Lp-PLA₂ activity and mass and CRP are associated with incident symptomatic peripheral arterial disease

Long follow up is needed in prospective cohort study evaluation of plasma biomarkers for incident peripheral arterial disease (PAD) Middle-aged PAD-free individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (n = 5550; 1991-94) were followed prospectively for a median time of 23.4 years. The plasma biomarkers lipoprotein-associated phospholipase A2 (Lp-PLA₂) activity and mass, proneurotensin, and CRP, were studied in relation to incidence of PAD until December 31^st, 2016. The diagnosis of PAD could be validated and confirmed in 98%. Cox regression was used to calculate hazard ratios (HR) per 1 standard deviation increment of each respective log transformed plasma biomarker. Cumulative incidence of PAD was 4.4% (men 5.9%, women 3.3%). Adjusting for age, gender, smoking, body mass index, hypertension, diabetes mellitus, Lp-PLA₂ activity (HR 1.33; 95% CI 1.17-1.52), Lp-PLA₂ mass (HR 1.20; 95% CI 1.05-1.37) and CRP (HR 1.55; 95% CI 1.36-1.76) remained independently associated with incident PAD. The plasma biomarkers Lp-PLA₂ activity and mass, and CRP were markers of PAD risk, implying that they might be useful biomarkers for subclinical atherosclerosis and atherosclerotic disease.