Premature coronary artery disease and apolipoprotein B and apolipoprotein A-I

Premature coronary artery disease classic risk factors primarily include increased low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C), as more recently shown elevated apolipoprotein B or reduced apolipoprotein A-I levels. Extensive characterization of familial and genetic dyslipidaemia has led to identification of specific defects in lipid metabolism associated with increased risk of premature coronary artery disease. Probands of these families with common genetic forms of dyslipidaemia were studied to determine if apoB or apoA-I defines genetic groups and if apoB or apoA-I levels relate to premature coronary artery disease risk. Elevated apoB was characteristic of familial hypercholesterolemia, familial combined hyperlipidaemia (FCHL and was seen in individuals with elevated Lp(a). Normal apoB levels were seen in familial hypertriglyceridaemia and in ‘coronary artery disease with low-HDL cholesterol’. ApoA-I levels were found to be low in FCHL and were decreased in familial hypoalphalipoproteinemia (FHA). However, in familial hypertriglyceremia, even though HDL-C levels were low, normal apoA-I and apoB levels were seen in the absence of premature coronary artery disease. Therefore, in genetic dyslipidaemias elevated apoB levels and reduced apoA-I levels (or increased apoB/A-I ratio) differ and predict premature coronary artery disease suggesting a great potential for routine screening of apoB and apoA-I in determination of CAD risk and response to therapy.