Vigorous Exercise May Be Best for Longevity in Stable CHD

Marlene Busko

October 11, 2017

AUCKLAND, NEW ZEALAND — In a large, global observational study of patients with stable coronary heart disease (CHD), those who reported the highest levels of physical activity were less likely to die of all causes or cardiovascular causes during a median follow-up of 3.7 years vs those who were sedentary[1].

However, even minimal exercise below current recommendations was associated with a 33% mortality risk reduction compared with being sedentary.

The study by Dr Ralph AH Stewart (University of Auckland, New Zealand) and colleagues was published in the October 3, 2017 issue of the Journal of the American College of Cardiology.

The researchers analyzed data from more than 15,000 patients from 39 countries who had stable CHD and were enrolled in the previously reported Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) clinical trial.

These new findings suggest two main messages, Stewart told | Medscape Cardiology in an email. "First, we observed that the lowest mortality was in people who had the highest levels of physical activity," he said, but they also showed that the decrease in mortality predicted by increasing physical activity is much greater for people who are sedentary.

"Doubling the amount of physical activity was associated with a greater reduction in mortality at low compared with high levels of exercise," he added. "The amount of exercise needed to double usual physical activity is small when you are sedentary."

The study "confirmed that taking no or little exercise is particularly hazardous for health, and mortality risk decreases significantly with relatively modest increases in physical activity, below those recommended in current guidelines," Stewart pointed out.

These "novel insights inform us about effective exercise regimens for secondary prevention" but need to be confirmed, Dr Thijs MH Eijsvogels (Radboud University Medical Center, Nijmegen, the Netherlands) and Dr Martijn FH Maessen (Liverpool John Moores University, UK) write in an accompanying editorial[2].

"In the interim, patients and clinicians should remember that a little is good, more is better, and vigorous is best," they summarize.

This latter finding "is important for patients," editorialist Eijsvogels told | Medscape Cardiology, "as it highlights that every minute of exercise is beneficial for your health."

So physicians can advise patients that "if you cannot achieve the national exercise recommendations (150 min/week), try to perform exercise at a volume that is feasible for you." The study findings "emphasize the potency of exercise as medicine for secondary prevention," he said.

Potent Medicine

Previous studies assessing the benefits of physical activity for cardiac patients mainly focused on supervised exercise training as part of a cardiac-rehabilitation program, Eijsvogels noted, and did not "provide insight in the dose-response relationship between exercise and clinical outcomes."

Stewart and colleagues aimed to determine the association between physical activity and mortality, MI, and stroke in patients with stable CHD who participated in the STABILITY trial. As previously reported, results of this trial showed darapladib (GlaxoSmithKline, London, UK), an investigational selective inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), failed to lower the risk of cardiovascular mortality, MI, or stroke in patients with stable coronary heart disease.

The researchers identified 15,486 patients who were enrolled in STABILITY and had chronic stable CHD (defined as prior MI, PCI, CABG, or angiography-confirmed multivessel CHD) plus at least one other CV risk factor and had provided information about physical activity.

The participants had a mean age of 65, and 19% were female. They filled in a questionnaire where they reported the typical number of hours a week they spent doing mild physical activity (walking, yoga, Tai Chi, mild housework), moderate physical activity (fast walking, jogging, aerobics, gardening, bicycling, dancing, swimming, or house cleaning), and vigorous exercise (running, lifting heavy objects, playing strenuous sports, or doing strenuous work).

They also reported how active they were at work and during leisure time.

The researchers converted the information to metabolic equivalent [MET] hours/week, by assigning 2 METs for mild, 4 METs for moderate, and 8 METs for vigorous exercise.

The patients were then grouped into three tertiles of mean physical activity (least active, 14 MET hours/week; intermediate activity, 40 MET hours/week; and most active, 90 MET hours/week), and they were also grouped into categories representing approximate doubling of exercise volume.

