Should the Concentration of Vitamin D Be Measured in All Patients With Hypertension?

Abstract

The importance of vitamin D in a variety of health areas has led to increased interest about the prevalence, etiologies and associated morbidities of hypovitaminosis D. The role of vitamin D in absorption of calcium and bone health is well known, but recent data support additional effects on the immune system, cancer, neuromuscular function, and cardiovascular system, including hypertension [1,2]. Vitamin D is converted to 25-hydroxyvitamin D (25-OH D) in the liver and then again to 1,25 dihydroxyvitamin D (1,25-OH D) in the kidney. While 1,25-OH D is the biologically active form of vitamin D, 25-OH D is considered the best indicator of vitamin D status in the body because it circulates in a higher concentration, has a long half-life and is the substrate for 1,25-OH D production [1]. There are several etiologies of vitamin D deficiency and insufficiency (Table 1). The lack of ultraviolet B radiation from sunlight is the most common reason for vitamin D deficiency - northern latitudes, the winter season, sun protection factors (SPF) in lotions to prevent skin exposure to the sun all contribute to this form of vitamin D deficiency or insufficiency. The most common biochemical definition of vitamin D deficiency is a 25-OH D level less than 20 ng/ml (50 nmol/L) while levels from 21 to 29 ng/ml are considered insufficiency [3]. Surveys show that large minorities (40-45%) of elderly Americans and approximately 50% of post-menopausal women in American are deficient or insufficient in Vitamin D [4]. Prevalence rates go up with increasing age due to lesser quantities of the vitamin D precursor in the skin, 7-dehydrocholesterol and in populations with high levels of melanin in the skin (e.g African-Americans and dark-skinned Hispanic populations) since melanin also impairs the absorption of ultraviolet B radiation (Table 1). Table 1 Common Causes of Vitamin D Deficiency Vitamin D and Cardiovascular Disease Vitamin D deficiency is associated with diabetes, obesity, metabolic syndrome and hypertension [5]. In addition, low 25-OH D levels (< 15 to 20 ng/ml) have been associated with the development of hypertension (6) and cardiovascular events (7). In the Framingham Offspring Study participants followed for a median interval of 5.4 years demonstrated a higher relative risk for a cardiovascular event with lower vitamin D levels (Figure 1). The risk of an event increased by 2.13 in subjects with hypertension with 25-OH D levels less than 15 ng/ml [7]. It is impressive that the general risk for cardiovascular disease associated with vitamin D deficiency is comparable to the Framingham-derived risk ratios if the patient has metabolic syndrome (relative risk of 2.1), hypertension (relative risk of 1.7), dyslipidemia (relative risk of 1.8), increased fibrinogen levels (relative risk of 2.42) and homocysteinemia (relative risk of 1.6) [8-11]. Figure 1 Five-year cardiovascular event rates (%) according to varying levels of 25-hydroxyvitamin D in the Framingham Offspring Study. Rates were adjusted for age and sex and grouped according to the presence or absence of hypertension. Modified from reference ... Vitamin D and Hypertension Epidemiologic association between Vitamin D deficiency and hypertension Data from the INTERSALT study suggest a rise in BP is proportional to distance from the equator [12] while seasonal variations in BP have also been reported in temperate climates [13]. Population studies have shown an inverse relationship between vitamin D levels and hypertension, with increasing incidence of hypertension as Vitamin D levels decrease [6, 14]. The largest database is from Forman and colleagues (6) using 117,730 subjects from the Health Professional follow-up study and the Nurse's Health Studies in which there was a median follow-up period of 4 years for the development of incident hypertension. When comparing those individuals whose 25-0H D levels were 30 ng/ml, the relative risk of developing hypertension was 3.18, with a marked gender difference (6.13 in men and 2.67 in women). Hence, a significant inverse relationship exists between vitamin D and development of hypertension.