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

Natalia Campos-Obando,Guy Brusselle,André G Uitterlinden,M Carola Zillikens,Bruno H Stricker,Lies Lahousse,Oscar H Franco,Albert Hofman

doi:10.1007/s10654-018-0407-7

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.

Highlights

Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Phosphorus is the sixth most common element in the human body and the second mineral in abundance [1]
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))
The association was found to be consistent in subjects without chronic kidney disease (CKD) (6.58 (2.59–16.7)); whereas we found no association in subjects with CKD (1.14 (0.20–6.63)), the latter analysis is constrained due to low number of events and driven only by RS-I

Summary

Introduction

Phosphorus is the sixth most common element in the human body and the second mineral in abundance [1]. It plays an important structural role in hard tissues, such as bone, and exerts critical regulatory roles in metabolic and signaling pathways [1]. The majority of phosphorus is stored in bone (85%) where it is complexed with calcium in the form of hydroxyapatite, whereas 15% of phosphorus is located in the intracellular compartment while less than 1% is present in extracellular fluids. Phosphorus exists in two main forms: a) an organic form bound to proteins (70%), b) an ionized form (30%), known as inorganic phosphorus, or phosphate, that circulates freely [1]. Phosphate homeostatic mechanisms have been ascribed to the actions of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) [1, 2]

Objectives

Methods

Results

Conclusion