The researchers also determined Age, Biomarkers, Clinical–Coronary Heart Disease (ABC-CHD) risk score of the patients, which estimates risk of CV death based on N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, LDL cholesterol, smoking, type 2 diabetes, and peripheral arterial disease.

Compared with patients in the least active tertile, those in the intermediate and most active tertiles had lower risks of all-cause mortality, CV mortality, and non-CV mortality during follow-up, after adjustment for multiple variables. Patients who were most active also had a lower risk of major adverse coronary events (MACE).

However, there were no significant differences in rates of MI or stroke across the three tertiles.

Risk of Outcomes, Intermediate and Most Active v Least Active Tertile*

Outcome Physical activity HR (95% CI) P
All-cause mortality Intermediate 0.75 (0.65– 0.87) <0.001
Most active 0.70 (0.60–0.82)
CV mortality Intermediate 0.89 (0.74–1.06) 0.0052
Most active 0.71 (0.58–0.88)
Non-CV mortality Intermediate 0.54 (0.41–0.72) <0.001
Most active 0.73 (0.55–0.96)
MACE Intermediate 0.96 (0.85 – 1.08) 0.0054
Most active 0.81 (0.71 – 0.92)
*Outcomes during a 3.7-year follow-up; HR adjusted for multiple variables

This "suggests regular exercise does not improve outcomes just by reducing atherosclerotic disease events," Stewart said. "The possible mechanisms for benefit from physical activity were not investigated in this study," but "it is likely exercise has multiple favorable effects on health."

The reduced risk of death during follow-up that was associated with increased exercise was greatest in patients who were sedentary or had dyspnea, significant renal dysfunction, diabetes, or a higher ABC-CHD risk score, which shows that "high-risk patients, who are often more cautious about physical activity, had the greatest benefits associated with more exercise."

Study Limitations, Clinical Implications

Patients may have reported being more active than they actually were, but this "suggests the true association may be even stronger than what was measured," Stewart said.

Patients with low physical activity may have been in poor health, so randomized trials are needed to confirm that increasing physical activity reduces early mortality in CHD patients.

In the meantime, the trial suggests that "people who are sedentary have the greatest potential to gain from increasing physical activity, and even modest increases are likely to be important, " according to Stewart.

"For people who are already active, the benefits of further increases are more modest and for most, advice to maintain and enjoy the current level of exercise is probably okay," he said. "However, advice needs to be individualized and will be influenced by what is likely to be achievable and accepted."

To Eijsvogels and Maessen, the data suggest that "as little as 10 min/day of brisk walking (ie, 3.5 mph) is associated with a risk reduction for all cause mortality. For those unable to walk at a brisk pace, 15 to 20 min/day at a slower pace (2 to 2.5 mph) will yield similar benefits."

The low volume of this minimal effective dose may stimulate patients to incorporate feasible physical-activity goals in their daily lives and may also eliminate barriers, such as insufficient time or self-confidence, to become physically active, they note.

"For cardiac patients who already regularly exercise, and thus benefit from their active lifestyle, adding a bout of vigorous exercise training or high-intensity interval training may further reduce their mortality risk," Eijsvogels.

"It is also important to emphasize that findings from this study clearly demonstrate that cardiac patients cannot exercise too much, as the highest dose of exercise was associated with the lowest mortality risk," he noted.

"We did not identify any increased risk associated with more physical activity, but for vigorous exercise there was no additional benefit from prolonged compared with less," Stewart said.

The researchers call for more study to find "simple strategies that encourage regular exercise in sedentary patients with stable coronary disease and . . . randomized trials to confirm that increasing exercise and reduced mortality are causally related."

The STABILITY trial and the lifestyle substudy were funded by GlaxoSmithKline. Stewart has received grants and nonfinancial support from GlaxoSmithKline. Disclosures for the coauthors are listed in the paper. Eijsvogels is supported by a European Commission Horizon 2020 grant and Maessen is supported by an INTERREG VA grant.

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