Low Vitamin D Plus Hypertension May Worsen Cardiovascular Risks

Low Vitamin D Plus Hypertension May Worsen Cardiovascular Risks

BOSTON, Jan. 7 -- Moderate vitamin D deficiency nearly doubles the risk of myocardial infarction, stroke, and heart failure over a mean of 5.4 years in patients with high blood pressure, researchers here said.

The finding emerged from the Framingham Heart Study, which now includes the adult offspring of the study's original participants.

The researchers focused on those offspring who had participated in their sixth or seventh quadrennial exams from 1996 to 2001, Thomas J. Wang, M.D., of Massachusetts General Hospital, and colleagues reported online in Circulation: Journal of the American Heart Association. Participants with known cardiovascular or kidney disease at that time were excluded.

Compared with patients with higher vitamin D levels, the adjusted rate of first cardiovascular events was 1.62 times higher (95% CI: 1.11 to 2.36, P=0.01) in those with levels of 25-dihydroxyvitamin D below 15 ng/mL.

This effect was evident in participants with hypertension (hazard ratio: 2.13, 95% CI: 1.30 to 3.48) but not in those without hypertension (HR: 1.04, 95% CI: 0.55 to 1.96).

Up to half of middle-age and older adults in the U.S. have low levels of circulating vitamin D, Dr. Wang and colleagues said. However, they stopped short of calling for routine vitamin D testing or for supplementation in patients with known deficiencies.

"What hasn't been proven yet is that vitamin D deficiency actually causes increased risk of cardiovascular disease," Dr. Wang said. "This would require a large randomized trial to show whether correcting the vitamin D deficiency would result in a reduction in cardiovascular risk."

Earlier research had suggested links between lower vitamin D levels and other factors related to heart disease, such as coronary artery calcification and blood pressure.

Dr. Wang and colleagues wanted to know whether vitamin D levels in the Framingham offspring from the 1996-2001 exams were correlated with the rate of first cardiovascular events occurring later. In addition to MI, ischemic stroke, and heart failure, these events included angina, coronary insufficiency episodes, transient ischemic attacks, and claudication.

The researchers also adjusted for such factors as age, gender, smoking and diabetes status, weight, and cholesterol levels in their statistical analyses. Mean follow-up after the exams was 5.4 years.

Patients with very low vitamin D levels -- less than 10 ng/mL -- along with hypertension were at substantially greater risk of cardiovascular events.

Dr. Wang and colleagues found a hazard ratio of 3.19 (95% CI: 1.70 to 5.99), adjusted for age and gender, for these individuals relative to hypertensive participants with vitamin D levels of 15 ng/mL or greater. When also adjusted for clinical parameters including C-reactive protein levels, the hazard ratio for these participants was 2.43 (95% CI: 1.23 to 4.80).

The study did not investigate potential mechanisms. However, Dr. Wang and colleagues pointed to other research indicating that vitamin D deficiency and hypertension independently affect vascular remodeling and cardiac hypertrophy.

Vitamin D deficiency may also directly promote development of hypertension, they suggested.
As a result, they wrote, "hypertension could magnify the adverse effects of vitamin D deficiency on the cardiovascular system."

Dr. Wang and colleagues could not rule out the possibility that vitamin D deficiency is not causative. "Unmeasured characteristics associated with vitamin D deficiency … could account for the increased cardiovascular risk," they acknowledged.

They pointed out that "an alternate explanation for the present findings is that vitamin D deficiency is a marker of chronic nonspecific illness rather than a direct contributor to disease pathogenesis."

They also noted that all the participants in their study were Caucasian, indicating that the results may not apply to non-whites who have a higher prevalence of vitamin D deficiency.
Dr. Wang said that until future studies confirm a causal link between vitamin D deficiency and cardiovascular risk, patients -- especially the elderly, who are at particular risk for low vitamin D levels -- should simply ensure their diets satisfy the recommended daily allowance of vitamin D.