Tag Archive for: CVD

Will the Polypill Reduce Second Heart Attacks?

/in /by

One of the issues with prevention is having people stick to a plan, even after an event as serious as a heart attack. Lifestyle changes are challenging to stick with, but so is something as simple as taking medications. Remember, this isn’t to prevent a heart attack; it’s to prevent a second one. That’s serious.

The concept of a polypill has been around for close to 15 years. The idea was to put medications together in one pill as a preventive that would reduce the risk of getting cardiovascular disease. For a long time, that idea never went anywhere, but recently researchers decided to resurrect the concept. This time, the objective was to monitor subjects with recent heart attacks. Would there be a difference in the rate of secondary events between subjects who took the polypill and those who took the same medications as individual pills? The medications used were aspirin, ace-inhibitor, and a statin. After three years of follow-up, the subjects in the polypill experienced significantly fewer secondary events, 9.5% versus 12.7%.

Can you figure out why the subjects who took the polypill did better than the subjects who took the same medications individually? I’ll tell you the secret to disease prevention on Saturday.

What are you prepared to do today?

        Dr. Chet

Reference: NEJM. 2022. DOI: 10.1056/NEJMoa2208275

Should People with CVD Take Omega-3s?

/in /by

Last time, I talked about some research that hasn’t been done to definitively know whether DHA contributes to arrhythmias or not, but I implied that there may be one issue that may have contributed to this latest study. Let’s talk about research bias.

Research Bias

Some of the researchers who examined the data from the longitudinal study I talked about on Tuesday were also involved in at least one of the clinical trials on Vascepa, the pharmaceutical form of EPA-only omega-3s. I know what you’re thinking: somehow they intentionally manipulated data so that it seemed DHA was bad. I wouldn’t assume that, because these are good scientists. However, there has to be an inherent bias—beliefs that set up space in your brain and affect your actions without you realizing it. Another way of stating this would be that you find what you look for. It would be very difficult to examine any data involving EPA, DHA, and cardiovascular disease and withhold bias. I don’t believe it was intentional, but I also believe that it could have influenced the results to some degree.

The INtermountain Healthcare Biological Samples Collection Project and Investigational Registry (INSPIRE for short) is not a randomized clinical trial; it’s an observational study. I’ve already talked about the data that are missing on diet, supplementation, and exercise. In addition, it’s a big stretch to suggest that 10 years after samples were taken during an angiographic procedure that the same distribution of EPA-DHA was maintained.

Prior Research

Let’s think about the studies from last week: they were test-tube studies. Those are the foundation you must build before you start doing animal testing; only after that do you get to human testing. One research group also did a study on rodents which demonstrated proof of possible benefit. Have we had that type of research on EPA and DHA as it relates to cardiovascular disease? I did find some.

There have been studies examining how omega-3s may positively affect heart rhythms. In studies on rodents and dogs, DHA but not EPA showed clear benefits on reducing atrial fibrillation and other forms of cardiovascular disease.

But when you examine research on humans, the data are conflicting. By that I mean that some studies show that higher DHA intake and/or levels are associated with the reduction of arrhythmias. Other more recent research shows that it may not. There’s simply not enough information to make a decision.

The Bottom Line

At this point, you have to be thinking “What the heck am I supposed to do?” I think that we stand in an area of research where we have to “reserve judgment,” or maybe it would be better to say to “reserve condemnation.” We just don’t have enough data to make an informed decision either way. I’ve illustrated some of the things that need to be answered as it relates to omega-3 intake, but there are many more questions.

So I’ll leave you with this. If you have had no signs or symptoms of cardiovascular disease, no matter your age, you can most likely continue taking the same omega-3 supplements you always have been. If you have had a heart attack with damage to the muscle tissue, that seems to be where the problem lies, but it isn’t the same for every person. I would have a discussion with your cardiologist before deciding whether to take just EPA or to continue taking combinations of EPA and DHA; that’s the prudent thing to do.

