SUPPLEMENTAL MATERIAL

SUPPLEMENTAL MATERIAL Supplemental Table 1. Distribution of Participants Characteristics by Treatment Group at Baseline - The Vitamin D and calcium (CaD) Trial of the Women s Health Initiative (WHI) Study, 1995 2005 Baseline characteristics Vitamin D and calcium (N=18,023) (N=17,960) No. (%) with data Age (years) 49 59 37.2 37.1 60 69 45.5 45.5 70 81 17.4 17.4 Race/Ethnicity White 83.0 83.6 Black 9.2 8.9 Hispanic 4.3 3.9 Other 3.6 3.6 Education None/grade school 2.2 2.0 High school/some college 61.6 61.8 College 10.3 10.3 Beyond college 26.0 26.0 Income ($) <25,000 21.0 21.0 25, 000 50,000 44.7 44.6 50,000 70,000 19.0 18.9 75,000 100,000 8.0 8.3 >100,000 7.3 7.2 Region by Solar Irradiance 475 500 21.3 21.2 400 430 16.6 16.6 375 380 11.0 11.1 350 21.6 21.4 300 325 29.5 29.6 High Cholesterol requiring pills ever 10.9 10.7 BMI (kg/m 2 ) 18.00 24.99 28.0 28.9 25.00 29.99 35.6 35.3 >30.00 36.5 35.8 Alcohol intake None 11.0 11.1 Past drinker 17.4 17.6 Less than 1 drink/month 13.9 13.9 Less than 7 drinks/week 47.1 46.8 More than 7 drinks/week 10.6 10.5 Physical activity level (total METs/week) Low 38.6 38.5 Moderate 12.9 13.1 High 48.5 48.3 Systolic blood pressure, mean (SD), mmhg 126 (17) 126 (17) Diastolic blood pressure, mean (SD), mmhg 75 (9) 75 (9)

Supplemental Table 1 (ct d). Distribution of Participants Characteristics by Treatment Group at Baseline - The Vitamin D and calcium (CaD) Trial of the Women s Health Initiative (WHI) Study, 1995 2005 No. (%) with data Smoking status None 52.4 53.1 Past 39.9 39.4 Current 7.8 7.5 Multivitamin use 34.1 34.8 Daily calcium (supplements + diet), mg/day Mean (SD) 1142 (669) 1144 (670) < 600 47.0 46.4 600 800 9.8 9.7 800 1,200 17.2 17.0 1,200 + 26.0 26.9 Daily vitamin D (supplements + diet), IU/day Mean (SD) 270.9 266.4 < 200 58.3 57.8 200 600 28.9 29.3 > 600 12.8 12.9 Ever received hormone replacement therapy 51.7 52.4 History of hypertension Never 59.7 59.4 Untreated 11.3 11.7 Treated 29.2 28.9 History of CVD 12.2 12.7 History of diabetes 5.6 5.6 History of CHD 4.5 4.6 Family history of CVD 65.6 65.5 Dietary modification trial assignment Not randomized 30.7 30.3 Intervention 26.2 26.9 Control 43.1 42.8 Hormone therapy trial assignment Not randomized 55.7 55.6 Estrogen alone intervention 8.4 8.5 Estrogen alone control 8.4 8.6 Estrogen + progesterone intervention 13.8 14.0 Estrogen + progesterone control 13.7 13.2 Abbreviations: SD, standard deviation; BMI, body mass index; MET, metabolic equivalent of task; CVD, cardiovascular disease; CHD, coronary heart disease.

Supplemental Table 2. Baseline Characteristics of Participants Stratified by Baseline Risk Status of Heart Failure and by Treatment Group - the Vitamin D and Calcium (CaD) Trial of the Women s Health Initiative (WHI) Study, 1995 2005 Baseline Risk Status Low-risk group High-risk group Baseline characteristics CaD (n = 9,307) (N = 18,534) (n = 9,227) CaD (n = 8,716) (N = 17,449) (n = 8,733) No. (%) with data Age (years) 49 59 44.2 44.2 29.7 29.7 60 69 43.0 43.2 48.1 48.1 70 81 12.8 12.7 22.3 22.3 Race/Ethnicity White 86.1 87.0 80.0 80.3 Black 5.9 5.6 12.4 12.1 Hispanic 4.8 4.3 3.8 3.6 Other 3.3 3.2 4.1 4.1 Education None/grade school 1.9 1.7 2.4 2.4 High school/some college 58.4 58.3 65.0 65.5 College 11.1 11.2 9.4 9.2 Beyond college 28.6 28.9 23.2 23.0 Income ($) <25,000 18.0 17.6 24.2 24.5 25, 000 50,000 42.6 43.8 46.9 45.5 50,000 70,000 20.5 20.2 17.4 17.6 75,000 100,000 9.7 9.6 6.1 6.9 >100,000 9.2 8.8 5.4 5.5 Region by Solar Irradiance 475 500 21.8 21.6 20.7 20.8 400 430 17.1 16.8 16.1 16.5 375 380 10.4 10.8 11.6 11.3 350 21.3 21.0 21.9 22.1 300 325 29.5 29.9 29.8 29.4 High Cholesterol requiring pills 6.9 6.5 15.1 15.2 ever BMI (kg/m 2 ) 18.00 24.99 34.7 36.3 20.8 21.1 25.00 29.99 36.9 36.7 34.2 33.9 >30.00 28.5 37.0 45.0 45.0 Alcohol intake None 10.1 10.0 12.1 12.3 Past drinker 14.5 14.6 20.2 20.8 Less than 1 drink/month 13.4 13.6 14.6 14.0 Less than 7 drinks/week 50.8 50.3 43.4 43.5 More than 7 drinks/week 11.3 11.6 9.7 9.5 Abbreviations: SD, standard deviation; BMI, body mass index; MET, metabolic equivalent of task; CVD, cardiovascular disease.

