Exercise: moderation is best for the heart

Exercise can benefit with surprisingly little effort and time as documented by recent studies, but like everything else there is a dose-response curve, meaning that the effect of exercise varies with the dose (intensity, duration). Now there is more evidence that exercising too intensively can do harm, particularly to the cardiovascular system. A study just published in the journal Heart associates too frequent intense physical activity (5 hours or more per week) at age 30 significantly increases the risk for atrial fibrillation. The authors sought to examine..

"...the influence of physical activity at different ages and of different types, on the risk of developing atrial fibrillation (AF) in a large cohort of Swedish men...We hypothesised that leisure-time exercise (considered as moderate-intensity to high-intensity activity) increases the risk of developing AF later in life, while walking/bicycling for transportation (low-intensity to moderate-intensity) decreases the risk."

They collected data on physical activity 44,410 men aged 45–79 years without atrial fibrillation at baseline in 1997 that included the amount of time spent and type of activity throughout their lives. They were then followed-up in the Swedish National Inpatient Register for ascertainment of AF. The data revealed a surprising association:

"During a median follow-up of 12 years, 4568 cases of AF were diagnosed. We observed a RR [relative risk] of 1.19 of developing AF in men who at the age of 30 years had exercised for >5 h/week compared with <1 h/week. The risk was even higher (RR 1.49) among the men who exercised >5 h/week at age 30 and quit exercising later in life (<1 h/week at baseline). Walking/bicycling at baseline was inversely associated with risk of AF (RR 0.87 >1 h/day vs almost never) and the association was similar after excluding men with previous coronary heart disease or heart failure at baseline."

The authors discuss important considerations based on age and intensity:

"This study, comprising 44 010 men followed for a median of 12 years, showed a complex association between physical activity and development of AF. High levels of leisure-time exercise (ie, exercising for more than 5 h a week), considered as moderate to high-intensity physical activity at the age of 30 years, was associated with an increased risk of AF later in life...The risk of AF was even greater (RR 1.49) among men who had exercised more than 5 h/week at the age of 30 years, and were inactive when they were older (mean age 60 years)...Our finding of an increased risk of AF with a high level of leisure-time exercise at a younger age is in agreement with the Physicians’ Health Study, a large prospective cohort study where subgroup analyses showed a 74% increased risk of AF associated with a high frequency of vigorous exercise (5–7 days/week) in men <50 years of age. Furthermore, previous case series and retrospective studies have found an increased risk of AF in young athletes and middle-aged men engaged in high-intensity exercise or endurance training."

But the benefits of exercise for older age must be maintained, and...

"Our data did not show that leisure-time exercise in older age (mean age in the cohort at baseline is 60 years) increased the risk for AF. Furthermore, our data showed no increase in risk of AF with walking or bicycling at any age. In fact, walking or bicycling in older age was inversely associated with risk of AF, a finding that is consistent with the results found in the Cardiovascular Health Study."

As for what would cause an increase in the risk for atrial fibrillation at higher exercise intensities:

"We think that a potential explanation for the different effects of exercise on the risk of AF depending on age could be because in older ages, the positive effects of physical activity on risk factors for AF dominate over the potential negative effects. Moreover, leisure-time exercise may be of lower intensity at an older age than at age 30 years."

The authors summarize their findings:

"In conclusion, our results suggest that a high level of leisure-time exercise (moderate-intensity to high-intensity physical activity) in younger men is associated with an increased risk of AF later in life, and that the increase in risk becomes even higher for those who quit exercising later in life. On the other hand, walking/bicycling (low-intensity to moderate-intensity) at an older age seems to reduce the risk of AF, a finding that might be due to positive effects on several traditional cardiovascular risk factors."  

Another study published in the same issue of Heart presents evidence that while physical inactivity is certainly a risk factor, daily strenuous exercise increased the risk of dying from cardiovascular disease. Referring to current guidelines for exercise in secondary prevention of cardiovascular disease the authors state:

"While such recommendations are based on numerous clinical trials clearly showing that exercise-based cardiac rehabilitation improves prognosis in heart disease patients, only a few prospective studies have examined the potential benefit of physical activity in clinical practice under real-life conditions...In this study, we investigated the association of leisure time physical activity level with prognosis in a cohort of patients with coronary heart disease (CHD). We were especially interested in the dose–response relationship with different levels of physical activity and also took changes in physical activity level during long-term follow-up into account."

