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Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study
BACKGROUND: Hyperphosphatemia has been associated with coronary artery calcification (CAC) mostly in chronic kidney disease, but the association between phosphate levels within the normal phosphate range and CAC is unclear. Our objectives were to evaluate associations between phosphate levels and CA...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375490/ https://www.ncbi.nlm.nih.gov/pubmed/35904204 http://dx.doi.org/10.1161/JAHA.121.023024 |
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author | Campos‐Obando, Natalia Bosman, Ariadne Kavousi, Maryam Medina‐Gomez, Carolina van der Eerden, Bram C. J. Bos, Daniel Franco, Oscar H. Uitterlinden, André G. Zillikens, M. Carola |
author_facet | Campos‐Obando, Natalia Bosman, Ariadne Kavousi, Maryam Medina‐Gomez, Carolina van der Eerden, Bram C. J. Bos, Daniel Franco, Oscar H. Uitterlinden, André G. Zillikens, M. Carola |
author_sort | Campos‐Obando, Natalia |
collection | PubMed |
description | BACKGROUND: Hyperphosphatemia has been associated with coronary artery calcification (CAC) mostly in chronic kidney disease, but the association between phosphate levels within the normal phosphate range and CAC is unclear. Our objectives were to evaluate associations between phosphate levels and CAC among men and women from the general population and assess causality through Mendelian randomization. METHODS AND RESULTS: CAC, measured by electron‐beam computed tomography, and serum phosphate levels were assessed in 1889 individuals from the RS (Rotterdam Study). Phenotypic associations were tested through linear models adjusted for age, body mass index, blood pressure, smoking, prevalent cardiovascular disease and diabetes, 25‐hydroxyvitamin D, total calcium, C‐reactive protein, glucose, and total cholesterol : high‐density lipoprotein cholesterol ratio. Mendelian randomization was implemented through an allele score including 8 phosphate‐related single‐nucleotide polymorphisms. In phenotypic analyses, serum phosphate (per 1 SD) was associated with CAC with evidence for sex interaction (P (interaction)=0.003) (men β, 0.44 [95% CI, 0.30–0.59]; P=3×10(−9); n=878; women β, 0.24 [95% CI, 0.08–0.40]; P=0.003; n=1011). Exclusion of hyperphosphatemia, chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m(2)) and prevalent cardiovascular disease yielded similar results. In Mendelian randomization analyses, instrumented phosphate was associated with CAC (total population β, 0.93 [95% CI: 0.07–1.79]; P=0.034; n=1693), even after exclusion of hyperphosphatemia, chronic kidney disease and prevalent cardiovascular disease (total population β, 1.23 [95% CI, 0.17–2.28]; P=0.023; n=1224). CONCLUSIONS: Serum phosphate was associated with CAC in the general population with stronger effects in men. Mendelian randomization findings support a causal relation, also for serum phosphate and CAC in subjects without hyperphosphatemia, chronic kidney disease, and cardiovascular disease. Further research into underlying mechanisms of this association and sex differences is needed. |
format | Online Article Text |
id | pubmed-9375490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93754902022-08-17 Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study Campos‐Obando, Natalia Bosman, Ariadne Kavousi, Maryam Medina‐Gomez, Carolina van der Eerden, Bram C. J. Bos, Daniel Franco, Oscar H. Uitterlinden, André G. Zillikens, M. Carola J Am Heart Assoc Original Research BACKGROUND: Hyperphosphatemia has been associated with coronary artery calcification (CAC) mostly in chronic kidney disease, but the association between phosphate levels within the normal phosphate range and CAC is unclear. Our objectives were to evaluate associations between phosphate levels and CAC among men and women from the general population and assess causality through Mendelian randomization. METHODS AND RESULTS: CAC, measured by electron‐beam computed tomography, and serum phosphate levels were assessed in 1889 individuals from the RS (Rotterdam Study). Phenotypic associations were tested through linear models adjusted for age, body mass index, blood pressure, smoking, prevalent cardiovascular disease and diabetes, 25‐hydroxyvitamin D, total calcium, C‐reactive protein, glucose, and total cholesterol : high‐density lipoprotein cholesterol ratio. Mendelian randomization was implemented through an allele score including 8 phosphate‐related single‐nucleotide polymorphisms. In phenotypic analyses, serum phosphate (per 1 SD) was associated with CAC with evidence for sex interaction (P (interaction)=0.003) (men β, 0.44 [95% CI, 0.30–0.59]; P=3×10(−9); n=878; women β, 0.24 [95% CI, 0.08–0.40]; P=0.003; n=1011). Exclusion of hyperphosphatemia, chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m(2)) and prevalent cardiovascular disease yielded similar results. In Mendelian randomization analyses, instrumented phosphate was associated with CAC (total population β, 0.93 [95% CI: 0.07–1.79]; P=0.034; n=1693), even after exclusion of hyperphosphatemia, chronic kidney disease and prevalent cardiovascular disease (total population β, 1.23 [95% CI, 0.17–2.28]; P=0.023; n=1224). CONCLUSIONS: Serum phosphate was associated with CAC in the general population with stronger effects in men. Mendelian randomization findings support a causal relation, also for serum phosphate and CAC in subjects without hyperphosphatemia, chronic kidney disease, and cardiovascular disease. Further research into underlying mechanisms of this association and sex differences is needed. John Wiley and Sons Inc. 2022-07-29 /pmc/articles/PMC9375490/ /pubmed/35904204 http://dx.doi.org/10.1161/JAHA.121.023024 Text en Copyright © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Research Campos‐Obando, Natalia Bosman, Ariadne Kavousi, Maryam Medina‐Gomez, Carolina van der Eerden, Bram C. J. Bos, Daniel Franco, Oscar H. Uitterlinden, André G. Zillikens, M. Carola Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study |
title | Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study |
title_full | Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study |
title_fullStr | Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study |
title_full_unstemmed | Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study |
title_short | Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study |
title_sort | genetic evidence for a causal role of serum phosphate in coronary artery calcification: the rotterdam study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375490/ https://www.ncbi.nlm.nih.gov/pubmed/35904204 http://dx.doi.org/10.1161/JAHA.121.023024 |
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