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. 2018 Sep;33(9):859-871.
doi: 10.1007/s10654-018-0407-7. Epub 2018 May 15.

Serum phosphate levels are related to all-cause, cardiovascular and COPD mortality in men

Affiliations

Serum phosphate levels are related to all-cause, cardiovascular and COPD mortality in men

Natalia Campos-Obando et al. Eur J Epidemiol. 2018 Sep.

Abstract

Hyperphosphatemia has been associated with increased mortality in chronic kidney disease but the nature of such a relation in the general population is unclear. To investigate the association between phosphate (P) levels and all-cause and cause-specific mortality, we assessed two cohorts from the Rotterdam Study, with follow-up of 14.5 (RS-I) and 10.9 (RS-II) years until January 2012 with availability of fasting phosphate levels. Deaths were classified according to International Classification of Diseases into 7 groups: cardiovascular, cancer, infections, external, dementia, chronic lung diseases and other causes. Sex-stratified Weibull and competing-risks models were adjusted for age, BMI and smoking. Hazard ratios are expressed per 1 mg/dL increase in phosphate levels. The total number of participants included 3731 (RS-I, 2154 women) and 2494 (RS-II, 1361 women) subjects. The main outcome measures were all-cause and cause-specific mortality. A significant positive association was found between phosphate and all-cause mortality in men (pooled HR (95% CI): 1.46 (1.26-1.69)) but not in women (0.90 (0.77-1.05)). In men, higher phosphate increased the risk for cardiovascular mortality (1.66 (1.29-2.14)), other causes (1.67 (1.16-2.40)) and chronic lung disease mortality (1.94 (1.02-3.72)), the latter driven by mortality due to chronic obstructive pulmonary disease (COPD) (4.44 (2.08-9.49)). No relations were found for mortality due to infections, cancer, dementia or external causes. In conclusion, serum P is associated with increased all-cause, cardiovascular and COPD mortality in men but not women. The association with COPD mortality is novel and needs further research on underlying mechanisms.

Keywords: COPD; Emphysema; Mortality; Phosphate; Phosphotoxicity.

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Conflict of interest statement

Conflict of interest

Authors declare that they have no conflict of interest.

Ethical approval

The Rotterdam Study was approved by the Medical Ethics Committee of Erasmus Medical Center.

Figures

Fig. 1
Fig. 1
Flowchart for time line, design and sample size for the analyses
Fig. 2
Fig. 2
Cox-Snell residuals plot for parametric models in the association between serum phosphate levels and all-cause mortality in men

References

    1. Koeppen BM, Stanton BA. The renal system. In: Koeppen BM, Stanton BA editors. Berne & Levy physiology, 6th edn. Philadelphia, PA; 2010. p. 557-636.
    1. Shimada T, Kakitani M, Yamazaki Y, et al. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest. 2004;113(4):561–568. doi: 10.1172/JCI200419081. - DOI - PMC - PubMed
    1. Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol. 2013;75:503–533. doi: 10.1146/annurev-physiol-030212-183727. - DOI - PMC - PubMed
    1. Lim K, Lu TS, Molostvov G, et al. Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation. 2012;125(18):2243–2255. doi: 10.1161/CIRCULATIONAHA.111.053405. - DOI - PubMed
    1. Martin A, David V, Quarles LD. Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev. 2012;92(1):131–155. doi: 10.1152/physrev.00002.2011. - DOI - PMC - PubMed

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