MD, PhD, FMedSci, FSB, FRCP, FRCPEd

coronary heart disease

Many experts are critical about the current craze for dietary supplements. Now a publication suggests that it is something that can save millions.

This article examines evidence suggesting that the use of selected dietary supplements can reduce overall disease treatment-related hospital utilization costs associated with coronary heart disease (CHD) in the United States among those at a high risk of experiencing a costly, disease-related event.

Results show that:

  • the potential avoided hospital utilization costs related to the use of omega-3 supplements at preventive intake levels among the target population can be as much as $2.06 billion on average per year from 2013 to 2020. The potential net savings in avoided CHD-related hospital utilization costs after accounting for the cost of omega-3 dietary supplements at preventive daily intake levels would be more than $3.88 billion in cumulative health care cost savings from 2013 to 2020.
  • the use of folic acid, B6, and B12 among the target population at preventive intake levels could yield avoided CHD-related hospital utilization costs savings of an average savings of $1.52 billion per year from 2013 to 2020. The potential net savings in avoided CHD-related health care costs after accounting for the cost of folic acid, B6, and B12 utilization at preventive daily intake levels would be more than $5.23 billion in cumulative health care cost net savings during the same period.

The authors conclude that targeted dietary supplement regimens are recommended as a means to help control rising societal health care costs, and as a means for high-risk individuals to minimize the chance of having to deal with potentially costly events and to invest in increased quality of life.

These conclusions read like a ‘carte blanche’ for marketing all sorts of useless supplements to gullible consumers. I think we should take them with more than a pinch of salt.

To generate results of this nature, it is necessary to make a number of assumptions. If the assumptions are wrong, so will be the results. Furthermore, we should consider that the choice of supplements included was extremely limited and highly selected. Finally, we need to stress that the analysis related to a very specific patient group and not to the population at large. In view of these facts, caution might be advised in taking this analysis as being generalizable.

Because of these caveats, my conclusion would have been quite different: provided that the assumptions underlying these analyses are correct, the use of a small selection of dietary supplements by patients at risk of CHD might reduce health care cost.

Cardiovascular (and most other types of) patients frequently use herbal remedies in addition to their prescribed medicines. Can this behaviour create problems? Many experts think so.

The aim of a new study was to investigate the effect of herbal medicine use on medication adherence of cardiology patients. All patients admitted to the outpatient cardiology clinics, who had been prescribed at least one cardiovascular drug before, were asked to complete a questionnaire. Participants were asked if they have used any herbals during the past 12 months with an expectation of beneficial effect on health. Medication adherence was measured by using the Morisky Scale. High adherence was defined as a Morisky score lower than 2 and a score of 2 or more was seen as low adherence.

A total of 390 patients participated in this study; 29.7% of them had consumed herbals in the past 12 months. The median Morisky score was significantly higher in herbal users than non-users. The number of herbals used was moderately correlated with the Morisky score. In stepwise, multivariate logistic regression analysis, herbal use was significantly associated with low medication adherence.

From these findings, the authors conclude that herbal use was found to be independently associated with low medication adherence in our study population.

So far, the main known risk of herbal medicine use was the possibility that there might be herb-drug interactions. To the best of my knowledge, nobody has yet studied the possibility that herbal medicine users might neglect to take their prescribed drugs. The results of this investigation are somewhat worrying but they do make sense. Some patients who buy and take herbal remedies might think that they do not need to regularly take their prescribed medications because they already take herbal medicine which takes care of their health problem. They might even have been told by their herbalist that the herbal remedies suffice.

If that is so, and if the phenomenon can be confirmed in further investigations, it should be relevant not just in cardiology but in all fields of medicine. And if that is true for herbal remedies, it might also be the case for other types of alternative medicine. In other words, alternative medicine use might be a marker for poor adherence to prescribed medication. I feel that this hypothesis merits further study.

It goes without saying that poor adherence to prescribed drugs can be a very dangerous habit. Clinicians should therefore warn their patients and tell them that herbal remedies are no replacement of prescription drugs.

