Correlation between calcium levels and coronary microvascular disease in high-altitude environments: nested case-control study

Q: What are the key findings of this study?

Higher pre-training serum calcium levels were independently associated with an increased prevalence of coronary microvascular disease in high-altitude trainees, with each 1 mmol/L increase associated with a 39% higher odds (OR 1.39).

Q: What is the clinical evidence from this study?

Study design: Case-Control. Population: Coronary microvascular disease (CMVD) (n=1175). Intervention: Serum calcium levels vs. Lower serum calcium levels. Primary outcome: Coronary microvascular disease (CMVD) (OR 1.39, 95% CI 1.20-1.61, p=<0.001).

Q: What does this research mean for the field?

Higher pre-training serum calcium levels are independently associated with an increased odds of coronary microvascular disease in individuals exposed to high-altitude environments. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To assess whether baseline serum calcium levels are independently associated with coronary microvascular disease among individuals undergoing training at high altitude.

Xiyang Rao; Xiao Chen; Wentao Zhang; Juan Lv; Yong Ren; Ruixi Zi; Chunping Bao; Yankun Shi; Lixia Yang; Yu Chen

doi:10.3389/fcvm.2026.1905691

September 16, 2026Frontiers in Cardiovascular MedicineOpen Access

Correlation between calcium levels and coronary microvascular disease in high-altitude environments: nested case-control study

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Key result

Higher pre-training serum calcium linked to ~39% greater CMVD odds per 1 mmol/L in high-altitude trainees.

OR 1.39
95% CI 1.20-1.61
P<0.001
n=1,175

Figures

Why the study?

Coronary microvascular disease is an emerging concern under high-altitude hypoxia, but data on modifiable correlates are scarce and the association between serum calcium and CMVD at high altitude has not been systematically examined.

Are higher pre-training serum calcium levels associated with an increased risk of coronary microvascular disease in adults undergoing high-altitude training?

Key Points

To assess whether baseline serum calcium levels are independently associated with coronary microvascular disease among individuals undergoing training at high altitude.
Conducted a nested case-control study within a cohort of 4,000 individuals undergoing 3–6 months of continuous altitude training at 3,000–3,500 m in Yunnan Province, China.
Identified cases (n = 235) with post-altitude electrocardiogram ST-T abnormalities and transthoracic Doppler echocardiography-confirmed coronary flow reserve ≤ 2.3, matched 1:4 by age and sex to controls without ECG abnormalities (n = 940; total N = 1,175).
Evaluated the association between pre-training serum calcium and coronary microvascular disease using multivariable logistic regression adjusted for age, sex, body mass index, systolic blood pressure, oxygen saturation, and other covariates.
Pre-training serum calcium levels were significantly higher in CMVD cases than in non-CMVD controls [median 2.42 (2.32–2.47) vs. 2.37 (2.31–2.42) mmol/L, P < 0.001].
Multivariable logistic regression demonstrated that each 1 mmol/L increase in serum calcium was independently associated with increased odds of CMVD (OR = 1.39, 95% CI: 1.20–1.61, P < 0.001).
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 systolic blood pressure (OR = 1.02, 95% CI: 1.00–1.03, P = 0.009) were also independently associated with CMVD.

Study Design

Type

Case-Control (n=1,175)

Multicenter

No

Structured PICO

Are higher pre-training serum calcium levels associated with an increased risk of coronary microvascular disease in adults undergoing high-altitude training?

P

Population

1,175 healthy adults (98.6% male, median age 24) undergoing 3-6 months of high-altitude training at 3,000-3,500 m, evaluated for coronary microvascular disease.

E

Exposure

Pre-training serum calcium levels (observational exposure)

C

Comparator

Matched controls without coronary microvascular disease (lower serum calcium levels)

O

Outcome

Coronary microvascular disease (CMVD) defined by ECG ST-T abnormalities and reduced coronary flow reserve (CFR ≤ 2.3) confirmed by transthoracic Doppler echocardiographysurrogate

Main Result

Odds Ratio: 1.39 (95% CI 1.2–1.61)

p-value: p=<0.001

Higher pre-training serum calcium levels are independently associated with an increased risk of coronary microvascular disease during high-altitude exposure, suggesting its potential utility as a screening biomarker.

Limitations

Single-center study design limits generalizability to other populations or geographic regions.
Study population consisted predominantly of healthy males (only 1.4% female), making sex-specific subgroup analyses underpowered.
Observational nature means residual confounding from unmeasured variables (e.g., dietary calcium intake, physical activity) cannot be entirely excluded.
Relied on total serum calcium rather than ionized calcium, and routine albumin adjustment was not performed.
Transthoracic Doppler echocardiography (TDE) was used to assess coronary flow reserve, which is not the invasive gold standard.
Relatively homogeneous study population of young, healthy military trainees limits generalizability to older adults or those with pre-existing conditions.
Did not extensively utilize invasive coronary angiography (the gold standard for diagnosing CMVD)
Small sample size in the female subgroup (n=16) leading to wide confidence intervals and unreliable estimates for women

Implication

Caution against using calcium for CMD screening in trainees; hypothesis-generating association requires prospective validation.

Abstract

Background 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. Methods 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 (Ca 2+ ) 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. Results 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. Conclusion 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.

Discussion

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Cite This Study

Rao et al. (2026) conducted a case-control in Coronary microvascular disease (CMVD) (n=1,175). Serum calcium levels vs. Lower serum calcium levels was evaluated on Coronary microvascular disease (CMVD) (OR 1.39, 95% CI 1.20-1.61, p=<0.001). Higher pre-training serum calcium levels were independently associated with an increased prevalence of coronary microvascular disease in high-altitude trainees, with each 1 mmol/L increase associated with a 39% higher odds (OR 1.39).

synapsesocial.com/papers/6aae0562322a2d038800ec03 https://doi.org/10.3389/fcvm.2026.1905691

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Correlation between calcium levels and coronary microvascular disease in high-altitude environments: nested case-control study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Correlation between calcium levels and coronary microvascular disease in high-altitude environments: nested case-control study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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