25-Hydroxyvitamin D and Risk of Myocardial Infarction in Men: A Prospective Study

Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA.
Archives of internal medicine (Impact Factor: 17.33). 06/2008; 168(11):1174-80. DOI: 10.1001/archinte.168.11.1174
Source: PubMed


Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans.
We assessed prospectively whether plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with risk of coronary heart disease. A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection. The blood samples were returned between April 1, 1993, and November 30, 1999; 99% were received between April 1, 1993, and November 30, 1995. During 10 years of follow-up, 454 men developed nonfatal myocardial infarction or fatal coronary heart disease. Using risk set sampling, controls (n = 900) were selected in a 2:1 ratio and matched for age, date of blood collection, and smoking status.
After adjustment for matched variables, men deficient in 25(OH)D (<or=15 ng/mL [to convert to nanomoles per liter, multiply by 2.496]) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D (>or=30 ng/mL) (relative risk [RR], 2.42; 95% confidence interval [CI], 1.53-3.84; P < .001 for trend). After additional adjustment for family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, marine omega-3 intake, low- and high-density lipoprotein cholesterol levels, and triglyceride levels, this relationship remained significant (RR, 2.09; 95% CI, 1.24-3.54; P = .02 for trend). Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels (22.6-29.9 ng/mL: RR, 1.60 [95% CI, 1.10-2.32]; and 15.0-22.5 ng/mL: RR, 1.43 [95% CI, 0.96-2.13], respectively).
Low levels of 25(OH)D are associated with higher risk of myocardial infarction in a graded manner, even after controlling for factors known to be associated with coronary artery disease.

