Early initiation of hormone replacement therapy (HRT) may benefit all racial/ethnic groups except Chinese women, and Chinese women with metabolic syndrome or elevated triglycerides may have increased risk of adverse cardiovascular outcomes with HRT, according to research from the MESA published Jan. 27 in JACC: Advances.

This MESA substudy focused on all-cause mortality and major adverse cardiovascular events (MACE; nonfatal myocardial infarction, resuscitated cardiac arrest, coronary revascularization, definite or probable heart failure or death from coronary heart disease) in 2,427 postmenopausal women (mean age 64 years) without baseline cardiovascular disease. Among patients, based on self-reporting, 304 were Chinese, 934 White, 648 Black and 541 Hispanic; 1,159 had prior HRT use.

Results at a median follow-up of 14 years showed that HRT use within five years of menopause was associated with decreased MACE (hazard ratio [HR] 0.72; p=0.021) and all-cause mortality (HR 0.62; p<0.001) among all patients, with no benefit from initiation beyond five years.

White participants saw a significant reduction in mortality (HR 0.65; p=0.006), Hispanic participants in MACE (HR 0.50; p=0.021) and Black participants in both MACE and mortality (HR 0.52, p=0.014 and HR, 0.65, p=0.028, respectively).

However, in Chinese participants, HRT initiation within five years was associated with increased MACE (HR 2.27; p=0.035) and a nonsignificant trend towards increased mortality (HR 1.34; p=0.347), specifically those with metabolic syndrome (MACE HR 3.45, p=0.022; mortality HR 2.28, p=0.053) or elevated triglyceride levels ≥150 mg/dL (MACE HR 4.38, p=0.032; mortality HR 3.20, p=0.012), regardless of timing of HRT initiation.

"To our knowledge, this finding has not been shown before," write authors Spencer Flynn, MD, et al., calling for additional analyses in East Asian cohorts.

"Taken together, these findings lend additional support to the 'timing hypothesis' that early initiation of HRT close to the time of menopause may decrease [cardiovascular disease] risk and death across diverse populations," the authors add. "Our findings also provide some support for the theory that atherogenic risk factors, particularly elevated triglycerides and the presence of metabolic syndrome, may underly the relationship between HRT and worse [cardiovascular disease] outcomes, specifically in women of Chinese ethnicity."