Dose-response association between moderate to vigorous physical activity and incident morbidity and mortality for individuals with a different cardiovascular health status: A cohort study among 142,493 adults from the Netherlands

Background. Regular moderate to vigorous physical activity (MVPA) is strongly associated with risk reductions of non-communicable diseases and mortality. Cardiovascular health status may influence the benefits of MVPA. This study compared the association between MVPA and incident major cardiovascular events (MACE) and mortality between healthy individuals, individuals with cardiovascular risk factors (CVRF), and cardiovascular disease (CVD).
Methods. We used prospectively collected data from 142,493 participants in the Lifelines Cohort Study and stratified participants as: 1) healthy , 2) CVRF, or 3) CVD. Individuals were categorised into “inactive” and 4 quartiles of least (Q1) to most (Q4) physically active based on self-reported volumes of total and domain-specific MVPA. The primary outcome was a composite of incident MACE and all-cause mortality. Multivariate Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) of MACE and all-cause mortality by total and domain-specific MVPA in healthy, CVRF and CVD.
Results. During a median follow-up of 7 years (IQR 6-9), 2,485 events occurred in the healthy (2% of n=112,018), 2,214 in the CVRF (8% of n=27,982), and 1,019 in the CVD (41% of n=2,493) subgroups. After adjusting for confounders and compared to the inactive participants, HRs in the healthy individuals were 0.81 (0.64-1.02), 0.71 (0.56-0.89), 0.72 (0.57-0.91) and 0.76 (0.60-0.96) in total MVPA Q1-Q4, respectively. In individuals with CVRF, HRs were 0.69 (0.57-0.82), 0.66 (0.55-0.80), 0.64 (0.53-0.77) and 0.69 (0.57-0.84) in total MVPA Q1-Q4, respectively. Finally, HRs for MVPA Q1-Q4 were 0.80 (0.62-1.03), 0.82 (0.63-1.06), 0.74 (0.57-0.95) and 0.70 (0.53-0.93) in CVD patients, and only significantly lower in the two most active groups. Leisure MVPA was associated with the most health benefits, non-leisure MVPA with little health benefits and occupational MVPA with no health benefits. 
Conclusions. MVPA is beneficial for reducing adverse outcomes, but the shape of the association depends on cardiovascular health status and the domain in which MVPA is performed. Current study results could further optimize PA recommendations, so that every individual, irrespective of cardiovascular health status, can optimally benefit from a physically active lifestyle.