Table 2.

Multivariable‐Adjusted Hazard Ratios for Time‐Updated Serum Bicarbonate on Heart Failure and Renal Events in the CRIC Using Marginal Structural Models

	Marginal Structural Model Hazard Ratio (95% Confidence Interval)
Heart failure
Continuous serum bicarbonate	Per 1 mmol/L increase in mean bicarbonate over time*
	1.08 (1.04 to 1.13)
Categorical serum bicarbonate* (reference 22 to 26 mmol/L)
Serum bicarbonate <22 mmol/L	1.00 (0.70 to 1.44)
Serum bicarbonate >26 mmol/L	1.66 (1.23 to 2.23)
Renal event*
Continuous serum bicarbonate	Per 1 mmol/L increase in mean bicarbonate over time*
	0.93 (0.89 to 0.96)
Categorical serum bicarbonate (reference 22 to 26 mmol/L)
Serum bicarbonate <22 mmol/L	1.97 (1.50 to 2.57)
Serum bicarbonate >26 mmol/L	1.07 (0.75 to 1.53)

Total of 3586 participants were included in each model. There were 512 participants with a heart failure event and 749 with a renal event. CRIC indicates Chronic Renal Insufficiency Cohort; eGFR, estimated glomerular filtration rate.

^*Results generated from a Marginal Structural Model with updated mean serum bicarbonate over time. All models are adjusted for age, gender, race/ethnicity, clinical center, eGFR, proteinuria, diabetes, hypertension, cardiovascular disease at baseline, chronic obstructive pulmonary disease, tobacco use, diuretic and alkali medication used, low density lipoprotein, fibroblast growth factor 23, high‐sensitivity C‐reactive protein. In order to evaluate the risk of events for participants with bicarbonate belonging to any category only a certain percent of time, the risk should be multiplied by that percent (ie, if a participant spends 50% of the time with bicarbonate >26 mmol/L, the risk of heart failure is 66×0.5=33%).

^*The 3 categories of serum bicarbonate, 22 to 26, <22 and >26 mmol/L, had the following distribution of CRIC participants: 2071, 610, and 905, with corresponding 259, 99 and 154 heart failure events and 401, 231 and 117 renal events in each group, respectively.