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.
Abbreviations and Acronyms:
CKD (chronic kidney disease), CVD (cardiovascular disease), eGFR (estimated glomerular filtration rate), HR (hazard ratio), IQR (interquartile range), NHANES (National Health and Nutrition Examination Survey)To read this article in full you will need to make a payment
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References
- Metabolic acidosis of CKD: diagnosis, clinical characteristics, and treatment.Am J Kidney Dis. 2005; 45: 978-993
- Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD.Nephrol Dial Transplant. 2009; 24: 1232-1237
- Association of serum bicarbonate with risk of renal and cardiovascular outcomes in CKD: a report from the Chronic Renal Insufficiency Cohort (CRIC) study.Am J Kidney Dis. 2013; 62: 670-678
- Persistent high serum bicarbonate and the risk of heart failure in patients with chronic kidney disease (CKD): a report from the Chronic Renal Insufficiency Cohort (CRIC) study.J Am Heart Assoc. 2015; 4: e001599
- Serum bicarbonate and mortality in stage 3 and stage 4 chronic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 2395-2402
- Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study.Clin J Am Soc Nephrol. 2016; 11: 308-316
- Higher serum bicarbonate levels within the normal range are associated with better survival and renal outcomes in African Americans.Kidney Int. 2011; 79: 356-362
- Current status of bicarbonate in CKD.J Am Soc Nephrol. 2015; 26: 515-523
- Serum bicarbonate and mortality in adults in NHANES III.Nephrol Dial Transplant. 2013; 28: 1207-1213
- Relationship between urinary calcium and net acid excretion as determined by dietary protein and potassium: a review.Nephron. 1999; 81: 18-25
- Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein contents.Am J Clin Nutr. 1998; 68: 576-583
- Clastogenicity of low pH to various cultured mammalian cells.Mutat Res. 1992; 268: 297-305
- Acidic pH induces topoisomerase II-mediated DNA damage.Proc Natl Acad Sci U S A. 2003; 100: 5205-5210
- The interactions of protons, calcium and potassium ions on cardiac Purkinje fibres.J Physiol. 1978; 282: 345-352
- The effects of acid-base disturbances on cardiovascular and pulmonary function.Kidney Int. 1972; 1: 375-389
National Center for Health Statistics. The Linkage of National Center for Health Statistics Survey Data to the National Death Index – 2015 Linked Mortality File (LMF): Methodology Overview and Analytic Considerations. Centers for Disease Control and Prevention website, https://www.cdc.gov/nchs/data/datalinkage/LMF2015_Methodology_Analytic_Considerations.pdf. Accessed April 4, 2019.
- A new equation to estimate glomerular filtration rate.Ann Intern Med. 2009; 150: 604-612
- National health and nutrition examination survey: analytic guidelines, 1999-2010.Vital Health Stat 2. 2013; 161: 1-24
- Comparison of confidence intervals for the Poisson mean: some new aspects.REVSTAT–Stat J. 2012; 10: 211-227
- A simple method to calculate the confidence interval of a standardized mortality ratio (SMR).Am J Epidemiol. 1990; 131: 373-375
- Flexible smoothing with B-splines and penalties.Stat Sci. 1996; 11: 89-121
- A proportional hazards model for the subdistribution of a competing risk.Journal of the American statistical association. 1999; 94: 496-509
- Serum bicarbonate concentration and the risk of cardiovascular disease and death in type 2 diabetes: the Fremantle Diabetes Study.Cardiovasc Diabetol. 2016; 15: 143
- Serum bicarbonate and kidney disease progression and cardiovascular outcome in patients with diabetic nephropathy: a post hoc analysis of the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) study and IDNT (Irbesartan Diabetic Nephropathy Trial).Am J Kidney Dis. 2015; 66: 450-458
- Microenvironmental acidosis in carcinogenesis and metastases: new strategies in prevention and therapy.Cancer Metastasis Rev. 2014; 33: 1095-1108
- Examining the relationship between diet-induced acidosis and cancer.Nutr Metab (Lond). 2012; 9: 72
- Acidity generated by the tumor microenvironment drives local invasion.Cancer Res. 2013; 73: 1524-1535
- pH regulators in invadosomal functioning: proton delivery for matrix tasting.Eur J Cell Biol. 2012; 91: 847-860
- Acid-sensitive ion channels and receptors.Handb Exp Pharmacol. 2009; 194: 283-332
- Reduced pathological angiogenesis and tumor growth in mice lacking GPR4, a proton sensing receptor.Angiogenesis. 2011; 14: 533-544
- The proton-sensing G-protein coupled receptor GPR4 promotes angiogenesis in head and neck cancer.PLoS One. 2016; 11: e0152789
- Acidic tumor microenvironment and pH-sensing G protein-coupled receptors.Front Physiol. 2013; 4: 354
- Bicarbonate increases tumor pH and inhibits spontaneous metastases.Cancer Res. 2009; 69: 2260-2268
- Diabetes and cancer: a consensus report.Diabetes Care. 2010; 33: 1674-1685
- The impact of National Death Index linkages on population-based cancer survival rates in the United States.Cancer Epidemiol. 2013; 37: 20-28
- Comparison of expert adjudicated coronary heart disease and cardiovascular disease mortality with the national death index: results from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.J Am Heart Assoc. 2017; 6: e004966
Article Info
Publication History
Published online: December 04, 2019
Footnotes
Potential Conflicts of Interest: The authors report no conflict of interest.
Identification
Copyright
© 2019 Mayo Foundation for Medical Education and Research
