Diabetes, statins and cardiovascular disease

Diabetics, whether type I or type 2, are at a substantially increased risk of developing cardiovascular diseases. '·2 Compared With non-diabetics they have a three to five times risk of dying from coronary heart disease, and when they develop cardiovascular disease the severity is worse than for non-diabetics. Diabetics are at a much greater overall risk, which in tum means an aggressive policy is needed to reduce their overall risk avoiding cigarette smoking, controlling blood pressure, achieving optimal glycaemic control and managing dyslipidaemia. The control of diabetic dyslipidaemia is of particular interest because of recent evidence to suggest pravastatin may be protective treatrnent.3 A post-hoc analysis of the West of Scotland Coronary Prevention Study demonstrated a 30% (p=0.042) reduction in the hazard of becoming diabetic when assigned to pravastatin therapy compared with placebo. The authors speculate that three potential mechanisms may explain these findings, either singly or in combination. Firstly, the triglyceride-lowering effect of pravastatin (average 12%) could be important over time in reducing the risk of developing insulin resistance; secondly, the anti-inflammatory properties of pravastatin (and other statins) by reducing cytokines interleukin-6 and TNF-a reduce the inhibition of lipoprotein lipase activity; and finally, pravastatin has been shown to improve endothelial function. The anti-inflammatory effects of the statins have been the focus of attention because of their potential importance in the management and prevention of acute coronary syndromes: Diabetics are particularly vulnerable to acute events due to their increased plaque instability and may therefore benefit from early statin use. Subgroup analysis of the Cholesterol and Recurrent Events (CARE) trial looked at cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant survivors of myocardial infarction (MI). 5 In the placebo group, diabetic patients suffered more recurrent coronary events death, non-fatal MI, revascularisation than non-diabetics (37% vs 25%). Pravastatin reduced the absolute risk of coronary events for diabetics by 8. l % and for non-diabetics by 5.2%, and the relative risk by 25% (p=0.05) and 23% (p<0.001), respectively. Importantly, pravastatin reduced the relative risk for the need for a revascularisation procedure by 32% (p=0.04) in diabetics. Non-diabetics with an impaired fasting glucose also had a reduced event rate when pravastatin was compared with placebo. This study clearly showed diabetics and non-diabetics with impaired glucose tolerance to be at high risk of recurrent coronary events and a substantial beneficial effect of pravastatin. Reducing the need for revascularisation has particularly important implications because diabetics, as well as having accelerated atheroma in general, also have accelerated restenosis after percutaneous intervention. Occlusive restenosis affected 18% in one study,7 increasing actuarial IO-year mortality to 59% compared with a 24% mortality in the 32% who avoided restenosis and a 35% mortality in the 50% with non-occlusive restenosis. These restenosis rates are substantially greater than those in non-diabetics, suggesting the need for reduced intervention and a more aggressive medical risk reduction strategy in diabetics. Statins correct only part of the diabetic dyslipidaemia but their additional properties may well increase their effectiveness. Fibrates, by raising HDL cholesterol and lowering triglycerides, may have additive effects, and combination therapy is theoretically attractive, though caution will be needed if diabetic renal dysfunction is present. Overall, diabetics are at such an increased risk of developing cardiovascular disease that so-called primary prevention is as important as secondary prevention in non-diabetics. Prevention is the key word and early initiation of statin therapy has a good evidence base and may well reduce the need for expensive interventions which, in diabetics, have a limited success rate.