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.

Download full-text


Available from: Bruce W Hollis, Dec 14, 2014
23 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "According with this, NGT ≥155 subjects, both in basal condition and after 1-hour during OGTT, are more insulin-resistant and have higher levels of hs-CRP than NGT < 155. On the basis of these evidences, present data contribute to extend previous knowledge about the association between hypovitaminosis D and cardiovascular events [3-6]. Additional mechanism involved in this association is the regulatory effect of vitamin D on the renin-angiotensin system activity. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A plasma glucose value ≥155 mg/dl for 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes and with subclinical organ damage. We designed this study to address if 25-hydroxyvitamin D [25(OH)D] circulating levels are associated with glucose tolerance status, and in particular with 1-hour post-load plasma glucose levels. We enrolled 300 consecutive Caucasian hypertensive never-treated outpatients (160 men and 140 women, aged 52.9 ± 9.2 years). Subjects underwent OGTT and measurements of 25(OH)D and standard laboratory tests. Estimated glomerular filtration rate (e-GFR) was calculated by CKD-EPI formula and insulin sensitivity was assessed by Matsuda-index. Among participants, 230 were NGT, 44 had impaired glucose tolerance (IGT) and 26 had type-2 diabetes. According to 1-h post-load plasma glucose cut-off point of 155 mg/dL, we divided NGT subjects into: NGT < 155 (n = 156) and NGT > 155 mg/dL (n = 74).NGT ≥ 155 had higher significant fasting and post-load glucose and insulin, parathyroid hormone and hs-CRP levels than NGT < 155. On the contrary, Matsuda-index, e-GFR, and 25(OH)D were significantly lower in NGT ≥ 155 than NGT < 155 subjects. In the multiple regression analysis, 25(OH)D levels resulted the major determinant of 1-h post-load plasma glucose in all population and in the four groups of glucose tolerance status. In the whole population, Matsuda-index, hs-CRP and e-GFR explained another 12.2%, 6.7% and 1.7% of its variation. Our data demonstrate a significant and inverse relationship between 25(OH)D levels and glucose tolerance status, particularly with 1-h post-load glucose.
    Cardiovascular Diabetology 02/2014; 13(1):48. DOI:10.1186/1475-2840-13-48 · 4.02 Impact Factor
Show more