Circulation August 9, 2016, Issue

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Carolyn: 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 National Heart Center and Duke National University in Singapore. Joining me today will be Dr. Katherine Mills and Dr. Andrew Moran to discuss the very striking findings of a new study on global disparities of hypertension prevalence and control, but first, here's the summary of this week's original papers.

In a study by first author, Dr. [Lu 00:00:42], corresponding author, Dr. Denny, from the Harvard TH Chan School of Public Health in Boston, Massachusetts and colleagues, authors aimed to investigate how the risk of cardiovascular disease is distributed among whites and blacks in the United States and how interventions on cardiovascular risk factors would reduce these racial disparities. To achieve these aims, the authors used a nationally representative sample of more than 6,000 adults, age 50-69 years of age, in the United States and developed a risk prediction model that was calibrated separately for blacks and whites.

The main results were that were substantial disparities in the risk of fatal cardiovascular disease; 25% of black men and 12% of black women were at high risk of fatal cardiovascular disease compared to only 10% of white men and 3% of white women, respectively. A large proportion of these fatal cardiovascular events among blacks were concentrated among this small proportion of the population. Now, whereas, population wide and interventions focused on single risk factors did not reduce black/white disparities in fatal cardiovascular risk and intervention that focused on high-risk individuals and reduced multiple risk factors simultaneously could indeed reduce black/white disparities in fatal cardiovascular disease by a quarter in men and a third in women.

These results really emphasize that focusing preventative interventions on the high-risk individuals has a large potential to improve overall cardiovascular health and reduce racial disparities in the United States.

The next paper is from first author, Dr. Lee, corresponding author, Dr. Federer, from Ohio State University Wexner Medical Center in Columbus Ohio and colleagues who looked at the issue of adenosine-induced atrial fibrillation and aimed to elucidate the molecular and functional mechanisms that may underlie this problem. To achieve this aim they integrated panoramic optical mapping and regional immunoblotting to allow them to resolve the protein expression of the two main components of the adenosine signaling pathway, mainly the A1R and GIRK4. They found that these signaling pathways were 2-3 times higher in the human right atrium compared to the left atrium leading to a greater right atrial action potential duration shortening in response to adenosine.

Furthermore, they showed that sustained adenosine-induced atrial fibrillation is maintained by re-entrant drivers localized in the lateral right atrial regions with the highest A1R and GIRK4 expression. Finally, the authors demonstrated that selective GIRK channel blockade successfully terminated and prevented atrial fibrillation. Thus, suggesting that the arrhythmogenic effect of adenosine in human atria may be mediated by activating GIRK channels. The take-home message, therefore, is that specific blockade of the GIRK channels may offer a novel mechanism to prevent adenosine mediated atrial fibrillation in patients.

The next study is from Dr. Nielsen and colleagues from the Copenhagen University Hospital of Bispebjerg in Copenhagen, Denmark, who aimed to assess the optimal blood pressure in patients with asymptomatic aortic valve stenosis. To achieve this aim, the authors used data from the simvastatin, ezetimibe in aortic stenosis or SEAS trial of 1,767 patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease. Outcomes that were studied included all-cause mortality, cardiovascular death, heart failure, stroke, myocardial infarction, and aortic valve replacement. The main findings were that an average diastolic blood pressure above 90 and a systolic blood pressure above 160 millimeters mercury were associated with a poor outcome.

Furthermore, low systolic blood pressure was also related to adverse outcomes while low average diastolic blood pressure was harmful in moderate aortic stenosis. In summary, the optimal blood pressure, which was associated with the lowest risk of adverse outcomes, were the systolic blood pressure between 130 and 139 and a diastolic blood pressure between 70 and 90 millimeters mercury. The clinical take-home message is that in the scarcity of randomized controlled evidence, these results may assist clinicians in their decisions in blood pressure measurements in patients with aortic stenosis, meaning that a blood pressure above 149D may be treated while a blood pressure lower than 120 systolic or 60 diastolic may be recognized as a warning signal for poor outcomes.

That was the summary of this week's original papers. Now for a discussion of our feature paper.

I am so excited to be joined by two guests today to discuss our feature paper entitled Global Disparities of Hypertension Prevalence and Control, a systematic analysis of population-based studies from 90 countries. We are so pleased to have the first author, Dr. Katherine Mills, from Tulane University School of Public Health and Tropical Medicine in New Orleans. Welcome, Katherine.

Katherine: Thank you. Good morning.

Carolyn: And a very special occasion indeed, we have an editorialist joining us, as well, in none other than Dr. Andrew Moran from Columbia University Medical Center in New York. Welcome, Andrew.

Andrew: Good morning. Thank you, Carolyn.

