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Exercise May Reverse Negative Cardiac Effects of Sedentary Life

Patrice Wendling
January 10, 2018

Two years of exercise begun in middle age can restore the heart's elasticity in previously sedentary adults and forestall the development of heart failure (HF) with preserved ejection fraction (HFpEF), results of a randomized study suggest.

"If you look at all the studies of patients with HFpEF, they all have small, stiff hearts with very rapid rises in filing pressure during exercise, and stiff blood vessels with impaired ventriculoarterial coupling; and what this kind of exercise training did was reverse the process that leads towards HFpEF," senior author, Dr Benjamin Levine (University of Texas Southwestern Medical Center, Dallas), said in an interview.

Levine and his colleagues have previously shown that sedentary seniors have small, stiff left ventricles (LVs) similar to those in patients with HFpEF, whereas older, competitive Masters athletes who trained at least 6 days a week over their lifetime have large, compliant LVs that look like those of a healthy 30-year-old.

Yet when the researchers put sedentary seniors (mean age, 70 years) through 1 year of moderate-intensity exercise training five to six times a week, they found little effect on LV stiffness; other work suggested that the heart makes the transition to the aged phenotype of reduced cardiac plasticity in middle age.

"We realized that starting at age 70 was too late and maybe 1 year was too short; so after we defined when in the aging process this stiffening begins, we thought, let's see if we can find the sweet spot and see if we can reverse it and that was the essence of this study," Levine explained.

To that end, 61 healthy, sedentary middle-aged (45 to 64 years) adults were randomly assigned to 2 years of yoga and balance training or supervised exercise training four to five times a week, totalling about 150 to 180 minutes.

The regimen included three to four 30- to 45-minute moderate-exercise sessions for the first 3 months, with either frequency or duration increased each month. Aerobic intervals were then added, consisting of so-called 4 � 4 sessions (4 minutes of exercise at 95% peak heart rate [HR] followed by 3 minutes of active recovery at 60% to 75% peak HR, repeated four times). Each interval day was followed by a recovery day that included 20 to 30 minutes of walking or light aerobic activity.

By the sixth month, the exercise group was training 5 to 6 hours per week, including two interval sessions, and one long (≥1 hour) and one 30-minute session performed at moderate intensity, meaning the participant would break a sweat but still be able to carry on a conversation. One to two weekly strength-training sessions were also prescribed.

Participants began a maintenance phase at 10 months, with training adjusted to reflect test results. To keep it fresh and avoid injuries, participants were encouraged to use a variety of exercise equipment and to exercise outdoors.

Most exercise sessions were not supervised, but all were tracked by using HR monitors. Adherence to the exercise program was 88% at 2 years, with a total of 53 participants completing the 2-year study, led by Dr Eric Howden (Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia) and published January 8 in Circulation.

At 2 years, maximal oxygen uptake (VO2max), a measure of exercise capacity, increased 18% in the exercise group and decreased 1.0% among controls (5.3 vs –0.3 mL/kg/min; P<0.0001).

LV stiffness, calculated by curve fit of the diastolic pressure-volume curve, was reduced in the exercise group (stiffness constant, 0.072 to 0.051; P=0.0018), with no change in controls (stiffness constant, 0.063 to 0.062; P=0.83).

"If you look at the curve, it's flattened and shifted to the right, and that is exactly what you see in an athletic heart," Levine said. "So this is not only a statistically but also a physiologically significant difference.

"It's an extraordinary reversal of the stiffening that occurs in the heart with sedentary living."

Exercise training increased LV end-diastolic volume compared with the control intervention (7.1 vs –1.0 mL/m2; P<0.001), while pulmonary capillary wedge pressure (PCWP) was unchanged, allowing for greater stroke volume for any given filling pressure in the exercise group (pre-/postexercise P=0.001; loading condition P=0.0075).

Exercise training lowered participants' heart rate from 63 to 58 beats/min (P=0.0003), while heart rate remained constant at 64 beats/min in the control group. Blood pressure was unchanged in either group.

Commenting for | Medscape Cardiology, Dr Carl "Chip" Lavie (medical director of cardiac rehabilitation and prevention, Ochsner Health System, New Orleans, LA), who was not involved in the study, said the study was small and had relatively soft endpoints, although its strength lies in being a randomized controlled trial with marked improvements in exercise capacity.

"An 18% improvement in VO2max is quite dramatic considering that the average improvement in VO2max in the HF-ACTION trial was only a 4% or 5% increase," he said in an email. "The improvement in LV stiffness should translate to reduced risk of HF with preserved ejection fraction, but this is theoretical."

Lavie said further research is needed to determine whether adherence to the 2-year exercise program translates into major reductions in hard endpoints, such as HF events or hospitalizations and mortality.

Industry-supported trials are unlikely, Levine said. However, epidemiological evidence suggests that each 1-metabolic equivalent increase in exercise capacity is associated with a 13% and 15% reduction in all-cause and cardiovascular disease mortality, respectively. Lower HR also has been associated with reductions in mortality, independent of fitness levels.

Limitations of the study are the evaluation of LV pressure curves by use of mean PCWP as a surrogate for LV end-diastolic pressure; enrolling volunteers willing and able to participate in an intensive exercise regimen; and the predominantly white cohort (about 80%), which may limit generalizability of the findings to other racial groups, the authors write.

As for whether middle-aged sedentary adults will adhere to the intensive exercise regimen, Levine said they can if exercise is viewed as part of their daily routines, like bathing or brushing their teeth, and if the decision is supported by the healthcare system.

"Remember, sedentary aging sets the stage for HFpEF by causing a small, stiff heart," he said. "Since our exercise intervention reversed this pathophysiology, and HFpEF is such a common, problematic disease, efforts to reduce it in an aging population should be high priority."

He continued: "Instead of just paying for pills, what our medical-industrial complex should pay for is the infrastructure to support physical activity. Why should the physical therapist be paid for someone after they have a knee operation but not be paid when someone has reduced physical activity on their Physical Activity Vital Sign?"

Large medical groups, such as Kaiser Permanente California, are already using the Physical Activity Vital Sign in their electronic medical records to flag patients for physical activity counseling, with Southwestern Medical recently following suit, Levine said. A recent American Heart Association scientific statement,[2] which Levine and Lavie coauthored with others, also emphasizes the importance of assessing cardiorespiratory fitness as part of the global assessment of individual health.

"I think the momentum is building for tracking physical activity, for improving exercise," Levine said. "You can nay-say all you want, but exercise training is among the most powerful tools we have."

This study was supported by a National Institute on Aging grant. Levine was also supported in part by the American Heart Association Strategically Focused Research Network. Lavie has disclosed no relevant financial relationships.

SOURCE: Medscape, January 10, 2018.

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