Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study

Abstract

Background and objectives: Low serum bicarbonate associates with mortality in CKD. This study investigated the associations of bicarbonate and acid-base status with mortality in healthy older individuals.

Design, setting, participants, & measurements: We analyzed data from the Health, Aging, and Body Composition Study, a prospective study of well functioning black and white adults ages 70-79 years old from 1997. Participants with arterialized venous blood gas measurements (n=2287) were grouped into <23.0 mEq/L (low), 23.0-27.9 mEq/L (reference group), and ≥28.0 mEq/L (high) bicarbonate categories and according to acid-base status. Survival data were collected through February of 2014. Mortality hazard ratios (HRs; 95% confidence intervals [95% CIs]) in the low and high bicarbonate groups compared with the reference group were determined using Cox models adjusted for demographics, eGFR, albuminuria, chronic obstructive pulmonary disease, smoking, and systemic pH. Similarly adjusted Cox models were performed according to acid-base status.

Results: The mean age was 76 years, 51% were women, and 38% were black. Mean pH was 7.41, mean bicarbonate was 25.1 mEq/L, 11% had low bicarbonate, and 10% had high bicarbonate. Mean eGFR was 82.1 ml/min per 1.73 m(2), and 12% had CKD. Over a mean follow-up of 10.3 years, 1326 (58%) participants died. Compared with the reference group, the mortality HRs were 1.24 (95% CI, 1.02 to 1.49) in the low bicarbonate and 1.03 (95% CI, 0.84 to 1.26) in the high bicarbonate categories. Compared with the normal acid-base group, the mortality HRs were 1.17 (95% CI, 0.94 to 1.47) for metabolic acidosis, 1.21 (95% CI, 1.01 to 1.46) for respiratory alkalosis, and 1.35 (95% CI, 1.08 to 1.69) for metabolic alkalosis categories. Respiratory acidosis did not associate with mortality.

Conclusions: In generally healthy older individuals, low serum bicarbonate associated with higher mortality independent of systemic pH and potential confounders. This association seemed to be present regardless of whether the cause of low bicarbonate was metabolic acidosis or respiratory alkalosis. Metabolic alkalosis also associated with higher mortality.

Keywords: acid-base equilibrium; acidosis; bicarbonate; body composition; follow-up studies; glomerular filtration rate; humans; mortality; prospective studies; renal insufficiency, chronic.

Figure 1.

Unadjusted survival in the study population according to bicarbonate category.

Figure 2.

Cubic spline regression analysis of the relationship between serum bicarbonate and mortality. Adjusted for age, sex, race, clinical site, eGFR, urinary albumin-to-creatinine ratio, chronic obstructive pulmonary disease, smoking, and pH. The line represents the hazard ratio point estimate, and the dashed lines represent the 95% confidence limits. Serum bicarbonate concentration of 25 mEq/L was the reference.