FAMILIAL HYPERCHOLESTEROLEMIA: THE IMPORTANCE OF EARLY RECOGNITION OF A SILENT DISEASE

Abstract

Objective. This literature review aims to synthesize the current scientific evidence in the literature on familial hypercholesterolemia, with a focus on genetic and pathophysiological mechanisms, diagnostic criteria, cardiovascular risk assessment, and treatment strategies, with a view to optimizing clinical practice and cardiovascular prevention.

Material and methods. A narrative review of the literature was conducted, prioritizing international guidelines, consensus statements, clinical trials, meta-analyses, and relevant observational studies identified in PubMed/MEDLINE, the Cochrane Library, and the reference lists of selected publications. Genetic and pathophysiological mechanisms, diagnosis, risk assessment, and treatment of familial hypercholesterolemia were reviewed.

Results. Evidence-based literature analysis shows that familial hypercholesterolemia is predominantly caused by mutations in the genes of the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes, which lead to impaired low-density lipoprotein cholesterol (LDL-C) clearance and increased cumulative exposure from childhood. Observational and genetic studies confirm the direct link between elevated LDL-C levels and the risk of premature atherosclerotic cardiovascular disease, independent of other traditional factors. International guidelines recommend the use of standardized clinical criteria for diagnosis, and data from various studies demonstrate that family screening significantly increases the rate of identification of undiagnosed cases and allows early initiation of treatment.

The results of randomized clinical trials and meta-analyses indicate that statins at the maximum tolerated dose are first-line therapy and cause significant reductions in LDL-C, and the combination with ezetimib produces an additional effect. PCSK9 inhibitors have been shown to be effective in achieving additional LDL-C reductions in patients who do not achieve therapeutic targets with conventional therapy or who are intolerant to statins. Available evidence shows that achieving the strict LDL-C targets recommended by the ESC guidelines, as well as significant percentage reductions in LDL-C according to the AHA/ACC recommendations, are associated with a substantial reduction in the risk of major cardiovascular events. Early initiation and long-term maintenance of lipid-lowering therapy are correlated with reduced atherosclerotic progression and improved cardiovascular prognosis in patients with familial hypercholesterolemia.

Conclusions. Familial hypercholesterolemia is a genetic pathology associated with increased cardiovascular risk, determined by early and persistent exposure to high LDL-C values. Early diagnosis, family screening and early initiation of intensive lipid-lowering therapy, according to international guidelines, are essential for reducing the risk of cardiovascular events and improving long-term prognosis.