Lipid Biomarker Linked to Higher Cardiovascular Risk

BARCELONA — Elevated lipoprotein-associated phospholipase A2 and metabolic syndrome are additive in their predictive power for future cardiovascular events, Dr. Margaretha Persson reported at the joint congress of the European Society of Cardiology and the World Heart Federation.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel biomarker reflecting a proinflammatory state. It has been shown to be an independent predictor of cardiovascular risk in the Atherosclerosis Risk in Communities Study (Circulation 2004;109:837–42) and the Rotterdam Study (Circulation 2005;111:570–5). Metabolic syndrome (MS) is also associated with systemic inflammation and increased cardiovascular risk.

To learn whether Lp-PLA2 provides additional clinically important prognostic information in patients with MS, Dr. Persson analyzed 10-year follow-up data on 4,480 healthy middle-aged nondiabetic participants in the Malmo (Sweden) Diet and Cancer Cardiovascular Cohort.

The baseline prevalence of MS as defined by National Cholesterol Education Program criteria was 14% in women and 20.5% in men. Mean plasma Lp-PLA2 activity was 51 nmol/mL per minute in those with MS and 43 nmol/mL per minute in those without. Of subjects with MS, 51% had an Lp-PLA2 level in the top tertile, compared with 30% of those without MS. The more components of MS an individual had, the higher the Lp-PLA2. Both the presence of MS and high Lp-PLA2 were independent of age, gender, smoking status, and LDL cholesterol level.

In a Cox multivariate analysis, subjects with high Lp-PLA2 had an adjusted 50% increased relative risk of having a first MI or ischemic stroke during 10 years of follow-up, compared with those with an Lp-PLA2 in the lower two tertiles. Subjects with MS had a 67% increased risk, compared with those without MS. And participants with both MS and high Lp-PLA2 had a 118% increase in risk, compared with those with neither, according to Dr. Persson of Malmo University Hospital.

Her study was sponsored by GlaxoSmithKline. The company's Diadexus PLAC blood test is Food and Drug Administration-approved for measurement of Lp-PLA2.

GlaxoSmithKline has large ongoing clinical trials studying an Lp-PLA2 inhibitor for the prevention of cardiovascular events.