One size doesn’t fit all? New steps towards individualized physical activity guidelines in cardiovascular disease prevention

This editorial refers to ‘Refined physical activity recommendations considering cardiovascular disease risk stratification: a cohort study’, by C. Yuan et al., https://doi.org/10.1093/eurjpc/zwag054. Growing evidence supports the role of physical activity (PA) as one of the most powerful tools for cardiovascular disease (CVD) prevention.1–3 Indeed, in the general population large-scale studies show a linear inverse dose-response association between PA levels (regardless of the intensity) and CVD incidence, with the greatest benefits observed in those who are more active.1 For this reason, international guidelines recommend that adults should perform at least 150 min/week of moderate-to-vigorous PA (MVPA) or 75 min/week of vigorous-intensity PA (VPA), recommending even higher PA levels (300 min/week of MVPA or 150 min of VPA) for additional health benefits.4 However, despite valid in overall terms, controversy exists on whether this ‘one-size-fits-all’ approach should be applied in all individuals, which is further supported by the recent findings by Yuan et al.5 In their prospective analysis of 72 884 participants of the UK Biobank cohort, the authors analyzed accelerometer-derived PA levels and stratified individuals in three groups (low-to-moderate-, high-, and very high-risk) according to their CVD risk by using updated SCORE2 algorithms, which consider variables such as smoking habits, blood pressure, and cholesterol levels, in addition to kidney function or the presence of diabetes. Over a median follow-up of 13.2 years, the authors observed that in the whole cohort there was an inverse association between total PA and MVPA levels with the risk of incident CVD, which confirms the preventive role of PA. These findings were separately confirmed for the different groups of CVD risk, but interestingly, the dose–response relationship between total PA or MVPA and CVD risk was particularly strong among those at very high predicted CVD risk. Thus, each additional 150 min/week of MVPA was associated with a 20% lower risk among individuals with very high risk of CVD, compared with 16% in those with high or low-to-moderate risk. These findings are of relevance as they show that individuals with the highest CVD risk are those who benefit the most from being physically active. In line with these results, evidence overall suggests that individuals with high CVD risk benefit more from PA compared with their healthy peers. For instance, a recent study in 94 734 participants reported that higher self-reported PA levels were inversely associated with the incidence of CVD, which was more pronounced among high-risk individuals.6 Similarly, in a study involving 131 558 subjects with prevalent CVD and 310 240 subjects without CVD, Jeong et al.7 showed that the former benefited more from PA (e.g. every 14% and 7% risk reduction in mortality, respectively, for every 500 MET-min/week increase in total PA).7 On the other hand, another major finding of the study by Yuan et al.5 was that whereas individuals with low-to-moderate CVD risk could benefit from any random combination of MPA and VPA (with additional risk reduction from higher proportions of VPA), among individuals with high or very high CVD risk there seemed to be a ceiling for these benefits. Specifically, the authors observed that the benefits of VPA diminished above 60 and 42 min/week among individuals with high and very high CVD risk, respectively. This interesting finding raises concerns about the one-size-fits-all PA recommendations, highlighting the need for personalized guidelines depending on participants’ characteristics (e.g. CVD risk). According to these results, while in an individual who presents a low CVD risk the current recommendation to perform up to ‘300 min MVPA with as much VPA as tolerated’ appears reasonable, in individuals categorized as high CVD risk the recommendations should be lower. These results should be, however, confirmed in other studies. Indeed, another study from the same cohort (UK Biobank) analyzed individuals with pre-existing CVD and observed that higher levels of VPA were inversely associated (albeit in a non-linear fashion) with the risk of mortality. Although health benefits were already highly remarkable with 45 min/week of VPA (50% reduction in all-cause mortality risk), higher VPA levels provided greater benefits. For instance, individuals performing 21–685 min of VPA had a ∼64% lower risk of CVD mortality compared with those not performing VPA, whereas the risk reduction was lower among individuals performing lower levels of PA (e.g. ∼33% risk reduction in those performing 11–20 min of VPA).8 Therefore, research is warranted to elucidate whether there is an upper limit of the health benefits of VPA depending on CVD risk. The findings by Yuan et al.5 open an interesting field of research, which should aim to individualize PA guidelines as much as possible. However, some limitations should be considered and addressed in future studies. These findings have been obtained from the UK Biobank cohort, and individuals in this cohort are healthier and less ethnically diverse than the general European population, facts that might limit generalizability. Moreover, due to the low representation of individuals older than 70 in the cohort, the generalization of the findings to these vulnerable populations should be confirmed.9 Most importantly, as an observational study causality remains inferential; randomized trials testing risk-stratified PA prescriptions are now urgently needed. Notwithstanding, the work of Yuan et al.5 complements recent calls for precision preventive cardiology and PA guidelines. The era of truly personalized CVD and physical activity recommendations has begun. It is now our responsibility (clinicians, researchers, and guideline developers) to translate these findings into routine practice and to test them in adequately powered randomized trials. The potential public-health gain is substantial: more effective, safer, and better-tolerated PA prescriptions that could meaningfully narrow the CVD burden across the entire risk spectrum. Alejandro Álvarez-Bustos [Writing—original draft (equal)], and Pedro L. Valenzuela (Conceptualization [lead], Writing—original draft, Writing—review & editing [equal]) P.L.V. is supported by a postdoctoral contract granted by Agencia Estatal de Investigacion (RYC2024-048275-I). This is a theoretical paper and requires no research data