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.
Highlights
Hypercalcemia and hypercholesterolemia are the two important risk factors for arterial stiffness or cardiovascular disease (CVD) [1–3]
Compared with the participants in the lowest quintile of serum calcium, the participants in the highest quintile are more likely to have greater increased in the serum cholesterol with adjustment for the potential confounders such as the baseline serum cholesterol (RR = 2.11, 95% CI: 1.74–2.55)
The path coefficient from the baseline serum calcium to the follow-up cholesterol (β2 = 0.110, 95% CI: 0.077–0.156, P < 0.001) is significantly greater than the path coefficient from the baseline cholesterol to the follow-up serum calcium (β1 = 0.047, 95% CI: 0.010–0.078, P = 0.035) after adjusting for age, sex, Body mass index (BMI), smoking, alcohol consumption, regular exercise, marriage, caloric intake, family history of CVD, TG, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and drug use for hypertension or dyslipidemia with
Summary
Hypercalcemia and hypercholesterolemia are the two important risk factors for arterial stiffness or cardiovascular disease (CVD) [1–3]. One animal study demonstrated that increased in serum calcium could elevate the circulating cholesterol through reducing its catabolism via G-protein coupled estrogen receptor and transient receptor potential canonical 1-dependent pathway [6], whereas the other animal study found that cholesterol could affect the serum calcium levels by decreased bone calcium, calcium redistribution in bone, and change of bone metabolism [7], indicating that the serum calcium and cholesterol could physiologically influence each other. 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)
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