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Available from: Bruce W Hollis, Dec 14, 2014
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    • "Over the last 20 years, scientific attention has focused on the associations of vitamin D (VitD) with multiple chronic and degenerative diseases, such as metabolic disorders (Yin et al., 2012; Al-Daghri et al., 2014a; Zhao et al., 2014), cancer (Lappe et al., 2007; Keum and Giovannucci, 2014), cardiovascular (Giovannucci et al. 2008; Wang et al. 2008), infectious (Yamshchikov et al.) and autoimmune diseases (Al-Daghri et al. 2014a; Roep 2013). These effects have been attributed primarily to the immune-modulatory and anti-inflammatory actions of VitD. "
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    ABSTRACT: Introduction: FokI polymorphism has been associated with obesity and type 2 diabetes (T2D) in some populations. Objective: To investigate the frequencies of a genetic polymorphism of Vitamin D receptor (FokI) in patients with T2D and control subjects and investigate the role of 1,25(OH)2D3 in the expression of pro-inflammatory markers in peripheral blood mononuclear cells (PBMCs). Methods: The case-control study was conducted in 160 patients with T2D and 160 control subjects, men and women (30-74years old). The genotype and allele frequency of FokI polymorphisms were determined in these subjects. Subsequently a subgroup of 40 subjects was included from which PBMCs were removed. In vitro, the culture medium was supplemented with two different concentrations of 1,25(OH)2D3(10-8M and 10-10M). The expression profiles of TNFα and mRNA were analysed by qPCR, and GAPDH and β-actin were used as housekeeping genes. Results: The control subjects have an increased frequency of the FF genotype. In subjects with T2D, the ff genotype was associated with higher HOMA-IR values than individuals with genotype Ff (p=0.021). In vitro study in PBMCs showed differential expression of TNFα mRNA by FokI genotype, with a lower expression of this marker of inflammation in FF genotype subjects at a concentration of 10-8M of 1,25(OH)2D3. Conclusion: Our data suggest that VDR FokI polymorphism is associated with T2D, and the genotypes Ff and ff of this variant show a reduced response or resistance to the anti-inflammatory action of VitD, which could indicate a functional role of FokI polymorphism of VDR.
    Meta Gene 10/2015; 7. DOI:10.1016/j.mgene.2015.10.003
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    • "Further emerging vitamin D health relationships include physiological parameters like improved immune response (Baeke et al., 2010; Schwalfenberg, 2011; Hewison, 2012; White, 2012), improved respiratory health(Berry et al., 2011; Charan et al., 2012; Choi et al., 2013; Hirani, 2013) possibly also relate to reduced tuberculosis incidence (Nnoaham and Clarke, 2008; Martineau et al., 2011; Mitchell et al., 2011; Coussens et al., 2012; Salahuddin et al., 2013; Huaman et al., 2014); and reduced risk to develop autoimmune diseases like multiple sclerosis (Solomon and Whitham, 2010; Cantorna, 2012; Dobson et al., 2013) or type 1 diabetes (Hypponen et al., 2001; Holick, 2003; Ramos-Lopez et al., 2006; Baeke et al., 2010; De Boer et al., 2012; Dong et al., 2013; Van Belle et al., 2013). In chronic, non-communicable diseases, vitamin D deficiency is being discussed to possibly ameliorate the incidence of some neoplastic diseases like colorectal, lung, prostate, and breast cancers (Ng et al., 2008; Rosen et al., 2012; Welsh, 2012; Cheng et al., 2013); cardiovascular diseases (CVDs) including hypertension, myocardial infarction, stroke (Forman et al., 2007; Giovannucci et al., 2008; Gardner et al., 2011; Bischoff-Ferrari et al., 2012; Tamez and Thadhani, 2012; Karakas et al., 2013; Pilz et al., 2013a; Schroten et al., 2013); life-style diseases like obesity and type 2 diabetes (Pittas et al., 2007; González-Molero et al., 2012; Khan et al., 2013; Pilz et al., 2013b; Schottker et al., 2013; Tsur et al., 2013; Van Belle et al., 2013; Bouillon et al., 2014); diseases related to the decline in sight function including age-related macular degeneration (Parekh et al., 2007; Millen et al., 2011; Lee et al., 2012); and neurological disorders including Alzheimer and Parkinson disease (Buell and Dawson-Hughes, 2008; Annweiler et al., 2012; Eyles et al., 2013; Zhao et al., 2013). One may wonder about the width of possible implications being looked at, but considering the more than 1000 genes which vitamin D is regulating through the VDR (Carlberg and Campbell, 2013), this may actually not be a surprise. "
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    ABSTRACT: Vitamin D is a micronutrient that is needed for optimal health throughout the whole life. Vitamin D3 (cholecalciferol) can be either synthesized in the human skin upon exposure to the UV light of the sun, or it is obtained from the diet. If the photoconversion in the skin due to reduced sun exposure (e.g. in wintertime) is insufficient, intake of adequate vitamin D from the diet is essential to health. Severe vitamin D deficiency can lead to multitude of avoidable illnesses; among them are well known bone diseases like osteoporosis, a number of autoimmune diseases, many different cancers and some cardiovascular diseases like hypertension are being discussed. Vitamin D is found naturally in only very few foods. Foods containing vitamin D include some fatty fish, fish liver oils, and eggs from hens that have been fed vitamin D and some fortified foods in countries with respective regulations. Base on geographic location or food availability adequate vitamin D intake might not be sufficient on a global scale. The International Osteoporosis Foundation (IOF) has collected the 25-hydroxy-vitamin D plasma levels in populations of different countries using published data and developed a global vitamin D map. This map illustrates the parts of the world, where vitamin D did not reach adequate 25-hydroxyvitamin D plasma levels: 6.7 % of the papers report 25-hydroxyvitamin D plasma levels below 25 nmol/L, which indicates vitamin D deficiency, 37.3 % are below 50 nmol/Land only 11.9% found 25-hydroxy-vitamin D plasma levels above 75 nmol/L target as suggested by vitamin D experts. The vitamin D map is adding further evidence to the vitamin D insufficiency pandemic debate, which is also an issue in the developed world. Besides malnutrition, a condition where the diet does not match to provide the adequate levels of nutrients including micronutrients for growth and maintenance, we obviously have a situation where enough nutrients were consumed, but lacked to reach sufficient vitam
    Frontiers in Physiology 07/2014; 5:248. DOI:10.3389/fphys.2014.00248 · 3.53 Impact Factor
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    • "Furthermore, we did not have information on non-fatal vascular events. Second, we have also no data available on vitamin D status, which is an important factor of calcium homeostasis and recognized cardiovascular risk factor [25]. It is generally assumed, that pathophysiological consequences of low D vitamin status also involves vascular calcification [26]. "
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    ABSTRACT: Background Vitamin K is the essential cofactor for activation of matrix Gla-protein (MGP), the natural inhibitor of tissue calcification. Biologically inactive, desphospho–uncarboxylated MGP (dp-ucMGP) is a marker of vascular vitamin K status and is described to predict mortality in patients with heart failure and aortic stenosis. We hypothesized that increased dp-ucMGP might be associated with mortality risk in clinically stable patients with chronic vascular disease. Materials and Methods We examined 799 patients (mean age 65.1±9.3 years) who suffered from myocardial infarction, coronary revascularization or first ischemic stroke (pooled Czech samples of EUROASPIRE III and EUROASPIRE-stroke surveys), and followed them in a prospective cohort study. To estimate the 5-year all-cause and cardiovascular mortality we ascertained vital status and declared cause of death. Circulating dp-ucMGP and desphospho-carboxylated MGP (dp-cMGP) were measured by ELISA methods (IDS and VitaK). Results During a median follow-up of 2050 days (5.6 years) 159 patients died. In the fully adjusted multivariate Cox proportional hazard model, the patients in the highest quartile of dp-ucMGP (≥ 977 pmol/L) had higher risk of all-cause and cardiovascular 5-year mortality [HRR 1.89 (95% CI,1.32–2.72) and 1.88 (95% CI,1.22–2.90)], respectively. Corresponding HRR for dp-cMGP were 1.76 (95% CI, 1.18–2.61) and 1.79 (95% CI, 1.12 –2.57). Conclusions In patients with overt vascular disease, circulating dp-ucMGP and dp-cMGP were independently associated with the risk of all-cause and cardiovascular mortality. Since published results are conflicting regarding the dp-cMGP, we propose only circulating dp-ucMGP as a potential biomarker for assessment of additive cardiovascular risk.
    Atherosclerosis 07/2014; 235(1). DOI:10.1016/j.atherosclerosis.2014.04.027 · 3.99 Impact Factor
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