Association of Physical Activity With Prognosis in CHD
Association of Physical Activity With Prognosis in CHD
In this observational study in more than 1000 patients with manifest CHD, we investigated the prognostic implications of self-reported leisure time physical activity. As expected, we observed evidence for a poorer prognosis in physically inactive patients. Furthermore, our data indicated a reverse J-shaped association of physical activity, especially with cardiovascular mortality: both inactive and daily active patients had increased hazards of mortality compared to the reference group of patients who were active 2 to 4 times per week, but with the hazards being highest in the inactive patient group.
Our data showed substantial decrease in engagement in physical activity over follow-up. The greatest and also a quite constant share of subjects were those who were moderately frequently active (2 to 4 times per week), which in our study was also the physical activity level that seemed to confer the greatest benefit in terms of survival. Pertinent current clinical practice guidelines however recommend physical activity on at least 5 days a week, which in our study was accomplished only in less than one third of the baseline sample with decreasing tendency over time, and which was associated with increased hazards of cardiovascular mortality. One possible explanation for our study findings not being in agreement with recommendations of current guidelines could be that these are mainly based on evidence from randomised controlled trials. Such trials undoubtedly are the gold-standard method when evaluating the efficacy of interventions such as cardiovascular rehabilitation, but may have limited external validity with regard to applicability to real-life conditions because they apply strict inclusion and exclusion criteria that might lead to an exclusion of subjects at highest risk for adverse outcomes. Such issues have also been criticised by a pertinent meta-analysis on the effectiveness of cardiovascular rehabilitation, which found that the population studied in the included trials was predominantly male, middle aged and at low risk, and thus not representative of usual clinical practice.
A potential explanation of our finding of worse prognosis in the most frequently physically active group could be that vigorous exercise increases the risk of ventricular arrhythmias and sudden cardiac death during or after exertion, especially in adults with heart conditions. While the risk of a cardiovascular event has been found to be low even during high-intensity exercise in a cardiovascular rehabilitation setting and especially with medical supervision, the risk could however be increased with unsupervised leisure time exercise of comparable intensity. Unfortunately, our data do not allow identifying whether the recorded deaths occurred in relation to physical activity.
The repeated measurement of physical activity provided us with the opportunity to account for changes in physical activity level over time. The first assessment of physical activity was at the year 1 follow-up and referred to the past 12 months, that is, to the first year after cardiovascular rehabilitation. Since lifestyle modifications that are achieved during rehabilitation are often not maintained in the long run, it is not unlikely that the first measurement at 12 months post-rehabilitation did not accurately reflect true long-term physical activity patterns. Considering only baseline level of physical activity, as done in previous studies with one notable exception, could therefore lead to an underestimation of the risk in the lowest activity group as demonstrated by a methodological study. This is supported by our results, which revealed higher HRs for inactive patients in the model taking time-dependence into account compared to the baseline prediction model with an identical set of adjustments. In addition, the HRs in the most active patient group tended to be underestimated in the baseline prediction models. Of note, besides accounting for changes in physical activity over time, using a medium exposure group as the reference group could also have contributed to reducing potential bias, since physically inactive subjects are possibly more likely to also have other unfavourable health behaviours or to have poorer health.
A major limitation of this study is the relatively crude assessment of our explanatory variable, which was solely based on self-report. The measure was further limited by relying on subjects' definitions of strenuous and sweat-inducing physical activity and not assessing type and intensity of activities. However, despite some potential for misclassification, solely assessing the time dimension of strenuous physical activity in our cohort of mostly older subjects with manifest CHD and frequent co-morbid conditions, whose abilities to exercise might be generally limited, could still be sufficient for ranking subjects with regard to their level of activity. In addition, even though the HRs in the most active group were consistently above 1 for the mortality outcomes, the confidence limits often included 1 and our results might thus also be due to chance. Although we believe that the consistency and robustness of our results support the general validity of our findings, a more detailed instrument would have provided the opportunity for more in-depth and confirmatory analyses.
Because patients with poorer health are less likely to engage in strenuous physical activity, reverse causation bias could have led to an overestimation of the hazards in the inactive patient group and to an underestimation in the most physically active. However, we adjusted for baseline history of co-morbid conditions and for self-reported poor health in order to limit the potential for bias.
Physical activity seemed to be most strongly associated with mortality outcomes, but it should be kept in mind that the presented endpoints are not distinct, with fatal cardiovascular events being a subset of both major cardiovascular events and all-cause mortality, which could partly explain similarities in observed associations.
Finally, although we carefully controlled for a number of potential confounders, we cannot rule out the possibility of residual confounding by imperfect measurement of characteristics or by unmeasured confounders.
To conclude, this study substantiated previous findings on the health benefits of physical activity in patients with manifest CHD: subjects who rarely or never engage in physical activity showed a substantially worse prognosis than those who were physically active for 2 to 4 times per week. Physical activity should thus be considered an integral part of a long-term secondary prevention strategy and further encouraged in inactive patients. In addition, consistent with the results of previous studies, despite differences in assessment of physical activity, we found that higher frequencies of physical activity did not confer additional benefit beyond that of physical activity of moderate frequency and duration, which suggests the existence of an upper limit for benefits. In some agreement with one previous study, our data even suggest that daily active subjects might have poorer prognosis compared to the moderately frequently active. Given the limitation of our physical activity assessment, further investigations of a potential reverse J-shaped association of physical activity with prognosis in CHD patients seem warranted. In order to inform recommendations on the optimal amount of physical activity for patients with cardiovascular disease, further research is particularly needed on whether there exists a threshold at which risks outweigh the benefits.
