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; Uitterlinden, André G; Zillikens, M Carola (2022). Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study. Journal of the American Heart Association, 11(15), e023024. American Heart Association 10.1161/JAHA.121.023024

[img]
Preview
Text
JAHA.121.023024.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC).

Download (769kB) | Preview

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 (Pinteraction=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 m2) 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)

UniBE Contributor:

Franco Duran, Oscar Horacio

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2047-9980

Publisher:

American Heart Association

Language:

English

Submitter:

Pubmed Import

Date Deposited:

02 Aug 2022 10:04

Last Modified:

05 Dec 2022 16:22

Publisher DOI:

10.1161/JAHA.121.023024

PubMed ID:

35904204

Uncontrolled Keywords:

Mendelian randomization chronic kidney disease coronary artery calcification hyperphosphatemia phosphate

BORIS DOI:

10.48350/171651

URI:

https://boris.unibe.ch/id/eprint/171651

Actions (login required)

Edit item Edit item
Provide Feedback