Acute cardiovascular effects of exposure to airborne particulate matter : a study of possible pathogenetic mechanisms

Introduction Increased levels of particulate matter air pollution (PM) have been associated with increased cardiovascular morbidity and mortality, especially in elderly adults and in people suffering from cardiovascular or lung diseases. The mechanisms behind these effects are still unknown, although some hypothesis have been postulated that include a modification of autonomic regulation of heart rhythm and the induction of arrhythmic events. Which fraction of PM is the most harmful is still controversial, and few studies investigated the role of personal exposure to different fractions, and in particular ultrafine particles. *Aim The aim of this thesis is to assess: i) the association between the individual exposure to PM and the modification of HRV (an index of autonomic regulation of heart rhythm) and QTec (an index of a pro-arrhythmic status), both in healthy subjects and in subjects suffering from chronic ischemic heart disease or chronic lung disease; ii) the potential role of inflammation and baseline health status in these associations; iii) the role of different PM fractions in these associations. *Materials and methods 27 healthy individuals (“Healthy” group), 34 individuals with chronic ischemic heart disease (Heart group), 18 with chronic asthma or COPD (Lung group) underwent a 24-hour exposure/clinical evaluation protocol during their habitual activities, both in the warm season (Summer) and in the cold season (Winter). Individual exposure to UFPs, fine and coarse particles number concentration, gravimetric PM2.5 and PM10 was assessed for each subject, along with a 24-hour ambulatory ECG, for the assessment of heart rate variability and QT period. Mixed effects models were used to evaluate the associations between exposure to particles and clinical parameters, during 24-hour, day- and night-time. *Results The mean±SD age of the study population was 64±10 years and 65% were male. 24-hour individual exposure levels to UFPs, PM2.5 and PM10 (median (25th-75th) or mean±SD) were 19.643 (14.520-30.328) #/cm3, 41,53±22,52 µg/m3 and 51,97±24,31 µg/m3 respectively. Higher individual exposure was observed during day-time, except for particles in the accumulation mode (FP0,3-1). A -5,69% (95% C.I. -10,76 to -0,62) and -8,61% (-17,57 to 0,35) decrease in night-time SDNN (night-SDNN) in the total sample and in the Heart group respectively, was observed for an interquartile range (IQR) increase in FP0,3-1 during the night period (night-FP0,3-1). The same, even stronger, association was observed between day-FP0,3-1 and night-SDNN, and was confirmed in all groups. In subjects with higher levels of hsCRP, an increase in all night-time vagal indices (PNN50>HF>rMSSD) was observed in the totality of subjects for an IQR increase in day-FP2.5-10, and confirmed in healthy subjects only. In all subjects with lower levels of hsCRP, a +12,21% (95% C.I. 2,67 to 22,64) and +7,09 (0,12 to 14,55) increase in night-HF for an IQR increase in night-FP0,3-1 and in night-FP2,5-10 respectively was found, coupled to a decrease in the LF/HF ratio. These findings were confirmed in healthy subjects only. These associations were even stronger between day-FP and night-HRV in the total sample, and confirmed in the “Healthy” and the Heart groups. *Discussion and conclusion The observed results suggest a major role of fine particles leading to acute and delayed alteration in autonomic control of heart rhythm in healthy subjects and subjects with chronic ischemic heart disease, probably not related to the inflammatory status. On the other hand, coarse particles possibly need higher concentrations to exert their effects on autonomic control of heart rhythm, and these effects could be linked to inflammatory mechanisms in healthy subjects. Ultrafine particles appear to be less involved in the observed associations suggesting for these particles mechanisms other than those investigated in this study.