Reducing vascular events risk in patients with dyslipidaemia: an update for clinicians.

Reducing the risk of vascular events in patients with dyslipidaemia requires cardiovascular disease risk stratification and lifestyle/pharmacological intervention on modifiable risk factors. Reduction of low-density lipoprotein cholesterol (LDL-C) with statins is highly effective in reducing cardiovascular disease in patients with and without diabetes, but leaves unaddressed a sizeable residual vascular risk (RvR), which is rarely quantified in routine clinical practice. Such RvR may relate to lack of strict target attainment for all atherogenic variables [LDL-C, non-high-density lipoprotein cholesterol (HDL-C) and/or apolipoprotein B(100)]. Another substantial lipid-related and modifiable RvR component is related to atherogenic dyslipidaemia, especially as global rates of obesity, type 2 diabetes and metabolic syndrome are increasing. Atherogenic dyslipidaemia is associated with insulin-stimulated very-low-density lipoprotein overproduction and reduced reverse cholesterol transport. The hallmark of atherogenic dyslipidaemia is the coexistence of low HDL-C and elevated triglycerides. Therapeutic lifestyle changes and combination lipid-lowering therapy with drugs targeting atherogenic dyslipidaemia (such as fibrates or innovative drugs targeting atherogenic dyslipidaemia and/or apolipoprotein B(100) metabolism) on top of background statins, have a potential to reduce RvR in high-risk groups, as shown in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, in which combination therapy with simvastatin plus fenofibrate decreased macrovascular risk in patients with diabetes and atherogenic dyslipidaemia, and retinopathy risk irrespective of baseline lipids.