So they analyzed data for 1038 subjects with stable CHD over 10 years of follow-up to assess the association of physical activity level with different outcomes of major cardiovascular events, cardiovascular mortality, all-cause mortality. Consonant with the study described above, a J-shaped pattern emerged:

"A decline in engagement in physical activity over follow-up was observed. For all outcomes, the highest hazards were consistently found in the least active patient group, with a roughly twofold risk for major cardiovascular events and a roughly fourfold risk for both cardiovascular and all-cause mortality in comparison to the reference group of moderately frequent active patients. Furthermore, when taking time-dependence of physical activity into account, our data indicated reverse J-shaped associations of physical activity level with cardiovascular mortality, with the most frequently active patients also having increased hazards (2.36, 95% CI 1.05 to 5.34)."

In other words, the least active group did the worst for cardiovascular and all-cause mortality, but the most active fared significantly more poorly than the moderately active group. The authors elaborate on their results:

"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."

Speculating on the reasons for the increased mortality in daily active group...

"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."

Clinical note: office assessment of heart rate variability is an invaluable tool in examining cardiac risk as well as a broad analysis of autonomic nervous system function.The authors summarize their findings:

"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."

 In an editorial accompanying these two studies published in Heart E. Guasch and L. Mont state:

"Physical activity aggravating ischaemic heart disease seems counterintuitive, but it is supported by previous small studies. Using calcium score assessment or cardiac MRI, ultra-endurance runners have been suggested to have increased coronary artery disease. Correlating with exercise duration and intensity, endurance training induces an acute, reversible proinflammatory state, which might mediate atherosclerotic processes if prolonged enough. Patients with a pre-existing cardiovascular condition, such as those studied by Mons et al, develop a significant proinflammatory state at lower exercise doses. A crossover study in patients with ischaemic heart disease demonstrated that daily 60 min intense training promoted an inflammatory state and increased aortic wall stiffness, but opposite effects were found in a shorter, 30 min, daily intensive training regimen."  

It broadens our perspective to note in this context a research just published in BMJ showing that greater time spent in light physical activity significantly reduces disability independent of higher levels of activity. The authors set out to...

"...investigate whether objectively measured time spent in light intensity physical activity is related to incident disability and to disability progression."

They used accelerometer monitoring to ascertain physical activity in 1680 community dwelling adults aged 49 years or older with knee osteoarthritis or risk factors for knee osteoarthritis and found that even an hour more per day of light physical activity can impart significant benefit.

"These prospective data from a large study of diverse community dwelling adults with or at high risk of knee osteoarthritis showed a significant and consistent relation between greater time spent in light intensity activity and a reduced risk of development or progression of disability. Our findings confirm that more moderate-vigorous activity time was related to less subsequent onset and progression of disability. Importantly, greater light activity time, independent of time spent in moderate-vigorous intensity activity, was significantly related to reduced risk and progression of disability. Our findings provide encouragement for adults who may not be candidates to increase the intensity of physical activity owing to health limitations. Greater daily physical activity time may reduce the risk of disability, even if the intensity of that additional activity is not increased."

Here I think we can appreciate the virtue of 'stand-up' desks whose height is easily adjusted to permit working while standing. Clinical bottom line: Exercise and physical activity are crucial but as with everything else recommendations should be tailored for the individual. There is a dose-response relationship, especially with exercise, and at a certain more can be worse than better. The editorialists in Heart comment:

"Research aiming at providing a safety threshold that avoids ‘exercise overdose’ and permits maximisation of benefits is warranted. Drca et al and Mons et al identify >5 h/week and daily intense exercise as thresholds for increased AF incidence and cardiovascular events, respectively. These values should be considered solely as vague guidelines and might have little value in exercise counselling. In the clinical setting, an individualised mechanistic approach aiming to identify individuals at risk and detect the development of a deleterious substrate might better serve to titrate an optimal individualised dose of exercise...The beneficial effects of exercise are definitely not to be questioned; on the contrary, they should be reinforced. The studies reviewed here and future studies will serve to maximise benefits obtained by regular exercise while preventing undesirable effects—just like all other drugs and therapies."