Serum Bicarbonate Concentration and Cause-Specific Mortality: The National Health and Nutrition Examination Survey 1999-2010

Abstract

Objective: To assess the association between serum bicarbonate concentration and cause-specific mortality in the US general population.

Methods: A total of 31,195 individuals enrolled in the National Health and Nutrition Examination Survey between 1999 and 2010 were followed for a median 6.7 (interquartile range, 3.7-9.8) years. Cause-specific mortality was defined as cardiovascular, malignancy, and noncardiovascular/nonmalignancy causes. Cox proportional hazards adjusted for demographics, comorbidities, medications, and renal function were used to test the association between baseline serum bicarbonate and the outcomes of interest.

Results: Of the 2798 participants who died, 722 had a cardiovascular- and 620 had a malignancy-related death. Compared with participants with serum bicarbonate 22 to 26 mEq/L, those with a level below 22 mEq/L had an increased hazard of all-cause and malignancy-related mortality (hazard ratio [HR], 1.54; 95% CI, 1.30-1.83; and HR, 1.46; 95% CI 1.00-2.13, respectively). The hazard for cardiovascular mortality was increased by 8% with each 1 mEq/L increase in serum bicarbonate above 26 mEq/L (HR, 1.08; 95% CI, 1.01-1.15). The findings were consistent in participants with or without chronic kidney disease, with no significant interactions observed.

Conclusion: In a large cohort of US adults, serum bicarbonate concentration level below 22 mEq/L was associated with malignancy-related mortality, whereas a concentration above 26 mEq/L was associated with cardiovascular mortality. Further studies to evaluate potential mechanisms for the differences in cause-specific mortality are warranted.

FIGURE 1.

Consort diagram.

FIGURE 2.. Demographic adjusted curves for cause-specific mortality by baseline serum bicarbonate strata (< 22 mEq/L, 22 – 26 mEq/L and > 26 mEq/L). (A) All-cause mortality (B) Cardiovascular mortality (C) Cancer mortality.

Analysis was done using Kaplan-Meier method accounting for complex survey design. P-values are of Log-Rank (Mantel-Cox) test.

FIGURE 3.

Adjusted (model 3) penalized smoothing splines for all-cause, cardiovascular- and cancer-mortality (unweighted data). Gray lines represent 95% confidence interval. Red line represents HR of 1.

FIGURE 4.. Bicarbonate levels and cause-specific mortality in subgroups

CKD=chronic kidney disease, DM=Diabetes Mellitus. P values are for interaction between subgroup and bicarbonate levels. Analysis was done using Cox regression accounting for complex survey design