***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Circulating 25-hydroxyvitamin D ( 25(OH)D ) has been associated with cardiovascular disease ( CVD ) risk in observational studies . Also , SNPs to explain variation in 25(OH)D have been identified by genome-wide association studies . Detection of direct associations between SNPs that significantly affect 25(OH)D and CVD risk would indicate a causal role of vitamin D , as reverse causation could be excluded and confounding could be better controlled . Thus , a combined analysis of c and i date SNPs in relation to circulating 25(OH)D and CVD risk was carried out . A case-cohort study within the EPIC-Germany study was conducted comprising a r and omly drawn subcohort of 2,132 subjects ( 57.9 % women , mean age : 50.6 years ) and incident cases of myocardial infa rct ion ( n=559 ) and stroke ( n=471 ) that occurred during a mean follow-up duration of 7.6 years .  25(OH)D concentrations were measured by LC-MS/MS in baseline plasma sample s. Additionally , eight c and i date SNPs were assayed . Associations between 25(OH)D , SNPs and the risks of myocardial infa rct ion and stroke were assessed by multivariable regression analyses . Mean 25(OH)D level was 47.2 nmol/L in the subcohort . Four SNPs were associated with 25(OH)D ( p<0.05 ) . In subjects with 25(OH)D levels < 25 nmol/L , the risks of CVD as composite endpoint ( Hazard Ratio : 1.53 , 95 % confidence interval : 1.12–2.09 ) , myocardial infa rct ion , and stroke were significantly increased compared to subjects with levels ≥50 nmol/L , while no significant linear associations were observed . A SNP score was not related to the risks of total CVD ( Hazard Ratio : 1.0 , 95 % confidence interval : 0.71–1.42 ) , myocardial infa rct ion , or stroke . The same was true concerning single SNPs . Given the lack of association between SNPs and the risks of stroke and myocardial infa rct ion , the present findings do not point to a major causal role of vitamin D in the development of these diseases . However , a detection of modest associations between genetic markers and CVD risk in larger consortia can not be ruled out Background and Purpose — Vitamin D deficiency has been reported to contribute to the risk of cardiovascular disease , especially stroke . We examined the relationship between dietary vitamin D intake and 34-year incident stroke . Methods — The Honolulu Heart Program is a prospect i ve population -based cohort study of 8006 Japanese-American men in Hawaii who were 45 to 68 years old at the baseline examination in 1965 to 1968 .  Dietary vitamin D intake was calculated using the Nutritionist IV Version 3 software from a 24-hour dietary recall .  Subjects with prevalent stroke were excluded , leaving 7385 men followed through 1999 for incident stroke . Subjects were divided into quartiles of dietary vitamin D for analyses . Results — During 34 years of follow-up , 960 subjects developed stroke . Age-adjusted rates of incident stroke were significantly higher in the lowest dietary vitamin D quartile compared with the highest ( all stroke : 6.38 versus 5.14 per 1000 person-years follow-up , P=0.030 ; thromboembolic stroke : 4.36 versus 3.30 , P=0.033 ) . Using Cox regression , adjusting for age , total kilocalories , body mass index , hypertension , diabetes mellitus , pack-years smoking , physical activity index , serum cholesterol , and alcohol intake , those in the lowest quartile had a significantly increased risk of incident stroke ( all stroke hazard ratio , 1.22 ; 95 % CI , 1.01–1.47 ; P=0.038 ; thromboembolic stroke hazard ratio , 1.27 ; 95 % CI , 1.01–1.59 ; P=0.044 ) with the highest as the reference . We found no significant associations between dietary vitamin D and hemorrhagic stroke . Conclusions — Low dietary vitamin D intake was an independent risk factor for 34-year incidence of all stroke and thromboembolic stroke in Japanese-American men . Additional research is needed on vitamin D supplementation to prevent stroke Background Black individuals are at greater risk of stroke and vitamin D deficiency than white individuals . Epidemiologic studies have shown that low 25-hydroxyvitamin D concentrations are associated with increased risk of stroke , but these studies had limited representation of black individuals . Methods We examined the association of 25-hydroxyvitamin D with incident stroke in the Reasons for Geographic and Racial Differences in Stroke ( REGARDS ) study , a cohort of black and white adults ≥45 years of age . Using a case – cohort study design ,  plasma 25-hydroxyvitamin D  was measured in 610 participants who developed incident stroke ( cases ) and in 937 stroke-free individuals from a stratified cohort r and om sample of REGARDS participants ( comparison cohort ) . Results In multivariable models adjusted for socio-demographic factors , co-morbidities and laboratory values including parathyroid hormone , lower 25-hydroxyvitamin D concentrations were associated with