The HF-ACTION trial showed that among patients with heart failure, regular exercise reduces the risk for all-cause mortality or hospitalization. The benefits were modest, to be sure, but Steven J. Keteyian, PhD, and colleagues have reviewed the data to determine whether greater volumes of exercise correlate with greater reductions in clinical events.

There is at least some evidence suggesting that exercise is effective in a “dose-dependent” manner. In one study, the adjusted relative risk for mortality was reduced almost 20% in patients with coronary heart disease (CHD) who attended 25 or more cardiac rehabilitation (CR) sessions versus those attending fewer sessions.¹ Similarly, among Medicare beneficiaries with HF who attended 36 versus 12 CR sessions, all-cause mortality and myocardial infarction (MI) were both reduced approximately 18%.²

Not all data have been consistent: Taylor et al. dichotomized exercise dose on the basis of patients completing more or less than 1,000 units of exercise and found no association between dose of exercise and clinical outcomes.³

Moderate Exercise Matters

Now we have the new data from Dr. Keteyian, published in JACC.⁴ Almost 1,000 subjects randomized to the exercise training arm of HF-ACTION were followed for a median of 28 months. For the endpoint of cardiovascular mortality or HF hospitalization, exercise volume was a significant linear and logarithmic predictor.

Moderate exercise volumes of 3 to <5 and 5 to <7 MET-h per week (Metabolic Equivalent of Task hours) were associated with reductions in subsequent risk that exceeded 30%. (As a reminder of what activities fall within these ranges, see the TABLE.)

The authors said their study provides new and important information concerning the association between the volume of exercise completed per week and subsequent risk for clinical events in a large cohort of stable outpatients with systolic HF. The results confirm that moderate levels (3–7 MET-h per week) of activity result in a clinical benefit. (The term exercise carries all kinds of baggage for most people and discussing level of activity is likely a better approach with patients.) Interestingly, those who managed more than 7 MET-h per week showed a smaller decrease in adjusted risk than both the 3 to <5 MET-h per week and the 5 to <7 MET-h per week groups, perhaps suggesting a plateau effect or a reduced risk in general among patients who can manage that level of activity.

Both levels of exercise volume—3 to <5 and 5 to <7 MET-h per week—were associated with reductions in subsequent risk for both all-cause mortality or hospitalization and CV mortality or HF hospitalization that exceeded 30%.

Among all 1,159 patients randomly assigned to the exercise group in the HF-ACTION trial, only about 40% reported exercising at or above the protocol prescribed minimum number of minutes per week during the first 12 months. Clearly, maintaining an exercise program can be a challenge for the patient with HF, a behavior that is influenced both by pre-existing comorbidities and what the HF-ACTION investigators say are too few practitioners who routinely assess a patient’s health beliefs and self-efficacy for change.

The authors noted, “Our observation that a large decrease in adjusted risk for both clinical endpoints occurred among patients training at only 3 to 5 MET-h per week may be a potentially important motivating strategy, especially when counseling sedentary patients with HF who experience exercise intolerance and are reluctant to exercise.”

Can Exercise Prevent HF?

Dr. Keteyian and colleagues just demonstrated (above) that even moderate levels (3–7 MET-h per week) of activity produced a strong clinical benefit in patients with HF, but how is activity as preventive medicine?

Now deFilippi et al. report an analysis of nearly 3,000 participants in the CHS (Cardiovascular Health Study) composed of older adults (65 years of age and older) who were free of HF at study onset.⁵ They measured N-terminal pro–B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) levels at baseline and 2–3 years later. They had data on self-reported physical activity and walking pace which were then developed into a previously validated composite activity score.

They found that the probability of significant increases in both biomarker concentrations between baseline and follow-up visits was inversely related to physical activity scores. Compared with participants with the lowest score (worst), those with the highest activity scores (best) had half the risk of a significant rise in NT-proBNP and one-third as likely to have a rise in cTnT. A higher activity score was also associated with a lower long-term incidence of HF. These findings suggest that moderate physical activity has protective effects on early HF phenotypes.

Within three clinically relevant categories of activity (low, moderate, or high), increases in either biomarker identified those at increased risk of new-onset HF.

The association remained when analyzing only subjects free of significant comorbidity or those participants who perceived their health to be good, very good, or excellent. This supports the hypothesis that regular moderate physical activity can mitigate or delay progressive pathophysiological processes that ultimately result in symptomatic HF.

A Hint at Mechanisms

In an accompanying commentary, Christopher M. O’Connor, MD (editor-in-chief of JACC: Heart Failure), and Tariq Ahmad, MD, MPH (both of Duke University), said the study simultaneously addresses key questions about the role of exercise in HF among the elderly at the population and molecular levels.⁶ The incidence and prevalence of HF are growing dramatically in this age group, but current therapeutic agents have failed to yield substantial improvements in clinically relevant outcomes. They noted that data from nonrandomized and 14 small phase II randomized, controlled trials—as well as the landmark HF-ACTION trial—all support the conclusion that exercise training improves quality of life and exercise capacity, and reduces the risk of HF hospitalization.

Professional societies advocate regular physical activity and exercise training in patients with HF and recently published European guidelines have afforded these recommendations 1A status.⁷ Nonetheless, Drs. O’Connor and Ahmad note that this treatment modality remains significantly underused in real-world settings, and its effectiveness in elderly patients with early stage HF has not been well studied. So, the work by Dr. deFelippi and colleagues adds credence to the notion that this population, too, may benefit from exercise.

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References

1. Suaya JA, et al. J Am Coll Cardiol. 2009;54:25-33. http://content.onlinejacc.org/article.aspx?articleid=1139816
2. Hammill BG, et al. Circulation. 2010;121:63-70.
3. Taylor RS, et al. Am J Med. 2004;116:682-92.
4. Keteyian SJ, et al. J Am Coll Cardiol. 2012;60:1899-905. http://content.onlinejacc.org/article.aspx?articleid=1377004
5. deFilippi CR, et al. J Am Coll Cardiol. 2012;60:2539-47. http://content.onlinejacc.org/article.aspx?articleid=138970
6. O’Connor CM, Ahmad T. J Am Coll Cardiol. 2012;60:2548-49. http://content.onlinejacc.org/article.aspx?articleid=1389702
7. McMurray JJ, et al. Eur Heart J. 2012;33:1787-847.

Keywords: Prevalence, Incidence, Risk, Myocardial Infarction, Quality of Life, Exercise, Heart Failure, Comorbidity, Coronary Disease, Metabolic Equivalent, Medicare, Hospitalization

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