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Cholesterol and statins are among the most extensively researched topics in clinical medicine, but controversy continues to rage over how to interpret this vast and growing body of evidence and translate it into better clinical care for patients. In 2013, after a 9-year hiatus, guidelines for treatment of high cholesterol were updated by the American College of Cardiology and the American Heart Association.1 The new guidelines shifted treatment recommendations in several important ways, perhaps the most important of which was to recommend that statin primary prevention treatment decisions be made nearly entirely on the basis of a patient's overall risk for atherosclerotic cardiovascular disease instead of accounting for the low-density lipoprotein cholesterol (LDL) level (unless LDL is extremely elevated). This increasing emphasis on risk-based statin prescribing strikingly demotes LDL levels in importance compared with previous guidelines, shifts prescribing towards older men who are at higher average short-term risk,2 and has elicited controversy.3
In this issue of EBM, Sauser and colleagues review the evidence for LDL-lowering treatment of persons with an elevated level of LDL cholesterol but relatively low short-term (10-year) cardiovascular risk.4 The basic rationale for the ‘early LDL treatment hypothesis’ is that high-LDL cholesterol causes cumulative damage to coronary arteries (in the form of atherosclerosis) even during young adulthood when risk of cardiovascular events is low, and that early LDL-lowering could reduce that damage accumulation and thereby reduce coronary heart disease risk in the long term more than waiting to treat LDL cholesterol until later in life when event risk becomes higher. To assess the evidence for this early LDL treatment hypothesis, the authors conducted an extensive review of randomised controlled trials of LDL-lowering and patient outcomes and …