Table 1.
Important Trials of Calcium +/– Vitamin D on Cardiovascular Outcomes
| Study | Population | Arms | Background calcium/VD | Duration | Outcome | Comments |
|---|---|---|---|---|---|---|
| Hsia et al. (2007) (WHI) [47] | n=36,282 | Calcium carbonate (500 mg)+vitamin D (200 IU twice daily) | Active arm (calcium: 1,148±654 mg/day; VD: 365±265 IU/day) | 7 years | Prespecified secondary outcomes | Secondary outcomes |
| Postmenopausal females | MI/coronary death: HR, 1.04; 95% CI, 0.92–1.18 | Background calcium/VD continued in the placebo arm | ||||
| Age 50 to 79 years | Placebo arm (calcium: 1,154±658 mg/day; VD: 368±266 IU/day) | |||||
| CV disease at baseline: Ca/VD (4.8%), placebo (4.7%) | Placebo | Stroke: HR, 0.95; 95% CI, 0.82–1.10 | Low VD supplementation | |||
| Bolland et al. (2008) [48] | n=1,471 | 1 g of elemental calcium as citrate | Active arm: 861±390 mg/day | 5 years | Secondary analysis | Secondary analysis |
| Postmenopausal women | MI: RR, 2.24; 95% CI, 1.2–4.17 | Slight difference in baseline CV risk factors | ||||
| Mean age 74 years | Placebo | Placebo: 853±381 mg/day | Angina, chest pain, MI, or sudden death: RR, 0.94; 95% CI, 0.72–1.24 | |||
| Angina: RR, 0.71; 95% CI, 0.50–1.01 | Relatively smaller number compared to WHI | |||||
| Stroke: RR, 1.44; 95% CI, 0.90–2.31 | ||||||
| Avenell et al. (2012) (RECORD trial) [53] | n=5,292 | VD: 800 IU | Calcium: ≤500 mg | 6 years | VD vs. placebo: vascular disease mortality (HR, 0.91; 95% CI, 0.79–1.05) | Prespecified secondary outcomes |
| Majority females | Calcium: 1,000 mg of elemental calcium (as carbonate) | Vitamin D: <200 IU (5 μg) | Poor compliance | |||
| Mean age 77 years | Calcium+VD | Calcium vs. placebo: vascular disease mortality (HR, 1.07; 95% CI, 0.92–1.24) | ||||
| Placebo | ||||||
| Lewis et al. (2011) [56] | n=1,460 | Calcium carbonate (1,200 mg) | Calcium (calcium arm: 961±356 mg; placebo arm: 970±352 mg) | 5 years | Hospitalization or death from ASCVD: HR, 0.938; 95% CI, 0.690–1.275 | Verified events |
| Female | Prespecified outcomes | |||||
| Mean age | Placebo | |||||
| 75.1±2.7 years |
VD, vitamin D; WHI, Women’s Health Initiative; CV, cardiovascular; IU, international unit; MI, myocardial infarction; HR, hazard ratio; CI, confidence interval; RR, relative risk; RECORD, Randomized Evaluation of Calcium Or vitamin D trial; ASCVD, atherosclerotic cardiovascular disease.