#538 - Polypill for CV Risk Reduction, Ultra-processed Foods, Say It Now!

First Pointer - make first two lines H3From the Literature

1)  A “Polypill” for Cardiovascular (CV) Risk Reduction

The notion of a “polypill” traces back to an article in the BMJ in 2003 by two epidemiologists, who wrote it up as a thought experiment. Then some researchers in India decided to try it, and we were off to the races! After 700+ Medline citations and several large randomized controlled trials in the interim, it is now pretty serious business.

Researchers in Iran performed this recent polypill study. They designed a cluster randomized trial (randomizing 91 villages) in the entire southern district in Iran to deliver education about healthy lifestyle vs. lifestyle education plus a polypill for everyone aged 50 and over. The polypill contained hydrochlorothiazide 12.5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg (people who developed cough got a formulation with valsartan 40 mg instead of the enalapril). Blood pressures were measured at baseline, and anyone with hypertension were referred to primary care for treatment (in addition to their study condition treatment), and clinicians were asked to adjust doses of any other medications to account for the ingredients of the polypill. The primary outcome was first occurrence of a major adverse cardiovascular outcome (MACE): non-fatal myocardial infarction, unstable angina, fatal myocardial infarction, non-fatal and fatal stroke, sudden death, or heart failure.

They recruited 4,415 subjects to the trial, mean age 59.9 years, and 55% female. Over the 5 years of the trial, the risk of MACE was reduced from 8% in the control group to 4% in the intervention group (absolute risk reduction 4%, 95% confidence interval 2.5% to 5.3%, number needed to treat ~ 25,). The effect was the same in both primary (lower-risk) and secondary (higher-risk) prevention patients (which is unusual, most ). Most of the difference in MACE was due to a reduction in non-fatal cardiovascular disease events, and there were no differences in any of the mortality rates (of course, the study was not powered to show them if they were present). Blood pressure (both systolic and diastolic) decreased in the intervention group dramatically at year 2, but control BP decreased also until at the end of year 5, there was no difference in BP between groups. There were tolerability issues of dyspepsia, nausea, etc. with the polypill, but the rate of intracranial hemorrhage was similar in both groups and there were no gastrointestinal hemorrhages or renal failures in the polypill group.

John’s Comments:

I love the idea of a polypill – it’s like House, MD meets Bertie Botts’ Every Flavor jellybeans. My specific reasons:

• It helps to overcome the limitations of traditional clinical health systems in impacting cardiovascular disease in the population. There’s much less cholesterol-checking, co-pays, and sitting quietly for 5 minutes to retake your blood pressure for a fairly large benefit.
• It works for both primary and secondary prevention and is cheap and easy.
• It can be given, as this study shows, in addition to routine medical care. It may even help overcome the therapeutic inertia that is often seen in patients with borderline risk levels.
• It makes an important pharmacologic point about the relative effectiveness of the first doses of most medications; that small doses of multiple different drugs may be more effective than pushing the dose of a single medication.
• I don’t think the polypill will ever catch on in the US – it doesn’t match our desire for high-tech solutions and (overly-) personalized medicine. My one beef with polypills is that they are, sadly, just a roughly equivalent substitute for a Mediterranean diet and regular physical activity.

References:

• Malekzadeh F, Gandomkar A, Poustchi H, et al. Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars). Heart. Published online March 14, 2024. Link
• Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326(7404):1419. Link

From the Literature

2)  The Health Impacts of Ultra-processed Foods

Ultra-processed foods, as defined using the Nova food classification system, encompass a broad range of ready to eat products, including packaged snacks, carbonated soft drinks, instant noodles, and ready-made meals.  These products are characterized as industrial formulations primarily composed of chemically modified substances extracted from foods, along with additives to enhance taste, texture, appearance, and durability, with minimal to no inclusion of whole foods.  Analyses of worldwide ultra-processed food sales data and consumption patterns indicate a shift towards an increasingly ultra-processed global diet.  In the US, the share of dietary energy derived from ultra-processed foods is estimated to be 58%, the highest in the world (compared to 10% in Italy and 42% in Australia).  Notably, over recent decades, the availability and variety of ultra-processed products sold has substantially and rapidly increased in countries across diverse economic development levels, but especially in many highly populated low- and middle-income nations.

