Numerous studies have found polymorphisms in the lipoprotein lipase (LPL) gene to be associated with the risk of coronary artery disease (CAD), implicating LPL in the development of atherothrombotic disease. It remains controversial, however, whether LPL acts in a pro- or anti-atherogenic fashion. We quantitated activity and concentration of LPL in post-heparin plasma from 194 male patients undergoing coronary angiography. HDL cholesterol was significantly associated with LPL activity quartiles (1.09+/-0.26 the highest vs. 0.96+/-0.25 mmol/l the lowest quartile, P<0.01). There was also a trend towards higher total (5.61+/-1.33 vs. 5.16+/-1.44 mmol/l, P=0.059) and LDL cholesterol (3.92+/-1.39 vs. 3.46+/-1.06 mmol/l, P=0.09) with higher LPL activity. In contrast, measures of CAD extent showed no differences between LPL quartiles (P>0.30 for prior myocardial infarction, number of diseased vessels, Gensini and extent scores). Additionally, there was no difference in LPL activity (CAD: n=158, 168+/-70 nmol/ml/min, no CAD: n=36, 180+/-89 nmol/ml/min, P=0.47) or concentration (280+/-121 ng/ml and 288+/-111 ng/ml, P=0.72) between patients with and without CAD. Our data show that, in spite of an association with lipoprotein parameters, LPL in post-heparin plasma is unrelated to the presence or the extent of CAD. Therefore, lipoprotein lipase determination in plasma does not appear to be a useful marker in the assessment of CAD risk.