Vitamin D, Cardiovascular Events, and Coronary Heart Disease
Baseline characteristics of the 946 study participants are displayed in Table 1 . The mean 25(OH)D concentration in this sample was 25.8 ng/mL. The prevalence of vitamin D deficiency (25(OH)D level <20 ng/mL) was 32%. Compared with participants with 25(OH)D levels greater than or equal to 20 ng/mL, those with levels under 20 ng/mL were younger, less likely to be male, and less likely to have graduated from college. Participants with vitamin D deficiency were more likely to use tobacco, less likely to take multivitamins, and less likely to engage in physical activity. Consistent with prior studies, participants with vitamin D deficiency were more likely to have hypertension, diabetes, and depression. They had higher systolic and diastolic blood pressures, higher levels of hemoglobin A1c, C-reactive protein, parathyroid hormone, fibroblast growth factor 23, and serum phosphorus, and higher urinary albumin:creatinine ratios. Serum calcium levels did not differ across categories ( Table 1 ).
During a median follow-up period of 8.0 years, 323 subjects (34.1%) experienced a cardiovascular event. We observed a nonlinear association, with a sharp increase in cardiovascular events at 25(OH)D levels less than 20 ng/mL (Figure 1). The question of whether 25(OH)D levels of 20–29.9 ng/mL (often referred to as vitamin D insufficiency) also confer adverse health consequences is currently controversial. Therefore, we performed additional exploratory analyses to compare annual cardiovascular event rates at 3 different 25-OH levels: <20 ng/mL, 20–29.9 ng/mL, and ≥30 ng/mL. These analyses confirmed that the cardiovascular event rates observed in participants with 25(OH)D levels of 20–29.9 ng/mL were similar to the rates observed in participants with 25(OH)D levels greater than or equal to 30 ng/mL (Figure 2).
(Enlarge Image)
Figure 1.
Nonlinearity of the association between 25-hydroxyvitamin D levels and subsequent cardiovascular events among 946 participants in the Heart and Soul Study, 2000–2012.
(Enlarge Image)
Figure 2.
Incidence of cardiovascular (CV) events during a median follow-up period of 8.0 years, by 25-hydroxyvitamin D status, among 946 participants in the Heart and Soul Study, 2000–2012.
After adjustment for age, sex, race/ethnicity, and season of blood draw, participants with 25(OH)D levels less than 20 ng/mL had a 50% greater rate of cardiovascular events (hazard ratio (HR) = 1.50, 95% confidence interval (CI): 1.19, 1.90) than participants with 25(OH)D levels of 20 ng/mL or higher. Further adjustment for poor health behaviors (tobacco use, no multivitamin use, low physical activity) modestly attenuated the association (HR = 1.31, 95% CI: 1.02, 1.69). Adjustment for comorbid health conditions (diabetes, hypertension, depression, higher body mass index) did not materially alter findings (HR = 1.30, 95% CI: 1.01, 1.67). Following further adjustment for potential biological mediators (systolic and diastolic blood pressure, high-density lipoprotein cholesterol, triglycerides, hemoglobin A1c, C-reactive protein, parathyroid hormone, phosphorus, and fibroblast growth factor 23), the association was no longer significant (HR = 1.11, 95% CI: 0.85, 1.44) ( Table 2 ). These associations were similar across individual outcomes ( Table 3 ). Results revealed that parathyroid hormone most strongly attenuated the association, resulting in a 10.5% change in the size of the association (Figure 3).
(Enlarge Image)
Figure 3.
Change in the strength of the association between 25-hydroxyvitamin D level (<20 ng/mL vs. ≥20 ng/mL) and cardiovascular events after adjustment for potential mediators (expressed as percent change in the age-adjusted log hazard ratio) among 946 participants in the Heart and Soul Study, 2000–2012. All models adjusted for sociodemographic factors (age, sex, white race/ethnicity, season of blood draw, and college graduation) and health behaviors (tobacco use, multivitamin use, and physical activity). BP, blood pressure; CRP, C-reactive protein; FGF-23, fibroblast growth factor 23; HDL, high-density lipoprotein; PTH, parathyroid hormone.
Stratified analyses revealed that the association between 25(OH)D levels and cardiovascular events was stronger in participants with diabetes (n = 249; HR = 1.62, 95% CI: 1.06, 2.48) than in participants without diabetes (n = 695; HR = 1.09, 95% CI: 0.79, 1.51 (P for interaction < 0.001)). The association was also stronger in participants with albuminuria (n = 207; HR = 1.66, 95% CI: 1.07, 2.57) than in those without albuminuria (n = 731; HR = 1.07, 95% CI: 0.77, 1.47 (P for interaction < 0.001)). The association was modestly greater in participants with chronic kidney disease (n = 290; HR = 1.44, 95% CI: 0.99, 2.08) than in those without chronic kidney disease (n = 656; HR = 1.27, 95% CI: 0.88, 1.81 (P for interaction < 0.001)). The association did not differ by age, sex, race/ethnicity, hypertension, obesity, or hyperparathyroidism.