But as you make that decision, consider all the other benefits of omega-3s. A search for “omega-3” at drchet.com yields several pages of results. Very rarely in life do we have simple decisions to make; it’s always a balancing act between competing objectives and imperfect information, and this is another one of those situations.

What are you prepared to do today?

        Dr. Chet

References:
1. J Am Coll Cardiol. 2021 May, 77 (18_Supplement_1) 1453.
2. Vascul Pharmacol. 2016 Jul;82:11-9. doi: 10.1016/j.vph.2016.03.007.
3. Can J Physiol Pharmacol. 2016 Mar;94(3):309-23. doi: 10.1139/cjpp-2015-0300.
4. Circulation: Arrhythmia and Electrophysiology. 2012;5:978–983.

Omega-3s and Heart Disease

/in /by

In addition to the research papers on omega-3s I talked about last week, another paper was presented at the American College of Cardiology in May that suggests EPA seems to reduce cardiovascular disease (CVD), while DHA seems to neutralize the benefits. Let’s take a look at this recent study to see what they found.

I haven’t seen the data, just press releases of varying lengths; I’ve written the authors but haven’t heard back yet. The problem with this recent study is that it’s a retrospective examination of a large group of people. The data are part of an ongoing study (much like the All Of Us study in which I’m a volunteer) that secured blood and tissue samples of volunteers; the researchers use that data as well as access to the volunteers’ medical records. In this case, they assessed the EPA and DHA levels of the blood samples and the CVD events that occurred in a random sample of the volunteers over the years. That’s how they determined that the EPA was beneficial in reducing CVD and as DHA levels rose, the benefits were negated.

The primary problem is that the blood samples are a snapshot of one day in the life of the volunteers. We have no idea if they took dietary supplements or if they happened to eat a lot of fish or a lot of nuts and other foods with omega-3s. No other dietary data, no supplement data, no exercise data—all things that we know are related to the development of cardiovascular disease. I think there’s a significant factor at play in this data analysis, and I’ll give you that observation in Saturday’s memo.

What are you prepared to do today?

        Dr. Chet

Reference: Press Release: Warning: Combination of Omega-3s in Popular Supplements May Blunt Heart Benefits. Intermountain Medical Center May 17, 2021

Omega-3s and A-Fib: More Analysis Required

/in /by

I hope that you took the time to review the paper on atrial fibrillation as well as the research letter on omega-3s and atrial fibrillation. If you haven’t, especially the primer on A-fib, please do it. It’s a serious condition that requires attention if you have it; in most cases, fixing it is surprisingly simple.

The research letter included five studies. I decided to look at each of those research papers individually to see how each trial was conducted, especially on the populations used in those experiments. Here’s what I found.

The Subjects

The subjects in the studies had several characteristics in common. First, they were, on average, in their mid 60s and older. Second, they had already had a myocardial infarction (heart attack) or were at high risk for cardiovascular disease due to factors such as obesity, hypertension, elevated triglycerides, and others. Third, most were taking multiple medications.

They definitely were not healthy and free of disease. The potential for a cardiac event increases if you’ve already had a cardiac event. On top of that, in the trials that used prescription fish oils, the attempt was to lower triglycerides in those patients who were taking a maximal dose of statins. There may be some interaction that hasn’t been identified yet between very high doses of omega-3s, equal to or greater than four grams, and statin medications or other pharmaceuticals the patients were taking to control blood pressure, heart rate, etc.

In short, this does not apply to everyone. In fact, in the concluding statement of the research letter, the researchers state that physicians should be cautious when prescribing high-dose omega-3s in patients with high triglycerides and an increased risk of cardiovascular disease.

Additional Analyses

As I alluded to in the prior paragraphs, I think the analysis should include factors such as exercise, diet, and especially prescription medications. It may be that the number of subjects might not be able to be broken down by statin intake, beta blocker intake, or ace inhibitors, but I think that it should at least be examined to see if there’s any trend.

Also, the data could be separated into those people who’ve had a heart attack and those that haven’t, even though they may have significant risk factors for cardiovascular disease. After a heart attack, there may be morphological changes such as damage to nerve conduction or the buildup of scar tissue that could impact how omega-3s impact the heart itself.

