Circulation March 13, 2018 Issue

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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.

Have you ever wondered, which is better for heart health, low calorie vegetarian or a Mediterranean diet? Well, this week's feature paper provides some answers with a very intriguing discussion coming right up after these summaries.

The first original paper this week suggests that human fat pools are not the same and in fact are highly diverse in their response to lifestyle interventions during weight reduction first author Dr. Gepner, co-corresponding authors Dr. Shai from Israel and Dr. Stampfer from Boston aim to assess whether distinct lifestyle strategies could differentially affect specific body adipose depos. They performed at 18-month randomized control trial among 278 sedentary adults with abdominal obesity or dyslipidemia in an isolated work place with a monitored, provided lunch.

Participants were randomized to an isocaloric low fat or a Mediterranean low carbohydrate diet with or without added moderate physical activity. The overall primary outcome was body fat redistribution and the main specific endpoint was visceral adipose tissue. The authors further followed the dynamics of different fat depos by magnetic resonance imaging. They found that Mediterranean diet was superior to the low fat diet in mobilizing specific ectopic fat depos such as visceral, hepatic, cardiac and pancreatic fats. Exercise had an additional independent contribution to visceral fat loss. Long term persistent moderate weight loss inadequately reflected the significant beneficial effects of diet and exercise on the fat depos. Independent of weight loss, visceral and hepatic fat reduction was mainly associated with improved lipids profile whereas deep subcutaneous fat loss was associated with improved insulin resistance and superficial fat loss was neutral.

In other words, two distinct patterns were identified, a differentially responsive depo that was sensitive to the type of intervention, and those recites mostly directly related cardiometabolic health and a uniformly responsive depo, which corresponded only to weight loss per se irrespective of the intervention. Overall, these results suggest that more specific strategies for weight loss may be considered to treat distinct organ specific fat depos in the management of cardiometabolic risk.

Current guidelines recommend nonvitamin K antagonist oral anticoagulants or NOACs in patients with nonvalvular atrial fibrillation as these drugs have several benefits over the vitamin K antagonists but do these benefits remain when NOACs have to be combined with aspirin therapy? Well co-first authors Dr. Bennaghmouch and de Veer, corresponding author Dr. ten Berg and colleagues from the Netherlands provided a meta analysis comparing NOACs and Vitamin K antagonists in more than 21700 patients with atrial fibrillation who are treated with concomitant aspirin therapy. NOACs were found to be more effective in terms of stroke or systemic embolism reduction as well as vascular death reduction and as safe as vitamin K antagonist with respect to major bleeding. NOACs were in fact safer with respect to the reduction of intracranial hemorrhage. Thus, these authors found that NOACs were an effective and safe alternative as compared to vitamin K antagonists in atrial fibrillation patients treated with concomitant aspirin therapy.

The next study shows that an integrative approach using genomics and proteomics has the potential to identifying new biological pathways for biomarker discovery and pharmacologic targeting in early cardiovascular disease. Co-first authors Dr. Benson and Yang, co-corresponding authors Dr. Wang and Gerszten from Beth Israel Deaconess Medical Center in Boston had recently identified 156 proteins in the human plasma that were each associated with a net Framingham cardiovascular disease risk score using an aptamer-based proteomic platform in the Framingham Heart Study Offspring participants.

Now, in the current student these authors hypothesized that performing a genome-wide association study and exome array analyses on the levels of each these 156 proteins may identify genetic determinants of risk associated circulating factors and provide insights into early cardiovascular pathophysiology. Indeed, they discovered dozens of novel genetic variants that were each strongly associated with circulating levels of the Framingham Risk Score associated proteins. They highlighted numerous examples of how these novel gene locus protein associations provided new insights into cardiovascular disease risk pathophysiology including a novel pathway by which the gene phosphatase 1G modulated circulating levels of apolipoprotein E, a key regulator of cholesterol handling.

The final study suggests that bariatric surgery represents an effective strategy for reducing antihypertensive drugs in patients with obesity and hypertension. First and corresponding author Dr. Schiavon from Heart Hospital in Sao Paulo, studied 100 patients with obesity and hypertension who were randomized to gastric bypass or medical therapy alone. The patients randomized the gastric bypass were six times more likely to reduce by 30% or more the total number of antihypertensive medications while maintaining controlled blood pressure levels. In addition, 51% of the patients undergoing gastric bypass showed remission of hypertension. Now, the authors are quick to alert that given the morbidity of surgery these results do not imply that all patients with obesity and hypertension should be submitted for bariatric surgery. Rather, these results suggest that gastric bypass surgery represents one extra option to consider in achieving blood pressure control in these patients.

That wraps it up for our summaries now for our feature discussion.

So, which is better for heart health the vegetarian or the Mediterranean diet? Oh, what an awesome topic and to be able to discuss it from Asia to the United States to Italy, I'm so please to have the first and corresponding author of our feature paper this week Dr. Francesco Sofi from University of Florence in Italy and our dear associate editor Dr. Wendy Post from Johns Hopkins. Francesco, could you please start by telling us what inspired you to do this trial?

Dr Francesco Sofi: The aim of the study was to compare two of the most beneficial diets we know from the literature in relation to the occurrence of many chronic degenerative diseases so the Mediterranean diet we have a lot of studies showing that Mediterranean diet is beneficial for many different diseases as well as we have some studies for the beneficial effect of a lacto-ovo vegetarian diet but no studies are available comparing these two diets' dietary profiles. Our hypothesis was to compare in the same population different times the two diets, which were the similar calories, the same isocaloric but just different in terms of composition especially for meat and fish.

Dr Carolyn Lam: Tell us the bottom line. I'm holding my breath because I think I've said it before, I'm vegetarian. Half my household is Mediterranean diet so what did you find?

