Abstract

BACKGROUND AND AIM: Perfluoroalkyl substances (PFAS) are widespread persistent pollutants and its exposure in humans relates to elevated cholesterol. However, the potential to impact public health globally by increasing risk of cardiovascular disease remains unexplored. Therefore, we investigated associations of PFAS exposure with risk of myocardial infarction and/or stroke and subsidiary, with baseline blood lipids. METHODS: A nested case-control study with first incident myocardial infarction and stroke and matched controls from two Swedish cohorts (Swedish Mammography Cohort-Clinical and Cohort of 60-year-olds) was used. Baseline blood sampling occurred during 2003-2009 and 1997-1999 with follow-up through 2017 and 2014 for the cohorts, respectively. Eight plasma PFAS´ concentrations were measured using targeted liquid chromatography-triple quadrupole mass spectrometry. Individual values and the standardized sum of five quantifiable PFAS were categorized into tertiles based on the controls. First incident myocardial infarction (n=345) and ischemic stroke (n=354) cases were ascertained via linkage to the National Inpatient Register and the Cause of Death Register. Control individuals, matched for age, sex and sample date, were randomly selected from each cohort. Baseline blood lipids were measured after overnight fasting. RESULTS:We investigated 1528 case-control subjects with mean [SD] age of 66 [7.7] years, 67% women and PFAS levels around or slightly below established benchmark doses. In multivariable-adjusted analyses, the third tertile of the standardized sum of five PFAS associated with higher total cholesterol and lower triglyceride levels amongst controls at baseline (n=631), but not with increased risk of cardiovascular disease (OR=0.70, 95% CI=0.53, 0.93), myocardial infarction (OR=0.60, 95% CI=0.39, 0.92) or stroke (OR=0.83, 95% CI=0.46-1.50). CONCLUSIONS:This study indicated that PFAS exposure, although associated with increased cholesterol levels, did not associate with increased risk of myocardial infarction, stroke or their composite endpoint. The findings improve our knowledge on cardiovascular health effects of environmental factors and suggest disturbances in pathways unrelated to cholesterol. KEYWORDS: Cardiovascular diseases, PFAS, Environmental Epidemiology

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