AACE 2011: Calcium, Vitamin D, and the Heart


Use a combination of recommendations and clinical judgment to determine the proper calcium and vitamin D requirements for each patient.

Use a combination of recommendations and clinical judgment to determine the proper calcium and vitamin D requirements for each patient.

Are serum 25(OH)D3 (vitamin D) or serum calcium intake associated with increased cardiovascular (CV) mortality? This was a question posed by Paul Miller, MD, medical director at the Colorado Center for Bone Research in Lakewood, Colorado at the 20th Annual Meeting and Clinical Congress of the American Association of Clinical Endocrinologists. “It is intuitive that they should have an impact somehow because blood vessels and bone are intertwined.” Some of the cells common to bone cells are also common to endothelial cells in terms of their origin, he explained. But we need a better understanding of how blood and bone interrelate.

Vascular calcification is a multifactorial process, said Miller. There have been many population studies examining the relationship between vitamin D, calcium, and CV mortality, but these studies either did not capture or did not adjust for the many independent risk factors that contribute to vascular calcification. “Hence the association does not imply causality.” Risk factors for CV mortality include age, hypertension, hyperlipidemia, obesity, diabetes, chronic kidney failure (CKF), smoking, family history, reduced bone turnover, low bone mineral density (BMD) and/or hip fractures, and low BMD at menopause.

Miller reviewed several studies investigating the relationship between vitamin D and CV risk or mortality, either from CV or all-cause. The Framingham Offspring study followed 1,739 men and women with a mean age 59 years for 5.4 years. Results showed CV disease was 1.62x greater in those with the lowest levels of 25(OH)D3 (<37.5 nmol/L) (<15 ng/ml). This was statistically significant. In a British community dwelling study of 2,686 men and women randomized to vitamin D3 every four months over five years, relative risk of CV deaths was .84 in the vitamin D3 group compared to placebo. In a systematic review of 17 trials examining vitamin D and DV events, findings revealed that low 25(OH)D3 is a risk factor for CAD and CV death. Finally, the NHANES study of 13,331 adults, followed for a median 8.7 years, found 1,806 deaths with 777 from CVD. The lowest quartile of vitamin D levels had a 1.2 higher risk of death from CVD. Contrary to these findings, the WHI study, which followed patients over eight years, found no difference between placebo and vitamin D replaced groups on mortality. Similar results were observed in a meta-analysis, which overall found no significant effects of vitamin D supplementation on mortality. “Is there sound scientific evidence that vitamin D, at the levels studied, is causally linked to an increase in CV mortality?” Miller posed. His answer was a resounding “No.”

Moving to public policy, Miller examined statements from the Food and Nutrition Board of the Institute of Medicine (IOM). There is scientific evidence supporting a key role of calcium and vitamin D in skeletal health, as measured by four major indicators: optimal calcium absorption, osteoporotic fractures, BMD, and osteomalacia (PTH and falls were not assessed). Similar to the conclusions about vitamin D, according to the IOM, there is no association between calcium intake and CV events.

The problem with these recommendations, said Miller, is that they are geared toward the population. “They are not disease-specific nor for individual patient management. For now,” he said, “it is important to use these recommendations in conjunction with clinical judgment to set the proper calcium and vitamin D requirements for any given patient.”

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