JPM, Vol. 12, Pages 1980: Cardiac Rehabilitation for Older Women with Heart Failure

Heart failure patients participating in CR research tend to be relatively young, predominantly males and with a low burden of comorbidities, thus limiting the transferability of research findings to the general HF population. In the ExTra-MATCH II Meta-Analysis, for example, the mean age was 61 years and only 28% of the participants were females [28]. Norris et al. recognized underrepresentation of women in cardiovascular research as a “barrier to generating knowledge and developing clinical practice guidelines” [29]. Three major findings emerged from this study. First, females had a lower risk of early adverse clinical outcome and long-term mortality compared with males. Second, no significant difference in the extent of functional improvement following CR between females and males was observed. Third, females were more likely to achieve an increase in 6MWD at discharge to values higher than the optimal threshold for predicting mortality, compared with males.Females had better prognosis than males. After full adjustment for well-established prognostic factors, females had a 29% lower risk of early adverse outcome and a 32% lower risk of death within 3 years, compared with their male counterparts. A female prognostic advantage in HF has been observed in previous studies. In a population-based cohort study of people with incident HF, age-adjusted mortality after HF diagnosis was 33% higher in males than in females [30]. In the MAGGIC individual patient meta-analysis, survival was better for females compared with men, irrespective of LVEF [31]. In the CHARM Program, which included a broad spectrum of patients with chronic HF, females had lower risks of most fatal and nonfatal outcomes that were not explained by LVEF, origin of the HF, or adherence to therapy [32]. In a clinical trial of advanced HF, females had better survival than their male counterparts [33]. Finally, in a registry of HF patients, females showed better survival than males across the EF spectrum, after extensive adjustments [34]. The present study adds to the existing knowledge by showing that the survival advantage for females extends to the rehabilitation setting. The biological mechanisms underlying the gender gap in survival in HF remain elusive. However, some observations may help the interpretation of the female survival advantage observed in the present and previous studies. First, as observed by Austad [35], females are less likely to succumb to most of the major causes of death. Second, studies suggest that the prognostic benefit of CR is greater in females than in males [36,37]. In the HF-ACTION trial [36], a significant 26% reduction in the primary endpoint of all-cause mortality or all-cause hospital stay in females and no reduction in males were observed. Third, recovery of LVEF from HF with reduced LVEF, which is strongly linked to improved survival [38], is more common in females than in males [39]. Finally, in a population-based study, females were significantly less likely to progress to advanced HF than males, after extensive adjustment for covariates [40].The patients’ baseline characteristics are indicative of a cohort of older, vulnerable patients with severely impaired functional capacity. In such patients, a 6MWT may represent maximal effort [41] and its responsiveness is greatest [42]. Despite a poorer functional status at admission, females garnered similar improvement in functional capacity compared with males. Indeed, no significant difference in the extent of 6MWD increase from admission to discharge between females and males was observed. The standardized mean difference in 6MWD increase between males and females was 0.10, indicating negligible difference. The thresholds of 225 m for 6MWD at discharge in females and of 287 m in males demonstrated the strongest association with mortality. The achievement of a 6MWD at discharge higher than these thresholds predicted markedly improved survival in both sexes. Females were >2 times more likely to achieve such an improvement in distance walked than males. These findings underscore the role of 6MWD as a key outcome measure for older patients with HF admitted to CR, suggest that the prognostic value of 6MWT should be assessed separately in males and females, and may have implications to explain the observed survival advantage for females.We focused on sex-related differences in clinical and functional outcomes. While sex refers to biological characteristics, gender refers to “psychological, social, and cultural factors that shape attitudes, behaviors, and knowledge” [43]. In contrast to sex, gender is not a binary term; as observed by Mauvais-Jarvis et al. [44], indeed, “traits of masculinity and femininity most often coexist, are expressed to different degrees and are dynamic”. As such, gender can influence health and disease outcomes differently than biological sex. Thus, integrating sex- and gender-based analysis can lead to improved assessment and knowledge of differences in disease outcomes [43].

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