Anastassios G. Pittas, MD, MS; Mei Chung, MPH; Thomas Trikalinos, MD; Joanna Mitri, MD; Michael Brendel, BA; Kamal Patel, MPH; Alice H. Lichtenstein, DSc; Joseph Lau, MD; Ethan M. Balk, MD, MPH
Disclaimer: The opinions expressed are those of the authors and do not reflect the official position of AHRQ, the National Institutes of Health, the U.S. Department of Health and Human Services, the Public Health Agency of Canada, or Health Canada.
Acknowledgment: The authors thank Stanley Ip, MD; Jounghee Lee, PhD; Gowri Raman, MD; Athina Tatsioni, MD, PhD; and Teruhiko Terasawa, MD, for their work on the Tufts Evidence-based Practice Center evidence report on vitamin D and calcium, although they were not primarily responsible for cardiometabolic outcomes and did not participate in the writing of this manuscript.
Grant Support: By AHRQ (contract HHSA 290-2007-10055-I), National Institutes of Health (research grants R01DK76092 and R01DK79003 from the National Institute of Diabetes and Digestive and Kidney Disease and the Office of Dietary Supplements and grant R21DK78867 from the National Institute of Diabetes and Digestive and Kidney Disease), U.S. Department of Health and Human Services, and the Public Health Agency of Canada.
Potential Conflicts of Interest: Dr. Pittas: Grants received (institution): National Institute for Diabetes and Digestive and Kidney Disorders. Ms. Chung: Grants received (institution): AHRQ. Dr. Trikalinos: Grants received (institution): AHRQ. Support for travel to meetings for the study or otherwise: Institute of medicine. Mr. Brendel: Grants received (institution): AHRQ. Dr. Patel: Grants received (institution): AHRQ. National Institute for Diabetes and Digestive and Kidney Disorders, Office of Dietary Supplements, Public Health Agency of Canada. Dr. Lau: Grants received (institution): AHRQ. Grants/grants pending (institution): AHRQ. Payment for writing or reviewing the manuscript: AHRQ. Dr. Balk: Grants received: AHRQ. Grants received (institution): AHRQ. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-2011.
Requests for Single Reprints: Ethan M. Balk, MD, MPH, Tufts Evidence-based Practice Center, Tufts Medical Center, Box 63, 800 Washington Street, Boston, MA 02111; e-mail, email@example.com.
Current Author Addresses: Drs. Pittas and Mitri: Tufts Medical Center, 800 Washington Street, Box 268, Boston, MA 02111.
Drs. Trikalinos, Lau, and Balk; Ms. Chung; Mr. Brendel; and Mr. Patel: Tufts Medical Center, 800 Washington Street, Box 63, Boston, MA 02111.
Dr. Lichtenstein: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111.
Author Contributions: Conception and design: A.G. Pittas, M. Chung, J. Mitri, A.H. Lichtenstein, J. Lau, E.M. Balk.
Analysis and interpretation of the data: A.G. Pittas, M. Chung, T. Trikalinos, J. Mitri, A.H. Lichtenstein, E.M. Balk.
Drafting of the article: A.G. Pittas, J. Mitri, E.M. Balk.
Critical revision of the article for important intellectual content: A.G. Pittas, M. Chung, T. Trikalinos, J. Mitri, A.H. Lichtenstein, J. Lau, E.M. Balk.
Final approval of the article: A.G. Pittas, M. Chung, T. Trikalinos, A.H. Lichtenstein, J. Lau, E.M. Balk.
Statistical expertise: M. Chung, T. Trikalinos, E.M. Balk.
Obtaining of funding: A.G. Pittas, J. Lau, E.M. Balk.
Administrative, technical, or logistic support: K. Patel, J. Lau.
Collection and assembly of data: A.G. Pittas, M. Chung, J. Mitri, M. Brendel, K. Patel, E.M. Balk.
Pittas A., Chung M., Trikalinos T., Mitri J., Brendel M., Patel K., Lichtenstein A., Lau J., Balk E.; Systematic Review: Vitamin D and Cardiometabolic Outcomes. Ann Intern Med. 2010;152:307-314. doi: 10.7326/0003-4819-152-5-201003020-00009
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Published: Ann Intern Med. 2010;152(5):307-314.
Vitamin D may modify risk for cardiometabolic outcomes (type 2 diabetes, hypertension, or cardiovascular disease).
To examine the association between vitamin D status, including the effect of vitamin D supplementation, and cardiometabolic outcomes in generally healthy adults.
English-language studies in MEDLINE (inception to 4 November 2009) and the Cochrane Central Register of Controlled Trials (fourth quarter of 2009).
11 reviewers screened citations to identify longitudinal cohort studies that reported associations between vitamin D status and cardiometabolic outcomes, including randomized trials of vitamin D supplementation.
