A secondary analysis of the Women’s Health Initiative (WHI)-Calcium and Vitamin D (CaD) clinical trial has concluded that vasomotor symptom severity is not linked to any clinical event.
However, the analysis, which was presented at the 2020 virtual annual meeting of the North American Menopause Society (NAMS), found that two or more moderate or severe menopausal symptoms are associated with an increased risk for cardiovascular disease and stroke.
Matthew Nudy, MD, a cardiology fellow at Penn State Hershey Medical Center, is the principal investigator on the analysis and he had completed prior research on cardiovascular disease in postmenopausal women for the WHI-CaD study. “We were interested in better understanding what is associated with cardiovascular disease in postmenopausal women and if calcium and vitamin D supplementation could alter those associations,” he said.
The multicenter WHI-CaD study across the United States was conducted from the early 1990s to 2005, and funded by the National Heart, Lung, and Blood Institute (NHLBI).
The double-blind, randomized, placebo-controlled study was designed to test the effects of 400 IU of 25-hydroxyvitamin-D and 1000 mg of elemental calcium per day on incident hip fracture and other health outcomes in women between the ages of 50 and 79. A total of 20,050 women were followed for a median of 7 years.
The outcomes assessed for the analysis were hip fracture, colorectal cancer, invasive breast cancer, all-cause mortality, CaD global index (composite endpoint of the aforementioned events), coronary heart disease, stroke, cardiovascular death, and total cardiovascular disease.
Menopausal symptoms included hot flashes, night sweats, dizziness, heart racing or skipping beats, tremors, feeling restless or fidgety, feeling tired, difficulty concentrating, forgetfulness, mood swings, vaginal dryness, breast tenderness, headache or migraine, and waking up multiple times at night.
The severity of menopausal symptoms (none; mild; moderate or severe) was measured via a baseline questionnaire.
The investigators found no association between the severity of vasomotor symptoms of hot flashes and night sweats; and any health outcome.
In contrast, the number of menopausal symptoms was significantly associated with risk for stroke: hazard ratio (HR) 1.41 for at least two menopausal symptoms; 95% confidence interval (CI): 1.04 to 1.91, compared to no menopausal symptoms.
For one menopausal symptom, the HR for stroke was 1.19; 95% CI: 0.88 to 1.61, compared to no menopausal symptoms.
The number of menopausal symptoms was also significantly connected to total cardiovascular disease: HR 1.37; 95% CI: 1.20 to 1.56, for at least two menopausal symptoms vs. none.
For one menopausal symptom, the HR for total cardiovascular disease was 1.00; 95% CI: 0.87 to 1.15, compared to no menopausal symptoms.
When stratified by randomization status, CaD did not influence any association evaluated. But the severities of most individual menopausal symptoms, including headaches or migraines, or difficulty concentrating, were linked to a higher total cardiovascular disease risk.
“I was surprised that the severity of vasomotor symptoms was not associated with any health outcome in our analysis,” Dr. Nudy told Contemporary OB/GYN. “In addition, calcium and vitamin D supplementation did not alter any association.”
Because patients with more moderate and severe menopausal symptoms may be likely to see a physician for treatment, “this may be an ideal time to assess their risk of cardiovascular disease,” Dr. Nudy said. “The number or type of moderate or severe menopausal symptoms, but not vasomotor symptoms alone, could be a marker of higher risk for cardiovascular disease.”
Dr. Nudy reports no relevant financial disclosures.