IJCS | Volume 31, Nº4, July / August 2018

426 Jorge et al. Vitamin D and cardiovascular disease Int J Cardiovasc Sci. 2018;31(4)422-432 Review Article beta cells in western populations. 31 While studying 1,807 healthy Korean individuals, Ock et al. 32 have recently reported that vitamin D has an inverse association with insulin resistance. 32 While analyzing the relationship between vitaminDdeficiency, diabetes, andCAD, Nardin et al. 33 evaluated 1,859 patients undergoing elective angiography for evaluation of CAD and concluded that diabetes is not an independent predictor of vitamin D deficiency, but diabetic patients with vitaminDdeficiency presented increase CAD prevalence and severity. 33 In a recent study, Schafer et al. 34 followed up more than 5,000 elderly women for 8.6 ± 4.4 years to investigate a possible relationship between vitamin D levels and the emergence of type 2 diabetes; the authors concluded that the serum levels of vitaminDwere not independent predictors of the incidence of type 2 diabetes in this population. 34 Obesity Recent evidence suggests that vitamin D deficiency is associated with obesity and other components of the metabolic syndrome. 35 Low levels of 25-hydroxyvitamin D are common in obese individuals, andmany studies have demonstrated an inverse relationship between serum vitamin D levels and body mass index (BMI). 36 Vitamin D has also been associated with regional fat distribution, and high levels of the vitamin have been associated with a lower amount of visceral and subcutaneous fat. 37 Some of the explanations proposed for this association are: differences in dietary intake between obese and nonobese individuals, decreased sun exposure among obese individuals, lower vitamin D bioavailability in obesity, and altered vitamin Dmetabolism in obese individuals. 38 Wortsman et al. 39 proposed the hypothesis of sequestration of vitamin D by fat tissue to explain the prevalence of low levels of this vitamin in obese individuals. 39 They demonstrated that obese individuals presented a lower increase in serum 25-hydroxyvitamin D when compared with nonobese individuals under the same conditions of exposure to sunlight and vitamin intake. Since vitamin D is liposoluble, they proposed that the vitamin must accumulate in fatty tissue and not be readily available in the circulation, which would lead to low serum levels of this vitamin. On the other hand, Drincic et al. 40 suggested that the difference in serum levels of vitamin D between obese and nonobese individuals is related to the distribution volume of this vitamin, which is greater in obese individuals and would justify its lower serum levels in these individuals. 40 Smoking and lifestyle habits Smoking is a risk factor for CVD and systemic inflammation, and vitamin D has been associated with both these conditions. Lee et al. 41 studied 560 Korean individuals aged 60 years or older to investigate the association between vitaminDand inflammatorymarkers and evaluate whether this associationwould change with the smoking profile of the patients. 41 The authors observed a significant association between vitamin D deficiency and high-sensitivity C-reactive protein (hsCRP) and a modifying effect of smoking on this association, in which smokers show a stronger association between vitamin D deficiency and hsCRP than nonsmokers. 41 With the aim of relating lifestyle characteristics with vitamin D deficiency, Skaaby et al. 42 conducted a longitudinal study with 4,185 individuals with a follow- up time of 5 years. In this study, multivariate analyses of repeated serummeasurements 25-hydroxyvitaminDwere used to evaluate the association of this vitamin deficiency with BMI, practice of physical activity, type of diet (more healthy versus less healthy), alcohol consumption, and smoking. As a result, lower serum levels of vitamin D were associatedwith higher BMI, lower levels of physical activity, consumption of a less healthy diet, increased alcohol consumption, and smoking. 42 Coronary artery disease The occurrence of CAD has been associated with vitamin D deficiency, but the pathophysiological mechanisms of this association have not been well understood yet. The main evidence to suggest such an association is the VDR presence in both the myocardium and vascular cells, and the demonstration by epidemiological studies that the incidence of both CAD and vitamin Ddeficiency increase inwinter months and in countries furthest from the Equator. 43 Vitamin D deficiency appears to be common in acute myocardial infarction (AMI), and preliminary studies indicate a possible association of vitamin deficiency with AMI prognosis in the short and long term. 43 Moreover, vitamin D deficiency seems to predispose to recurrent adverse cardiac events, due to its association with the number of affected coronary arteries, AMI complications, and cardiac remodeling. 44