Abstract
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 31st, 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.
Highlights
Atherosclerosis is a systemic disease, often affecting the lower extremity arteries first[1]
In the multi-variable adjusted analysis, lipoprotein-associated phospholipase A2 (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 C-reactive protein (CRP) (HR 1.55; 95% CI 1.36–1.76) were all independently associated with incident peripheral arterial disease (PAD) (Table 2)
When CRP was added as a covariate together with Lp-PLA2, besides age at study entry, sex, BMI, current smoking, diabetes mellitus, hypertension, in the extended multi-variable analysis, Lp-PLA2 activity (HR 1.33; 95% CI 1.17–1.52; p < 0.001), Lp-PLA2 mass (HR 1.16; 95% CI 1.01–1.32; p = 0.038) and CRP (HR 1.36; 95% CI 1.18–1.58; p < 0.001) remained associated with incident PAD
Summary
Atherosclerosis is a systemic disease, often affecting the lower extremity arteries first[1]. Peripheral arterial disease (PAD), defined as occlusive atherosclerosis of the lower extremity arteries[2] or the arteries distal to the aortic bifurcation, is highly associated with concomitant coronary, carotid and cerebral artery disease, an increased cardiovascular and overall mortality, despite secondary preventive efforts such as smoking cessation, antiplatelet and statin therapy[3]. Plasma biomarkers measured in healthy individuals may be useful to detect individuals at increased risk for developing PAD, and may serve to identify factors enhancing or halting development of the disease. The main aim of this longitudinal cohort study was to evaluate Lp-PLA2 and proneurotensin in relation to an established risk marker such as CRP and known confounders for incident PAD risk at long term follow up
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