Objective

Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).

Approach and results

Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged ≥65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95% confidence interval 1.09, 1.50).

Conclusions

Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD.

Background

Air pollution alters small pulmonary vessels in animal models. We hypothesised that long-term ambient air pollution exposure would be associated with differences in pulmonary vascular volumes in a population-based study.

Methods

The Multi-Ethnic Study of Atherosclerosis recruited adults in six US cities. Personalised long-term exposures to ambient black carbon, nitrogen dioxide (NO₂), oxides of nitrogen (NO _x ), particulate matter with a 50% cut-off aerodynamic diameter of <2.5 μm (PM_2.5) and ozone were estimated using spatiotemporal models. In 2010-2012, total pulmonary vascular volume was measured as the volume of detectable pulmonary arteries and veins, including vessel walls and luminal blood volume, on noncontrast chest computed tomography (TPVV_CT). Peripheral TPVV_CT was limited to the peripheral 2 cm to isolate smaller vessels. Linear regression adjusted for demographics, anthropometrics, smoking, second-hand smoke, renal function and scanner manufacturer.

Results

The mean±sd age of the 3023 participants was 69.3±9.3 years; 46% were never-smokers. Mean exposures were 0.80 μg·m^-3 black carbon, 14.6 ppb NO₂ and 11.0 μg·m^-3 ambient PM_2.5. Mean±sd peripheral TPVV_CT was 79.2±18.2 cm³ and TPVV_CT was 129.3±35.1 cm³. Greater black carbon exposure was associated with a larger peripheral TPVV_CT, including after adjustment for city (mean difference 0.41 (95% CI 0.03-0.79) cm³ per interquartile range; p=0.036). Associations for peripheral TPVV_CT with NO₂ were similar but nonsignificant after city adjustment, while those for PM_2.5 were of similar magnitude but nonsignificant after full adjustment. There were no associations for NO _x or ozone, or between any pollutant and TPVV_CT.

Conclusions

Long-term black carbon exposure was associated with a larger peripheral TPVV_CT, suggesting diesel exhaust may contribute to remodelling of small pulmonary vessels in the general population.