Association of Vasomotor and Other Menopausal Symptoms with Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis

Abstract

Importance: Vasomotor symptoms (hot flushes and night sweats) and other symptoms, including depression, anxiety and panic attacks, are commonly experienced by menopausal women and have been associated with an unfavourable cardiovascular risk profile.

Objective: To investigate whether presence of menopausal symptoms is associated with the development of cardiovascular disease (CVD).

Methods: Five electronic databases (Medline, EMBASE and Web of Science) were search until February 17th, 2015 to identify relevant studies. Observational cohort studies or randomised intervention studies were eligible for inclusion if they followed participants prospectively (at least 1 year of follow-up), and reported relevant estimates on the association of any vasomotor symptoms, or other menopausal symptoms, with risk of CVD, coronary heart disease (CHD), or stroke in perimenopausal, menopausal, or postmenopausal women. Data were extracted by two independent reviewers using a pre-designed data collection form. Separate pooled relative risks (RRs) for age and non-established cardiovascular risk factors (e.g., education, ethnicity) adjusted data and for established cardiovascular risk factors and potential mediators-adjusted data (e.g., smoking, body mass index, and hypertension) were calculated.

Results: Out of 9,987 initially identified references, ten studies were selected, including 213,976 women with a total of 10,037 cardiovascular disease outcomes. The age and non-established cardiovascular risk factors adjusted RRs) [95% confidence intervals] for development of CHD, Stroke and CVD comparing women with and without any menopausal symptoms were 1.34 [1.13-1.58], 1.30 [0.99-1.70], 1.48 [1.21-1.80] respectively, and the corresponding RRs adjusted for cardiovascular risk factors and potential mediators were 1.18 [1.03-1.35], 1.08 [0.89-1.32], 1.29 [0.98-1.71]. However, these analyses were limited by potential unmeasured confounding and the small number of studies on this topic.

Conclusion: Presence of vasomotor symptoms and other menopausal symptoms are generally associated with an increased risk of cardiovascular disease, which is mainly explained by cardiovascular risk factors.

Fig 1. Flow diagram of studies included in the current review.

Fig 2. Relative risks of coronary heart disease associated with menopausal symptoms.

Basic model: adjusted for age and non-established cardiovascular risk factors; Fully-adjusted model, adjusted for established cardiovascular risk factors and potential mediators. VMS, vasomotor symptoms; vasomotor symptoms include hot flashes and /or night sweats; All, includes vasomotor and other menopausal symptoms; Other, includes menopausal symptoms such as depression, insomnia, and panic attacks. Assessment of heterogeneity for basic model: All symptoms, X2 7 = 81.22, I2 = 91%, 85 to 95%; P < 0.001; vasomotor symptoms, X2 1 = 1.55, I2 = 35%; P = 0.213; other symptoms, X2 5 = 63.48, I2 = 92%, 86 to 96%; P < 0.001. Assessment of heterogeneity for fully-adjusted model: All symptoms, X2 6 = 29.20, I2 = 79%, 58 to 90%; P < 0.001; vasomotor symptoms, X2 1 = 0.09, I2 = 0%; P = 0.762; other symptoms, X2 4 = 22.63, I2 = 82%, 59 to 92%; P < 0.001.

Fig 3. Relative risks of stroke associated with menopausal symptoms.

Basic model: adjusted for age and non-established cardiovascular risk factors; Fully-adjusted model, adjusted for established cardiovascular risk factors and potential mediators. VMS, vasomotor symptoms; vasomotor symptoms include hot flashes and /or night sweats; All, includes vasomotor and other menopausal symptoms; Other, includes menopausal symptoms such as depression, insomnia, and panic attacks. Assessment of heterogeneity for basic model: All symptoms, X² ₂ = 3.26, I² = 39%, 0 to 81%; P = 0.196; other symptoms, X² ₁ = 2.03, I² = 51%, 0 to 87%; P = 0.154. Assessment of heterogeneity for full-adjusted model: All symptoms, X² ₂ = 1.86, I² = 0%, 0 to 90%; P = 0.395; other symptoms, X² ₁ = 1.72, I² = 42%; P = 0.189.

Fig 4. Relative risks of cardiovascular disease associated with menopausal symptoms.

Basic model: adjusted for age and non-established cardiovascular risk factors; Fully-adjusted model, adjusted for established cardiovascular risk factors and potential mediators. VMS, vasomotor symptoms; vasomotor symptoms include hot flashes and /or night sweats; All, includes vasomotor and other menopausal symptoms; Other, includes menopausal symptoms such as depression, insomnia, and panic attacks. Assessment of heterogeneity for basic model: All symptoms, X2 3 = 9.95, I2 = 70%, 13 to 90%; P = 0.019; other symptoms, X2 2 = 7.05, I2 = 72%, 4 to 92%; P = 0.045. Assessment of heterogeneity for full-adjusted model: All symptoms, X2 3 = 8.68, I2 = 65%, 0 to 88%; P = 0.034; other symptoms, X2 2 = 8.67, I2 = 77%, 25 to 93%; P = 0.013.