Serum chloride is an independent predictor of mortality in hypertensive patients

Linsay McCallum, Panniyammakal Jeemon, Claire E. Hastie, Rajan K. Patel, Catherine Williamson, Adyani Md Redzuan, Jesse Dawson, William Sloan, Scott Muir, David Morrison, Gordon T. McInnes, Ellen Marie Freel, Matthew Walters, Anna F. Dominiczak, Naveed Sattar, Sandosh Padmanabhan

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 197 101 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.

Original languageEnglish
Pages (from-to)836-843
Number of pages8
JournalHypertension
Volume62
Issue number5
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

Fingerprint

Chlorides
Mortality
Serum
Blood Pressure
Bicarbonates
Proportional Hazards Models
Electrolytes
Anions
Sodium
Confidence Intervals
Survival

Keywords

  • chlorides
  • epidemiology
  • hypertension
  • mortality
  • sodium

ASJC Scopus subject areas

  • Internal Medicine

Cite this

McCallum, L., Jeemon, P., Hastie, C. E., Patel, R. K., Williamson, C., Md Redzuan, A., ... Padmanabhan, S. (2013). Serum chloride is an independent predictor of mortality in hypertensive patients. Hypertension, 62(5), 836-843. https://doi.org/10.1161/HYPERTENSIONAHA.113.01793

Serum chloride is an independent predictor of mortality in hypertensive patients. / McCallum, Linsay; Jeemon, Panniyammakal; Hastie, Claire E.; Patel, Rajan K.; Williamson, Catherine; Md Redzuan, Adyani; Dawson, Jesse; Sloan, William; Muir, Scott; Morrison, David; McInnes, Gordon T.; Freel, Ellen Marie; Walters, Matthew; Dominiczak, Anna F.; Sattar, Naveed; Padmanabhan, Sandosh.

In: Hypertension, Vol. 62, No. 5, 11.2013, p. 836-843.

Research output: Contribution to journalArticle

McCallum, L, Jeemon, P, Hastie, CE, Patel, RK, Williamson, C, Md Redzuan, A, Dawson, J, Sloan, W, Muir, S, Morrison, D, McInnes, GT, Freel, EM, Walters, M, Dominiczak, AF, Sattar, N & Padmanabhan, S 2013, 'Serum chloride is an independent predictor of mortality in hypertensive patients', Hypertension, vol. 62, no. 5, pp. 836-843. https://doi.org/10.1161/HYPERTENSIONAHA.113.01793
McCallum, Linsay ; Jeemon, Panniyammakal ; Hastie, Claire E. ; Patel, Rajan K. ; Williamson, Catherine ; Md Redzuan, Adyani ; Dawson, Jesse ; Sloan, William ; Muir, Scott ; Morrison, David ; McInnes, Gordon T. ; Freel, Ellen Marie ; Walters, Matthew ; Dominiczak, Anna F. ; Sattar, Naveed ; Padmanabhan, Sandosh. / Serum chloride is an independent predictor of mortality in hypertensive patients. In: Hypertension. 2013 ; Vol. 62, No. 5. pp. 836-843.
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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 197 101 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.",
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AU - Jeemon, Panniyammakal

AU - Hastie, Claire E.

AU - Patel, Rajan K.

AU - Williamson, Catherine

AU - Md Redzuan, Adyani

AU - Dawson, Jesse

AU - Sloan, William

AU - Muir, Scott

AU - Morrison, David

AU - McInnes, Gordon T.

AU - Freel, Ellen Marie

AU - Walters, Matthew

AU - Dominiczak, Anna F.

AU - Sattar, Naveed

AU - Padmanabhan, Sandosh

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N2 - 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 197 101 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.

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