Discussion
In this observational study in more than 1000 patients with manifest CHD, we investigated the prognostic implications of self-reported leisure time physical activity. As expected, we observed evidence for a poorer prognosis in physically inactive patients. Furthermore, our data indicated a reverse J-shaped association of physical activity, especially with cardiovascular mortality: both inactive and daily active patients had increased hazards of mortality compared to the reference group of patients who were active 2 to 4 times per week, but with the hazards being highest in the inactive patient group.
Our data showed substantial decrease in engagement in physical activity over follow-up. The greatest and also a quite constant share of subjects were those who were moderately frequently active (2 to 4 times per week), which in our study was also the physical activity level that seemed to confer the greatest benefit in terms of survival. Pertinent current clinical practice guidelines however recommend physical activity on at least 5 days a week, which in our study was accomplished only in less than one third of the baseline sample with decreasing tendency over time, and which was associated with increased hazards of cardiovascular mortality. One possible explanation for our study findings not being in agreement with recommendations of current guidelines could be that these are mainly based on evidence from randomised controlled trials. Such trials undoubtedly are the gold-standard method when evaluating the efficacy of interventions such as cardiovascular rehabilitation, but may have limited external validity with regard to applicability to real-life conditions because they apply strict inclusion and exclusion criteria that might lead to an exclusion of subjects at highest risk for adverse outcomes. Such issues have also been criticised by a pertinent meta-analysis on the effectiveness of cardiovascular rehabilitation, which found that the population studied in the included trials was predominantly male, middle aged and at low risk, and thus not representative of usual clinical practice.
A potential explanation of our finding of worse prognosis in the most frequently physically active group could be that vigorous exercise increases the risk of ventricular arrhythmias and sudden cardiac death during or after exertion, especially in adults with heart conditions. While the risk of a cardiovascular event has been found to be low even during high-intensity exercise in a cardiovascular rehabilitation setting and especially with medical supervision, the risk could however be increased with unsupervised leisure time exercise of comparable intensity. Unfortunately, our data do not allow identifying whether the recorded deaths occurred in relation to physical activity.
The repeated measurement of physical activity provided us with the opportunity to account for changes in physical activity level over time. The first assessment of physical activity was at the year 1 follow-up and referred to the past 12 months, that is, to the first year after cardiovascular rehabilitation. Since lifestyle modifications that are achieved during rehabilitation are often not maintained in the long run, it is not unlikely that the first measurement at 12 months post-rehabilitation did not accurately reflect true long-term physical activity patterns. Considering only baseline level of physical activity, as done in previous studies with one notable exception, could therefore lead to an underestimation of the risk in the lowest activity group as demonstrated by a methodological study. This is supported by our results, which revealed higher HRs for inactive patients in the model taking time-dependence into account compared to the baseline prediction model with an identical set of adjustments. In addition, the HRs in the most active patient group tended to be underestimated in the baseline prediction models. Of note, besides accounting for changes in physical activity over time, using a medium exposure group as the reference group could also have contributed to reducing potential bias, since physically inactive subjects are possibly more likely to also have other unfavourable health behaviours or to have poorer health.
A major limitation of this study is the relatively crude assessment of our explanatory variable, which was solely based on self-report. The measure was further limited by relying on subjects' definitions of strenuous and sweat-inducing physical activity and not assessing type and intensity of activities. However, despite some potential for misclassification, solely assessing the time dimension of strenuous physical activity in our cohort of mostly older subjects with manifest CHD and frequent co-morbid conditions, whose abilities to exercise might be generally limited, could still be sufficient for ranking subjects with regard to their level of activity. In addition, even though the HRs in the most active group were consistently above 1 for the mortality outcomes, the confidence limits often included 1 and our results might thus also be due to chance. Although we believe that the consistency and robustness of our results support the general validity of our findings, a more detailed instrument would have provided the opportunity for more in-depth and confirmatory analyses.
Because patients with poorer health are less likely to engage in strenuous physical activity, reverse causation bias could have led to an overestimation of the hazards in the inactive patient group and to an underestimation in the most physically active. However, we adjusted for baseline history of co-morbid conditions and for self-reported poor health in order to limit the potential for bias.
Physical activity seemed to be most strongly associated with mortality outcomes, but it should be kept in mind that the presented endpoints are not distinct, with fatal cardiovascular events being a subset of both major cardiovascular events and all-cause mortality, which could partly explain similarities in observed associations.
Finally, although we carefully controlled for a number of potential confounders, we cannot rule out the possibility of residual confounding by imperfect measurement of characteristics or by unmeasured confounders.
To conclude, this study substantiated previous findings on the health benefits of physical activity in patients with manifest CHD: subjects who rarely or never engage in physical activity showed a substantially worse prognosis than those who were physically active for 2 to 4 times per week. Physical activity should thus be considered an integral part of a long-term secondary prevention strategy and further encouraged in inactive patients. In addition, consistent with the results of previous studies, despite differences in assessment of physical activity, we found that higher frequencies of physical activity did not confer additional benefit beyond that of physical activity of moderate frequency and duration, which suggests the existence of an upper limit for benefits. In some agreement with one previous study, our data even suggest that daily active subjects might have poorer prognosis compared to the moderately frequently active. Given the limitation of our physical activity assessment, further investigations of a potential reverse J-shaped association of physical activity with prognosis in CHD patients seem warranted. In order to inform recommendations on the optimal amount of physical activity for patients with cardiovascular disease, further research is particularly needed on whether there exists a threshold at which risks outweigh the benefits.
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