Lipoprotein-associated phospholipase A2 activity, ferritin levels, metabolic syndrome, and 10-year cardiovascular and non-cardiovascular mortality: results from the Bruneck study

• Published in: European heart journal 2009-01, Vol.30 (1), p.107-115
• Main Authors: Tsimikas, Sotirios, Willeit, Johann, Knoflach, Michael, Mayr, Manuel, Egger, Georg, Notdurfter, Marlene, Witztum, Joseph L., Wiedermann, Christian J., Xu, Qingbo, Kiechl, Stefan
• Format: Article
• Language: English
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine Esterase - blood; Aged; Aged, 80 and over; Anti-oxidants; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular Diseases - blood; Cardiovascular Diseases - mortality; Coronary heart disease; Female; Ferritins - blood; Heart; Humans; Lipoprotein-associated phospholipase A2; Male; Medical sciences; Metabolic diseases; Metabolic Syndrome - blood; Metabolic Syndrome - mortality; Middle Aged; Miscellaneous; Myocardial infarction; Myocarditis. Cardiomyopathies; Other metabolic disorders; Oxidation; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehn502

Aims To identify factors that influence plasma levels and assess the prognostic value of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in a prospective, population-based survey of the epidemiology and pathogenesis of atherosclerosis. Methods and results The Bruneck study is a prospective, population-based survey initiated in 1990. Lp-PLA2 activity and baseline variables for the current analysis were measured in 765 subjects aged 45–84 years in 1995. Incident cardiovascular disease (CVD) (cardiovascular death, myocardial infarction, stroke, and transient ischaemic attack) and rates of non-CVD mortality were assessed between 1995 and 2005. Subjects with incident CVD had higher levels of Lp-PLA2 activity (884 ± 196 vs. 771 ± 192 µmol/min/L, P < 0.001). Increased Lp-PLA2 activity was significantly related to incident CVD [age- and sex-adjusted hazard ratio (95%CI) 2.9 (1.6–5.5); third vs. first tertile group; P < 0.001] and with vascular mortality but not with non-CVD mortality. Lp-PLA2 activity was enhanced in subjects with the metabolic syndrome and showed highly significant positive associations with LDL-C, apoB-100, ferritin, and HOMA-IR, and inverse associations with HDL-C and anti-oxidant levels. Conclusion Increased Lp-PLA2 activity is associated with metabolic syndrome and incident fatal and non-fatal CVD, but not with non-CVD mortality. Furthermore, Lp-PLA2 activity is strongly influenced by ferritin levels, LDL-C, and apoB-100 supporting its integral role in lipid peroxidation. Clinical utility of Lp-PLA2 activity for prediction of cardiovascular risk has to be explored in future studies.