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Circulation on the Run

Mar 9, 2020

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, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, the feature article today is really interesting. It's evaluating the evolution of cardiovascular disease associated adverse events in developing countries and It's really fascinating looking at differences between Russia, China, India, and Brazil, but more to come. Don't want to spoil all that. How about we get started with a cup of coffee and discussing some of the articles in the Journal.

Dr Carolyn Lam: You bet, Greg. Well, I want to start off with this paper that provides really novel insights into the pathogenesis of hypertrophic cardiomyopathy.

Dr Greg Hundley: Carolyn, you're one of the cardiomyopathy experts. Can you give us a little background before we get started?

Dr Carolyn Lam: Not sure about expert, but I can sure give you a background. So. Hypertrophic cardiomyopathy remember, is caused by pathogenic variants in the sarcomere protein genes, and that evokes hypercontractility, poor relaxation, and increased energy consumption by the heart and increases the patient's risk for arrhythmias and heart failure. Recent studies show that the pathogenic missense variants in myosin are clustered in residues that participate in dynamic confirmational states of the sarcomere proteins.

In today's paper from co-corresponding authors Dr Seidman and Toepfer from Harvard Medical School, authors hypothesized that these confirmations were essential to adapt contractile output for energy conservation and that pathophysiology of hypertrophic cardiomyopathy resulted from destabilization of these confirmations.

So they assayed myosin ATP binding to define the proportions of myosin in two confirmational states called SRX or DRX. This was done in healthy rodent and human hearts at baseline and in response to reduced hemodynamic demands of hibernation or pathogenic hypertrophic cardiomyopathy variants.

They found that hypertrophic cardiomyopathy mutations that disrupted the physiologic balance of SRX and DRX altered cardiomyocyte contraction, relaxation and metabolism, and conveyed increased risk for heart failure and atrial fibrillation. In fact, a small molecule could restore the physiologic balance of SRX and DRX and improve functional energetic and cellular abnormalities that occurred in hypertrophic cardiomyopathy.

Dr Greg Hundley: Very interesting, Carolyn. Well, let me tell you about my paper. It's called The OUTSMART Heart Failure. It's a randomized controlled trial of routine versus selective use of cardiovascular magnetic resonance for patients with non-ischemic heart failure. And it's from Dr David Ian Paterson at the University of Alberta.

This is a study from Canada randomizing 500 patients with suspected non-ischemic heart failure to either having a cardiac MRI as the first imaging study or have an echo, and then based on the echo, order an MRI if the physician so indicates. It was an older version of MRIs, so it's a SUNY assessment of function, including the EF, and then delayed enhancement, a technique that again has been available for the past 20 years and incorporates gadolinium contrast.

Dr Carolyn Lam: Greg, this is so unfair. I'm an echo person, you're an MRI person, but you get to tell us the results and inject your thoughts.

Dr Greg Hundley: No bias. So, Clinical outcomes, Carolyn, you'll be very appreciative, were similar for the two groups of subjects, although the heart failure etiology was more frequently derived in those that received an MRI, whether you're randomized to an MRI first or if you had an echo and they said, "Oh, go get an MRI." The patients with specific heart failure etiologies from imaging had worse outcomes, whereas the heart failure etiologies defined clinically did not.

So, if you didn't take the imaging into account, it didn't discriminate. Importantly, the authors note that more modern techniques, involving mapping with or without contrast, were not employed. It's an older form of the MRI imaging, but the results would suggest that physician decisions regarding the potential use of MRI are important. Bringing us in to decide when to get it is a good idea based on these results.

Dr Carolyn Lam: That was very balanced. Thank you, Greg. But I've got a question for you now. What do you think of coconut oil? Do you take it?

Dr Greg Hundley: Well, I love coconut cake. Does that count?

Dr Carolyn Lam: Well, I have to tell you, I cannot even begin to name the number of people, it's friends and relatives and patients, who take coconut oil because they believe it's good for them. They literally spoon it into their mouths. The truth is coconut oil has been accorded much attention in the popular media as a potential beneficial food product. In fact, a survey in 2016 found that 72% of Americans viewed coconut oil as a healthy food. This represents a remarkable success in marketing by coconut oil and related industries calling coconut oil a natural healthful product despite its known action to increase LDL cholesterol. Of course, we know that, that's an established cause of atherosclerosis and cardiovascular events.

