Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemia

ABSTRACT Background Recent data indicate that statins could offer coronary artery disease (CAD) benefit even by mechanisms beyond lipid lowering. Genetic influence has been shown for some antithrombotic actions of statins via oxidized‐low‐density lipoprotein cholesterol (ox‐LDL) receptors and nitric oxide synthase (NOS) activity modulation. The present study was designed to evaluate the influence of ox‐LDL lectin‐like receptor‐1 (LOX‐1) and NOS polymorphisms in the incidence of cardiovascular events in pure hypercholesterolaemic subjects during statin treatment. Materials and methods A prospective 4‐year study involving 1039 event‐free subjects (643 males, 396 females) treated with atorvastatin (10–40 mg day−1) to reach the appropriate Adult Treatment Panel‐III LDL target of 3·36 mmol L−1. Enrolled subjects were evaluated every 6 months or at a clinical event. LOX‐1 3′UTR/T‐C and NOS G894T polymorphisms were detected by allelic discrimination assays (polymerase chain reaction), lipid profile by enzymatic‐colorimetric method, ox‐LDL by enzyme linked immunosorbent assay, platelet activation by P‐selectin (P‐sel) expression (FACScan), NOS activity (by intracellular citrullin recovery) and homocysteine (high performance liquid chromatography), C‐reactive protein (CRP) by sensitive nephelometric technique. Results LOX‐1 3′UTR/T showed the strongest association with events in the whole cohort with respect to each other variable including LDL reduction and NOS G894T (OR 4·90, 95% CI 3·19–6·98, P