There may be drugs that help prevent disease. As physicians, we want to do what is best and right — and easiest — for our patients. In an ideal world, we could prescribe a pill to drastically reduce the risk of chronic disease. In our zeal, we have to tread cautiously, though, and remember the adage from the Hippocratic Oath: first, do no harm.
More drugs are being evaluated for primary prevention, meaning stopping disease from occurring in the first place. Doesn’t it seem paradoxical that we would give “healthy” people medications? However, there are several recent trials with seemingly impressive results that looked at preventing cancer and its metastases, prostate cancer, high blood pressure, diabetes, strokes and even heart attacks.

Preventing cancer and its metastases

There has been much discussion over the years about using aspirin for the prevention of colorectal cancer. I was at a lecture a month ago where the lecturer said the results were so convincing he might even consider taking aspirin. There are three new studies investigating aspirin’s potential role in cancer and its distant metastases — tumors in other parts of the body.

One of the trials was a meta-analysis (group of 34 trials) of over 69,000 participants that was published in The Lancet online on March 21. The results showed a 15 percent reduction in the risk of deaths from cancer when taking aspirin on a daily basis compared to no aspirin. This means we should all be taking aspirin, right? Not so fast.

This trial had several limitations (The Lancet editorial online, March 21). First, there was a significant risk of bleeding in the first three years of taking the drug, after which time the bleed risk diminished and the cancer benefit continued. Second, these trials were designed for cardiovascular disease, so there was no initial assessment for cancer.

Third, two very large, randomized clinical trials, the Women’s Health Study and the Physicians’ Health Study, were excluded from the analysis, because they gave aspirin every other day. However, neither of these trials showed any cancer reduction benefit. Therefore, in order to benefit, it would seem that people would have to be diligent about taking medication every day, even without symptoms. We all know how well that works.

Another meta-analysis (group of five studies) showed a significant reduction in distant metastases — 36 percent. For those who developed cancer, there was a 70 percent reduction in distant metastases (The Lancet online, March 21). These results are impressive. However, yet again, the analyses were of trials designed for cardiovascular disease, not cancer.

In a third meta-analyses using aspirin, there were conflicting results. Five studies showed a reduction in disease metastases of 31 percent, while seven studies did not show this effect (The Lancet Oncology online, March 21). We may need studies focused on preventing cancer deaths as their primary endpoints in order to make definitive statements about using aspirin in healthy patients.

Prevention of prostate cancer

Avodart (dutasteride) is a drug used for the treatment of enlarged prostate: BPH. In a randomized controlled trial called the REDUCE trial, results showed that Avodart could reduce the risk of prostate cancer by almost 23 percent over four years with healthy men who were at high risk of the disease (N Engl J Med. 2010;363;1192-1202). These positive results were due mainly to a reduction in low-risk benign tumors.

However, beyond the drug’s common side effect of impotence, it also has a twofold increased risk of metastatic prostate cancer. Therefore, the FDA not only rejected the drug for prevention, but also issued a warning about the risk of high-grade prostate cancer risk. These drugs also appear to suppress PSA levels, giving patients a false sense of security.

Prevention of strokes and heart attacks

In last week’s article on the role of statins, I wrote that the JUPITER trial showed statins may be beneficial for primary prevention (N Engl J Med 2008; 359). The FDA approved a statin, Crestor (rosuvastatin) for primary prevention of heart disease in patients without high cholesterol but a slightly elevated inflammatory factor, hsCRP, in February 2010. However, a Cochrane meta-analysis of 14 studies refuted this claim (Cochrane Database Syst Rev 2011; 1: CD004816).

Unfortunately, there is not a panacea. With many, if not all, drugs come side effects. One of the big problems with drugs is that they throw off our bodies’ homeostasis (equilibrium), making them hard to justify for primary prevention. However, we control our own fates, and lifestyle changes play a tremendous role in shaping our futures. All of the diseases mentioned above are impacted substantially by the choices we make every day: our environment, exercise and the food we eat.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

When statins were developed and approved, they were thought to be a drug class with a very clean side-effect profile. They are among the most widely prescribed medications in the U.S. Statins are used to treat high cholesterol and to prevent cardiovascular disease. Under the right circumstances, they can be quite effective. However, their side-effect profile is no longer considered benign or pristine.

