Does the Dose-dependent Association between Physical Activity and Cardiac Morbidity and Mortality Differ between Healthy Controls and Cardiovascular Disease or Cardiovascular Risk?

The number of deaths from cardiovascular diseases (CVD) declines due to improvements in disease prevention and treatment of the last decades. However, this decline leads to a drastic escalation of the prevalence of CVD patients1. Apart from medical therapy, lifestyle modifications, such as increasing physical activity (PA), are key elements in the prevention of CVD recurrence and in the reduction of CVD mortality. The beneficial effects of PA in healthy individuals are well established for primary prevention. Therefore the WHO recommends adults to perform at least 150 minutes of moderate-intensity aerobic PA or at least 75 minutes of vigorous-intensity aerobic PA throughout the week, or an equivalent combination of moderate- and vigorous-intensity PA2. The recommend guidelines for high risk individuals with more than one cardiovascular risk factor, such as hypertension, high cholesterol, or diabetes, and for CVD patients are similar 3, 4. However, the evidence for the dose-response relationship between PA volume and CVD morbidity / mortality for high risk individuals and CVD patients is limited and inconsistent.

Only a few studies5-10 examined the dose-response relationship between habitual PA and health outcomes in CVD patients. All studies found that CVD patients performing PA have a reduced risk of all-cause mortality compared to patients not performing PA. However, the dose-response relationship and the optimal amount of PA differed between the studies. Most studies5-8 found a potential reverse J-shaped association between PA and clinical health outcomes compared to the non-exercise reference group. This suggest that the inactive patients had the highest risk of adverse health outcomes, and that increase of PA reduced the risks of major cardiovascular events, non-fatal cardiovascular events, cardiovascular mortality and all-cause mortality. However, health benefits were smaller for the group with highest levels of PA, but the risks were still lower compared to the inactive group. Another large prospective study9 found a curvilinear relationship suggesting that a change from an inactive to a mild or moderately active lifestyle yields the largest risk reduction, whereas further increasing exercise volumes produce smaller risk reductions. The results of the other two cohort studies10, 11 indicated a linear dose-response relationship, in which increasing PA volume and PA intensity was associated with additional risk reductions of all-cause mortality. The inconsistent dose-response relationship might be due to differences in sample size, CVD patient groups (i.e. coronary heart disease and heart failure), measures of PA, and follow-up time. In addition, the dose-response relationship in CVD patients was not compared to the dose-response relationship in high-risk individuals with CVD risk factors, and healthy controls. Furthermore, all mentioned studies used only PA levels at baseline assuming that PA does not change over time, which does not fit the real-life situation.

Therefore, our research aim is to examine the dose-dependent association between physical activity and cardiac morbidity and mortality and whether this relationship differs between healthy controls and cardiovascular disease patients or individuals with high cardiovascular risk.  Secondly, we want to investigate whether changes in PA levels alter the risk for adverse events.

year of approval



  • Radboud Institute for Health Sciences, Department of Physiology

primary applicant

  • Eijsvogels, T