cohorts I think that if a surgeon does not feel comfortable with repairing the valve and would rather replace it, he might refer the patient to another surgeon that is capable of repairing the valve. The impact and outcome is such that I think this really supports the idea that the patient should be referred to high volume and skilled centers. Dr Carolyn Lam:                Could you give us an idea of what kind of impact you're talking about, what kind of numbers that you see? Dr Jean-Louis Vanoverschelde:  It's the same in all the analysis, whether it's in the overall population or in the matched cohorts by 20 years, we have something like 20 to 25% survival difference, absolute survival difference between the two groups. So it's a reduction of mortality approximately by half if you perform repair compared to replacement, and it is increasing with time, so it's not something that is only present in the first years but is increasing with time, so it's about 20 to 25% absolute difference between the two cohorts. Dr Carolyn Lam:                That truly is remarkable. Congratulations again on such a landmark paper like Victoria said. Now to either of you, question that's a bit left field maybe, but what do you think the role is now for percutaneous techniques of mitral valve repair or replacement then? Dr Jean-Louis Vanoverschelde:  That's an interesting question. I think that if you really look far away into the future probably everything at some point in time will be percutaneous. At this stage I'm not sure that the percutaneous technique able to mimic what we can do with surgery in terms of mitral valve repair. So, it's an alternative to surgery in patients who are inoperable. In those who can undergo a surgical mitral repair, my first choice will certainly be to go surgically rather than percutaneously, at least right now. Dr Carolyn Lam:                Victoria? Dr Victoria Delgado:        I also agree with those comments. I think that now we have a lot of possibilities to treat these patients but the most important thing is to have the entire clinical picture of the patient, to see the pros and cons of preparing the patient for surgery or for percutaneous valve. There should be also an integration of imaging to know which is the cause of the valve dysfunction and to see whether the anatomy could be easily repaired by surgery or instead if the patient has contraindication for surgery, if it could be repairable as well with transcatheter therapy. But then for that I think that is really important and this is what the editorial also highlights, the role of the heart team, where there are different specialist surgeons, clinical cardiologists, heart failure specialists, imaging specialists that can integrate the entire information of the patient in order to select the most appropriate therapy. But still for patients who do not have contraindications for surgery who have repairable valve and as you can see from this registry, the percentage of repairability is quite high, I would still refer the patient as well for surgical valve repair. Dr Carolyn Lam:                You heard it right here. Thank you so much for joining us today and please don't forget to tune in next week.  

In the May issue of Clinical Chemistry, researchers involved in the Copenhagen City Heart Study found that lower nonfasting, circulating triglyceride concentrations are associated with lower all-cause mortality.

Increased nonfasting plasma triglycerides indicating increase amounts of cholesterol in remnant liver proteins and are important risk factors for cardiovascular disease. In the May issue of Clinical Chemistry, researchers involved in the Copenhagen City Heart Study found that lower circulating triglyceride concentrations are associated with lower all-cause mortality.