Supplemental Table 2 (ct d). Baseline Characteristics of Participants Stratified by Baseline Risk Status of Heart Failure and by Treatment Group - the Vitamin D and Calcium (CaD) Trial of the Women s Health Initiative (WHI) Study, 1995 2005 Baseline Risk Status Low-risk group High-risk group Baseline characteristics CaD (n = 9,307) (N = 18,534) (n = 9,227) CaD (n = 8,716) (N = 17,449) (n = 8,733) No. (%) with data Physical activity level (total METs/week) Low 37.3 36.9 39.7 40.0 Moderate 12.2 12.8 13.8 13.4 High 50.6 50.3 46.5 46.7 Smoking status None 52.0 52.9 53.1 53.5 Past 39.7 39.2 39.9 39.5 Current 8.3 7.9 7.0 7.0 Multivitamin use 34.1 35.3 34.6 34.9 Daily calcium (supplements + diet), mg/day Mean (SD) 1170 (680) 1167 (660) 1113 (656) 1120 (680) < 600 51.2 50.3 53.4 53.2 600 800 19.8 19.4 19.9 19.5 800 1,200 28.9 30.3 26.7 27.4 Personal calcium (alone) 49.7 50.4 50.0 50.0 supplements Daily vitamin D (supplements + diet), IU/day Mean (SD) 368 (273) 368 (268) 365 (268) 367 (265) < 200 45.0 44.1 44.6 44.9 200 600 41.3 42.2 41.7 41.3 > 600 13.7 13.8 13.7 13.8 Personal vitamin D (alone) 49.6 50.4 50.1 49.9 supplements Ever received hormone 52.4 53.6 50.9 51.0 replacement therapy Family history of CVD 61.5 61.7 70.0 69.5 Dietary modification trial assignment Not randomized 31.7 30.6 30.0 30.1 Intervention 26.2 27.2 26.4 26.8 Control 42.1 42.2 43.6 43.1 Hormone therapy trial assignment Not randomized 54.8 56.1 56.2 54.9 Estrogen alone intervention 7.0 7.2 9.9 9.8 Estrogen alone control 7.6 7.5 9.4 9.9 Estrogen + progestin 15.5 14.8 12.2 13.3 intervention Estrogen + progestin control 15.1 14.4 12.4 12.1 Abbreviations: SD, standard deviation; BMI, body mass index; MET, metabolic equivalent of task; CVD, cardiovascular disease.

Supplemental Table 3. Results of Sensitivity Analysis Estimating the Association between CaD Supplementation and Heart Failure Incidence - The Vitamin D and calcium (CaD) Trial of the Women s Health Initiative (WHI) Study, 1995 2005 Study population *IPCW method (N = 35,983) Total HR (95% CI) P Overall Control 17,960 1.00 CaD 18,023 0.92 (0.7-1.15) 0.49 Low-risk Control 9,227 1.00 CaD 9,307 0.64 (0.35-1.16) 0.14 High-risk Control 8,733 1.00 CaD 8,716 1.05 (0.85-1.28) 0.67 Abbreviations: CaD, calcium plus vitamin D trial; HR, hazard ratio; CI, confidence interval; IPCW, Inverse Probability of Censored Weights; CI, confidence interval; P, P value *Analysis are based on entire baseline population (N = 35,983) adjusted for age, education, use of personal calcium, vitamin D or multivitamin supplements, history of heart failure risk factors (hypertension, CVD, CHD/coronary events, or diabetes), family history of CVD, and enrollment in other clinical trials

Supplemental Table 4. Distribution of Baseline Mean Concentrations of Total Calcium and Vitamin D Intakes and Measured Serum 25-Hydroxyvitamin D Levels by Heart Failure Incidence Cohorts - The Vitamin D and calcium (CaD) Trial of the Women s Health Initiative (WHI) Study, 1995 2005 Study population Mean baseline levels Total (diet + supplements) calcium, mean (SD), mg/day Total (diet + supplements) vitamin D, mean (std), IU/day *Serum 25(OH)D, mean (std), ng/ml HF (n = 736) 811.07 (697.16) 299.77 (273.70) 18.09 (6.29) Overall CaD (n=35,633) Low risk (n=18,339) High risk (n=17,295) No HF (n = 34,897) 875.04 (724.15) 308.78 (270.5) 20.49 (9.18) P 0.02 0.37 HF (n = 155) 790.19 (687.91) 295.40 (300.74) 0.10 17.54 (6.20) No HF (n = 18,184) 892.29 (731.21) 308.59 (271.32) 21.36 (9.24) P 0.08 0.55 HF (n = 581) 816.64 (700.08) 300.94 (266.29) No HF (n = 16,714) 856.27 (715.94) 308.98 (269.54) P 0.19 0.48 0.17 18.29 (6.42) 19.60 (9.04) 0.43 Abbreviations: HF, heart failure; P, P value; SD, standard deviation * Values reported are based on data from a random sample of 2,012 participants with measured serum 25(OH)D levels at baseline.

Supplemental Table 5. Interaction between cardiovascular disease medications and calcium and vitamin D supplements. Cardiovascular disease medications Users of cardiovascular disease medications, n (%) P-value for interaction between baseline use of CVD medications and CaD ACE inhibitors 5,554 (31.8) 0.62 Angiotensin II receptor blockers 1,934 (11.1) 0.04 Statins 5,731 (32.8) 0.74 Betablockers 876 (5.0) 0.44 Calcium blockers 5,691 (32.6) 0.29 Composite 9,501 (54.5) 0.35

Supplemental Figure 1: Schoenfeld residual plots to evaluate the Cox proportional hazards assumption