This paper in our journal really deserves attention. It's from corresponding author Dr Rob van Dam from Saw Swee Hock School of Public Health and the National University of Singapore. He and his colleagues conducted a systematic review of the effect of coconut oil consumption on blood lipids and other cardiovascular risk factors compared with other cooking oils using data from clinical trials. In a meta-analysis of 16 trials, they found that coconut oil consumption significantly increased LDL cholesterol concentrations as compared with non-vegetable oils. Although coconut oil consumption also increased HDL cholesterol concentrations, we need to remember that efforts to reduce cardiovascular risk by increasing HDL, have not really been successful in the past.

Anyway, there was no evidence of benefits of coconut oil over non-tropical vegetable oils for adiposity or glycemic or inflammatory markers. Now, this is discussed in an editorial by Dr Frank Sacks at Harvard T.H. Chan School of Public Health and it's entitled: “Coconut Oil and Heart Health. Fact or Fiction?”

Dr Greg Hundley: Very nice, Carolyn. Well, I guess I can't use my coconut cake to lower my LDL. How about we get on to what else is in the journal? You want to go first?

Dr Carolyn Lam: Yeah. We have an important white paper by Dr Sharma on the impact of regulatory guidance on evaluating cardiovascular risk of new glucose lowering therapies, to treat type two diabetes. It talks about lessons learned and future directions. All of this was occurring in February 2018 when a think tank comprising representatives from academia, industry, and regulatory agencies convened to consider the guidance in light of findings of the completed CV outcome trials. Very, very important read. We also have a research letter from Dr Wanken entitled, “Characterization of Endovascular Abdominal Aortic Aneurysm Repair Surveillance in the Vascular Quality Initiative.” You got to read about that.

Dr Greg Hundley: Well, Paul Ridker writes a very nice perspective piece. Will all atherosclerosis patients soon be treated with combination lipid lowering and inflammatory inhibitors? Very interesting read. In a separate article, there's a nice ECG challenge from Dr Andrei Margulescu, An Irregular Tachycardia that's not Responsive to Medical Treatment: What is the Diagnosis? A great read for those in training.

Got a couple letters to tell you about. One is the research letter on filamin-C and it's essential for heart function from Professor Ju Chen University of California, San Diego. Then, there's a letter to the editor regarding the article, Stroke Risk as a Function of Atrial Fibrillation Duration in CHA2DS2-VASc Scores from Dr Ming-Wu Xia from Hefei Affiliated Hospital and Anhui Medical University. Then there's a response letter from Rod Passman from the Feinberg School of Medicine at Northwestern University. Well, Carolyn, how about we go to learn about the evolution of cardiovascular events and how they're evolving in Russia, China, India, and Brazil.

Dr Carolyn Lam: Super excited about this one. Let's go, Greg. Our feature paper today focuses on cardiovascular disease burden in the BRICS, and that stands for Brazil, Russia, India, China, and South Africa, B. R. I. C. S. Which is a grouping of upper and lower middle-income countries constituting almost half the world's population and contributing almost a third of the world's GDP. A really, really important paper here. I'm so pleased to have with us the corresponding author of this paper, Dr Zhiyong Zou from Peking University School of Public Health.

Dr Jo, can you please start by telling us a little bit about how you did this study? I thought the methods were amazing.

Dr Zhiyong Zou: There was little study on cardiovascular disease in breaks. So most of the studies have focused just fatality across year, and then reported change in different age groups. However, this fails to distinguish cohort from period effects. So our study aims to examine the time change and also the relative contribution of period and cohort facts.

Dr Carolyn Lam: Wow. So that's big and an acute area. So could you tell us a little bit more about how you did this? Like the databases and then some of the very interesting methodology such as net drift, age curves, period, relative effects. Could you maybe describe those?

Dr Zhiyong Zou: The data was derived from global burden disease 2017 which was as estimate by the university of Washington. This data was estimate for the whole population in each country from many original data sources. Our study used a new method, age period, cohort model.

