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.