Yoga, it is often claimed, might be a unique method for disease prevention. One website, for instance, states that numerous studies show how yoga can help prevent these diseases: Heart disease, Alzheimer’s, Osteoporosis and Type II Diabetes. 

Cardiovascular diseases (CVD) are responsible for more deaths than any other disease category. Preventing CVD is therefore of prime importance. But are the claims made for yoga really true? What does the reliable evidence tell us?

The aim of our systematic review was to determine the effects of yoga on the primary prevention of CVD. Extensive literature searches were performed to identify all RCTs lasting at least three months, involving healthy adults or people at high risk of CVD. Trials examined any type of yoga and the comparison groups received no intervention or minimal interventions. Outcomes of interest were clinical CVD events and major CVD risk factors. Trials that involved multifactorial lifestyle interventions or weight loss programmes were excluded.

We identified 11 RCTs with a total of just 800 participants. Style and duration of yoga differed between trials. About half of all the trial participants were at high risk of CVD. Most of the studies were at risk of performance bias, with inadequate details reported in many of them to judge the risk of selection bias. None of the studies reported cardiovascular mortality, all-cause mortality or non-fatal events, and most studies were small and short-term.

Yoga was found to produce an average reduction in diastolic blood pressure of 2.90 mmHg. The effect that was small but stable on sensitivity analysis. Triglycerides (-0.27 mmol/l) and high-density lipoprotein (HDL) cholesterol (0.08 mmol/l) were also positively affected. However, these findings were based on small, short-term studies at unclear or high risk of bias. There was no clear evidence of an effect on low-density lipoprotein (LDL) cholesterol. Adverse events, occurrence of type 2 diabetes and costs were not reported in any of the included studies. Quality of life was measured in three trials but the results were inconclusive.

Our conclusion: The limited evidence comes from small, short-term, low-quality studies. There is some evidence that yoga has favourable effects on diastolic blood pressure, HDL cholesterol and triglycerides, and uncertain effects on LDL cholesterol. These results should be considered as exploratory and interpreted with caution.

This systematic review thus offers both good and bad news. The good news is that yoga seems to hold some promise in the prevention of CVD. The bad news, however, is diverse:

  • We cannot be sure what type of yoga is best; yoga can entail anything from regular exercise, to breathing techniques, to a complete and comprehensive change of life style.
  • The effect sizes are far from remarkable.
  • The quality of the research tends to be poor.
  • Once again, we have to note that, by not reporting on adverse effects, alt med researchers are violating fundamental research ethics.

Many systematic reviews conclude by stating that more and better research is required – in the case of yoga, this platitude might actually be true.

In China (and increasingly elsewhere too), the gentle, meditative exercise of tai chi is being promoted and used for disease prevention, particularly for the prevention of cardiovascular disease (CVD). But are these exercises effective? We carried out a Cochrane review to find out.

We searched both English language and Asian electronic databases as well as trial registers and reference lists for relevant studies. No language restrictions were applied. We considered randomised clinical trials (RCTs) of tai chi lasting at least three months and involving healthy adults or adults at high risk of CVD. The comparison groups received no or only minimal interventions. Our outcome measures were CVD clinical events and CVD risk factors. We excluded trials involving multifactorial lifestyle interventions or focusing on weight loss. Two reviewers independently selected trials for inclusion, abstracted the data and assessed the risk of bias of each included study.

We identified 13 trials with a total of 1520 participants and three on-going studies. All of them had at least one domain with unclear risk of bias, and some were at high risk of bias. Duration and style of tai chi differed between trials. Seven studies recruited 903 healthy participants, the other studies recruited people with hypertension, elderly people at high risk of falling, and people with ‘liver or kidney yin deficiency syndromes’.

No studies reported on cardiovascular mortality, all-cause mortality or non-fatal events as most studies were short-term. There was also considerable heterogeneity between studies, which meant that it was not possible to combine studies statistically for cardiovascular risk. Nine trials measured systolic blood pressure (SBP), and 6 of them found reductions in SBP. Two trials found no clear evidence of a difference, and one trial found an increase in SBP with tai chi. A similar pattern was seen for diastolic blood pressure (DBP): three trials found a reduction in DBP, while three found no clear evidence of a difference.

