What intervention trials don’t tell us: the residual risk in primary prevention

A number of epidemiological studies and intervention clinical trials demonstrated that the in spite of the achievement of recommended targets of low-density lipoprotein (LDL)-cholesterol in subjects not yet affected by cardiovascular diseases, a substantial percentage of them still remain at risk of acute events. Beyond LDL-c, additional abnormalities of lipid profile, consisting of low high-density lipoprotein (HDL)-cholesterol and high levels of triglycerides or the combination of the two, may play a role in determining the cardiovascular prognosis. The mentioned lipid abnormalities, together with elevated apolipoprotein B and non-HDL cholesterol, do represent the burden of the so-called residual cardiovascular risk of lipid nature. Although it is plausible that there is benefit in normalizing lipid abnormalities other than LDL-C in primary prevention, it is still controversial that this actually reduces clinical events. Recent attempts to further reduce the risk of patients already given statin therapy with drugs raising HDL-c or lowering triglycerides levels failed to demonstrate a favorable impact on secondary prevention. Of importance, evidence is completely lacking for people at lower risk such as those requiring primary prevention. New and more safe/effective drugs are currently under investigation in this field. Until further information is available on the efficacy and safety of interventions aimed at restoring normal levels of triglycerides and HDL, we have to continue to implement safe and effective methods we already have to blunt the cardiovascular risk, consisting mainly of lifestyle changes and statin therapy.