Temporal Relationship Between Changes in Serum Calcium and Hypercholesteremia and Its Impact on Future Brachial-Ankle Pulse Wave Velocity Levels

Abstract

Background: The high levels of serum calcium and cholesterol are the important risk factors of cardiovascular disease (CVD), which frequently influence each other during the development of CVD. However, few studies have examined their temporal relationship to confirm the precursor, and it is still largely unknown whether and how their temporal relationship would influence the development of CVD. This study aimed to establish the temporal relationship between the changes in serum calcium and cholesterol using the longitudinal cohort data, and examine whether this temporal relationship influenced the arterial elasticity indicated by brachial-ankle pulse wave velocity (baPWV). Methods: This is a cohort study with a sample of 3,292 Chinese participants (aged 20-74 years) with 5.7 years follow-up. Serum calcium and cholesterol were measured at baseline and follow-up survey. The cross-lagged path analysis was used to examine their temporal relationship, and mediation analysis was performed to evaluate the potential mediating effect. Results: The cross-lagged path coefficients (β₂ values) from baseline serum calcium to follow-up cholesterol was significantly greater than the path coefficients (β₁ values) from baseline cholesterol to follow-up serum calcium (β₂ = 0.110 vs. β₁ = 0.047; P = 0.010) after adjusting for the multiple covariates. The path coefficients from baseline serum calcium to follow-up cholesterol in the participants with high baPWV was significantly greater than the participants with low baPWV (β₂ = 0.155 for high baPWV and β₂ = 0.077 for low baPWV, P = 0.028 for the difference between the β₂ values). Moreover, cholesterol partially mediated the association between the higher serum calcium and greater subsequent baPWV values, the percentage of the total effect mediated by cholesterol was estimated at 21.7%. Conclusion: Our findings indicate that increased serum calcium precedes increased in serum cholesterol, and this temporal relationship may contribute to the development of higher baPWV levels.

Keywords: brachial-ankle pulse wave velocity; cardiovascular diseases; cholesterol; cohort study; serum calcium.

Figure 1

A cross-lagged path analysis of serum calcium and total cholesterol, adjusted for the covariates (covariates such as age, sex, body-mass index [BMI], smoking, alcohol consumption, regular exercise, marriage, caloric intake, family history of cardiovascular disease [CVD], triglyceride [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and drug use for hypertension or dyslipidemia) in the total sample (N = 3,292); β₁ cross-lagged path coefficient from the baseline total cholesterol to follow-up serum calcium, β₂ cross-lagged path coefficient from the baseline serum calcium to follow-up total cholesterol, r₁ represents synchronous correlations, r₂ and r₃ represent tracking correlations, R² variance explained. **P < 0.001 for coefficients being different from 0; ^†difference between β₁ and β₂ for being different from 0.

Figure 2

The receiver operating characteristics (ROC) curve for brachial-ankle pulse wave velocity (baPWV) to detect CVD.

Figure 3

A cross-lagged path analysis of serum calcium and total cholesterol in the low baPWV group and high baPWV group, adjusted for the covariates (covariates included age, sex, BMI, smoking, alcohol consumption, regular exercise, marriage, caloric intake, family history of CVD, TG, HDL-C, LDL-C, and drug use for hypertension or dyslipidemia) in the total sample (N = 3,292); β₁ and β₂ are cross-lagged path coefficients, r₁ represents the synchronous correlations, r₂ and r₃ represent tracking correlations, R² variance explained. **P < 0.001 for coefficients being different from 0. ^†difference between β₁ and β₂ for being different from 0.

Figure 4

The mediation effect of follow-up cholesterol on the baseline serum calcium with future value of baPWV association with adjustment for the covariates (covariates included age, sex, BMI, smoking, alcohol consumption, regular exercise, marriage, caloric intake, family history of CVD, TG, HDL-C, LDL-C, and drug use for hypertension or dyslipidemia) in the total sample (N = 3,292). The data were standardized regression coefficients; ***P < 0.001, **P < 0.01 for coefficients being different from 0.

Figure 5

(A) A cross-lagged path analysis of serum calcium and total cholesterol in men (N = 1202) and women (N = 2090); (B) A cross-lagged path analysis of serum calcium and total cholesterol in menopause (N = 1053) and non-menopausal (N = 1037). Adjusted for covariates (covariates included age, BMI, smoking, alcohol consumption, regular exercise, marriage, caloric intake, family history of CVD, TG, HDL-C, LDL-C, and drug use for hypertension or dyslipidemia); β₁ and β₂ are the cross-lagged path coefficients, r₁ represents synchronous correlations, r₂ and r₃ represent the tracking correlations, R² variance explained. ***P < 0.001 for the coefficients being different from 0.