Exercise training in cardiovascular disease: are we closing the gender gap?

Abstract

Throughout history, inequalities were the mainstay of mankind. Many have survived to date and even today we are still faced with differences related to gender. Medicine, including cardiovascular disease (CVD), is no exception to the rule. This was picked up by the European Society of Cardiology, which among other activities organised a workshop in 2010 on gender differences in cardiovascular research, that also suggested an action plan to be implemented over the next few years. It can be argued that such initiatives take time but even then the interim reports are not encouraging: women remain underrepresented in many aspects of cardiovascular research and, maybe due to less robust evidence, also in clinical practice. Apparently, gender disparities extend from pharmacological to lifestyle interventions, such as regular physical activity, exercise training and cardiac rehabilitation, which is endorsed as a class IA recommendation for treatment of patients with CVD. This perspective was highlighted in an excellent review by Witvrouwen et al. The authors reported that women are less frequently enrolled into exercise training studies and cardiac rehabilitation; moreover, if enrolled, they show a lower adherence compared to men with coronary artery disease and/or heart failure. The authors argue that if gender-specific psychosocial (e.g. available time outside family commitments, motivation, fear, stress) and physical factors (incontinence, menstrual cycle, pregnancy) are taken into account when prescribing exercise training, multiple benefits could be shown (e.g. improved exercise capacity, physical activity and quality of life, and decreased cardiovascular and metabolic risk). If so, there should be no relevant differences in the scientific and clinical aspects of cardiac rehabilitation. As is generally seen, this unfortunately is not the case, as fewer women than men at any time point prior to or post myocardial infarction are physically active at moderate and vigorous physical activity levels. Nevertheless, the lower baseline exercise capacity and physical activity levels in women can be improved during exercise training in cardiac rehabilitation. Recent research suggests that participants with low baseline fitness but major improvement in exercise capacity after cardiac rehabilitation had a 59% reduced risk of cardiac hospitalisation or all-cause mortality. An even higher benefit of exercise training was observed in participants with higher baseline fitness and major improvement in exercise capacity post cardiac rehabilitation training. In a recent large individual patient meta-analysis investigating the effects of exercise training predominantly in patients with heart failure with reduced ejection fraction, only 29% of included patients were women. The study reported a significant improvement of the 6-minute walking test (mean difference 21.0m, 95% confidence interval (CI) 1.6, 40.4, P1⁄4 0.034), but no improvement in peak aerobic capacity (VO2 peak) (mean difference 1.01ml/kg/min, 95% CI –0.42, 2.44, P1⁄4 0.168). However, in the sub-analysis women showed greater benefit from exercise training compared to men in VO2 peak (mean difference 0.57ml/kg/min, 95% CI 0.04, 1.11, P1⁄4 0.036). Most of the literature is in line with previous statements but there may be some specifics. The most recent meta-analysis in heart failure patients with preserved ejection fraction showed that exercise training improves peak VO2 (mean difference 1.660ml/min/kg, 95% CI 0.973, 2.348, P< 0.001), 6-minute walking distance (mean difference 33.883m, 95% CI 12.384, 55.381, P< 0.01), and Minnesota living with heart failure questionnaire total score (9.059 points, 95% CI 3.083, 15.035, P< 0.01) compared to usual care. From the gender perspective, it needs to be emphasised that this meta-analysis (and actually all individual studies) included predominantly women (35% men vs. 65% women). The latter could be explained by the