Why patients with familial hypercholesterolemia are at high cardiovascular risk? Beyond LDL-C levels

Familial hypercholesterolemia (FH) is a common genetic cause of elevated low-density lipoprotein cholesterol (LDL-C) due to defective clearance of circulating LDL particles. All FH patients are at high risk for premature cardiovascular disease (CVD) events due to their genetically determined lifelong exposure to high LDL-C levels. However, different rates of CVD events have been reported in FH patients, even among those with the same genetic mutations and comparable LDL-C levels. Hence, additional CVD risk modifiers, beyond LDL-C, may contribute to increase CVD risk in the FH population. In this review, we discuss the overall CVD risk burden of the FH population. Additionally, we revise the prognostic impact of several traditional and emerging predictors of CVD risk and we provide an overview of the role of specific tools to stratify CVD risk in FH patients in order to ensure them a more personalized treatment approach.