Traditional cardiovascular disease risk factors predict acrolein metabolite level in a population-based study

Background: Cardiovascular disease (CVD) is the top cause of death worldwide. Ambient exposures to combustion-derived products including particulate matter and volatile gases including acrolein are associated with increased cardiovascular disease (CVD) morbidity and mortality. Acrolein exposure in mice causes endothelial dysfunction, the hallmark of atherosclerosis. To better define how exposure to acrolein relates to CVD in humans, we investigated the relationship between the major urine product of acrolein metabolism (hydroxypropylmercapturic acid (HPMA)) and traditional CVD risk factors. Methods: In a cross-sectional assessment, participants were recruited from the University of Louisville Preventive Cardiology Clinic. Urinary HPMA and cotinine (nicotine metabolite) levels were measured by gas chromatography / mass spectrometry (GC/MS). Generalized linear mixed-effects modeling was used to examine whether HPMA levels were predicted by CVD risk factors, smoke exposure, and alcohol consumption. Model fit statistics (log-likelihood) were used to develop the most parsimonious model. Results: The sample population (n=118) was mostly men (54%), middle-aged (50±1 years), had a low average Framingham Risk Score (8±7%), a high smoking rate (44%), and smoked 2.7 packs/week on average. We found a significant positive association between cotinine levels and HPMA values: cotinine was the strongest predictor of HPMA values (βstd=0.494). Additional significant independent predictors were smoking status (β=1.468, p=0.0346), BMI (β=2.649, p=0.0308), alcohol consumption (β=68.749, p=0.0060), and exercise (β=-112.383, p=0.0426). Smoking status, alcohol consumption, and exercise accounted for nearly 60% of the variance in responses (R2=0.584). Conclusions: These findings suggest that smoking, obesity, alcohol consumption, and exercise independently and significantly impact HPMA levels. Positive associations between HPMA, BMI, and alcohol consumption suggest that obesity and ethanol affect acrolein metabolism and that removal of acrolein is increased by exercise. Further exploration of these factors could be important in understanding the contribution of acrolein in causing long-term cardiovascular pathogenesis.