Calcium, phosphate and the risk of cardiovascular events and all-cause mortality in a population with stable coronary heart disease.

OBJECTIVE: High serum calcium and phosphate levels have been linked to cardiovascular diseases and all-cause mortality but evidence from longitudinal studies is scarce, especially among patients with pre-existing coronary heart disease. The association between baseline calcium and phosphate and prognosis was examined in a cohort study of patients with stable coronary heart disease. METHODS: Serum calcium and phosphate were measured in a cohort of initially 1206 patients undergoing a 3 week rehabilitation programme after an acute cardiovascular event and subsequently being followed-up for 8 years. Multivariate Cox regression was employed to assess the association of quartiles and continuous levels of calcium and phosphate with secondary cardiovascular events and all-cause mortality. RESULTS: No significant risk elevations were observed for secondary cardiovascular event incidence in models adjusted for a variety of potential confounders. High calcium levels, however, were strongly associated with mortality risk in adjusted models (HR(Q4vsQ1)=2.39 (1.22 to 4.66)). In additional multivariable analyses, the calcium/albumin ratio was predictive for all-cause mortality (HR(Q4vsQ1)=2.66 (1.35 to 5.22)) and marginally predictive for cardiovascular event incidence (HR(Q4vsQ1)=1.74 (1.00 to 3.05)). CONCLUSIONS: Calcium and the ratio of calcium with albumin, its major binding protein, were strongly associated with all-cause mortality among patients with coronary heart disease. The underlying mechanisms and the clinical implications of these findings deserve further study.

Serum parathyroid hormone and risk of adverse outcomes in patients with stable coronary heart disease.

BACKGROUND AND OBJECTIVE: Recent longitudinal studies have suggested an association of high serum parathyroid hormone levels (PTH) with elevated cardiovascular risk in the general population. This study presents analyses of the prognostic value of baseline PTH for subsequent cardiovascular events and all-cause mortality in a high-risk population with stable coronary heart disease. METHODS: Based on measurements of PTH levels in 1133 patients recruited at two German rehabilitation clinics and followed over 8 years, multivariate Cox regression analysis was performed to estimate the risk of secondary cardiovascular events (including myocardial infarction, stroke and death due to cardiovascular diseases) and all-cause-mortality according to PTH quartiles (Q1-Q4) and continuous PTH concentrations. RESULTS: During follow-up, 153 cardiovascular events and 124 deaths occurred. Age and sex-adjusted Cox regression analysis yielded statistically significant positive associations of PTH with both cardiovascular event incidence and all-cause mortality (HR (95% CI) per SD increase of PTH: 1.35 (1.21-1.51) and 1.25 (1.11-1.42), respectively). Associations remained essentially unchanged after additional adjustment for multiple cardiovascular risk factors. More detailed dose-response analyses showed strong risk elevation for above-normal levels of PTH (> 95th percentile), with essentially no association at lower levels. CONCLUSION: The results of this first detailed study in a cohort of patients with stable coronary heart disease suggest an independent predictive value of above-normal PTH for the prognosis in patients with stable coronary heart disease.

Serum vitamin D and risk of secondary cardiovascular disease events in patients with stable coronary heart disease.

BACKGROUND: Recent longitudinal analyses suggested that low levels of serum 25-hydroxyvitamin D (25-OH-D) predict incident cardiovascular disease in initially healthy populations. Because the prognostic value of vitamin D for the occurrence of secondary cardiovascular events remains unclear, we examined the association of baseline 25-OH-D levels with prognosis in patients with stable coronary heart disease (CHD). METHODS: Serum 25-OH-D levels from 1,125 CHD patients of 2 German clinics undergoing a 3-week rehabilitation program after an acute cardiovascular event were measured, and participants were followed for up to 8 years. We used multivariate Cox regression analysis to model cardiovascular event incidence (fatal and nonfatal, including myocardial infarction, stroke, and death due to cardiovascular diseases) and all-cause mortality according to 25-OH-D quartiles, categories based on cut points of 15 and 30 ng/mL, or continuous vitamin D concentrations. RESULTS: During follow-up, 148 cardiovascular events and 121 deaths were recorded. Elevation of risk for the lowest quartile or category in comparison to the highest category was weak and nonsignificant for both incidence (hazard ratio [HR](quartile1) = 1.15 [0.72-1.84], HR(<15 ng/mL) = 1.17 [0.61-2.23]) and mortality (HR(quartile1) = 1.29 [0.77-2.14], HR(<15 ng/mL) = 1.87 [0.91-3.82]) in unadjusted Cox regression analysis and disappeared entirely after adjustment for potential confounders (cardiovascular events: HR(quartile1) = 0.84 [0.47-1.50], HR(<15 ng/mL) = 0.90 [0.41-1.96]; mortality: HR(quartile1) = 0.63 [0.33-1.21], HR(<15 ng/mL) = 0.93 [0.39-2.21]). Models treating vitamin D as a continuous variable likewise suggested no significant associations. CONCLUSIONS: Unlike previous population-based studies, our analysis in high-risk patients with stable CHD does not support a prognostic value of baseline-25-OH-D levels for secondary cardiovascular event incidence or all-cause mortality.