Geert Kleinnibbelink

General Discussion 10 213 10.4.2 – Combining exercise and cardiovascular disease The work in my thesis has importantly contributed to a better understanding of acute and chronic responses of the cardiovascular system to exercise. To further elaborate on this, “exercise as medicine” has been one of the cornerstones in the (primary and) secondary prevention in the treatment of cardiovascular disease as it improves exercise capacity, health-related quality of life, and reductions in hospital admissions. 59-61 However, the direct association between exercise-based CR and mortality disappeared in randomized controlled trials in patients with coronary heart disease as demonstrated by the most recent Cochrane meta-analysis. 61 One possible explanation may be the heterogeneity of the coronary heart disease populations included in most recent studies. Better insight into these topics may clarify the impact of exercise-based CR on all-cause mortality and contribute to a personalised approach of CR for individual patients with coronary heart disease. Therefore, we are currently conducting a CR meta-analysis on patients with coronary heart disease using individual-participant data. 62 Adopting this approach, we are able to determine the influence of individual patient (e.g. age, sex, risk factors) or exercise characteristics (e.g. location, type, intensity, duration of exercise) on the effectiveness of CR. Improved insight into whether patient or exercise characteristics affect all-cause mortality or hospitalisation following CR, will ultimately enhance the benefits of CR. This will increase insight and provide the potential to personalise CR for coronary heart disease patients such that a more targeted approach to CR allows us to leave behind the simplicity of ‘one size fits all’. With this project, I will continue my research career alongside my clinical registry to become a consultant cardiologist. As discussedabove, exercise-basedCR is frequently explored in theprimary, secondary and tertiary prevention of cardiovascular disease. Unfortunately, few studies have examined the impact of CR in PH. This topic is highly relevant, since long-term survival in PH remains poor. 63, 64 Several studies have shown that exercise-based CR in patients with PH improved exercise capacity, quality of life and improve symptoms 65-71 but hard clinical endpoints on mortality are lacking. It is debated whether improvement in these surrogate endpoints reflect improvement in clinical outcome. 72 In this thesis, we showed that exercise-based CR in patients with primary PH was associated with significantly better 1-year survival than those without exercise-based CR ( Chapter 9 ). This is the first evidence that shows the