Three trials reported lipid levels and two found reductions in total cholesterol, LDL-C and triglycerides, while the third study found no clear evidence of a difference between groups on lipid levels. Quality of life was measured in only one trial: tai chi improved quality of life at three months. None of the included trials reported on adverse events, costs or occurrence of type 2 diabetes.

From these findings, we drew the following conclusions: “There are currently no long-term trials examining tai chi for the primary prevention of CVD. Due to the limited evidence available currently no conclusions can be drawn as to the effectiveness of tai chi on CVD risk factors. There was some suggestion of beneficial effects of tai chi on CVD risk factors but this was not consistent across all studies. There was considerable heterogeneity between the studies included in this review and studies were small and at some risk of bias. Results of the ongoing trials will add to the evidence base but additional longer-term, high-quality trials are needed.”

These findings are somewhat disappointing. Tai chi might convey many health benefits, but whether a reduction of cardiovascular risk is amongst them seems doubtful. Even if a risk reduction were established beyond doubt, one would need to ask whether its effect size is larger than that achievable through regular conventional exercise. In my view, this is unlikely.

Many dietary supplements are heavily promoted for the prevention of chronic diseases, including cardiovascular disease (CVD) and cancer. But do they actually work or are they just raising false hopes? The evidence on this subject is confusing and proponents of both camps produce data which seemingly support their claims. In this situation, we need an independent analysis of the totality of the evidence to guide us. And one such review has just become available

The purpose of this article was to systematically review evidence for the use of multivitamins or single nutrients and functionally related nutrient pairs for the primary prevention of CVD and cancer in the general population.

The authors searched 5 databases to identify literature that was published between 2005 and January 29, 2013. They also examined the references from the previous reviews and other relevant articles to identify additional studies. In addition, they searched Web sites of government agencies and other organizations for grey literature. Two investigators independently reviewed identified abstracts and full-text articles against a set of a priori inclusion and quality criteria. One investigator abstracted data into an evidence table and a second investigator checked these data. The researchers then qualitatively and quantitatively synthesized the results for 4 key questions and grouped the included studies by study supplement. Finally, they conducted meta-analyses using Mantel-Haenzel fixed effects models for overall cancer incidence, CVD incidence, and all-cause mortality.

103 articles representing 26 unique studies met the inclusion criteria. Very few studies examined the use of multivitamin supplements. Two trials showed a protective effect against cancer in men; only one of these trials included women and found no effect. No effects of treatment were seen on CVD or all-cause mortality.

Beta-carotene showed a negative effect on lung cancer incidence and mortality among individuals at high risk for lung cancer at baseline (i.e., smokers and asbestos-exposed workers); this effect was persistent even when combined with vitamin A or E. Trials of vitamin E supplementation showed mixed results and altogether had no overall effect on cancer, CVD, or all-cause mortality. Only one of two studies included selenium trials showed a beneficial effect for colorectal and prostate cancer; however, this trial had a small sample size. The few studies addressing folic acid, vitamin C, and vitamin A showed no effect on CVD, cancer, and mortality. Vitamin D and/or calcium supplementation also showed no overall effect on CVD, cancer, and mortality. Harms were infrequently reported and aside from limited paradoxical effects for some supplements, were not considered serious.

The authors’ conclusion are less than encouraging: there are a limited number of trials examining the effects of dietary supplements on the primary prevention of CVD and cancer; the majority showed no effect in healthy populations. Clinical heterogeneity of included studies limits generalizability of results to the general primary care population. Results from trials in at-risk populations discourage additional studies for particular supplements (e.g., beta-carotene); however, future research in general primary care populations and on other supplements is required to address research gaps.

A brand-new RCT provides further information, specifically on the question whether oral multivitamins are effective for the secondary prevention of cardiovascular events. In total, 1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier with elevated serum creatinine levels were randomly assigned to an oral, 28-component, high-dose multivitamin and multi-mineral mixture or placebo. The primary end point was time to death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. Median follow-up was 55 months. Patients received treatments for a median of 31 months in the vitamin group and 35 months in the placebo group. 76% and 76% patients in the vitamin and placebo groups completed at least 1 year of oral therapy, and 47% and 50% patients completed at least 3 years. Totals of 46% and 46% patients in both groups discontinued the vitamin regimen, and 17% of patients withdrew from the study.