The FDA, in a Feb. 28, press release, announced new warnings for statin labels related to memory loss and increased risk of diabetes. The one positive change to the label is that serial blood tests to monitor liver enzymes are no longer required when taking this class of drug (www.fda.gov).

Examples of statins include Lipitor (atorvastatin), Crestor (rosuvastatin), Zocor (simvastatin) and Vytorin (simvastatin/ezetimibe).

The heyday of statins: the JUPITER trial

In the JUPITER trial, which I mentioned in a previous article entitled “High cholesterol: a cautious tale on treatment” (June 23, 2011), it was shown that statins may lower the relative risk of heart attacks by 54 percent and strokes by 48 percent. This trial showed that statins were useful potentially for primary prevention; healthy patients without high cholesterol, but with moderately raised inflammation (high-sensitivity C-reactive protein of greater than 2.0 mg/l), may benefit from statin use (N Engl J Med 2008; 359:2195-2207).

However, controversy brews with statins. There was a meta-analysis (a group of 14 trials with over 34,000 patients) done that disputes the benefit of using statins for primary prevention. The authors concluded that, although statins reduced mortality in this setting, the benefit may not outweigh the risks and cost (Cochrane Database Syst Rev 2011; 1 [CD004816]).

Muscle-ache side effects

Ironically, the reason I wrote my previous article was mainly due to the FDA warning about using high dose simvastatin, 80 mg, and the increased risk of muscle aches and pains, referred to as myopathies (www.fda.gov). It seems that the higher the dose of any of the statins, not just simvastatin, the greater the chances of muscle-related pain (Pharmacotherapy. 2010 Jun;30(6):541-53).

Effects on exercise

It appears now that statins may interfere with exercise. Myopathies affect about 10 percent of the patients; however, that percentage increases to 25 percent of people who regularly exercise. Statins have a detrimental epigenetic effect, which means they affect gene expression, with skeletal muscle. Genes associated with muscle building and repair in the legs were suppressed to some degree in healthy young patients taking statins (Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2560-6).

The authors concluded that statins could potentially cause increased risk of muscle damage during and after exercise. This creates an unusual dynamic, since these results are in stark contrast to the recommendations that all Americans exercise.

The diabetes evidence

The JUPITER trial showed that healthy participants had a 27 percent increased risk of type 2 diabetes from the use of statins (N Engl J Med 2008; 359:2195-2207).
This was reinforced by the Women’s Health Initiative study. The results of this study showed an adjusted 48 percent increased risk of type 2 diabetes in postmenopausal women ages 50 to 79 taking statins (Arch Intern Med. 2012 Jan 23;172(2):144-52). The authors emphasize a need for lifestyle changes. There were 153,000 women in the WHI study. It did not matter which statin was used — it was a class effect.

Mild cognitive impairment data

It appears that statins may be associated with mild cognitive impairment, including memory loss and confusion in patients who are susceptible. In a large case series involving 171 patients, approximately 75 percent of cognitive decline was most likely related to statin use. In this group, 143 patients stopped statins, and 90 percent of them subsequently recorded significant improvements in cognitive functioning. According to the authors, the higher the dose, the more pronounced the memory loss and confusion became (Pharmacotherapy. 2009 Jul;29(7):800-11).

What can be done?

Lifestyle modification may provide significant results in a short time. A patient in my practice, who adopted intensive lifestyle modifications, including increasing fiber, lowered his total cholesterol and his LDL (“bad”) cholesterol dramatically over only two weeks. Increasing fiber has been shown to decrease heart disease through lowering of cholesterol and lowering blood pressure (Curr Atheroscler Rep. 2003 Nov;5(6):500-5).

The good news with the side effects is that they seem to be transient and dose related, meaning the higher the dose, the greater the side effects. After stopping statins, symptoms from side effects seem to dissipate, although time frames for this vary.