We can use this model to estimate first cohort from period effects so we can compare different post cohort population and the different period population. They have different effects. And also, we can estimate the net drift, net drift is the overall annual percentage change. It is different from other study. Just to calculate the average percentage change. It is different. It was adjusted for period effects.

Dr Carolyn Lam: Audience, I really have to refer you to the figures of this paper. They're beautiful and that really... Pictures say a thousand words, but Dr Zou, could you now tell us what were the key findings?

Dr Zhiyong Zou: First, although there have been reductions in the breaks of the CVD mortality, they have lagged behind North American by over 15%. Yes, it is very decreased slowly but there is a notable exception of Brazil and the second, there was striking difference between countries. Russia consistently has the highest CVD mortality and Brazil have the lowest. Brazil and China have had continuing vitality improvements since 1992 but there has been little decry in India for middle age Indian males. CVD mortality has increased.

The last one is China has a high rate of out of hospital ischemia heart disease test reflecting poor pre-hospital care. Only 11% of the out of hospital desks received a basic cardiopulmonary citation. And the yes in China, this situation is very serious.

Dr Carolyn Lam: So really fascinating results. And maybe I could just add that you observed over a 25-year period from 1992 to 2016 the general picture is at least there's a decline in these areas, but definitely not as much as that observed during the same time in North America. But I absolutely agree that the striking country differences, so you know, maybe we should start with something positive. Dr Zou, what lessons do you think we could learn from Brazil's strikingly exceptional example?

Dr Zhiyong Zou: Brazil stands out for successful epidemiological transition. Yes, they with a rapid reduction. There are two important factors: The first one is Brazil investment in health with a decrease in smoking from 13.5% in 1999 to 17% in 2009 it decreased by 15%. Another factor is Brazil reform of primary health care focus on the family health program and the prevention and the care for the management of SADs.

Dr Carolyn Lam: I like that. From this paper we could get very, very important public health messages that may inform countries on how this burden can be tackled better like that. Good example of Brazil, but now maybe the tougher topic of in China, what do you think is the reason for the continuing problem with ischemic heart disease

Dr Zhiyong Zou: In China? The real mortality of ischemia heart disease increased very quickly, around 13.5% Increase. Compare that with other countries or declined. So in China with that, there were about 300 million more smokers in China. It was the biggest number in the world? Yes. So it's a big challenge for the government to control the smoking rate. And also, we mentioned that only 11% of the outside hospital Does received a cardiopulmonary citation.

Dr Carolyn Lam: Yeah. And so the point about the low CPR rates may point to more systematic issues in a primary care and public setting, isn't it? And it must be so difficult in a place as huge as China with such diversity in rural communities versus urban and so on. So very important points. I mean, do you have any insights for the issues that are seen in, for example, South Africa, Russia and India?

Dr Zhiyong Zou: We don't have data from the other countries.

Dr Carolyn Lam: Sure. One postulation I suppose thinking about things could be just very rapid transition from the era of infectious disease, communicable diseases to noncommunicable diseases. But you know, the diversity even among those is really, really astounding.

And I think everyone really just has to pick up your paper and have a good read. So could I ask, what are some of the take home messages and next steps that you may have in further research?

Dr Zhiyong Zou: The take home message is, Brazil's success suggest that the prevention policies can both reduce the risk for younger both cohorts and also, the greater risk for all age groups indicating greater progress in achieving CVD health is possible in rapid three in merging economics, which provide example for China and for India. And also a failure to investigate CVD prevention in countries undergoing rapid economic change will exert huge human and economic costs. So that's the take home message.

Dr Carolyn Lam: And those are great, great summaries. And do you have personal plans for further research in this area?

Dr Zhiyong Zou: Yes. In future, we will forecast on the risk factors because in this paper we find many priority age groups in different countries like example, in China those aged over 15 years old, is the prime priority age groups. But in India, 35-60 years old is the most priority age group because in these people, they are most of the productive age, but the mortality increased very quickly.

Dr Carolyn Lam: Yeah, a very good point. And investigating those risk factors would be so informative. Well, thank you so much, Dr Zou for sharing your incredible work with us. We're so proud to be publishing this important work.

Thank you, audience, for joining us today. You've been listening to Circulation on the Run. Please tune in again next week.

Dr Greg Hundley: This program is copyright, the American Heart Association 2020.