We aimed to examine associations between serum 25-hydroxyvitamin D (25[OH]D) concentration and mortality from heart failure (HF) and cardiovascular disease (CVD) and premature death from all causes using data from the Third National Health and Nutrition Examination Survey, which included 13,131 participants (6,130 men, 7,001 women) ≥35 years old at baseline (1988 to 1994) and followed through December 2000. Premature death was defined all-cause death at <75 years of age. Results indicated that during an average 8-year follow-up, there were 3,266 deaths (24.9%) including 101 deaths from HF, 1,451 from CVD, and 1,066 premature all-cause deaths. Among HF deaths, 37% of decedents had serum 25(OH)D levels <20 ng/ml, whereas only 26% of those with non-HF deaths had such levels (p <0.001). Multivariate-adjusted Cox model indicated that subjects with serum 25(OH)D levels <20 ng/ml had 2.06 times higher risk (95% confidence interval 1.01 to 4.25) of HF death than those with serum 25(OH)D levels ≥30 ng/ml (p <0.001). In addition, hazard ratios (95% confidence intervals) for premature death from all causes were 1.40 (1.17 to 1.68) in subjects with serum 25(OH)D levels <20 ng/ml and 1.11 (0.93 to 1.33) in those with serum 25(OH)D levels of 20 to 29 ng/ml compared to those with serum 25(OH)D levels ≥30 ng/ml (p <0.001, test for trend). In conclusion, adults with inadequate serum 25(OH)D levels have significantly higher risk of death from HF and all CVDs and all-cause premature death.
"Initial clinical trials to test whether supplementation with vitamin D is beneficial in patients with CVD have shown benefit . Both low circulating 25(OH)D levels and high plasma renin activity are associated independently with poor prognosis in patients with chronic heart failure [75, 76]. A recent open-label, blinded, endpoint, phase II trial in cardiac heart failure patients showed that vitamin D3 supplementation lowers plasma renin activity using 2,000 IU daily . "
[Show abstract][Hide abstract] ABSTRACT: There is substantial genetic and epidemiological evidence implicating vitamin D in the pathogenesis of many common diseases. A number of studies have sought to define an association for disease with sequence variation in the VDR gene, encoding the ligand-activated nuclear hormone receptor for vitamin D. The results of such studies have been difficult to replicate and are likely to need to account for specific environmental exposures. Here, we review recent work that has begun to study the interactions between VDR gene polymorphisms, vitamin D blood levels, and complex disease susceptibility, notably in the context of major clinical outcomes. We highlight the challenges moving forward in this area and its importance for effective clinical translation of current research.
[Show abstract][Hide abstract] ABSTRACT: Context:Low serum calcidiol has been associated with multiple co-morbidities and mortality but no "safe" range has been found for the upper concentration.Objective:To establish the upper threshold of serum calcidiol, beyond which there is an increased risk for acute coronary syndrome and/or mortality.Design, Setting, and Participants:We extracted data for 1,282,822 Clalit Health Services members aged > 45 between July 2007 and December 2011. Records of mortality or acute coronary syndrome were extracted during the follow-up period. Kaplan Meier analysis calculated time to episode and Cox regression models generated adjusted hazard ratios for episode by calcidiol group (< 10, 10.1-20, 20.1-36 and > 36.1 ng/mL).Outcome Measures:Acute coronary syndrome subsuming all-cause mortality.Results:During the 54-month study period, 422,822 Clalit Health Services members were tested for calcidiol of which 12,280 died of any cause (905 with acute coronary syndrome) and 3,933 were diagnosed with acute coronary syndrome. Compared to those with 20-36 ng/ml, the adjusted hazard ratios among those with levels of < 10, 10-20 and > 36 ng/ml were 1.88 [CI: 1.80-1.96], 1.25 [CI:1.21-1.30] and 1.13 [CI:1.04-1.22], (P < 0.05) respectively.Limitations:The study cohort comprised only 30% of the population, those tested for vitamin D. The small sample size of those with calcidiol > 36 ng/mL prevented further analysis of this group.Conclusions:Vitamin D in the 20-36 ng/ml range was associated with the lowest risk for mortality and morbidity. The hazard ratio below and above this range increases significantly.
The Journal of Clinical Endocrinology and Metabolism 03/2013; 98(5). DOI:10.1210/jc.2013-1185 · 6.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE Low circulating concentrations of 25-hydroxyvitamin D (25[OH]D) have been consistently associated with an increased risk of coronary heart disease (CHD) in white populations. This association has not been rigorously evaluated in other races or ethnicities, in which the distributions of 25(OH)D concentration and possibly other aspects of 25(OH)D metabolism differ. OBJECTIVE To examine the association of serum 25(OH)D concentration with risk of CHD in a multiethnic population. DESIGN, SETTING, AND PARTICIPANTS We studied 6436 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), recruited from July 2000 through September 2002, who were free of known cardiovascular disease at baseline. We measured baseline serum 25(OH)D concentrations using a mass spectrometry assay calibrated to established standards. We tested associations of 25(OH)D with adjudicated CHD events assessed through May 2012. MAIN OUTCOME AND MEASURES Primary outcome measure was time to first adjudicated CHD event, defined as myocardial infarction, angina, cardiac arrest, or CHD death. RESULTS During a median follow-up of 8.5 years, 361 participants had an incident CHD event (7.38 events per 1000 person-years). Associations of 25(OH)D with CHD differed by race/ethnicity (P for interaction < .05). After adjustment, lower 25(OH)D concentration was associated with a greater risk of incident CHD among participants who were white (n = 167 events; hazard ratio [HR], 1.26 [95% CI, 1.06-1.49] for each 10-ng/mL decrement in 25(OH)D) or Chinese (HR, 1.67 [95% CI, 1.07-2.61]; n = 27). In contrast, 25(OH)D was not associated with risk of CHD in participants who were black (HR, 0.93 [95% CI, 0.73-1.20]; n = 94) or Hispanic (HR, 1.01 [95% CI, 0.77-1.33]; n = 73). CONCLUSIONS AND RELEVANCE Lower serum 25(OH)D concentration was associated with an increased risk of incident CHD events among participants who were white or Chinese but not black or Hispanic. Results evaluating 25(OH)D in ethnically homogeneous populations may not be broadly generalizable to other racial or ethnic groups.
JAMA The Journal of the American Medical Association 07/2013; 310(2):179-88. DOI:10.1001/jama.2013.7228 · 35.29 Impact Factor
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