title: Serum chloride is an independent predictor of mortality in hypertensive patients.
abstract: Chloride (Cl-) is the major extracellular anion in the body, accompanying sodium (Na+), and is primarily derived from dietary sources. Data suggest that increased dietary Cl- intake increases blood pressure, yet paradoxically, higher serum Cl- appears associated with lower mortality and cardiovascular risk. This implies that serum Cl- also reflects risk pathways independent of blood pressure, serum Na+, and bicarbonate (HCO3-). We analyzed 12,968 hypertensive individuals followed up for 35 years, using Cox proportional hazards model to test whether baseline serum Cl- was an independent predictor of mortality. To distinguish the effect of Cl- from Na+ and HCO3-, we adjusted for these electrolytes and also performed the analysis stratified by Na+ /HCO3- and Cl- levels. Generalized estimating equation was used to determine the effect of baseline Cl- on follow-up blood pressure. The total time at risk was 19,7101 person-years. The lowest quintile of serum Cl- (<100 mEq/L) was associated with a 20% higher mortality (all-cause, cardiovascular and noncardiovascular) compared with the remainder of the subjects. A 1 mEq/L increase in serum Cl- was associated with a 1.5% (hazard ratio, 0.985; 95% confidence interval, 0.98-0.99) reduction in all-cause mortality, after adjustment for baseline confounding variables and Na+, K+ , and HCO3- levels. The group with Na+ > 135 and Cl- > 100 had the best survival, and compared with this group, the Na+ >135 and Cl- <100 group had significantly higher mortality (hazard ratio, 1.21; 95% confidence interval, 1.11-1.31). Low, not high Serum Cl- (<100 mEq/L), is associated with greater mortality risk independent of obvious confounders. Further studies are needed to elucidate the relation between Cl- and risk.
authors: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, United Kingdom. sandosh.padmanabhan@glasgow.ac.uk.
authors: Linsay
authors: L
authors: McCallum
authors: Panniyammakal
authors: P
authors: Jeemon
authors: Claire E
authors: CE
authors: Hastie
authors: Rajan K
authors: RK
authors: Patel
authors: Catherine
authors: C
authors: Williamson
authors: Adyani Md
authors: AM
authors: Redzuan
authors: Jesse
authors: J
authors: Dawson
authors: William
authors: W
authors: Sloan
authors: Scott
authors: S
authors: Muir
authors: David
authors: D
authors: Morrison
authors: Gordon T
authors: GT
authors: McInnes
authors: Ellen Marie
authors: EM
authors: Freel
authors: Matthew
authors: M
authors: Walters
authors: Anna F
authors: AF
authors: Dominiczak
authors: Naveed
authors: N
authors: Sattar
authors: Sandosh
authors: S
authors: Padmanabhan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002712:Chlorides / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000401:mortality*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology; D017673:Sodium Chloride, Dietary
chemical_list: D002712:Chlorides; D017673:Sodium Chloride, Dietary
keywords: chlorides; epidemiology; hypertension; mortality; sodium