Interplay of menopause, coronary artery calcium score and cardiovascular disease risk

Table 1 Chronological snapshot of 10 studies focusing on the relationship between menopause, coronary artery calcium score, and cardiovascular disease

Ref.	Title	Year	Country	Objectives	Sample population	Conclusion
Gurbuz et al[13]	Correlation between coronary artery calcium score and triglyceride-glucose index in post-menopausal women	2023	Turkey	To clarify the correlation between CACS and TyG index in post-menopausal women	228	A high correlation was found between the TyG index and CACS (CC: 0.424, P = 0.001) in post-menopausal patients. In addition, patients with increased age, patients with higher glucose levels, and diabetic patients had significantly higher CACS
Cherukuri et al[10]	Coronary artery calcium and bone mineral density by serial CTA: Impact of menopausal hormone therapy	2022	United States	Both osteoporosis and CVD increase in women after menopause. Estrogen deficiency is thought to be an underlying mechanism for both these conditions	374	At baseline 374 women, 40 participants with CAC > 0 had greater decrements in BMD than the 334 participants with CAC = 0 at baseline, The average change in BMD in o-CEE group with CAC was -9.6 ± 13.3 vs -3.1 ± 19.5 in those with zero CAC, P = 0.0018
Chu et al[11]	CAC and atherosclerotic cardiovascular disease risk in women with early menopause: The multi-ethnic study of atherosclerosis	2022	United States	To determine the utility of CAC for atherosclerotic cardiovascular disease risk stratification in women with and without EM	2456	In MESA, > 50% of middle-aged postmenopausal women with EM had CAC = 0, similar to those without EM. Among women with CAC = 0, those with EM had a low to borderline 10-year risk of ASCVD, but the 15-year risk was significantly higher for women with EM vs those without EM. When CAC ≥ 1, the incidence of ASCVD was similar for women with and without EM. These findings support the use of CAC to help improve ASCVD risk stratification in women with EM
Fonseca et al[41]	Menopause and coronary artery calcium score: Results from the ELSA-Brazil study	2022	Brazil	To compare a broad cardio metabolic risk profile of women according to their menopausal status and investigated if menopause per se is associated with presence of CAC in the ELSA-Brasil study	2047	Associations of menopause with CAC, independent of traditional and nontraditional cardiovascular risk factors, suggest that hormonal decline per se may contribute to calcium deposition in coronary arteries
Freaney et al[12]	Association of premature menopause with coronary artery calcium: The CARDIA study	2021	United States	To determine whether premature menopause was associated with higher odds of CAC stratified by race	1785	Premature menopause was not associated with higher odds of any (> 0) or significant (≥ 100) CAC in mid-life compared with women without premature menopause. These findings suggest no difference in subclinical ASCVD as assessed by CAC in mid-life based on menopausal status. It is possible that CAC score alone does not fully capture plaque burden in women, as women may have a higher proportion of mixed and noncalcified plaques not well-identified by quantitative CAC testing
El Khoudary et al[17]	Associations of HDL metrics with CAC score and density in women traversing menopause	2021	United States	To test whether associations of comprehensive HDL metrics with CAC score and density vary by menopause stage or estradiol level in women transitioning through menopause	294	Associations of HDL phospholipid and triglyceride content and HDL-CEC with CAC measures did not vary by menopause stage or estradiol level. We concluded that HDL subclasses may impact the likelihood of CAC presence and the stability of coronary plaque differently over the menopause transition. Endogenous estradiol levels may contribute to this observation
Nudy et al[55]	The severity of VMS and number of menopausal symptoms in postmenopausal women and select clinical health outcomes in the women's health initiative CaD randomized clinical trial	2020	United States	Evaluate whether VMS severity and number of moderate/severe menopausal symptoms were associated with health outcomes, and whether CaD modified the risks	20050	Severe vasomotor and multiple menopausal symptoms were linked to worse health outcomes; CaD supplementation had no effect
Keshawarz et al[35]	Type 1 diabetes and CAC progression over menopausal transition: The CACTI study	2019	United States	To examine whether risk of CVD changes differentially in women with and those without type 1 diabetes over the transition through menopause	636	Type 1 diabetes was associated with higher CAC volume and accelerated progression of CAC over time. Menopause increased CAC progression more in women with diabetes than in women without diabetes independent of age and other CVD risk factors known to worsen with menopause
Subramanya et al[15]	Endogenous sex hormone levels and CAC progression in post-menopausal women	2018	United States	To study whether sex hormone levels were associated with CAC progression among women in the multi-ethnic study of atherosclerosis	2759	A more androgenic hormone profile of higher free testosterone and lower SHBG is associated with a greater CAC progression up to 10-years in post-menopausal women. Sex hormone levels may help identify women at increased risk for CVD who may benefit from additional risk-reducing strategies
Wassel et al[16]	Abdominal muscle area and CAC change by ethnicity in post-menopausal women	2015	United States	To examine the association of abdominal muscle area with CAC) presence, extent, and progression in a multi-ethnic cohort of older, community-dwelling post-menopausal women	439	There was a significant interaction of ethnicity with baseline oblique muscle area, and marginally significant interactions with baseline total and paraspinal muscle for change in CAC. Among Filipina women, each standard deviation greater total muscle area was associated with a 26% reduced rate of change in CAC; higher paraspinal and oblique muscle area were associated with a 24% and a 37% reduced rate of change in CAC, respectively

CACS: Coronary artery calcium score; TyG index: Triglyceride-glucose index; BMD: Bone mineral density; CTA: Computed tomography angiography; EM: Early menopause; ASCVD: Atherosclerotic cardiovascular disease; CAC: Coronary artery calcium; VMS: Vasomotor symptoms; CaD: Calcium and vitamin D; CVD: Cardiovascular disease; SHBG: Sex hormone-binding globulin.