5 independent reviewers extracted data about study conduct, participant characteristics, outcomes, and quality. Differences were resolved by consensus.
13 observational studies (14 cohorts) and 18 trials were eligible. Three of 6 analyses (from 4 different cohorts) reported a lower incident diabetes risk in the highest versus the lowest vitamin D status groups. Eight trials found no effect of vitamin D supplementation on glycemia or incident diabetes. In meta-analysis of 3 cohorts, lower 25-hydroxyvitamin D concentration was associated with incident hypertension (relative risk, 1.8 [95% CI, 1.3 to 2.4]). In meta-analyses of 10 trials, supplementation nonsignificantly reduced systolic blood pressure (weighted mean difference, âˆ’1.9 mm Hg [CI, âˆ’4.2 to 0.4 mm Hg]) and did not affect diastolic blood pressure (weighted mean difference, âˆ’0.1 mm Hg [CI, âˆ’0.7 to 0.5 mm Hg]). Lower 25-hydroxyvitamin D concentration was associated with incident cardiovascular disease in 5 of 7 analyses (6 cohorts). Four trials found no effect of supplementation on cardiovascular outcomes.
Studies included primarily white participants. Observational studies were heterogeneous. Several trials reported post hoc analyses.
The association between vitamin D status and cardiometabolic outcomes is uncertain. Trials showed no clinically significant effect of vitamin D supplementation at the dosages given.
National Institute of Diabetes and Digestive and Kidney Disease, the National Institutes of Health Office of Dietary Supplements, U.S. Food and Drug Administration, Agency for Healthcare Research and Quality, and Public Health Agency of Canada.
Francisco Ramirez Lafita MD, FACP
ANAV Dept of Health. L'Hospitalet de l'Infant 43890, Spain
March 18, 2010
Vitamin D as Emerging Risk Factor for CVD?
Papers by Pittas, Wang and Guallar (1,2, 3) bring up a hot topic on emerging risk factors for cardiovascular disease (CVD). Beside the traditional risk factors for CVD, studies have found consistent relationships between markers of inflammation and risk of future cardiovascular events. In fact, C-reactive protein (CRP) has been proposed as an emerging risk factor for CVD as have been inflammatory diseases (RA, SLE, Vasculitis) In the last years, a growing number of reports describe that vitamin D holds anti-inflammatory properties as vitamin D was found to inhibit pro-inflammatory cytokines.
Increasing data suggest an inverse relationship between vitamin D deficiency and the prevalence of cardiovascular disease and classical risk factors as hypertension, diabetes, dyslipemia and the metabolic syndrome (4). The current review by Pittas et al on different longitudinal observational studies found that lower vitamin D status was associated with increased risk for CVD, but vitamin D supplements did not prevent diabetes, hypertension nor heart attack and stroke incidence. The potential protective role of vitamin D in the heart and the mechanism of action in this organ, are poorly understood (5). Results are controversial and a role for confounding factors as age, diet, etc, cannot be excluded as potential contributors for cardiovascular risk. As Pittas and at point out at their discussion, vitamin D is an excellent marker of good health and its presence in dairy products and fish might modify cardiovascular risk. .
Cross-sectional studies reflecting a hypothetical relationship between 25OHD levels and the presence of traditional (Framingham) cardiovascular risk factors as hypertension, cholesterol levels, diabetes, or the metabolic syndrome, should be interesting to perform.
1. Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, et al. Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med. 2010;152:307-314.
2. Wang L, Manson JE, Song Y, Sesso HD. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med. 2010;152:315-323.
3. Guallar E, Miller ER III, Ordovas JM, Stranges S. Vitamin D supplementation in the age of lost innocence. Ann Intern Med. 2010;152:327 - 329.
4. Baz-Hecht M, Goldfine AB.The impact of vitamin D deficiency on diabetes and cardiovascular risk. Curr Opin Endocrinol Diabetes Obes. 2010; 17: 113 -119
5. Lee W, Kang PM. Vitamin D deficiency and cardiovascular disease: Is there a role for vitamin D therapy in heart failure? Curr Opin Investig Drugs. 2010; 11: 309-314
Adarsh J. Sai
Creighton University School of Medicine Omaha NE
March 22, 2010
Effect of calcitriol on cardiometabolic outcomes
1. Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, et al. Systematic review: Vitamin D and cardiometabolic outcomes Ann Intern Med. 2010 Mar 2;152(5):307-14.
2. Wang L, Manson JE, Song Y, Sesso HD. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events Ann Intern Med. 2010 Mar 2;152(5):315-23.
3. Gallagher JC, Fowler SE, Detter JR, Sherman SS. Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss J Clin Endocrinol Metab. 2001 Aug;86(8):3618-28.
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