Calcium plus vitamin D was associated with increased cardiovascular risk in women not taking personal calcium supplements

Subgroup analysis of a randomized placebo-controlled trial (Women’s Health Initiative [WHI] Calcium/Vitamin D Supplementation [CaD] study) using a limited access dataset. Analyses were prespecified before access to data was provided.

{Concealed}*.†

Blinded (participants, {clinicians, data collectors, outcome assessors, and data monitoring committee}*).†

{Mean 7 years}‡.

{40 clinical centers in the USA}‡.

36 282 community-dwelling, postmenopausal women {50 to 79 years of age}‡ (mean age 63 y at WHI CaD study randomization). 54% were taking personal calcium supplements at randomization; users and nonusers of supplements differed on several baseline variables.

Calcium, 1 g/d, plus vitamin D, 400 IU/d (n = 18 176), or placebo (n = 18 106). {Personal, nonprotocol use of calcium ≤ 1000 mg/d and vitamin D ≤ 1000 IU/d was allowed}‡.

Myocardial infarction (MI), stroke, coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft), and composites of the individual endpoints with or without death due to coronary heart disease.

{97%}‡ ({intention-to-treat analysis}*).

The main results for individual endpoints are shown in the Table. Calcium plus vitamin D was associated with a borderline significant increase in risk for the composite of clinical MI or stroke in nonusers but not in users of personal calcium (P = 0.006 for interaction) (Table); there was no interaction between treatment and personal calcium use for other composite endpoints.

In postmenopausal women, supplementation with calcium and vitamin D was associated with increased risk for some cardiovascular outcomes in nonusers of personal calcium supplements.