Results
Baseline characteristics of the 946 study participants are displayed in Table 1 . The mean 25(OH)D concentration in this sample was 25.8 ng/mL. The prevalence of vitamin D deficiency (25(OH)D level <20 ng/mL) was 32%. Compared with participants with 25(OH)D levels greater than or equal to 20 ng/mL, those with levels under 20 ng/mL were younger, less likely to be male, and less likely to have graduated from college. Participants with vitamin D deficiency were more likely to use tobacco, less likely to take multivitamins, and less likely to engage in physical activity. Consistent with prior studies, participants with vitamin D deficiency were more likely to have hypertension, diabetes, and depression. They had higher systolic and diastolic blood pressures, higher levels of hemoglobin A1c, C-reactive protein, parathyroid hormone, fibroblast growth factor 23, and serum phosphorus, and higher urinary albumin:creatinine ratios. Serum calcium levels did not differ across categories ( Table 1 ).
During a median follow-up period of 8.0 years, 323 subjects (34.1%) experienced a cardiovascular event. We observed a nonlinear association, with a sharp increase in cardiovascular events at 25(OH)D levels less than 20 ng/mL (Figure 1). The question of whether 25(OH)D levels of 20–29.9 ng/mL (often referred to as vitamin D insufficiency) also confer adverse health consequences is currently controversial. Therefore, we performed additional exploratory analyses to compare annual cardiovascular event rates at 3 different 25-OH levels: <20 ng/mL, 20–29.9 ng/mL, and ≥30 ng/mL. These analyses confirmed that the cardiovascular event rates observed in participants with 25(OH)D levels of 20–29.9 ng/mL were similar to the rates observed in participants with 25(OH)D levels greater than or equal to 30 ng/mL (Figure 2).
(Enlarge Image)
Figure 1.
Nonlinearity of the association between 25-hydroxyvitamin D levels and subsequent cardiovascular events among 946 participants in the Heart and Soul Study, 2000–2012.
(Enlarge Image)
Figure 2.
Incidence of cardiovascular (CV) events during a median follow-up period of 8.0 years, by 25-hydroxyvitamin D status, among 946 participants in the Heart and Soul Study, 2000–2012.
After adjustment for age, sex, race/ethnicity, and season of blood draw, participants with 25(OH)D levels less than 20 ng/mL had a 50% greater rate of cardiovascular events (hazard ratio (HR) = 1.50, 95% confidence interval (CI): 1.19, 1.90) than participants with 25(OH)D levels of 20 ng/mL or higher. Further adjustment for poor health behaviors (tobacco use, no multivitamin use, low physical activity) modestly attenuated the association (HR = 1.31, 95% CI: 1.02, 1.69). Adjustment for comorbid health conditions (diabetes, hypertension, depression, higher body mass index) did not materially alter findings (HR = 1.30, 95% CI: 1.01, 1.67). Following further adjustment for potential biological mediators (systolic and diastolic blood pressure, high-density lipoprotein cholesterol, triglycerides, hemoglobin A1c, C-reactive protein, parathyroid hormone, phosphorus, and fibroblast growth factor 23), the association was no longer significant (HR = 1.11, 95% CI: 0.85, 1.44) ( Table 2 ). These associations were similar across individual outcomes ( Table 3 ). Results revealed that parathyroid hormone most strongly attenuated the association, resulting in a 10.5% change in the size of the association (Figure 3).
(Enlarge Image)
Figure 3.
Change in the strength of the association between 25-hydroxyvitamin D level (<20 ng/mL vs. ≥20 ng/mL) and cardiovascular events after adjustment for potential mediators (expressed as percent change in the age-adjusted log hazard ratio) among 946 participants in the Heart and Soul Study, 2000–2012. All models adjusted for sociodemographic factors (age, sex, white race/ethnicity, season of blood draw, and college graduation) and health behaviors (tobacco use, multivitamin use, and physical activity). BP, blood pressure; CRP, C-reactive protein; FGF-23, fibroblast growth factor 23; HDL, high-density lipoprotein; PTH, parathyroid hormone.
Stratified analyses revealed that the association between 25(OH)D levels and cardiovascular events was stronger in participants with diabetes (n = 249; HR = 1.62, 95% CI: 1.06, 2.48) than in participants without diabetes (n = 695; HR = 1.09, 95% CI: 0.79, 1.51 (P for interaction < 0.001)). The association was also stronger in participants with albuminuria (n = 207; HR = 1.66, 95% CI: 1.07, 2.57) than in those without albuminuria (n = 731; HR = 1.07, 95% CI: 0.77, 1.47 (P for interaction < 0.001)). The association was modestly greater in participants with chronic kidney disease (n = 290; HR = 1.44, 95% CI: 0.99, 2.08) than in those without chronic kidney disease (n = 656; HR = 1.27, 95% CI: 0.88, 1.81 (P for interaction < 0.001)). The association did not differ by age, sex, race/ethnicity, hypertension, obesity, or hyperparathyroidism.
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