Dr Francesco Sofi: We found that in the same group of patients, which were a low risk population because a low risk population here in Italy they were already following a Mediterranean diet but if you control their calories and their composition in terms of the Mediterranean, which included all the different food groups and the lacto-ovo vegetarian diet so all the different groups except for meat and meat-based and fish we noticed that after three months, the lacto-ovo vegetarian diet already determined a reduction of total cholesterol and LDL cholesterol and Mediterranean diet already determined reduction of triglycerides and both were effective for reduction of body weight and fat mass.

We noticed with great interest that after three months, all the study population were quite good in [inaudible 00:09:45] with this diet. I mean they didn't have any kind of problems. This is the one of the most important thing and most of the population or many of the patients after the end of the study they started or continued to follow a vegetarian diet. It means that they accepted very well. There was no problem at all. Also, in feasibility and acceptability of this diet and in relation to this also they have a beneficial effect in some parameters such as also oxidative stress parameters and the inflammatory parameters.

Dr Carolyn Lam: Right, so if I could summarize maybe crudely so the vegetarian diet, very effective for LDL, the Mediterranean very effective for triglycerides. I know that's a simplification but Wendy, I'd like to know do you think this is the dawn of maybe a more, "Oh, here we go again individualized diet planning"?

Dr Wendy Post: I think that this study is really important because there really have been few randomized trials about the vegetarian diet and we've learned a lot of the potential beneficial effects of a Mediterranean diet. I think what was really interesting about this study is seeing that they were both equally effective as a low calorie Mediterranean diet or vegetarian diet at reducing body weight, which is most often the biggest challenge for our patients who are either at risk for cardiovascular disease like these patients potentially were or who have cardiovascular disease.

I think the vegetarian diet is potentially an excellent option for some of our patients but it really is an individual choice and I have trouble getting some patients to just give up the red meat let alone any kind of animal meat. I think it really is potentially an individual choice and those who are interested in becoming vegetarian for either health reasons or other reasons these are additional data to suggest potential beneficial effects more to the Mediterranean diet.

Dr Francesco Sofi: I think one of the most important things to know from this study is that we have now two options. We need to individualize the diets to patients but if a person wants to follow a vegetarian diet for different reasons including also healthy reasons, we can say that it's beneficial. He or she can follow this diet without no problems so without having any health problems as well as if a person wants to follow also a Mediterranean diet, which included meat and fish with a regular and moderate consumption during the week.

Dr Wendy Post: Right but this is just a three month trial with intermediate outcomes so I'm not sure we can necessarily make definitive statements that this is potentially not leading to any adverse effects or some of the other statements that you made. I think we could just make the statements better relative to the outcomes that were seen here related to weight loss and traditional cardiovascular risk factors. Whereas, we have had long term clinical trials of the Mediterranean diet suggesting reduction in risk for events so I think this is definitely supportive of the vegetarian diet but I think we can't say that more studies aren't needed to potentially look at longer term outcomes and more definitive events as opposed to intermediate outcomes that this is a great first start and is really helpful in trying to understand some of the potential differences between the vegetarian diet and the Mediterranean diet.

Dr Francesco Sofi: Of course, I completely agree on that. We need more studies and larger studies and longer duration to establish some things but it was just a pilot study but the good thing is the first comparing two beneficial diets. In the literatures now, most of the studies were investigated either already a vegetarian person or vegetarian diet versus a westernized diet so probably there were some biases.

Dr Carolyn Lam: Indeed, I want to just echo in these words. Congratulations, Francesco. Beautifully done, very elegant, controlled in terms of caloric intact and I like that message that it's not saying that one is bad and the other is good. It's saying, "They're different but they both resulted in weight loss". I love that comment about getting a bigger study. I want to do it right here in Asia because the diets are just so different here and I'm just wondering how about in the US? Wendy, your perspective? How adoptable are these results?

Dr Wendy Post: Well, again I think it's a personal choice and if somebody is willing to become vegetarian then that's potentially wonderful especially if they have high LDL cholesterol and are trying to lose weight but we have to be careful about with the vegetarian diet is the carbohydrate intake, which might affect triglycerides. It might be an individualized approach based on the patient's individual risk factor profile and they're preferences but this is really impressive data suggesting that the vegetarian diet is very similar to the Mediterranean diet in many aspects especially as it relates to weight loss, which is really important.

Dr Carolyn Lam: You've hit the nail on the head. Let's remember that this is a low calorie vegetarian diet. I think that's the issue. Sometimes when I say vegetarian diet to some communities here in Asia that is actually a lot of calories and a lot of starch, which is not what we're talking about here.

Dr Wendy Post: Right, a low calorie diet so that's the key. That's the hard part isn't it?

Dr Carolyn Lam: Yeah, sadly.

Francesco?

Dr Francesco Sofi: We should say that most diets are similar background I mean in the backbone is similar so a dietary profile full of fruit and vegetables, complex carbohydrates, fiber, so the different things are meat and fish but with you can see in a regular consumption also Mediterranean diet of course, especially Mediterranean diet is beneficial for cardiovascular profile.

Dr. Wendy Post: Yeah, if we could get our patients in the United States to follow either the vegetarian or the Mediterranean diet that would be fabulous because they are obviously eating too much in the way of sugar sweetened beverages and deserts and fast food so just trying to follow either of these diets would be especially beneficial if it was a low fat vegetarian or Mediterranean diet. I think we need to get all our patients to be eating more fruits and vegetables, which is a key component of both of these diets and what they share in common, which often can lead to beneficial effects with weight loss due to the increased fiber and satiety and the healthful benefits of high fruit and vegetable diet.

Dr Carolyn Lam: Thank you so much.

Audience, thanks also for joining us. You've been listening to Circulation on the Run. Don't forget to tune in again next week.

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