Are all of these possible? I would think it would be with over 150,000 subjects from all the studies included in the meta-analysis.

Two More Things

I still have not found a single nutritionist involved in any of this research. When you look at prior studies that seemed to benefit heart rhythms, it’s DHA omega-3, not EPA, which is the factor related to better heart rhythms.

Take a look at the map that’s in the primer on atrial fibrillation. It applies to those on Medicare who are 65 and older, but there’s an amazing and obvious trend. I’m even going to give it a name; I’ll tell you that next Tuesday. The only clue that I’ll give you is to think maps and what they’re typically used for.

The Bottom Line

While interesting, the Research Letter on the update of omega-3s in relation to atrial fibrillation leaves more questions than answers. So far, it applies only to people over 65 with high triglycerides and other risk factors for cardiovascular disease. If you already take omega-3 fatty acids, there’s probably no reason to stop, but it’s a discussion you should have with your physician.

It’s also obvious that if you do have high triglycerides, you can work on changing that by changing your diet first. Reducing refined carbohydrates is the key; eating more vegetables helps as well.

It always comes back to this: eat better. Eat less. Move more.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal – CVD Pharm. 2021 doi:10.1093/ehjcvp/pvab008
2. Curr Atheroscler Rep. 2020. https://doi.org/10.1007/s11883-020-00865-5
3. Atrial Fibrillation Primer. https://www.cdc.gov/heartdisease/atrial_fibrillation.htm

Omega-3s and Cardiac Events

/in /by

There was another study this week on omega-3 fatty acids. While the study I talked about last Thursday was small with only 21 subjects, this trial contained over 13,000 subjects from 675 hospitals and clinical centers all around the world. In this five-year study, one of the omega-3 fish oil medications was being tested to see if it would reduce cardiac events such as heart attacks, stroke, and death when compared with subjects taking a corn-oil placebo. The study was stopped early when it was clear there were going to be no significant differences in any of the outcomes that were being studied. In other words, the prescription fish oil did not reduce cardiovascular disease events.

While that may seem disappointing, there are some factors that most likely impacted the outcome and a couple that may have but could not be tested.

The Subject Pool

The subjects in this clinical trial had significant risk for CVD; they were required to have established coronary artery disease or significant risk factors to be included in the clinical trial. Those risk factors included being a type 1 or type 2 diabetic, with at least one additional risk factor including chronic smoking, hypertension, hs-CRP higher than two mg/L, moderately increased protein loss, or being older with similar factors as the diabetics.

The Data Not Collected

In reading the study, there were three criteria that came to mind that could have impacted the outcome if the corresponding data had been collected and considered in the statistical analysis. I emailed the relevant author and got the answers.

1. Were data collected on exercise habits of the subjects? No.

2. Were nutritional data collected on the subjects? No.

3. Was the form of omega-3 used, a highly purified carboxylic acid form, assessed as to how the metabolism impacts the omega-3s’ mechanism of action? No.

It seems to me that if the data could be analyzed on exercisers versus sedentary as well as using nutritional factors, even just daily caloric intake, there may have been significant results. As for the form of omega-3s, the CA form is highly absorbed and doesn’t require a fat in the diet to assist with that process. There might have been something else that happens during metabolism that normally assists in the risk reduction. We just don’t know.

The Bottom Line

The authors acknowledge that this subject pool was at high risk for cardiac events. One explanation is that the progression of disease may have already been too advanced and could have impacted the efficacy of the medication. For people with less established CVD, the omega-3s might have been more effective.

Many in the medical field wrote about the failure of omega-3s in medication or supplement form to prove that they have any impact on CVD events or mortality. I think they’re wrong. The one outcome they never test is the quality of life. Granted, it’s difficult to assess but if people can live their lives even 10% better, regardless of CVD events, that seems worth it. Paula and I are still taking our omega-3 supplements; in fact Riley takes one, too, even though he’s only five and we’re not concerned about his heart. Whether you’re worried about your heart or not, omega-3s have many benefits. This study shows no reason why you or I should stop taking them.

