Discriminating dyslipidemias - a South African perspective

Clinical observation and scientific research have established that premature atherosclerotic vascular disease is strongly associated with markedly elevated low-density lipoprotein (LDL) cholesterol levels. Genetic disorders that impair LDL clearance via LDL receptors (LDLRs) are classified into heterozygous and homozygous familial hypercholesterolemia (FH) phenotypes. The heterozygous FH (HeFH) phenotype is characterized by LDL cholesterol levels exceeding 4.9 mmol/L, the presence of tendon xanthomas, and premature heart disease. In contrast, homozygous FH (HoFH) is characterised by LDL cholesterol levels above 13 mmol/L, both cutaneous and tendon xanthomas, and may lead to atherosclerotic vascular disease manifesting in childhood. FH is relatively common and occurs at even higher frequencies in populations founded by small ancestral groups, as documented in South Africa through investigations conducted in tertiary healthcare settings. Despite significant advances in the diagnosis and treatment of lipid and lipoprotein disorders - many of which are part of the differential diagnosis of FH - support for the diagnosis and management of FH has declined. While existing clinical guidelines address most cases of hypercholesterolemia, a subset of individuals with severe dyslipidemias requires more specialized evaluation. Referral criteria are proposed to help identify these patients. Given the high cardiovascular risk associated with severe hypercholesterolemia and the availability of effective treatments, there is an urgent need to strengthen, coordinate, and integrate clinical and laboratory services in South Africa to differentiate among the various causes of these disorders.