higher risk of stroke ( 25-hydroxyvitamin D > 30 ng/mL reference ; 25-hydroxyvitamin D concentrations 20–30 ng/mL , hazard ratio 1.33 , 95 % confidence interval ( 95 % CI ) 0.89,1.96 ; 25-hydroxyvitamin D < 20 ng/mL , hazard ratio 1.85 , 95 % CI 1.17 , 2.93 ) . There were no statistically significant differences in the association of lower 25-hydroxyvitamin D with higher risk of stroke in black vs. white participants in fully adjusted models ( hazard ratio comparing lowest vs. highest 25-hydroxyvitamin D category 2.62 , 95 % CI 1.18 , 5.83 in blacks vs. 1.64 , 95 % CI 0.83 , 3.24 in whites , Pinteraction = 0.82 ) . The associations were qualitatively unchanged when restricted to ischemic or hemorrhagic stroke subtypes or when using race-specific cut-offs for 25-hydroxyvitamin D categories . Conclusions Vitamin D deficiency is a risk factor for incident stroke and the strength of this association does not appear to differ by race Vitamin D recently has been proposed to play an important role in a broad range of organ functions , including cardiovascular ( CV ) health ; however , the CV evidence -base is limited . We prospect ively analyzed a large electronic medical records data base to determine the prevalence of vitamin D deficiency and the relation of vitamin D levels to prevalent and incident CV risk factors and diseases , including mortality . The data base contained 41,504 patient records with at least one measured vitamin D level . The prevalence of vitamin D deficiency ( ≤30 ng/ml ) was 63.6 % , with only minor differences by gender or age . Vitamin D deficiency was associated with highly significant ( p < 0.0001 ) increases in the prevalence of diabetes , hypertension , hyperlipidemia , and peripheral vascular disease . Also , those without risk factors but with severe deficiency had an increased likelihood of developing diabetes , hypertension , and hyperlipidemia . The vitamin D levels were also highly associated with coronary artery disease , myocardial infa rct ion , heart failure , and stroke ( all p < 0.0001 ) , as well as with incident death , heart failure , coronary artery disease/myocardial infa rct ion ( all p < 0.0001 ) , stroke ( p = 0.003 ) , and their composite ( p < 0.0001 ) . In conclusion , we have confirmed a high prevalence of  vitamin D deficiency in the general healthcare population and an association between vitamin D levels and prevalent and incident CV risk factors and outcomes . These observations lend strong support to the hypothesis that vitamin D might play a primary role in CV risk factors and disease . Given the ease of vitamin D measurement and replacement , prospect i ve studies of vitamin D supplementation to prevent and treat CV disease are urgently needed BACKGROUND Vitamin D insufficiency was shown to be associated with adverse musculoskeletal and nonskeletal outcomes in numerous observational studies . However , some studies did not control for confounding factors such as age or seasonal variation of 25-hydroxyvitamin D [ 25(OH)D ] . OBJECTIVE We sought to determine the effect of vitamin D status on health outcomes . DESIGN Healthy community-dwelling women ( n = 1471 ) with a mean age of 74 y were followed in a 5-y trial of calcium supplementation .  25(OH)D was measured at baseline in all women .  Skeletal and nonskeletal outcomes were evaluated according to seasonally adjusted vitamin D status at baseline . RESULTS Fifty percent of women had a seasonally adjusted 25(OH)D concentration < 50 nmol/L. These women were significantly older , heavier , and less physically active and had more comorbidities than women with a seasonally adjusted 25(OH)D concentration > or = 50 nmol/L. Women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L had an increased incidence of stroke and cardiovascular events that did not persist after adjustment for between-group differences in age or comorbidities . Women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L were not at increased risk of adverse consequences for any musculoskeletal outcome , including fracture , falls , bone density , or grip strength or any nonskeletal outcomes , including death , myocardial infa rct ion , cancer , heart failure , diabetes , or adverse changes in blood pressure , weight , body composition , cholesterol , or glucose . CONCLUSIONS Vitamin D insufficiency is more common in older , frailer women . Community-dwelling older women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L were not at risk of adverse outcomes over 5 y after control for comorbidities . R and omized placebo-controlled trials are needed to determine whether vitamin D supplementation in individuals with vitamin D insufficiency influences health outcomes . This trial was registered at www.anzctr.org.au as ACTRN 012605000242628 
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In conclusion , our meta- analysis supported the hypothesis that lower vitamin D status was associated with an increased risk of ischemic stroke .