Regular leisure-time physical activity (LTPA) of at least 500 to 1000 metabolic equivalent of task (MET)-minutes per week without upper limits is consistently advised in patients at high cardiovascular risk [1], based on the evidence of its advantages in lowering the incidence and mortality of cardiovascular disease (CVD) [2]. Nevertheless, in this population, left ventricular hypertrophy (LVH) is a prevalent condition related to poor prognosis, and has a complicated relationship with LTPA at different levels [3, 4, 5]. Several studies have shown that moderate LTPA intensity and duration was related to a reduced risk of LVH and might produce regression of LVH among high-cardiovascular risk patients [6, 7, 8]. In contrast, some studies found that strenuous physical activity was linked with increased left ventricular mass, which may induce hypertrophy, moreover increase the risk of death [9, 10, 11, 12]. In healthy individuals, exercise is commonly linked with benign and reversible cardiac remodeling [9]. Nonetheless, in individuals with certain predisposing risk factors such as electrical cardiac abnormalities and pathological hypertrophy, etc., high-intensity exercise might be linked with an unfavorable prognosis and increased risk of mortality [13]. High-risk cardiovascular populations exhibited multiple risk factors, including hypertension, diabetes, etc., which might contribute to electrical cardiac remodeling, myocardial fibrosis, and pathological hypertrophy [14].

In this case, the influence of LVH on the dose-response association between LTPA and mortality risk in high-risk cardiovascular populations remains unknown. In other words, whether the benefits of moderate to high volumes of LTPA regarding mortality risk could be modified by the presence of LVH has not been extensively studied. This is critical for providing tailored prevention measures, particularly in high cardiovascular risk population.

Therefore, we analyzed the data from a national population-based cohort, with standardized echocardiography conducted in individuals with high cardiovascular risk at baseline. We aimed to evaluate whether the existence of LVH alters the associations between LTPA levels and all-cause and cardiovascular mortality risks.

In this study involving a large cohort of high CVD risk individuals with or without LVH, we identified significant associations between moderate and high volumes of LTPA and the risk of deaths from all causes or CVD. The correlation patterns appeared distinct between those with LVH and those without. Overall, the associations were not modified by the presence of LVH, despite high LTPA volumes being linked with increased LVMI; while interestingly, the modification of LVH was significant in females regarding all-cause mortality risk.

Both the LVH and LVH-free populations may derive some benefit from moderate and high LTPA, although the dose-relationship of LTPA and mortality risk in the LVH group differs from that of the general population. Our finding was consistent with the results from a prior study including 3078 of the general population, which showed that moderate and high LTPA were linked with a decreased risk of death both in individuals with normal blood pressure and hypertensive patients with a high prevalence of LVH [23]. Moreover, in our study, we extended their result by illustrating the dose-relationship between LTPA and mortality risk in the LVH and non-LVH populations, providing additional evidence that patients with LVH should engage in sufficient volumes of regular physical activity. Notably, in our large-scale study, information on medication and intensity and duration of LTPA was collected, and the latter was quantified as MET-min/week according to the intensity and duration of certain activities, making the results more robust [24]. And this could address the shortcomings of a previous study regarding its small sample size and lack of information on antihypertensive medication information. Additionally, our study focuses on populations at high cardiovascular risk without established CVD and provides fresh insights into the influence of physical exercise on outcomes for this specific group, which had not been accurately characterized in earlier research [23].

High LTPA was more effective than moderate and low LTPA in lowering all-cause mortality risk in the population with LVH. A possible explanation is that high volume LTPA may involve cardiac adaptations which could improve prognosis. Previous studies have demonstrated that long-term strenuous exercise could result in detrimental heart remodeling, including cardiac enlargement, inappropriate myocardial thickening and other abnormalities of diastolic dysfunction [9, 10, 11]. However, these studies focused mostly on athletics and certain specific trainings. Our study indicates that even high volumes of daily physical activity would not increase the risk of mortality in non-athletes, and the increase in volume may be associated with cardiac fitness. Similarly, it is plausible to hypothesize that inappropriate remodeling of the heart may be associated more with the intensity than with the volumes of LTPA. Previous studies have observed that LVH regression could be achieved by pharmacological treatment [25, 26] and modest physical activity (PA) [27, 28], which is consistent with our findings. Additionally, we observed a significantly lower LVMI at about 2000 MET-min/week of LTPA volumes across the subgroups of a high cardiovascular risk population, despite the fact that increased levels of physical activity or exercises were related to a rise in LV mass in patients without LVH at baseline and Asian athletes [11, 23, 29]. The different designs of the study populations might contribute to this contrast. Individuals with high CVD risk factors may be in a different risk category. Therefore, LTPA may have a different effect on their left ventricular mass.

