Cholesterol reduction?

The role of blood cholesterol levels in coronary heart disease (CHD) and the true effect of cholesterol-lowering statin drugs are debatable. In particular, whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently, the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes, cancer, and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD 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.

Keywords: Cholesterol, Statins, Coronary heart disease, Mediterranean diet, Cardiovascular disease, Mortality

Core tip: Traditional efforts to prevent cardiovascular disease have emphasized the benefits of cholesterol lowering and statin drugs. Often overlooked is the fact that numerous studies of cholesterol lowering have failed to demonstrate a mortality benefit and the benefits of statins may have been overstated. The Mediterranean diet has consistently lowered cardiovascular events and mortality in numerous studies and does not typically lower cholesterol levels. Alternative theories of atherosclerosis are independent of cholesterol metabolism and may provide the key to future preventive strategies.

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INTRODUCTION

Nearly twenty years ago two landmark randomized clinical trials appeared in The Lancet which forever changed the course of medicine for patients with coronary heart disease (CHD). The 4S study employed a cholesterol-lowering statin drug and reported a 30% mortality reduction[1]. The Lyon Diet Heart Study utilized the Mediterranean diet and reported a 70% mortality reduction[2]. Subsequent studies of the Mediterranean diet have confirmed these findings and also shown a reduced risk of cancer, diabetes, and Alzheimer’s disease[3-6]. Subsequent statin studies have led the United States Food and Drug Administration to issue warnings regarding the increased risk of diabetes and decreased cognition with statin drugs. Paradoxically, statins have gone on to become a multi-billion dollar industry and the foundation of many cardiovascular disease prevention guidelines while the Mediterranean diet has often been ignored. We believe this statin-centric cholesterol-lowering approach to preventing CHD may be misguided.

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ASSOCIATION DOES NOT EQUAL CAUSATION

The cholesterol hypothesis links cholesterol intake and blood levels to cardiovascular disease. Because cholesterol is considered a risk factor for atherosclerosis many believe that lowering cholesterol in the blood is the best way to prevent CHD. Ideally, risk factors should help us distinguish those who will develop a disease from those who will not. However, if one examines the original Framingham Heart Study data (as an example) it is clear that the cholesterol levels of those who developed CHD and those who did not overlap except when the total cholesterol level exceeded 380 mg/dL or was less than 150 mg/dL (Figure ​(Figure1).1). Moreover, cholesterol may be associated with CHD but that does not prove causation. Despite the fact that high triglycerides and low HDL have long been associated with CHD, studies designed to raise HDL or lower triglycerides have failed to reduce CHD mortality. Similarly, cholesterol should not automatically become a treatment target. It may be a leap of faith to assume that lowering cholesterol is the best way to prevent CHD.

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