Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.


Epidemiology and Population Health

Committee Chair

Hornung, Carlton

Author's Keywords

Vitamin D; Calcium; Heart failure; Cardiovascular; Randomized controlled trial; Women's health


Vitamin D--Therapeutic use; Heart diseases in women--Prevention; Heart diseases in women--Risk factors; Women's Health Initiative (U.S.)


This study evaluates the impact of vitamin D plus calcium supplementation as a primary intervention for heart failure (HF) prevention and examines whether preexisting conditions that are precursors of HF modify this relationship in a large cohort of postmenopausal women. Analysis included 35,113 postmenopausal women (17,595 intervention, 17,518 control) aged 50 to 81 years enrolled in the randomized trial of vitamin D plus calcium (CaD) in the Women’s Health Initiative (WHI) study. The women in this analysis cohort were free of HF at the time of randomization and during the first year of the trial. The intervention consisted of 1,000 mg/day of calcium and 400 IU/day of vitamin D3. Incident HF cases over an average follow-up period of 7.13 (standard deviation, 1.33) years were identified from hospital discharge records and adjudicated by a physician committee. An intention-to-treat (ITT) approach was used to estimate hazard ratios (HR) and 95% confidence (CI) intervals from multivariable Cox Proportional Hazards regression models. A formal test of interaction between the intervention and a composite of risk factors that predispose towards the development of HF (hypertension, cardiovascular diseases, coronary heart diseases/events, and diabetes) and define ‘Stage A’ HF was performed. CaD was associated with a non-significant 7% reduced risk of heart failure (HR = 0.92; 95% CI, 0.79 –1.06) in a multivariable model in the overall study cohort. However, CaD was associated with a clinically and statistically significantly lower risk (35%) of HF (HR = 0.65; 95% CI, 0.46 – 0.92; P = 0.01) among participants who were free of Stage A HF but neither a clinically nor a statistically significant effect among those with Stage A HF (HR = 1.02; 95% CI, 0.85 – 1.21; P = 0.87). Moreover, these effect estimates were not modified by baseline total (diet and supplements) vitamin D and calcium intake and persisted in a per-protocol and other sensitivity analyses. These findings suggest that a low cost daily supplementation with vitamin D plus calcium may be an effective primary prevention strategy in postmenopausal without major cardiovascular precursors of HF but of little value in those with these risk factors.