In many cases, statins’ benefits still outweigh their side effects. They can be highly effective in treating high cholesterol and preventing heart attacks and strokes. However, lifestyle modifications should either be done in concert with these drugs or as the first line of therapy before statins are initiated.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

What if I told you that you could practically eliminate your chances of getting heart disease? I was at a Harvard/Brigham and Women’s Hospital conference last week in Boston where several seminars addressed this very topic. I had to share the good news with you.

The risk of mortality from heart disease has decreased by 30 percent over the last few decades, which is very impressive (www.cdc.gov; www.nhlbi.nih.gov).

However, before we start celebrating, it is still the No. 1 cause of death in the United States; in 2008, heart disease was responsible for one in four deaths (National Center for Health Statistics. 2011).

The seven factors

There are two recent studies that look at the reduction in risk factors for heart disease. If we reduce the seven key modifiable risk factors, the chance of heart disease goes down to about 1 percent. These seven factors are smoking, body mass index (goal BMI of less than 25 kg/m2), physical activity (at least 150 minutes of moderate activity weekly), diet (at least similar to the DASH diet), cholesterol (total cholesterol less than 200 mg/dl without medication), blood pressure (less than 120/80 mmHg without medication) and blood glucose (fasting glucose less than 100 without medication).

So what did the researchers find?

In one recent study, researchers found that we are doing best with smoking cessation (Circulation. 2012;125(1):45-56). The prevalence of nonsmoking ranged from 60 percent to 90 percent, depending on demographics.

On the other hand, healthy diet scores were not very good; from 0.2 percent to 2.6 percent of participants have achieved ideal levels. Obviously, diet is an area that needs attention. This observational study involved 14,515 participants who were at least 20 years old. The authors garnered their results from NHANES data from 2003 through 2008.

How many participants actually reached all seven goals? About 1 percent. This means we have the ability to alter our history of heart disease dramatically. There is a dose-response curve. In other words, there is a direct relationship between the effort you apply to attain these goals and the outcomes of reduced risk.

In the other study, those who had an optimal risk factor profile at age 55 were significantly less likely to die from cardiovascular disease than those who had two or more risk factors. These differences were maintained at least through the age of 80 (N Engl J Med 2012; 366:321-329). The lifetime risk of fatal heart disease or a nonfatal heart attack in the optimal group was less than 1 percent for women and 3.6 percent for men.

In terms of sex differences, men were 10 times less likely and women were 18 times less likely to die from heart disease if they were in the optimal risk-stratification group. This was a meta-analysis (a group of 18 observational studies) with more than 250,000 participants.

Dietary approaches

The good news is that there are several diets that have shown dramatic results in preventing and treating heart disease, such as the Ornish, DASH, Mediterranean-type and Esselstyn diets. These diets all have one thing in common: they rely on nutrient-dense, plant-based foods. As I wrote in my March 1 article, “Heart attacks and women: There is a difference,” both the Ornish and the Esselstyn diets showed reversal of atherosclerosis (JAMA. 1998;280(23):2001-2007; J Fam Pract. 1995;41(6):560-8) and, as we know, atherosclerosis (plaques in the arteries) is the foundation for heart disease.

Exercise affect

For the most beneficial effects on preventing heart disease, both the American College of Sports Medicine and the U.S. Department of Health and Human Services recommend that most Americans get at least 30 minutes of moderate aerobic exercise five times a week, for a total of 150 minutes, or 75 minutes of vigorous aerobic exercise per week (Med Sci Sports Exerc. 2011;43(7):1334-59).

Moderate aerobic exercise includes brisk walking, as demonstrated in the Women’s Health Initiative, a large observational study. This study showed a 28 percent to 53 percent reduction in heart disease risk in women ages 50 to 79 (N Engl J Med 2002; 347:716-725). Resistance training is also very important. The Health Professionals Follow-up Study showed at least 30 minutes a week resulted in a 23 percent risk reduction for heart disease and running for only 60 minutes resulted in a 42 percent risk reduction (JAMA. 2002;288(16):1994-2000).

