“AGING,
FITNESS AND FAILURE”: EFFECTS OF AGE AND PHYSICAL ACTIVITY ON CARDIOVASCULAR
STRUCTURE AND FUNCTION
Benjamin
D. Levine
Institute for Exercise and
Environmental Medicine,
Aging leads to a loss of functional
capacity which is compounded by reductions in physical activity. Indeed, we demonstrated recently that 3
weeks of bedrest causes a greater reduction in
maximal oxygen transport than 30 years of aging. Comprehensive invasive assessment of LV
performance and pressure-volume (p/v) relations as well as Doppler assessment
of relaxation demonstrated that healthy but sedentary aging leads to: 1) a
leftward and upward shift of the diastolic p/v curve leading to increased
static chamber stiffness and decreased distensibility; 2) this change in
cardiac compliance can be prevented by life-long endurance training – Masters
athletes (>25 yrs training) have p/v curves that are identical to young
individuals; 3) despite this clear preservation of cardiac compliance,
life-long training does NOT prevent the slowing of ventricular relaxation
associated with aging.
Specifically, across a wide range of cardiac filling pressures (LVEDP
from ~ 3 mmHg to ~ 20 mmHg) IVRT was much slower in both sedentary
seniors and Masters athletes compared to young controls at any given level of
cardiac filling, with no effect of fitness; myocardial relaxation velocities
(TDI) were also slower in both senior groups, as was propagation velocity. Thus life-long endurance training has
differential effects on static vs dynamic diastolic function. We are currently studying the “dose” of
exercise that is required to obtain the maximum protective effects on
cardiovascular structure with aging.
Using these same methods, we recruited a
highly selected set of patients with heart failure and a preserved ejection
fraction (HFpEF) to compare with healthy, aged matched controls. As a group, HFpEF patients had p/v
curves that were shifted even further upward and leftward compared to healthy
seniors. On closer inspection
though, there was a marked gender difference in these curves: male HFpEF patients had much stiffer
hearts than their healthy sedentary controls; however female HFpEF patients hearts were not any stiffer than sedentary aged
matched women; both groups had static chamber stiffness that was equivalent to
the male HFpEF patients. TDI
velocities were much slower in HFpEF patients than sedentary seniors. Surprisingly, despite marked reductions
in VO2max in HFpEF patients compared to age matched controls, their cardiac
power output reserve was the same, and the increase in cardiac output per unit
increase in oxygen uptake was dramatically elevated, to a level typically seen
in patients with mitochondrial myopathies. These data
suggest that: 1) compared to healthy sedentary seniors, male HFpEF patients
have hearts that are stiffer and relax much more slowly; 2) both healthy,
sedentary senior females and female HFpEF patients have hearts that are equally
as stiff and slowly relaxing as HFpEF men, providing at least one explanation
why this disease is more prevalent in women. During exercise, a reduced capacity for
mitochondrial oxidation leads to a signal for elevated cardiac output during
exercise which given their stiff, slowly relaxing hearts provide the substrate
for dyspnea and exercise intolerance.
Key words: aging, diastolic function, heart failure,
exercise capacity