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ROCHESTER, Minn., Jan. 20 -- Exercise may be good for the heart, but good diastolic function also appears to protect the capacity for exercise, researchers found.

Any level of resting diastolic dysfunction, whether moderate-to-severe or mild, substantially lowered exercise capacity (both PJournal of the American Medical Association.

Their cross-sectional study of echocardiography patients revealed a reduction in exercise capacity with increased resting and post-exercise left ventricular filling pressures as well (both P=0.007).

These findings, if validated, may offer a way to halt the progressive decline in exercise capacity that comes with age and has been linked to worsening functional capacity, disability, quality of life, and less independence, the researchers said.

"Unlike many other factors that are an inevitable consequence of aging," they wrote, "diastolic dysfunction may be a preventable factor in the development of exercise intolerance."

This was encouraging, the researchers noted, because the most consistently reported factor accountable for declining exercise capacity with age -- reduction in maximal heart rate -- appeared unavoidable.

Dr. Pellikka's group studied 2,867 consecutive patients undergoing exercise echocardiography with routine measurements of left ventricular systolic and diastolic function by two-dimensional and Doppler techniques at the Mayo Clinic in 2006.

The study included only those patients who did not have echocardiographic evidence of exercise-induced ischemia, ejection fractions lower than 50%, or significant valvular heart disease.

Compared with patients who had normal diastolic function, the 27% with mild diastolic dysfunction and 10% with moderate-to-severe dysfunction had a significant reduction in exercise capacity (-0.70 and -1.30 metabolic equivalents [METs], respectively, both P
These findings in the multivariate analysis were significant despite adjustment for resting heart rate, blood pressure, medication use, comorbid medical conditions, and other echocardiographic parameters.

Diastolic dysfunction was among the strongest independent predictors of reduced ability to exercise in the multivariate analysis, along with older age, female sex, and high body mass index.

Notably, the effect of even mild diastolic dysfunction was twice that of a 10-beat-per-minute decrease in resting heart rate (-0.70 versus -0.24 MET) or the effects of smoking, beta-blocker use, hypertension, or diabetes (-0.27 to -0.43 METs).

Co-author Garvan C. Kane, M.D., of the Mayo Clinic, said his group was surprised by magnitude of the association and the degree to which it explained exercise performance.

Normal variation of ejection fraction did not correlate with exercise capacity.

But left ventricular filling pressures measured by a ratio of 15 or greater for early mitral inflow velocity to peak early diastolic velocity of the medial mitral annulus predicted reduced exercise capacity whether at rest or after exercise (both -0.41 METs, P=0.007).

Mild diastolic dysfunction or elevated resting filling pressures were associated with progressively greater reduction in exercise capacity with older age (PP=0.02, respectively).

The researchers suggested that one mechanism for the effect of diastolic parameters on exercise capacity might be through their role in generating maximal cardiac output.

"Abnormalities in diastolic relaxation and filling of the left ventricle can result in filling rates that might be too low to achieve adequate cardiac output during exercise even if ventricular systolic properties are normal," they wrote.

The most promising route to reverse this effect is treatment with angiotensin receptor blockers, Dr. Pellikka's group said, since these "block angiotensin II action that is thought to be responsible for slowed left ventricular relaxation during exercise."

Until this is better studied, "current approaches should include aggressive treatment of risk factors such as hypertension and coronary artery disease to prevent development of diastolic abnormalities and related exercise limitations," they concluded.

The authors noted that "although this is a very large study characterizing the association of age and sex with exercise capacity, results are limited to patients in whom a complete echocardiographic assessment as outlined was possible."

They also pointed out several other limitations including the fact that "because patients recruited into our study were middle-aged and referred for a clinically indicated stress echocardiogram, there is the potential for a referral bias related to a higher prevalence of comorbidities." They said that they did not ascertain whether patients had anemia or obstructive lung disease."

The study was supported in part by a grant from the National Center for Research Resources, by the NIH Roadmap for Medical Research, and by the Mayo Foundation. The researchers reported no conflicts of interest.

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