Paulette D Chandler1, Jamil B Scott2, Bettina F Drake3, Kimmie Ng4, John P Forman5, Andrew T Chan6, Gary G Bennett7, Bruce W Hollis8, Edward L Giovannucci9, Karen M Emmons10, Charles S Fuchs11. 1. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address: pchandler@partners.org. 2. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing. 3. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Mo. 4. Harvard Medical School, Boston, Mass; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Mass. 5. Harvard Medical School, Boston, Mass; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Mass. 6. Harvard Medical School, Boston, Mass; Department of Gastroenterology, Massachusetts General Hospital, Boston, Mass; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass. 7. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass. 8. Department of Psychology and Neuroscience, Duke University, Durham, NC. 9. Harvard Medical School, Boston, Mass; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass; Division of Pediatrics, Medical University of South Carolina, Charleston. 10. Harvard Medical School, Boston, Mass; Department of Nutrition, Harvard School of Public Health, Boston, Mass; Center for Community-Based Research, Dana-Farber Cancer Institute, Boston, Mass. 11. Harvard Medical School, Boston, Mass; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Mass; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass.
Abstract
INTRODUCTION:Hydrochlorothiazide, an effective antihypertensive medication commonly prescribed to blacks, decreases urinary calcium excretion. Blacks have significantly higher rates of hypertension and lower levels of 25-hydroxyvitamin D. Thus, they are more likely to be exposed to vitamin D supplementation and thiazide diuretics. The risk for hypercalcemia among blacks using vitamin D and hydrochlorothiazide is undefined. METHODS: We assessed the frequency of hypercalcemia in hydrochlorothiazide users in a post hoc analysis of a randomized, double-blind, dose-finding trial of 328 blacks (median age 51 years) assigned to eitherplacebo, or 1000, 2000, or 4000 international units of cholecalciferol (vitamin D3) daily for 3 months during the winter (2007-2010). RESULTS: Of the 328 participants, 84 reportedhydrochlorothiazide use and had serum calcium levels assessed. Additionally, a comparison convenience group of 44 enrolled participants who were not takinghydrochlorothiazide had serum calcium measurements at 3 months, but not at baseline. At 3 months, hydrochlorothiazide participants had higher calcium levels (0.2 mg/dL, P <.001) than nonhydrochlorothiazide participants, but only one participant in the hydrochlorothiazide group had hypercalcemia. In contrast, none of the nonhydrochlorothiazide participants had hypercalcemia. In a linear regression model adjusted for age, sex, 25-hydroxyvitamin D at 3 months, and other covariates, only hydrochlorothiazide use (Estimate [SE]: 0.05 [0.01], P = .01) predicted serum calcium at 3 months. CONCLUSION: In summary, vitamin D3 supplementation up to 4000 IU in hydrochlorothiazide users is associated with an increase in serum calcium but a low frequency of hypercalcemia. These findings suggest that participants of this population can use hydrochlorothiazide with up to 4000 IU of vitamin D3 daily and experience a low frequency of hypercalcemia.
RCT Entities:
INTRODUCTION:Hydrochlorothiazide, an effective antihypertensive medication commonly prescribed to blacks, decreases urinary calcium excretion. Blacks have significantly higher rates of hypertension and lower levels of 25-hydroxyvitamin D. Thus, they are more likely to be exposed to vitamin D supplementation and thiazide diuretics. The risk for hypercalcemia among blacks using vitamin D and hydrochlorothiazide is undefined. METHODS: We assessed the frequency of hypercalcemia in hydrochlorothiazide users in a post hoc analysis of a randomized, double-blind, dose-finding trial of 328 blacks (median age 51 years) assigned to either placebo, or 1000, 2000, or 4000 international units of cholecalciferol (vitamin D3) daily for 3 months during the winter (2007-2010). RESULTS: Of the 328 participants, 84 reported hydrochlorothiazide use and had serum calcium levels assessed. Additionally, a comparison convenience group of 44 enrolled participants who were not taking hydrochlorothiazide had serum calcium measurements at 3 months, but not at baseline. At 3 months, hydrochlorothiazideparticipants had higher calcium levels (0.2 mg/dL, P <.001) than nonhydrochlorothiazideparticipants, but only one participant in the hydrochlorothiazide group had hypercalcemia. In contrast, none of the nonhydrochlorothiazideparticipants had hypercalcemia. In a linear regression model adjusted for age, sex, 25-hydroxyvitamin D at 3 months, and other covariates, only hydrochlorothiazide use (Estimate [SE]: 0.05 [0.01], P = .01) predicted serum calcium at 3 months. CONCLUSION: In summary, vitamin D3 supplementation up to 4000 IU in hydrochlorothiazide users is associated with an increase in serum calcium but a low frequency of hypercalcemia. These findings suggest that participants of this population can use hydrochlorothiazide with up to 4000 IU of vitamin D3 daily and experience a low frequency of hypercalcemia.
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