Metabolic Acidosis Predictor of Adverse Cardiovascular Outcomes

Studies have established metabolic acidosis as a risk factor for progression of chronic kidney disease (CKD). There are few data on the association between metabolic acidosis and cardiovascular disease in patients with CKD. Nancy L. Reaven, MA, and colleagues conducted a longitudinal observational study to examine the association of metabolic acidosis and adverse cardiovascular outcomes as well as the role of metabolic acidosis as an independent predictor of cardiovascular outcomes in patients with pre-dialysis CKD. Results of the study were reported during a poster session at Kidney Week 2019 in a poster titled Association of Metabolic Acidosis with Adverse Cardiovascular Outcomes in Patients with CKD.

The researchers utilized de-identified 2001-2017 electronic medical records (Optum® EMR) to identify patients with CKD stages 3-5. Inclusion criteria were more than two consistent serum bicarbonate values 28 to 365 days apart, more than three estimated glomerular filtration rate (eGFR) values >10 and <60 mL/min/1.73 m², and two or more years of post-index data (or until death). Follow up continued for up to 10 years for evidence of new onset heart failure.

Patients with metabolic acidosis and those with normal serum bicarbonate levels were defined by two serum bicarbonate values between 12 and <22 mEq/L and 22 to 29 mEq/L, respectively. Potential confounders, including age, sex, race, eGFR, diabetes, hypertension, heart failure, coronary artery disease, peripheral vascular disease, hemoglobin, and serum albumin, were examined using Cox proportional hazards models.

The study included 51,558 patients. At 2 years, the incidence of adverse cardiovascular events was significantly higher among the patients in the metabolic acidosis group compared with those with normal serum bicarbonate levels: heart failure, 29.8% vs 22.8%, P<.001; stroke, 19.5% vs 17.2%, P<.001; and myocardial infarction (MI), 17.2% vs 12.3%, P<.0001, respectively.

During follow-up, there was an independent association between serum bicarbonate and adverse cardiovascular outcomes. The hazard ratios per 1 mEq/L change were: new onset heart  failure, 0.976, 95% confidence interval [CI], 0.971-0.981; stroke, 0.979; 95% CI, 0.973-0.985; and MI, 0.964; 95% CI, 0.958-0.970, respectively.

“In this longitudinal analysis of >51,000 non-dialysis CKD patients followed for up to 10 years, serum bicarbonate levels below 22 mEq/L were associated with increased incidence of major adverse cardiovascular events independent of age, comorbid conditions, and kidney function. Studies evaluating the mechanisms of these associations are needed,” the researchers said.

Source: Reaven NL, Funk SE, Mathur VS, Tangri N. Association of metabolic acidosis with adverse cardiovascular outcomes in patients with CKD. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2019 (Abstract TH-PO693), November 7, 2019, Washington, DC.