Residual inflammatory risk: addressing the obverse side of the atherosclerosis prevention coin

Abstract

Twenty-two years ago, the landmark 4S trial demonstrated that statin therapy could reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among secondary prevention patients with overt hyperlipidaemia.1 Since that time, large-scale statin trials have shown that an exceptionally wide range of patients benefit from statins, including those without evidence of underlying vascular disease or hyperlipidaemia. Yet many statin-treated patients continue to suffer from life-threatening vascular events, an issue commonly described in the clinical literature as the problem of ‘residual risk’. One side of the residual risk coin undoubtedly relates to further reduction in low-density lipoprotein cholesterol (LDLC). Ever more aggressive cholesterol reduction is the cornerstone for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors that dramatically lower LDLC among those on statins, among those with statin intolerance, and among those with forms of familial hyperlipidaemia characterized by residual LDL receptor function.2–4 In contrast, therapies addressing residual cholesterol risk on the basis of high triglycerides or low HDL cholesterol have not to date proved effective for event reduction in randomized clinical trials. Yet focusing solely on ‘residual cholesterol risk’ among statin-treated patients ignores the fact …