000270145 001__ 270145 000270145 005__ 20260310111149.0 000270145 0247_ $$2doi$$a10.1007/s12403-023-00622-4 000270145 0247_ $$2ISSN$$a2451-9766 000270145 0247_ $$2ISSN$$a1876-1658 000270145 0247_ $$2ISSN$$a1876-1666 000270145 0247_ $$2ISSN$$a2451-9685 000270145 0247_ $$2altmetric$$aaltmetric:160671806 000270145 037__ $$aDZNE-2024-00743 000270145 082__ $$a550 000270145 1001_ $$0P:(DE-HGF)0$$aFaquih, Tariq O.$$b0 000270145 245__ $$aPer- and Polyfluoroalkyl Substances Concentrations are Associated with an Unfavorable Cardio-Metabolic Risk Profile: Findings from Two Population-Based Cohort Studies 000270145 260__ $$a[Dordrecht]$$bSpringer Netherlands$$c2024 000270145 3367_ $$2DRIVER$$aarticle 000270145 3367_ $$2DataCite$$aOutput Types/Journal article 000270145 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1747922696_19988 000270145 3367_ $$2BibTeX$$aARTICLE 000270145 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000270145 3367_ $$00$$2EndNote$$aJournal Article 000270145 520__ $$aPer- and polyfluoroalkyl substances (PFAS) are widely used and persistent chemicals, leading to ubiquitous exposure. Although high PFAS levels have been associated with an adverse cardiovascular risk profile, the distribution of levels and relations with cardio-metabolic risk markers in the general population have not been fully characterized. We assessed the association between blood levels of perfluorooctaneic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) and a range of lipoproteins and metabolites as well as clinical lipid measurements. We used data from participants of the Netherlands Epidemiology of Obesity study (NEO) (n = 584) and the Rhineland Study (n = 1962), jointly spanning an age range of 30 to 89 years. PFAS were measured with the Metabolon HD4 platform, and lipoprotein and metabolite profiles were measured using Nightingale’s nuclear magnetic resonance-spectroscopy platform, and mainly comprised lipoprotein markers. Using linear regression analyses, we quantified age-, sex-, and education-adjusted associations of PFOA, PFOS, and PFHxS with clinical lipid measurements and 224 lipoproteins and metabolites. Higher levels of PFAS, particularly PFOS and PFHxS, were associated with higher concentrations of total lipid, cholesterol and phospholipid content in most HDL, IDL, LDL, and VLDL subclasses. The effect sizes were age-dependent for the majority of the associations, with the deleterious effects of PFAS being generally stronger in people below compared to those above median age. Our observation that in the general population even low PFAS concentrations are associated with an unfavorable lipid profile, calls for further critical regulation of PFAS substances. 000270145 536__ $$0G:(DE-HGF)POF4-354$$a354 - Disease Prevention and Healthy Aging (POF4-354)$$cPOF4-354$$fPOF IV$$x0 000270145 588__ $$aDataset connected to CrossRef, Journals: pub.dzne.de 000270145 693__ $$0EXP:(DE-2719)Rhineland Study-20190321$$5EXP:(DE-2719)Rhineland Study-20190321$$eRhineland Study / Bonn$$x0 000270145 7001_ $$0P:(DE-2719)9000634$$aLandstra, Elvire N.$$b1 000270145 7001_ $$0P:(DE-HGF)0$$avan Hylckama Vlieg, Astrid$$b2 000270145 7001_ $$0P:(DE-2719)2812578$$aAziz, N. Ahmad$$b3 000270145 7001_ $$0P:(DE-HGF)0$$aLi-Gao, Ruifang$$b4 000270145 7001_ $$0P:(DE-HGF)0$$ade Mutsert, Renée$$b5 000270145 7001_ $$0P:(DE-HGF)0$$aRosendaal, Frits R.$$b6 000270145 7001_ $$0P:(DE-HGF)0$$aNoordam, Raymond$$b7 000270145 7001_ $$0P:(DE-HGF)0$$avan Heemst, Diana$$b8 000270145 7001_ $$0P:(DE-HGF)0$$aMook-Kanamori, Dennis O.$$b9 000270145 7001_ $$0P:(DE-HGF)0$$avan Dijk, Ko Willems$$b10 000270145 7001_ $$0P:(DE-2719)2810403$$aBreteler, Monique M. 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