The specific features of ultra-processed foods raise concerns about overall diet quality and the health of populations more broadly. For example, some characteristics of ultra-processed foods include alterations to food matrices and textures, potential contaminants from packaging material and processing, and the presence of food additives and other industrial ingredients, as well as nutrient poor profiles (for example, higher energy, salt, sugar, and saturated fat, with lower levels of dietary fiber, micronutrients, and vitamins).  Although mechanistic research is still in its infancy, emerging evidence suggests that such properties may pose synergistic or compounded consequences for chronic inflammatory diseases and may act through known or plausible physiological mechanisms including changes to the gut microbiome and increased inflammation.

No comprehensive umbrella review has offered a broad overview and assessment of the existing meta-analytic evidence on potential adverse health outcomes from ultra-processed food consumption.  To bridge this gap in evidence and contribute to the ongoing discussion on the role of ultra-processed food exposure in chronic diseases, a recent umbrella review was published. 

The review included 45 distinct pooled analyses, encompassing a total population of almost 10 million participants and spanning seven health parameters related to mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes.  Across the pooled analyses, greater exposure to ultra-processed foods, whether measured as higher versus lower consumption, additional servings per day, or a 10% increment, was consistently associated with a higher risk of adverse health outcomes (71% of outcomes).

The authors found the strongest available evidence pertained to direct associations between greater exposure to ultra-processed foods and higher risks of all-cause mortality, cardiovascular disease related mortality, common mental disorder outcomes, overweight and obesity, and type 2 diabetes. Evidence for the associations of ultra-processed food exposure with asthma, gastrointestinal health, some cancers, and intermediate cardiometabolic risk factors was limited and the authors felt warranted further investigation.  They concluded that the findings provided a rationale to develop and evaluate the effectiveness of using population based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved health.  They also call for urgent research on causative mechanisms. 

Mark’s Comments:

This data is sobering, and in particular for “Western” and “Westernizing” countries.  Ultra-processed foods, including breads, cookies, savory snacks, reconstituted meat products, milk-based drinks, breakfast cereals, juices and sodas, and frozen and ready-to-eat meals tend to be high in refined carbohydrates and added fats are highly rewarding, appealing, and when consumed compulsively, may be addictive.  There is an entire body of science behind the creation of these foods that is highlighting some of our evolutionary programming regarding our drive to eat.  Unless we are very conscious about countering this programming, these trends do not bode well for our future health as individuals and as a society. 

Reference:

Lane M, et al.  Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta-analyses. BMJ 2024;384:e077310 (Published online 28  February 2024.  Link

From PeerRxMed ( www.PeerRxMed.org )

3)  Say It Now!  Gratitude is for Sharing, Not Saving

“The deepest principle in human nature is the craving to be appreciated.”  William James, MD, considered to be the “Father of American Psychology”

His smile of surprised glee radiated as we put a “Birthday Prince” hat (with the two “s’s” crossed out) and golden cape on our friend and colleague and seated him at the head of the table.  The occasion was a “significant decade” birthday, and six of us had gathered to celebrate this time with him.

Our celebration, however, was going to be different than the typical birthday party.  Though there were silly hats and some singing (accompanied by a ukelele), we all had come ready to honor him very intentionally.  In preparation for the celebration, we each took time to reflect on what he had meant to us using the following guidance: 

• Remembering the first time we met him or a formative time early in our getting to know him
• A quality we admired in him
• Something about him that we found endearing or cracked us up
• A story about how he had positively impacted our life or something that he has taught us
• Our hopes for him for the next 5 years accompanied by a representative small gift of some sort (funny was preferred over serious, though meaningful symbols were encouraged as well)

And now, between appetizers and drinks, we were going around the table, one question at a time, and sharing our sentiments.  There was much laughter, meaningful heart-felt  stories, and a deep sense of admiration and love.  It was an incredible time and a forever memory for all who were there.

Our gathering was inspired by the "Say It Now" movement, which was launched in 2022 by founder Walter Green after he noted how often we wait to honor and share our deepest admiration and gratitude for others until the “end,” whether that “end” be in retirement, on their death beds, or most tragically, at their funerals.  His intention was to change how and when we express gratitude for the people who’ve meant so much in our lives – from too late to right now, by providing encouragement and simple tools to help facilitate our expressions of gratitude.  Whether expressed in writing, verbally, or as a group event, he believes that letting someone know how much you appreciate them can become a transformative experience – for their life and yours!  

I believe that as well, and experienced it once again during our recent celebration.   Which leaves me wondering, what important people in each of our lives don’t know how much they are appreciated – what they mean to us and how they’ve positively impacted our lives?  As Walter Green has said, “There is no benefit in waiting – this is the moment!”  Give them, and you, a wonderful gift.  Say it now …

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Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org