Interestingly, although medications may be important for people who have high levels of blood pressure, cholesterol and glucose, they do not get you to the goal of achieving lowest-risk stratification. Lifestyle modification is the only way to approach ideal cardiovascular health. Thus, if we worked on these factors to attain the appropriate levels, this disease would no longer be on the top 5 list for highest incidence and mortality rates.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

A heart attack is a heart attack, right? Not necessarily. All heart attacks cause infarction (death of heart tissue/muscle), but in terms of severity and presentation, they vary significantly. There may be gender differences in symptoms between men and women.

Most of us are familiar with the classic sign of a heart attack. It is chest pain, or pressure in the center of your chest. However, many patients experience heart attacks without chest pain. And women tend to have atypical symptoms more frequently than men.

Anecdotally, I have always erred on the side of caution. I was summoned on a plane to help a 52-year-old diabetic female suffering from nausea, sweating, indigestion, fatigue and a weak and inconsistent (thready) pulse. We had to make an emergency landing — the patient was having a heart attack.

In general, those with atypical symptoms, such as these, tend to present later for treatment and are treated less urgently and aggressively, resulting in a twofold increase in hospital mortality versus those with chest pain (JAMA. 2000;283(24):3223–3229).

Gender differences in symptoms and severity

JAMA reports in its Feb. 22-29 issue on an observational study of over one million patients that examined heart attacks which occurred without chest pain as it related to gender, age and mortality (JAMA. 2012;307(8):813-822). Two out of five women having heart attacks did not have chest pain associated, a significantly higher proportion compared to men. This difference was greatest among those women who were younger than 55. The good news is that this difference seems to dissipate with increasing age.

Moreover, there was a 50 percent higher risk of mortality in women than men in the same age group. These atypical symptoms may delay treatment, resulting in women’s higher death rate.

In addition, women who have had a heart attack have a much greater risk of death two years after discharge from the hospital versus men. These results were significant for women less than 60 years old (Ann Intern Med. vol. 134 no. 3 173-181).

Cholesterol impact

There is some good news for women on the heart-attack front. In the Women’s Health Study, HDL (“good” cholesterol) was shown to reduce the risk of heart attacks (Ann Intern Med 2011;155:742). In fact, those patients who had an HDL of less than 40 mg/dl compared to those who had more than 62 mg/dl were at two-times higher risk of a cardiovascular event. This study followed 27,000 women over an 11-year period. Unfortunately, HDL-raising drug therapies do not seem to change the outcomes for women with low HDL.

Aerobic exercise, however, may raise HDL. According to the Mayo Clinic, HDL may rise by 5 percent within two months with 30 minutes per day of vigorous exercise five times a week (www.mayoclinic.com). This includes playing sports, swimming, running or even raking leaves.

Solution: risk reduction

How do we avoid sending patients with indigestion to the emergency room? We don’t want to flood hospitals and waste a finite amount of resources by raising the number of false alarms significantly.

The answer lies in reducing the risk factors. Approximately 90 percent of heart attacks are a result of atherosclerosis (plaques in arteries) that result in the blockage of a coronary artery (www.medscape.com). Dean Ornish, M.D., showed that, with intensive lifestyle modifications, including a plant-based diet, exercise and stress reduction, it is possible to reverse atherosclerosis.

The study showed an 8 percent reversal in the treatment group compared to a 28 percent worsening in the group that followed more common moderate changes (JAMA. 1998;280(23):2001-2007).

Caldwell Esselstyn, M.D., did a small study with patients who had severe coronary artery disease. These patients followed a plant-based diet and did not have a single cardiac event over a 10-year period. They also experienced some reversal in atherosclerosis (J Fam Pract. 1995;41(6):560-8). These patients had a combined 50 cardiac events within the eight years before the study.

Fiber has been shown to decrease the risk of heart attacks. In a meta-analysis (a group of 10 studies), for every 10 gram increase in fiber there was an inverse 14 percent reduction in cardiac events (Arch Intern Med. 2004;164(4):370-376). If we increased the fiber intake daily by threefold to fourfold, we would achieve around a 50 percent reduction in risk. Considering most of us get 8 to 15 grams, it should be easy.

Raising the awareness that patients who are having a heart attack can present without chest pain, especially women, is extremely important in improving mortality. In addition, lifestyle modifications have shown a very powerful effect time and time again in reducing the risk of heart attacks and reversing the cause: atherosclerosis.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.