What are you prepared to do today?

        Dr. Chet

Reference: JAMA. 2020;324(22):2268-2280. doi:10.1001/jama.2020.22258

Research Update on Fish Oil Supplements

/in /by

Researchers performed a meta-analysis of studies that examined EPA and DHA as dietary supplements to see if there was a reduction in CVD events and mortality. In this study, researchers included 40 studies with 135,267 participants. While they examined many different variables, including whether EPA was better than DHA and whether they could find the best combination or ratio, almost every analysis they ran demonstrated benefits for those who use fish oil supplements: a 13% decrease in the risk of a heart attack, a 10% decrease in any coronary heart disease event, and a 35% reduction in the risk of a fatal heart attack.

For me, the most significant finding was that there was a dose-response effect of taking fish oil supplements. In other words, CVD events decreased with higher intake of fish oil supplements.

The Problems with the Prescription Study

There were three issues with the EVAPORATE study I talked about in Thursday’s Memo. First, there was a significant loss of subjects. Most of the loss was in the experimental group, which reduced the number of subjects from 40 to 31.

Second, they did not compare the prescription fish oil with an equivalent amount of fish oil dietary supplement, whether it contained DHA or not, which seems to be a glaring omission to me.

Finally, the study was funded by the manufacturer; several of the researchers had a relationship with the pharmaceutical manufacturer as well. That doesn’t mean anything shady was going on, but it does put in question the conclusions that can be drawn about the significance of the entire clinical trial.

The Problem with the Fish Oil Supplement Study

The primary problem with the fish oil supplement study is that it was a meta-analysis. Even though that method is becoming popular, and even though by all accounts the researchers tried their best in selecting the correct studies for inclusion, there’s always the specter that they may have left out some studies. To their credit, they re-ran the analysis without several of the clinical trials and did get slightly different findings. However, it did not change the outcomes related to heart attacks or coronary heart disease events.

The study was funded by Global Organization for EPA and DHA Omega-3s. Just as with the pharmaceutical study, there’s an inherent bias implied. In both cases though, if the funding organizations didn’t sponsor the research, who would? There are only so many research dollars available, and many dollars are being siphoned off to fund urgent COVID-19 studies.

The Bottom Line

I think that these studies establish that fish oil is beneficial to reduce CVD events and reduce disease progression. Because there appears to be a dose-response relationship to fish oil and the reduction of CVD risk, the higher amount of fish oil a person takes, up to four grams, the better the potential outcomes.

Which one is better: prescription versus supplements? Until there’s a study that directly compares prescription fish oil to fish oil supplements, I don’t believe it matters; both studies we reviewed demonstrate benefits. The key is that if you have been diagnosed with CVD, you should take fish oil. Talk it over with your physician first and then get going. Your heart will love you for it. And don’t forget to eat better and move more as well.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal (2020) 00, 1–8 doi:10.1093/eurheartj/ehaa652
2. https://doi.org/10.1016/j.mayocp.2020.08.034

Research Update on Prescription Fish Oil

/in /by

Let’s begin by taking a look at the prescription fish oil supplement medication. To review, this is a 100%-EPA fish oil that received FDA approval in December of 2019. The amount prescribed for people with high triglycerides is four grams of highly processed fish oil per day. Data from the REDUCE-IT trial suggested that there was a 25% decrease in mortality in the experimental group compared with the control group.

The current trial was called the EVAPORATE trial: Effect of Vascepa on Improving Coronary Atherosclerosis in People with High Triglycerides Taking Statin Therapy. The study began with 80 men and women, ages 30-85, with greater than 20% blockage in at least one of their coronary arteries, elevated triglycerides, and taking statin therapy; 68 subjects completed the 18-month study. The primary endpoint was to see if there was any reduction in plaque buildup in the coronary arteries.