The primary end point occurred in 27% patients in the vitamin group and 30% in the placebo group. No evidence suggested harm from vitamin therapy in any category of adverse events. The authors of this RCT concluded that high-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate.

These findings are sobering and in stark contrast to what the multi-billion dollar supplement industry promotes. The misinformation in this area is monumental. Here is what one site advertises for heart disease:

Vitamin C could be helpful, limit dosage to 100 to 500 mg a day.

Vitamin E works better with CoQ10 to reduce inflammation in heart disease. Limit vitamin E to maximum 30 to 200 units a few times a week. Use a natural vitamin E complex rather than synthetic products.

CoQ10 may be helpful in heart disease, especially in combination with vitamin E. I would recommend limiting the dosage of Coenzyme Q10 to 30 mg daily or 50 mg three or four times a week.

B complex vitamins reduce levels of homocysteine. Keep the vitamin B dosages low, perhaps one or two times the RDA. Taking higher amounts may not necessary be a healthier approach.

Curcumin protects rat heart tissue against damage from low oxygen supply, and the protective effect could be attributed to its antioxidant properties. Curcumin is derived from turmeric, which is often used in curries.

Garlic could be an effective treatment for lowering cholesterol and triglyceride levels for patients with a history or risk of cardiovascular disease, especially as a long term strategy.

Terminalia arjuna, an Indian medicinal plant, has been reported to have beneficial effects in patients with ischemic heart disease in a number of small studies. Arjuna has been tested in angina and could help reduce chest pain.
Magnesium is a mineral that could help some individuals. It is reasonable to encourage diets high in magnesium as a potential means to lower the risk of coronary heart disease.

Danshen used in China for heart conditions.

And in the area of cancer, the choice is even more wide and audacious as this web-site for example demonstrates.

So, the picture that emerges from all this seems fairly clear. Despite thousands of claims to the contrary, dietary supplements are useless in preventing cardiovascular diseases or cancer. All they do produce, I am afraid, is rather expensive urine.

Antioxidant vitamins include vitamin E, beta-carotene, and vitamin C. They are often recommended and widely used for preventing major cardiovascular outcomes. However, the effect of antioxidant vitamins on cardiovascular events remains unclear. There is plenty of evidence but the trouble is that it is not always of high quality and confusingly contradictory. Consequently, it is possible to cherry-pick the studies you prefer in order to come up with the answer you like. That this approach is counter-productive should be obvious to every reader of this blog. Only a rigorous systematic review can provide an answer that is as reliable as possible with the data available to date. Chinese researchers have just published such an assessment.

They searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the proceedings of major conferences for relevant investigations. To be eligible, studies had to be randomized, placebo-controlled trials reporting on the effects of antioxidant vitamins on cardiovascular outcomes. The primary outcome measures were major cardiovascular events, myocardial infarction, stroke, cardiac death, total death, and any adverse events.

The searches identified 293 articles of which 15 RCTs reporting data on 188209 participants met the inclusion criteria. In total, these studies reported 12749 major cardiovascular events, 6699 myocardial infarction, 3749 strokes, 14122 total death, and 5980 cardiac deaths. Overall, antioxidant vitamin supplementation, as compared to placebo, had no effect on major cardiovascular events (RR, 1.00; 95% CI, 0.96-1.03), myocardial infarction (RR, 0.98; 95% CI, 0.92-1.04), stroke (RR, 0.99; 95% CI, 0.93-1.05), total death (RR, 1.03; 95% CI, 0.98-1.07), cardiac death (RR, 1.02; 95% CI, 0.97-1.07), revascularization (RR, 1.00; 95% CI, 0.95-1.05), total CHD (RR, 0.96; 95% CI, 0.87-1.05), angina (RR, 0.98; 95% CI, 0.90-1.07), and congestive heart failure (RR, 1.07; 95% CI, 0.96 to 1.19).

