Correlation between calcium levels and coronary microvascular disease in high-altitude environments: nested...

Coronary microvascular disease (CMVD) is an emerging concern under high-altitude hypoxia, but data on modifiable correlates are scarce. Serum calcium regulates vascular tone and coagulation, making it a plausible candidate marker. However, its association with CMVD at high altitude has not been systematically examined.

This nested case-control study enrolled 1,175 participants undergoing high-altitude training at 3,000-3,500 m. Participants were classified into CMVD and non-CMVD groups based on electrocardiogram (ECG) screening and coronary flow reserve (CFR ≤ 2.3) confirmed by transthoracic Doppler echocardiography. Cases (n = 235) were individuals with ECG ST-T abnormalities and reduced CFR, while controls (n = 940) were randomly matched by age and sex from those without such abnormalities. Pre-training serum calcium (Ca²⁺) levels, along with age, sex, body mass index (BMI), systolic blood pressure (SBP), oxygen saturation (OS), low-density lipoprotein cholesterol (LDL-C), smoking status, and SCOPA-AUT scores, were collected. Multivariable logistic regression was employed to evaluate the independent association between serum calcium and CMVD, adjusting for age, sex, BMI, SBP, and other covariates. Variance inflation factor (VIF < 7) was used to exclude multicollinearity.

Serum calcium levels were significantly higher in the CMVD group than in the non-CMVD group [2.42 (2.32-2.47) vs. 2.37 (2.31-2.42) mmol/L, P < 0.001]. Multivariable logistic regression revealed that serum calcium was independently associated with CMVD (OR = 1.39, 95% CI: 1.20-1.61, P < 0.001), indicating that each 1 mmol/L increase in calcium was associated with a 39% higher odds of CMVD. Age (OR = 1.05, 95% CI: 1.02-1.09, P = 0.001), female sex (OR = 4.13, 95% CI: 1.44-11.89, P = 0.009), and SBP (OR = 1.02, 95% CI: 1.00-1.03, P = 0.009) were also independently associated with CMVD. Subgroup analyses showed consistent associations across most strata, except in underweight and obese BMI categories and former smokers.

In this nested case-control sample of high-altitude trainees, higher serum calcium levels were significantly associated with an increased prevalence of CMVD. These findings suggest that serum calcium may serve as a potential screening indicator for CMVD in high-altitude settings.