Association between long-term exposure to air pollution and incidence of peripheral artery disease: Evidence from a longitudinal study

Introduction: The association between air pollution and cardiovascular diseases is well established. However, fewer studies focused on the relationship between air pollution and peripheral artery disease (PAD), notwithstanding that not only it is a predictor of CVD mortality but also that incidence is globally rising, particularly in low-middle income countries. Objectives: The aim of this study is to estimate the association between long-term exposure to air pollutants and the incidence of PAD in the Rome Longitudinal Study (RLS) during 2011-2019. Methods: Using the Health Information Systems, we identified the first episodes of hospitalizations with discharge diagnosis for PAD (ICD-9 codes: 440.20-24; 444.0; 444.21; 444.22; 444.81; 447.1), lower limb vascular surgery (ICD-9 codes: 38.18; 39.29; 39.50; 39.90; 84.11; 84.12; 84.15; 84.17) or drug prescription (ATC code: B01AC23) in the period 2011-2019. In order to focus on incidence, we excluded from the population at risk prevalent cases based on hospital discharges in the 10 years before enrolment (October 9th, 2011). We assigned to the participants one-year average exposure to PM2.5, NO2 and black carbon (BC) from the ELAPSE Europe-wide hybrid land-use regression (LUR) models at 100 m2 spatial resolution on the basis of their baseline geocoded addresses. We also applied Cox regression models adjusted for individual and area-level covariates. The estimates were expressed as hazard ratios (HR) and 95 % confidence intervals (95 % CI) per pollutant-specific interquartile range (IQR) increase. We also analyzed any effect modification by socio-demographic and comorbidity variables and explored concentration-response curves using natural splines with 3 degrees of freedom. Results: Starting from a population at risk of 1,719,475 subjects aged 30 years or above, a total of 14,629 incident cases were identified. An IQR (1.13 mu g/m3) increase in PM2.5 was positively associated with a HR of 1.011 (95 % CI: 0.988, 1.034). Positive associations were also obtained for NO2 ([IQR 7.86 mu g/m3] HR: 1.022 (95 % CI: 0.998, 1.048)) and black carbon ([IQR 0.39 x10-5/m] HR: 1.020 (95 % CI: 0.994, 1.047)). Effect modification analysis showed stronger associations when considering males and individuals in the 55-69 age class. Concentration- response curve for NO2 showed a linear shape, with increases of risk already at low concentrations. Conclusions: Long-term exposure to PM2.5, NO2 and BC is associated with an increased incidence of PAD, and male subjects and individuals aged between 55-69 years were at greater risk.