Interestingly, the modification of LVH between LTPA and mortality risk was pronounced in the female population. The PA levels in females were found to be different from those in males both in the healthy and CVD population [30, 31]. Although the precise underlying processes have not been identified, one possible explanation could be females’ particular LV anatomy and high sensitivity to the advantages of LTPA. Females have smaller hearts, which makes the LV more sensitive to myocardial fibrosis [32, 33]. In contrast to males, females tended to have poorer glucose absorption and utilization, higher fatty acid intake and metabolic inefficiency [34], and increased vagal tone due to sex hormones [35]. Additionally, myocardial fibrosis [36], myocardial substrate [37, 38], and autonomic nervous system [39] were the targets of PA on prognosis, which may strengthen the modification of LVH regarding the benefits of LTPA on mortality risk. Overall, the modification of LVH was not significant in the overall population regarding the effects of LTPA on risk of deaths, which could be partly explained by the increased LTPA influence on deaths through its beneficial effect on improving vascular endothelial function [40], lowering blood pressure levels [41], increasing insulin sensitivity, and decreasing CVD risk profiles [42]. These positive effects of LTPA on other established risk factors might affect their interaction, rather than LTPA itself. Nonetheless, the reason for the observed modification is likely to be multi-factorial, which merits further evaluation.

Our study has several clinical implications. First, this study provides new insights into the preventive effects of moderate to high LTPA in LVH patients with high cardiovascular risk. Second, it demonstrates that individuals with LVH tend to acquire lower LTPA levels. In addition to being typically older and suffering from various comorbidities, their myocardial dysfunction impairs their physical performance. Nonetheless, clinicians should emphasize to their patients the value of an active lifestyle. The patients should be encouraged to increase their regular LTPA volume; above 2000 MET-min/week could be considered an applicable requirement for LVH individuals for reducing mortality risk, while volumes above 500 MET-min/week could be beneficial for those without LVH. Third, and more importantly, women are more likely to have LVH, and a regular high LTPA is required to attenuate the mortality risk in LVH individuals. It is probable that women will experience notable advantages, potentially resulting in a decrease in the utilisation of alternative treatments such as pharmaceutical interventions.

Limitations of this study should be acknowledged. First, LTPA was self-reported and whether the LTPA levels changed during the follow-up period was unknown. A large-scale study, however, had verified the accuracy of the PA-related questions [17]. Therefore, we made an assumption that the recollection bias could be minimal. Second, despite rigorous statistical adjustments, it is not possible to exclude the presence of unadjusted confounding factors, such as cardiorespiratory fitness, which was linked to a better prognosis [43]. Notwithstanding these constraints, the majority of participant variables deemed pertinent to mortality risk were incorporated into the models. The findings were robust in sensitivity analysis, thereby enhancing the credibility of the conclusion. However, limited statistical power was observed in some subgroups due to an inadequate sample size.

In conclusion, our findings indicated that LVH does not significantly modify the link between LTPA and mortality risk in the overall high cardiovascular risk population. However, the presence of LVH altered this correlation in females regarding the all-cause mortality risk.

BMI, body mass index; BSA, body surface area; CVD, cardiovascular disease; China PEACE MPP, China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project; CI, confidence interval; DBP, diastolic blood pressure; FBG, fasting blood glucose; HR, hazard ratio; ICD-10, International Classification of Diseases, 10th edition; LTPA, leisure-time physical activity; LVM, left ventricular mass; LVMI, left ventricular mass index; LVH, left ventricular hypertrophy; MET, metabolic equivalent of task; PA, physical activity; SD, standard deviation; SBP, systolic blood pressure.

The China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project (China PEACE MPP) data that supported this study are restricted and not publically available. Data are available upon reasonable request and with China PEACE MPP authorization. China PEACE MPP grants conditional data access to qualified researchers with valid requests. Please contact http://cvd-project@nccd.org.cn to seek approval for data access.

XZ, XL and HJJ designed the research study. XL conceived of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project (China PEACE MPP) and takes responsibility for all aspects of it. HD, JLC, BWC, CQW, XYZ, and YW participated in the project operation. XLW, HD, JLC, BWC, CQW, XYZ, AXT and YW made substantial contributions to the data acquisition process. HJJ analyzed the data. BWC performed the validation. HJJ wrote the manuscript, with further contributions from XZ, XL, XLW, AXT, HD, JLC, BWC, CQW, XYZ, and YW. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. All authors contributed to editorial changes in the manuscript and approved the final manuscript.

The study was conducted following the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Fuwai Hospital, Beijing, China (Approval No. 2014-574). All participants provided their informed consent in writing.

We appreciate the multiple contributions made by study teams at the National Center for Cardiovascular Diseases, and the local sites in the collaborative network in the realms of study design and operations.

This research was funded by the CAMS Innovation Fund for Medical Sciences (CIFMS), grant number [2021-I2M-1-011].

The authors declare no conflict of interest.