Elsevier

Atherosclerosis

Volume 205, Issue 1, July 2009, Pages 255-260
Atherosclerosis

25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Examination Survey

https://doi.org/10.1016/j.atherosclerosis.2008.10.033Get rights and content

Abstract

Objective

Serum 25-hydroxyvitamin D [25(OH)D] levels are inversely associated with important cardiovascular disease (CVD) risk factors. However, the association between 25(OH)D levels and prevalent CVD has not been extensively examined in the general population.

Methods

We performed a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey (1988–1994) and examined the association between serum 25(OH)D levels and prevalence of CVD in a representative population-based sample of 16,603 men and women aged 18 years or older. Prevalence of CVD was defined as a composite measure inclusive of self-reported angina, myocardial infarction or stroke.

Results

In the whole population, there were 1308 (8%) subjects with self-reported CVD. Participants with CVD had a greater frequency of 25(OH)D deficiency [defined as serum 25(OH)D levels <20 ng/mL] than those without (29.3% vs. 21.4%; p < 0.0001). After adjustment for age, gender, race/ethnicity, season of measurement, physical activity, body mass index, smoking status, hypertension, diabetes, elevated low-density lipoprotein cholesterol, hypertriglyceridemia, low high-density lipoprotein cholesterol, chronic kidney disease and vitamin D use, participants with 25(OH)D deficiency had an increased risk of prevalent CVD (odds ratio 1.20 [95% confidence interval (CI) 1.01–1.36; p = 0.03]).

Conclusions

These results indicate a strong and independent relationship of 25(OH)D deficiency with prevalent CVD in a large sample representative of the US adult population.

Introduction

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in the United States, accounting for greater than 900,000 deaths per year [1]. Death rates from CVD are partly due to the high prevalence of traditional CVD risk factors such as hypertension, type 2 diabetes and dyslipidemia [1]. Recent reports from the National Health and Nutrition Examination Survey [2], [3], [4], [5], [6] and several other cohort studies [7], [8], [9], [10], [11] have found that serum levels of 25-hydroxyvitamin D [25(OH)D] are inversely associated with hypertension, diabetes, carotid atherosclerosis, myocardial infarction, congestive heart failure, stroke, microalbuminuria and decreased kidney function.

Although, persons with lower serum 25(OH)D levels appear to be at increased risk for cardiovascular risk factors [12], [13], it is unclear if 25(OH)D deficiency is related with prevalent CVD in the US population.

Humans get vitamin D from exposure to sunlight, from diet, and from dietary supplements [13]. Only a few natural food sources (i.e., diets rich in oily fish) contain significant amounts of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3), but many foods are now fortified with vitamin D [13]. Nonetheless, vitamin D insufficiency or deficiency persists in most of the world including North America and Europe possibly due to nutritional deficits and perhaps to avoidance of sunlight and the use of sunscreens [13]. 25(OH)D is formed in the liver and it represents the principle storage form of vitamin D, which is used to clinically monitor overall vitamin D3 status [13]. The discovery that most tissues in the body possess vitamin D receptors (VDR) has provided new insights into the broad functions of vitamin D and the non-calcemic adverse effects of its deficiency [13], [14]. Although 25(OH)D has a relatively low affinity for the VDR [15], many cells including vascular smooth muscle and endothelial cells also express 1-α-hydroxylase that converts 25(OH)D to the active form 1,25(OH)2D locally [16]. Thus, extra-renally produced 1,25(OH)2D primarily serves autocrine or paracrine cell-specific functions, instead of endocrine functions.

Because the implications of vitamin D insufficiency or deficiency for overall health could be substantial, we examined the association between prevalent CVD and 25(OH)D levels among the US adult population. To examine the relation of serum 25(OH)D deficiency with clinical CVD defined as a composite measure inclusive of angina, myocardial infarction and stroke, we analyzed data collected from a large representative sample of the US adult population enrolled in the Third National Health and Nutrition Examination Survey (NHANES III).

Section snippets

Study population and sample

Data for this analysis were obtained from the NHANES III, a national cross-sectional survey conducted by the National Center for Health Statistics between 1988 and 1994 [17]. The survey was designed to obtain information representative to the non-institutionalized US population on health and nutritional status between 1988 and 1994. A stratified, multistage sampling design was used, with over-sampling of non-Hispanic Blacks, Mexican–Americans and persons over the age of 60 years. Data

Prevalence of traditional cardiovascular risk factors in participants with CVD

Among 16,603 adult participants for whom self-reported CVD history was available, there were 1308 (8%) subjects with CVD, 681 (4.1%) of whom with a history of angina, 537 (3.2%) with a history of myocardial infarction and 309 (1.9%) with a history of stroke. Of note, some participants had more than one identifying CVD event.

Table 1 shows the age- and gender-adjusted, weighted prevalence of cardiovascular risk factors among participants with and without clinical CVD. The prevalence of

Discussion

In the present study, we have shown that serum levels of 25(OH)D were below the recommended levels [13] for a large portion of the general adult population [i.e., 22% of participants had a serum 25(OH)D level <20 ng/mL], and that 25(OH)D deficiency was associated with a composite of self-reported angina, myocardial infarction and stroke, independently of several established risk factors, in a nationally representative sample of the US adult population. These findings converge with a growing body

Disclosures

None of the authors have any conflicts of interest.

Acknowledgments

The principal investigator had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial support: Amgen Fellowship Grant.

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