Effects of sex, age, and body mass index on serum bicarbonate

Abstract

Rationale: Obesity hypoventilation syndrome (OHS) is often underdiagnosed, with significant morbidity and mortality. Bicarbonate, as a surrogate of arterial carbon dioxide, has been proposed as a screening tool for OHS. Understanding the predictors of serum bicarbonate could provide insights into risk factors for OHS. We hypothesized that the bicarbonate levels would increase with an increase in body mass index (BMI), since the prevalence of OHS increases with obesity.

Methods: We used the TriNetX Research Network, an electronic health record database with de-identified clinical data from participating healthcare organizations across the United States, to identify 93,320 adults without pulmonary or advanced renal diseases who had serum bicarbonate and BMI measurements within 6 months of each other between 2017 and 2022. We used linear regression analysis to examine the associations between bicarbonate and BMI, age, and their interactions for the entire cohort and stratified by sex. We also applied a non-linear machine learning algorithm (XGBoost) to examine the relative importance of age, BMI, sex, race/ethnicity, and obstructive sleep apnea (OSA) status on bicarbonate.

Results: This cohort population was 56% women and 72% white and 80% non-Hispanic individuals, with an average (SD) age of 49.4 (17.9) years and a BMI of 29.1 (6.1) kg/m². The mean bicarbonate was 24.8 (2.8) mmol/L, with higher levels in men (mean 25.2 mmol/L) than in women (mean 24.4 mmol/L). We found a small negative association between bicarbonate and BMI, with an expected change of -0.03 mmol/L in bicarbonate for each 1 kg/m² increase in BMI (p < 0.001), in the entire cohort and both sexes. We found sex differences in the bicarbonate trajectory with age, with women exhibiting lower bicarbonate values than men until age 50, after which the bicarbonate levels were modestly higher. The non-linear machine learning algorithm similarly revealed that age and sex played larger roles in determining bicarbonate levels than the BMI or OSA status.

Conclusion: Contrary to our hypothesis, BMI is not associated with elevated bicarbonate levels, and age modifies the impact of sex on bicarbonate.

Keywords: BMI; bicarbonate; obesity; obesity hypoventilation syndrome; sex; sleep apnea.

FIGURE 1

Flow diagram of included and excluded patients in the analytic sample.

FIGURE 2

(A) Association between bicarbonate levels and body mass index (BMI) for the entire cohort. Each dot represents an individual patient measure (with 0.5 jitter applied to improve visualization of overlapping data), and the line represents a smoothed average of bicarbonate levels as a function of BMI. (B) Association between bicarbonate levels and BMI stratified by sex. (C) Association between bicarbonate levels and age for the entire cohort. Each dot represents an individual patient measure (with 0.5 jitter applied to improve visualization of overlapping data), and the line represents a smoothed average of bicarbonate levels as a function of age. (D) Association between bicarbonate levels and age stratified by sex.

FIGURE 3

(A) Association between serum bicarbonate and age across body mass index (BMI) categories, stratified by sex. Each dot represents an individual patient measure (with 0.5 jitter applied to improve visualization of overlapping data), and the line represents a smoothed average of bicarbonate levels as a function of age, within each BMI category. (B) Estimates for the eect of age on serum bicarbonate (outcome) from the linear regression models that include BMI categories (indicator variables), age, and the interactions between BMI categories and age. The reference BMI category was (20–25 kg/m²). The numerical values of estimates are summarized in Supplementary Table S1. (C) Association between serum bicarbonate and BMI across age categories, stratified by sex. Each dot represents an individual patient measure (with 0.5 jitter applied to improve visualization of overlapping data), and the line represents a smoothed average of bicarbonate levels as a function of BMI, within each age category. (D) Estimates for the eect of BMI on serum bicarbonate (outcome) from the linear regression models that include age categories (indicator variables), BMI, and the interactions between age categories and BMI. The reference age category was (18–35 years). Numerical values for estimates are summarized in Supplementary Table S2. Note: [ indicates inclusive; ( indicates exclusive.

FIGURE 4

The relative importance of preselected predictors for serum bicarbonate levels from gradient-boosted models. Gradient-boosted model elucidates the relative importance of each predictor on serum bicarbonate levels. Numerical values for fractional gain and relative importance are found in Table 2. *The predictor for sex refers to male sex. OSA, obstructive sleep apnea.