Dyslipidemias in the prevention of cardiovascular disease: risks and causality.

Atherosclerotic cardiovascular disease is now the major global cause of death, despite reductions in CVD deaths in developed societies. Dyslipidemias are a major contributor, but the mass occurrence of CVD relates to the combined effects of hyperlipidemia, hypertension, and smoking. Total blood cholesterol and LDL-cholesterol relate to CVD risk in an independent and graded manner and fulfill the criteria for causality. Therapeutic reduction of these lipid fractions is associated with improved outcomes. There is good evidence that HDL-cholesterol, triglycerides, and Lp(a) relate to CVD although the evidence for a causal relationship is weaker. The HDL association with CVD is largely independent of other risk factors whereas triglycerides may be more important as signaling a need to look intensively for other measures of risk such as central obesity, hypertension, low HDL-cholesterol, and glucose intolerance. Lp(a) is an inherited risk marker. The benefit of lowering it is uncertain, but it may be that its impact on risk is attenuated if LDL-cholesterol is low.