Supplementary Material for: Serum Bicarbonate Is Associated with Heart Failure in the Multi-Ethnic Study of Atherosclerosis

Background: Low serum bicarbonate concentrations are
associated with mortality and kidney disease progression. Data regarding
associations between bicarbonate and cardiovascular disease (CVD) are
scarce. Methods: We performed a cohort study of 6,229
adult participants from the Multi-Ethnic Study of Atherosclerosis, a
community-based cohort free of CVD at baseline. Serum bicarbonate was
measured at baseline. Cardiovascular outcomes were defined as: (1)
subclinical CVD (left ventricular mass [LVM] and aortic pulse pressure
[PP] measured at baseline), (2) incident atherosclerotic cardiovascular
events (CVE; composite of myocardial infarction, resuscitated cardiac
arrest, stroke, coronary heart disease death, and stroke death), and (3)
incident heart failure. Results: During a median
(interquartile range) follow-up of 8.5 (7.7-8.6) years, 331 (5.3%)
participants had an incident CVE and 174 (2.8%) developed incident heart
failure. We stratified analyses by use of diuretics because we observed
a significant interaction between diuretic use and bicarbonate with
study outcomes. Among diuretic nonusers, with adjustment, bicarbonate
≥25 mEq/L was associated with an estimated 3.0 g greater LVM (95% CI
0.5-5.0) and 1.0 mm Hg higher aortic PP (95% CI 0.4-2.0) compared to
bicarbonate 23-24 mEq/L. Each 1 mEq/L of bicarbonate increase was
associated with a 13% higher risk of incident heart failure (hazards
ratio 1.13, 95% CI 1.01-2.11). Among diuretic users, higher bicarbonate
was not associated with CVD. Bicarbonate was not associated with
incident atherosclerotic CVE irrespective of diuretic use. Conclusion:
Among nonusers of diuretics in a large community-based study, higher
serum bicarbonate concentrations are associated with subclinical CVD and
new heart failure.