Circulating 25-Hydroxy-Vitamin D and Risk of Cardiovascular Disease A Meta-Analysis of Prospective Studies

Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Circulation Cardiovascular Quality and Outcomes (Impact Factor: 5.66). 11/2012; 5(6). DOI: 10.1161/CIRCOUTCOMES.112.967604
Source: PubMed


Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear.

Methods and results:
We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent studies with 6123 CVD cases in 65 994 participants were included for a meta-analysis. In a comparison of the lowest with the highest 25(OH)-vitamin D categories, the pooled relative risk was 1.52 (95% confidence interval, 1.30-1.77) for total CVD, 1.42 (95% confidence interval, 1.19-1.71) for CVD mortality, 1.38 (95% confidence interval, 1.21-1.57) for coronary heart disease, and 1.64 (95% confidence interval, 1.27-2.10) for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and were better controlled for season and confounding. We used a fractional polynomial spline regression analysis to assess the linearity of dose-response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below ≈60 nmol/L, with a relative risk of 1.03 (95% confidence interval, 1.00-1.06) per 25-nmol/L decrement in 25(OH)-vitamin D.

This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D ranging from 20 to 60 nmol/L and risk of CVD. Further research is needed to clarify the association of 25(OH)-vitamin D higher than 60 nmol/L with CVD risk and assess causality of the observed associations.

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Available from: Charles Eaton, Nov 22, 2015
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    • "Europeans are therefore much more likely to die now from cancer or cardiovascular disease. Ecological and observational studies offer moderate evidence that vitamin D reduces the risk of cancer [67–69] and cardiovascular disease [70]. Thus, raising serum 25(OH)D concentrations above 30–40 ng/mL should reduce mortality rates by about 15% and increase life expectancy by 2 years in Europe [71]. "
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    ABSTRACT: Little published information is available regarding epidemiological data on vitamin D status in the large geographical region of Central Europe (CE). We searched the journal literature with regard to 25(OH)D concentrations among community-dwelling or healthy people living in CE. 25(OH)D concentrations varied by age, season, study sample size, and methodological approach [i.e., 25(OH)D assay used]. Concentrations of 25(OH)D in CE appeared lower than 30 ng/mL, and the magnitude of hypovitaminosis D was similar to that reported in Western Europe. While most of the studies reviewed were cross-sectional studies, a longitudinal study was also included to obtain information on seasonal variability. The longitudinal study reported wintertime 25(OH)D values close to 21-23 ng/mL for all studied age groups, with a significant increase of 25(OH)D in August reaching 42 ng/mL for those aged 0-9 years, but only 21 ng/mL for the elderly aged 80-89 years. The decrease in 25(OH)D with respect to age was attributed to decreased time spent in the sun and decreased vitamin D production efficiency. Based on the literature review on vitamin D status in the CE populations, it can be concluded that 25(OH)vitamin D levels are on average below the 30 ng/mL level.
    International Journal of Endocrinology 03/2014; 2014(1):589587. DOI:10.1155/2014/589587 · 1.95 Impact Factor
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    • "This chronic inflammatory process is responsible for the atherosclerotic plaque structure (including the necrotic lipid core and the fibrous cap) and promotes plaque instability [32]. Several observational studies and recent meta-analyses in humans showed that circulating 25(OH) vitamin D was inversely correlated with poor CV outcomes [8] [33] [34]. However, the first randomized clinical trials have provided even more discouraging results [34] [35]. "
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    ABSTRACT: Vitamin D has been shown to play critical activities in several physiological pathways not involving the calcium/phosphorus homeostasis. The ubiquitous distribution of the vitamin D receptor that is expressed in a variety of human and mouse tissues has strongly supported research on these "nonclassical" activities of vitamin D. On the other hand, the recent discovery of the expression also for vitamin D-related enzymes (such as 25-hydroxyvitamin D-1 α -hydroxylase and the catabolic enzyme 1,25-dihydroxyvitamin D-24-hydroxylase) in several tissues suggested that the vitamin D system is more complex than previously shown and it may act within tissues through autocrine and paracrine pathways. This updated model of vitamin D axis within peripheral tissues has been particularly investigated in atherosclerotic pathophysiology. This review aims at updating the role of the local vitamin D within atherosclerotic plaques, providing an overview of both intracellular mechanisms and cell-to-cell interactions. In addition, clinical findings about the potential causal relationship between vitamin D deficiency and atherogenesis will be analysed and discussed.
    12/2013; 2013:620504. DOI:10.1155/2013/620504
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    • "These results are in line with reports showing (1) a high prevalence of hypovitaminosis D and SHPT in poststroke patients [15, 69, 93–97] and HF patients [98–100], (2) an association of vitamin D insufficiency and especially elevated serum PTH levels with cardiovascular disease [31, 101–111] including stroke [69, 93, 112], hypertension [94, 104, 113–124], CAD [125], and carotid artery intima-media thickness (IMT) [126, 127], and (3) a high prevalence of osteoporosis in stroke patients [128] and a negative balance between bone formation and resorption in poststroke HF subjects [15–17, 21, 46, 47, 93, 129, 130]. "
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    ABSTRACT: Objective. To assess the prevalence, clinical and laboratory characteristics, and short-term outcomes of poststroke hip fracture (HF). Methods. A cross-sectional study of 761 consecutive patients aged ≥60 years (82.3 ± 8.8 years; 75% females) with osteoporotic HF. Results. The prevalence of poststroke HF was 13.1% occurring on average 2.4 years after the stroke. The poststroke group compared to the rest of the cohort had a higher proportion of women, subjects with dementia, history of TIA, hypertension, coronary artery disease, secondary hyperparathyroidism, higher serum vitamin B12 levels (>350 pmol/L), walking aid users, and living in residential care facilities. The majority of poststroke HF patients had vitamin D insufficiency (68%) and excess bone resorption (90%). This group had a 3-fold higher incidence of postoperative myocardial injury and need for institutionalisation. In multivariate analysis, independent indicators of poststroke HF were female sex (OR 3.6), history of TIA (OR 5.2), dementia (OR 4.1), hypertension (OR 3.2), use of walking aid (OR 2.5), and higher vitamin B12 level (OR 2.3). Only 15% of poststroke patients received antiosteoporotic therapy prior to HF. Conclusions. Approximately one in seven HFs occurs in older stroke survivors and are associated with poorer outcomes. Early implementation of fracture prevention strategies is needed.
    Stroke Research and Treatment 09/2013; 2013:641943. DOI:10.1155/2013/641943
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