Is cholesterol the chief culprit behind heart disease? For decades Americans have been told that to lower their risk of a heart attack they had to lower their cholesterol levels, especially LDL cholesterol, also known as “bad cholesterol” to distinguish it from HDL cholesterol, aka “good” cholesterol. A cardiology friend of ours likes to say that you could never have too low a golf score or too low a cholesterol level.
A Mystery from the American College of Cardiology:
Cardiologists from all over the world gathered in Chicago for the annual ACC (American College of Cardiology) meetings between April 2-4, 2016. Details of a large randomized, double-blind, placebo-controlled trials were finally released and the results shocked the cardiology community.
The drug under consideration was a tongue twister called evacetrapib. It belongs to a class of cholesterol-lowering compounds called CETP (cholesterol ester transfer protein) inhibitors.
Evacetrapib was the star in a study of 12,000 patients at 540 health centers around the world. Patients at high risk for cardiovascular complications were assigned to either placebo or medication and followed for at least a year and a half. In addition, many of the patients also received state of the art treatment for heart disease.
The drug was wildly successful but it failed miserably. Huh? How can that be?
Well, let us explain. Evacetrapib lowered bad cholesterol phenomenally well. Patients averaged LDL cholesterol levels of 55 milligrams per deciliter (a 37% reduction). Most cardiologists would view that as an amazing achievement. In addition, this medication raised good HDL cholesterol to an average of 104 (an improvement of 130% over placebo). That was also a home run.
No other drug known to man has produced such extraordinary results. To lower bad cholesterol so much and raise good cholesterol so high is truly unprecedented. If we are to believe the cholesterol theory of heart disease, these numbers should have resulted in fabulous outcomes.
The Envelope Please:
When the data were analyzed it turned out that 255 patients who were at high risk for a cardiac event suffered a heart attack while taking evacetrapib. There were 256 heart attacks in the group of patients getting placebo. In other words, there was NO DIFFERENCE! This is a bit like the surgeon telling the family that, “the surgery was a great success but the patient died.”
When it came to strokes, 95 patients getting placebo had what is called a cerebrovascular accident (CVA) and 92 people getting the active drug had a CVA. In essence that means there was no difference. When it came to the ultimate “end point” which is called death, the results were not statistically significant. There were 434 high-risk patients who died while taking evacetrapib and 444 subjects who died while taking placebo. That was not enough to prove meaningful.
Gina Kolata, writing in the New York Times (April 3, 2016) quoted a key player in the research:
“‘We had an agent that seemed to do all the right things,’ said Dr. Stephen J. Nicholls, the study’s principal investigator and the deputy director of the South Australian Health and Medical Research Institute in Adelaide. ‘It’s the most mind-boggling question. How can a drug that lowers something that is associated with benefit not show any benefit?’ he said, referring to the 37 percent drop in LDL levels with the drug.”
Is the Cholesterol Theory Crumbling?
In recent months there have been some dramatic changes in public health policy. For one thing, the new Dietary Guidelines for Americans don’t emphasize avoiding cholesterol in your food. Instead, Americans are advised to limit saturated and trans fats, added sugars and sodium. Eggs are now considered part of a healthy eating pattern. (Dietary Guidelines for Americans, 2015)
The American Heart Association (AHA) and the American College of Cardiology (ACC) issued their own guidelines late in 2013. These organizations recommend that if diet doesn’t lower blood cholesterol, statins are the solution. According to their guidelines, at least one third of American adults would be taking a prescribed statin. Nearly everyone between the ages of 66 and 75 would be on one of these drugs (JAMA Internal Medicine, Jan. 2015).
But not all cardiologists agree that lowering blood cholesterol is the most important approach to preventing heart disease. Robert DuBroff, MD, is a cardiologist and lipid specialist at the University of New Mexico. He has pointed out that high-risk populations don’t consistently benefit from statin therapy (American Journal of Medicine, March, 2016). In his view, doctors do not have a good way to tell who might benefit from taking a statin to prevent heart disease. Clinical benefits, particularly survival, don’t correspond well to the amount that a statin lowers bad cholesterol (Preventive Medicine, Apr.,2016).
Dr. DuBroff, together with French physician Michel de Lorgeril, MD, who oversaw the ground-breaking Lyon Heart Study in the 1990s, has written:
“We conclude that the expectation that CHD [coronary heart disease] could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary, we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD” (World Journal of Cardiology, July 26, 2015).
What Can Patients Do?
If cardiologists can’t agree on the importance of lowering cholesterol with statins, it is hardly any wonder that patients are confused. What else can people do to keep their hearts healthy?
There are many non-drug approaches that are beneficial. You can learn more about them in our Guide to Cholesterol Control and Heart Health. Anyone who would like a copy, please send $3 in check or money order with a long (no. 10) stamped (71 cents), self-addressed envelope: Graedons’ People’s Pharmacy, No. C-8, P. O. Box 52027, Durham, NC 27717-2027. It can also be downloaded for $2 from this website.
Physical activity is important for health. If statins cause muscle pain or weakness that interferes with exercise, that could be counterproductive. So would be elevations in blood sugar. Diabetes is one of the leading causes of heart disease and a known complication of statins.
A Mediterranean diet, as Drs. de Lorgeril and DuBroff mentioned, is also great for the heart. A large randomized trial called PREDIMED showed that this type of diet with lots of olive oil or nuts prevented heart disease in high-risk individuals (New England Journal of Medicine, Apr. 4, 2013). Such a diet rich in vegetables and fruits is also helpful in reducing (not increasing) the risk of diabetes (Journal of Nutrition, online, March 9, 2016).
If you are beginning to appreciate that cholesterol is only one piece of the heart disease puzzle you may find our chapter on this topic in Best Choices from The People’s Pharmacy of great interest. In it we point out that cardiologists have known for decades that there are are over 246 “risk factors” for heart disease (New England Journal of Medicine, Nov. 14, 2002). You will discover that many of the other risk factors can be modified best through lifestyle, as Drs. DuBroff and Lorgeril describe above. Just because doctors can prescribe statins does not mean they are the only or best solution to heart disease. Find out about other strategies in Best Medicine.
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