25-hydroxyvitamin D and cardiovascular risk factors in women with systemic lupus erythematosus.

Increasing evidence supports an inverse association between vitamin D deficiency and cardiovascular disease (CVD) in the general population (1, 2). Low or deficient levels of 25-hydroxyvitamin D (25[OH]D) have been linked to stroke (3), ischemic heart disease (4, 5), and heart failure (5), as well as hypertension (6), diabetes(1, 6), hypertriglyceridemia (1, 6), obesity (7), and the metabolic syndrome (8). The Third National Health and Nutrition Examination Survey (NHANES-III) (6), found that the frequency of selected cardiovascular risk factors including obesity, hypertension, diabetes, and hypertriglyceridemia was significantly higher in the lowest (<21 ng/ml) quartile of serum vitamin D levels compared to the highest (≥37ng/ml). Similarly, a study using NHANES data from 2001–2004 noted that adults with 25(OH)D levels <20 ng/ml compared to those with 25(OH)D levels ≥30 had an increased frequency of CVD including coronary heart disease, heart failure, stroke, and peripheral arterial disease (5). A link has also been established between vitamin D and the immune system, and vitamin D has been studied as a modifiable environmental factor (9) in autoimmune disease animal models including systemic lupus erythematosus (SLE, lupus) (10), experimental autoimmune encephalomyelitis (a model for multiple sclerosis) (11), rheumatoid arthritis (12), type I diabetes (13), and inflammatory bowel disease (14). Epidemiological evidence also supports an association between vitamin D and the susceptibility and severity of these autoimmune disorders (15–17). SLE is the prototypical autoimmune disease and patients with SLE are known to have lower levels of 25(OH)D with measurements around or less than 20 ng/mL (16, 17) and in some cases critically low at less than 10 ng/ml (17, 18). Lower levels of vitamin D have been shown to correlate with increased SLE disease activity (19) and studies using animal models of SLE (10) demonstrated attenuation of some manifestations with increasing vitamin D intake (10, 20). A leading cause of morbidity and mortality in women with SLE, including those who are premenopausal, is CVD (21–23). Patients with lupus have an increased incidence of myocardial infarction up to 5 times that of the general population, with an age-specific incidence in young women up to 50 times higher (21). Evidence has shown that, like diabetes mellitus, SLE itself is an independent risk factor for the development of atherosclerosis (24). The cardiovascular and autoimmune actions of vitamin D are relevant in the setting of SLE given the significant role CVD can play in the lives of these women. Vitamin D deficiency could be a potential modifiable risk factor in SLE-related CVD as suggested by the clinical observations of vitamin D deficiency and its association with CVD in non-SLE patients (1, 6). However, there is minimal information in the literature to document an association between vitamin D levels and cardiovascular risk factors and/or outcomes in SLE. A necessary first step before proposing vitamin D supplementation as a preventive treatment in SLE is to document a relationship between the vitamin D deficient state and CVD risk in SLE. For this study, we examined the association of vitamin D levels with cardiovascular risk factors in women with SLE and propose that lower 25(OH)D levels are associated with an increased risk of cardiovascular risk factors in women with SLE.