Lipoprotein-associated phospholipase A2 (Lp-PLA2) Impact and role as cardiovascular risk marker

Abstract: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is today considered a novel specific vascular inflammatory biomarker. The general aim of this thesis was to study the role and impact of Lp-PLA2 as cardiovascular (CV) risk marker in an epidemiologic perspective. Specific aims were to explore the cross-sectional association of Lp-PLA2 with traditional CV risk factors, to asses the genetic influence of PLA2G7 on plasma levels of Lp-PLA2, and to study the morbidity and mortality of cardiovascular disease (CVD) in relation to Lp-PLA2. Data from the population-based “Malmö Diet and Cancer” CV cohort (n=6103) was used. Information on Lp-PLA2 was available on 5393 subjects (41 % men) with a mean follow-up of 10.6 years. National and local registers were used to retrieve the incidence of coronary events (CE), ischemic stroke and mortality.
Lp-PLA2 (assessed as activity or mass) increases with age, is higher in males and in current smokers. Lp-PLA2 is strongly correlated with blood lipids (especially LDL-cholesterol), however, is weakly correlated to glucose and to the extent of carotid asymptomatic atherosclerosis (i.e. intima-media thickness and plaque).
Genetic variation at the PLA2G7 gene locus significantly influences plasma Lp-PLA2 activity and mass levels, in a position and sex-specific manner.
Both elevated levels of Lp-PLA2 activity and mass, respectively, are independent of blood lipids, hs-CRP and other traditional cardiovascular risk factors, associated with an increased risk for incident ischemic stroke. No similar independent relationship was observed between Lp-PLA2 and CE.
Lp-PLA2 activity, compared with mass, is more strongly correlated to all five components constituting the metabolic syndrome (MetS) and increased more linearly with number of MetS components. Elevated levels of Lp-PLA2 activity was related to increased risk for incident CVD regardless of MetS. High Lp-PLA2 levels and presence of MetS were additive predictors of those who experienced a CV event.
It is concluded that both genetic and life-style factors are related to elevated levels of Lp-PLA2. Lp-PLA2 is independently associated with increased CVD risk, in particular ischemic stroke. There is an additive effect of Lp-PLA2 to presence of MetS on incident CVD risk, which may identify an especially high risk individual.