The authors’ conclusion from these data could not be clearer: Antioxidant vitamin supplementation has no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, total death, and cardiac death.

Few subjects in the realm of nutrition have attracted as much research during recent years as did antioxidants, and it is hard to think of a disease for which they are not recommended by this expert or another. Cardiovascular disease used to be the flag ship in this fleet of conditions; not so long ago, even the conventional medical wisdom sympathized with the notion that the regular supplementation of our diet with antioxidant vitamins might reduce the risk of cardiovascular disease and mortality.

Today, the pendulum has swung back, and it now seems to be mostly the alternative scene that still swears by antioxidants for that purpose. Nobody doubts that antioxidants have important biological functions, but this excellent meta-analysis quite clearly and fairly convincingly shows that buying antioxidant supplements is a waste of money. It does not promote cardiovascular health, it merely generates very expensive urine.

Still in the spirit of ACUPUNCTURE AWARENESS WEEK, I have another critical look at a recent paper. If you trust some of the conclusions of this new article, you might think that acupuncture is an evidence-based treatment for coronary heart disease. I think this would be a recipe for disaster.

This condition affects millions and eventually kills a frighteningly large percentage of the population. Essentially, it is caused by the fact that, as we get older, the blood vessels supplying the heart also change, become narrower and get partially or even totally blocked. This causes lack of oxygen in the heart which causes pain known as angina pectoris. Angina is a most important warning sign indicating that a full blown heart attack might be not far.

The treatment of coronary heart disease consists in trying to let more blood flow through the narrowed coronaries, either by drugs or by surgery. At the same time, one attempts to reduce the oxygen demand of the heart, if possible. Normalisation of risk factors like hypertension and hypercholesterolaemia are key preventative strategies. It is not immediate clear to me how acupuncture might help in all this – but I have been wrong before!

The new meta-analysis included 16 individual randomised clinical trials. All had a high or moderate risk of bias. Acupuncture combined with conventional drugs (AC+CD) turned out to be superior to conventional drugs alone in reducing the incidence of acute myocardial infarction (AMI). AC+CD was superior to conventional drugs in reducing angina symptoms as well as in improving electrocardiography (ECG). Acupuncture by itself was also superior to conventional drugs for angina symptoms and ECG improvement. AC+CD was superior to conventional drugs in shortening the time to onset of angina relief. However, the time to onset was significantly longer for acupuncture treatment than for conventional treatment alone.

From these results, the authors [who are from the Chengdu University of Traditional Chinese Medicine in Sichuan, China] conclude that “AC+CD reduced the occurrence of AMI, and both acupuncture and AC+CD relieved angina symptoms and improved ECG. However, compared with conventional treatment, acupuncture showed a longer delay before its onset of action. This indicates that acupuncture is not suitable for emergency treatment of heart attack. Owing to the poor quality of the current evidence, the findings of this systematic review need to be verified by more RCTs to enhance statistical power.”

As in the meta-analysis discussed in my previous post, the studies are mostly Chinese, flawed, and not obtainable for an independent assessment. As in the previous article, I fail to see a plausible mechanism by which acupuncture might bring about the effects. This is not just a trivial or coincidental observation – I could cite dozens of systematic reviews for which the same criticism applies.

What is different, however, from the last post on gout is simple and important: if you treat gout with a therapy that is ineffective, you have more pain and eventually might opt for an effective one. If you treat coronary heart disease with a therapy that does not work, you might not have time to change, you might be dead.

Therefore I strongly disagree with the authors of this meta-analysis; “the findings of this systematic review need NOT to be verified by more RCTs to enhance statistical power” — foremost, I think, the findings need to be interpreted with much more caution and re-written. In fact, the findings show quite clearly that there is no good evidence to use acupuncture for coronary heart disease. To pretend otherwise is, in my view, not responsible.

There might be an important lesson here: A SEEMINGLY SLIGHT CORRECTION OF CONCLUSIONS OF SUCH SYSTEMATIC REVIEWS MIGHT SAVE LIVES.

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