Carolyn: It's wonderful to have you discuss this. This paper has so many key findings that really struck me. If you don't mind, I am just going to summarize some of these. For example, Katherine, you reported globally more than 30% of the adult population, amounting to almost 1.4 billion people have hypertension in 2010, and the prevalence of hypertension was higher in low and middle income countries than in the high income countries, making it, therefore, that approximately 75% of people living with hypertension live in the low and the middle income countries. Yet, hypertension awareness, treatment, and control were much lower in the low and middle income countries compared to the high income countries. That is really striking. Katherine, I'd really love for you to share with us what was the inspiration to look at this and what do you think was the most striking finding?

Katherine: We know that hypertension is a very important risk factor for cardiovascular and kidney disease. It's the leading cause of cardiovascular disease in the world and for premature death. A previous study in our research group found that about 26% of the world's adult population had hypertension in 2000, but since then there really hasn't been any global estimate made. Basically, since 2000, a lot of studies from individual countries and high income countries have shown a leveling off or decrease of hypertension prevalence, but studies from individual low and middle income countries have actually shown an increase in hypertension prevalence.

Given these trends in individual countries and the importance of hypertension prevalence and treatment and control, to prevent cardiovascular disease, we really wanted to look and see what the disparities were in high income compared to low and middle income countries. I think the most striking findings to me was that we found that over 75% of adults with hypertension globally are in low and middle income countries, and that's over a billion people. We also found that only 7.7% of those people with hypertension and low and middle income countries have controlled hypertension. That represents a huge global public health problem that could lead down the road to a large burden of cardiovascular and kidney disease if it's not effectively addressed.

Carolyn: Katherine, I could not agree with you more because it's actually a living reality that I'm seeing where I come from in Asia. We have just so much hypertension, and what struck me was that from 2000 to 2010, while the prevalence increased here, it decreased in high income countries. Yet, this is where the greatest need is and where the control is the lowest. That was striking. Can you just articulate a bit further how your data now add to the knowledge that was there before your paper?

Katherine: Basically, this is the first paper to show that the prevalence of hypertension is higher in low an middle income countries compared to high income countries. It's the first paper since 2000 to quantify the global burden of hypertension, and it's the first paper to really compare rates of awareness, treatment, and control comparing high income to low and middle income countries.

Carolyn: That is fantastic and really striking. I think that's why the Circulation Editorial Board to invite an editorial by Andrew to discuss this. Andrew, your editorial was entitled Still on the Road to Worldwide Hypertension Control, and even in the first sentence of your editorial, you mention that hypertension is a preventable risk factor, and that's why this is so important. I really like that your first subheading has this big word, action. Maybe you could tell us a bit more. What are the implications of these findings for worldwide hypertension control and actions that we can take?

Andrew: There's a growing attention to noncommunicable diseases worldwide as a lot of maternal and fetal deaths, those rates have improved worldwide, and so really as the world population ages, problems like hypertension and related noncommunicable diseases are becoming a bigger and bigger health problem for people around the world, not just in high income countries. As a matter of fact, recently the World Health Organization set a 25 by 25 goal, meaning to reduce deaths from noncommunicable diseases by 25% by the year 2025. A big part of that effort is going to be an effort to control hypertension. The World Heart Federation has set a goal of improving hypertension control by 25% as part of that overall effort.

Carolyn: Yes. You mentioned that I think in the editorial, as well, but are there some action steps that we could take globally as a community?

Andrew: Yes. It's striking to me as a practicing physician that something so basic as measuring blood pressure and recommending treatment for people with elevated blood pressure, which is so integral to our daily practice in medicine, that we still have so far to go in achieving control both in high income settings and low and middle income country settings. One of the most basic cornerstones of achieving control is proper measurement of blood pressure. I think one of the goal efforts has to involve making sure that primary care settings and even community centers have available well-calibrated and validated blood pressure measurement devices and that people know how to measure blood pressure accurately.

The other problems that come up with controlling hypertension are for people who have a diagnosis that is accurately made, are they able to follow up with a primary care provider to monitor their blood pressure, and do they have medications available to them that are affordable? It's important to note that especially in low and middle income countries, most people have to pay for their medications out of their own pockets, so the affordability and availability of medications is a really important part of achieving our goals. I think it's important to see that low and middle income countries, even though it can seem like a daunting setting in which to implement improvements in the quality of healthcare delivery, there also important places to experiment with improving the quality of care delivery worldwide.

For example, the concept of having a community health worker make home visits and reach out into the community was something that was developed in low and middle income countries and now is becoming a popular and effective method of delivering care in all countries worldwide.

Katherine: One thing I would add is that I think we really need collaborations from the international level because so many of these low and middle income countries have very limited healthcare resources, and there still dealing with a lot of infectious diseases, so I think it really is going to take an international effort to address this problem in low and middle income countries.

Carolyn: Thank you so much for joining us for another episode of Circulation on the Run. Tune in next week for more summaries and highlights.

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