The subjects in the prescription fish oil group saw a 17% decrease in overall arterial plaque; there was a plaque increase in the placebo group. The researchers did not track cardiovascular events or mortality in this study. We’ll take a look at the OTC fish oil supplement study on Saturday as well as determine the clinical significance of each trial.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal (2020) 00, 1–8 doi:10.1093/eurheartj/ehaa652
2. https://doi.org/10.1016/j.mayocp.2020.08.034

Research Update: Fish Oil and Heart Disease

/in /by

The prescription fish oil Vascepa has been approved since December of last year. The fish oil medication was originally intended for those who had a family history of high triglycerides of 500 mg/dl or greater. In the approval process, the recommendation was lowered to those whose triglycerides were at least 150 mg/dl and who were taking a statin medication. But the research hasn’t stopped.

Research on Vascepa as well as over-the-counter (OTC) fish oil supplements continues. From the pharmaceutical perspective, more research on the use of the medication could result in an increase in the potential applications of this pharmaceutical. From the dietary supplement perspective, research may help establish the efficacy of using fish oil dietary supplements instead of the prescription medication

Last week within one day of each other, studies on prescription fish oil and fish oil supplements were published that both demonstrated significant benefits. We’ll review those studies the rest of the week and see if we can find out whether fish oil dietary supplements match up with pharmaceutical fish oil. If you want a preview of the studies, check the references below; they’re both open access.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal (2020) 00, 1–8 doi:10.1093/eurheartj/ehaa652
2. https://doi.org/10.1016/j.mayocp.2020.08.034

The Health Benefits of Spices

/in /by

Continuing our look at the research study on the effect of spices on markers of inflammation, there were some interesting results. The high-fat, high-carbohydrate meal was coconut curry chicken, a cornbread muffin, and a biscuit; that strikes me as an odd meal, but you do what you must for research. The only difference was the spices added to allow for comparative results.

Examining the effect of the 1,000-calorie, high-fat, high-carbohydrate meal, the researchers found an increase in the release of inflammatory hormones above baseline in all subjects. So that’s the first result: inflammation was increased after eating the test meal with no spices added.

Compare that to consumption of the same meal with six grams of spice blend: it significantly reduced IL-1β secretion at four hours after the meal compared with the meal with none of the spice blend. Also, IL-6, IL-8, MCP-1, and TNF-α secretion after the meal containing six grams of the spice blend was below baseline values for each cytokine (inflammatory hormone). These results suggest that spice consumption may reduce inflammation after a high-fat, high-carbohydrate meal for hours after eating. The paper is Open Access, so you can read it yourself at the link in the references.

Those are interesting results, and I’m guessing you really would like to know which spices were used in the study. I’m going to give you that spice blend and put this research in context in Saturday’s memo. But if you haven’t done our little experiment with the teaspoon, half teaspoon, and eighth teaspoon, please do it before then.

What are you prepared to do today?

        Dr. Chet

Reference: J Nutr 2020;150:1600–1609.

Can Spices Make You Healthier?

/in /by

I’d like you to do something before you read the rest of this memo. Go to your drawer that contains measuring spoons, and pull out the teaspoon, half teaspoon, and eighth teaspoon. Then measure out salt or sugar for each different volume and put it on a plate. Notice how little there is by the time you get to the eighth teaspoon. Keep that image in your mind for the remainder of the week.

Too often, nutrition research lacks a practical approach; researchers try to drill down into the details before they look at the larger response to any intervention. In other words, examining what people actually eat and cook, then changing something and seeing what happens. I don’t mean exaggerated results such as weight loss, but more subtle effects such as changes in triglycerides, cholesterol, blood sugar, and in this case, markers of inflammation.

This week we’re going to take a look at a recently published paper that took exactly that approach. Researchers selected a group of 12 overweight male subjects with at least one additional risk factor for cardiovascular disease and fed them a high-fat, high-carbohydrate, 1,000-calorie meal. They fed them the same meal on three different days: once without any specific spice blend, second with two grams of a spice blend, and the third time with six grams of the same spice blend. They tested the subjects to see what markers of inflammation were changed after each feeding. I’ll give you the results in Thursday’s memo.

What are you prepared to do today?

        Dr. Chet

Reference: J Nutr 2020;150:1600–1609.