The Cholesterol and Calorie Hypotheses are Both Dead — The Real Culprit is Insulin ResistanceAggressive lowering of low-density lipoprotein cholesterol (LDL-C) has been the cornerstone of preventative cardiology for decades. Statins are widely used as the go-to solution for the prevention of heart disease owing to their ability to slash LDL-C levels, a ‘surrogate marker’ of cardiovascular disease (CVD). Indeed, statins are one of the most widely prescribed class of drugs in the world. But this phenomenon begs two questions: is the enthusiasm for aggressive lowering of LDL-C justified; and is pharmacotherapy superior to lifestyle intervention? In summary, for many patients at high risk of CVD, one of the safest and most effective ways to reduce the risk of heart attack and stroke is to consume a high fat and low glycaemic load Mediterranean diet and engage in regular exercise. At the very least, exercise interventions are often similar to drug interventions in terms of their mortality benefits in the secondary prevention of coronary heart disease, and do not come with side effects.