Per- and polyfluoroalkyl substances concentrations are associated with an unfavorable cardio-metabolic risk profile: findings from two population-based cohort studies

medRxiv

Abstract

Abstract Per- 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= 1,962), 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.

Authors 12

1. Tariq O. Faquih Aachen Department of Clinical Epidemiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

2. Elvire Nadieh Landstra

   German Center for Neurodegenerative Diseases

   Affiliation as printed

   Population Health Sciences, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany

3. Astrid van Hylckama Vlieg Aachen Department of Clinical Epidemiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

4. N. Ahmad Aziz

   University of Bonn · German Center for Neurodegenerative Diseases

   Affiliation as printed

   Department of Neurology, Faculty of Medicine, University of Bonn, Bonn, Germany

   Population Health Sciences, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany

5. Ruifang Li‐Gao Aachen Department of Clinical Epidemiology

   Leiden University Medical Center · Metabolon (United States)

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

   Metabolon, Inc. Morrisville, North Carolina, United State of America

6. Renée de Mutsert Aachen Department of Clinical Epidemiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

7. Frits Richard Rosendaal Aachen Department of Clinical Epidemiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

8. Raymond Noordam Aachen Department of Internal Medicine Section of Gerontology and Geriatrics

   Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

9. Diana van Heemst Aachen Department of Internal Medicine Section of Gerontology and Geriatrics

   Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

10. Dennis Owen Mook-Kanamori Aachen Department of Clinical Epidemiology Department of Public Health and Primary Care

    Leiden University Medical Center

    Affiliation as printed

    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

    Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands

11. Ko Willems van Dijk Aachen Department of Human Genetics Department of Internal Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

    Leiden University Medical Center

    Affiliation as printed

    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

    Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands

    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

12. Monique M.B. Breteler corresponding

    University of Bonn · German Center for Neurodegenerative Diseases · Institut für Medizinische Biometrie, Informatik und Epidemiologie

    Affiliation as printed

    Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn, Germany

    Population Health Sciences, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany