Serum bicarbonate and cardiovascular events in hypertensive adults: results from the Systolic Blood Pressure Intervention Trial

Abstract

Background: Low serum bicarbonate level is associated with increased mortality, but its role as a predictor of cardiovascular disease (CVD) is unclear. This study evaluates the association between serum bicarbonate concentration and CVD and whether the effect of intensive blood pressure (BP) lowering on CVD outcomes is modified by serum bicarbonate level.

Methods: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized participants to a systolic BP target <120 mmHg (intensive treatment) or <140 mmHg (standard treatment). The primary CVD outcome was a composite of nonfatal myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure and CVD death. Cox proportional hazards models adjusted for demographic, clinical and laboratory characteristics were used to evaluate the association of interest in 9334 SPRINT participants (ClinicalTrials.gov: NCT01206062).

Results: Over a median follow-up of 3.33 years (interquartile range 2.87-3.87 years), 618 (6.6%) participants experienced a primary CVD outcome. Participants with serum bicarbonate <22 mEq/L had a significantly higher risk of the primary CVD outcome (hazard ratio 1.54; 95% confidence interval 1.11-2.14, P = 0.01), compared with participants with bicarbonate 22-26 mEq/L. The magnitude of the CVD risk reduction with intensive BP lowering was similar across bicarbonate strata (P-value for interaction = 0.97).

Conclusions: In hypertensive individuals, serum bicarbonate level <22 mEq/L was associated with an increased CVD risk. The effect of intensive BP lowering on CVD outcomes was not modified by the serum bicarbonate level.

Keywords: cardiovascular disease; mortality; serum bicar-bonate.

© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Figures

FIGURE 1

Incidence of the primary CVD outcome, heart failure and all-cause mortality by baseline serum bicarbonate. The primary CVD outcome includes nonfatal MI, acute coronary syndrome not resulting in an MI, nonfatal stroke, nonfatal acute decompensated heart failure and death from cardiovascular causes. Heart failure includes nonfatal and fatal acute decompensated heart failure. Shaded areas denote 95% point-wise CIs.

FIGURE 2

HR estimates for the association of serum bicarbonate with the primary CVD outcome, heart failure and all-cause mortality. HRs were estimated (relative to the mean serum bicarbonate level in SPRINT of 26.3 mEq/L) using B-splines within a Cox regression model, adjusting for the treatment group, age, sex, race/ethnicity, smoking status, history of CVD, systolic BP and use of ACEi, angiotensin II receptor blockers or diuretics, eGFR, log of UACR and serum potassium. The primary CVD outcome includes nonfatal MI, acute coronary syndrome not resulting in an MI, nonfatal stroke, nonfatal acute decompensated heart failure and death from cardiovascular causes. Heart failure includes nonfatal and fatal acute decompensated heart failure.

FIGURE 3

Forest plot comparing intensive-treatment to standard-treatment for the primary CVD outcome, heart failure and all-cause mortality by subgroups of serum bicarbonate. HRs compare intensive-treatment group to standard-treatment group. The primary CVD outcome includes nonfatal MI, acute coronary syndrome not resulting in an MI, nonfatal stroke, nonfatal acute decompensated heart failure and death from cardiovascular causes. Heart failure includes nonfatal and fatal acute decompensated heart failure.