Effects of age and aerobic fitness on myocardial lipid content

Abstract

Background: Aging and sedentary lifestyles lead to cardiac atrophy, ventricular stiffening, and impaired diastolic function. Both conditions are marked by increased adiposity, which can lead to ectopic fat deposition in nonadipocyte tissues including the myocardium. The effect of excess intramyocardial fat on cardiac function in nonobese individuals is unknown.

Methods and results: Cardiac lipid content was measured by magnetic resonance spectroscopy in 153 healthy nonobese subjects with varying fitness levels quantified by peak oxygen uptake during treadmill exercise. Cardiac function (echo) and left ventricular (LV) filling pressures (right heart catheterization) were measured under varying preloads. LV stiffness was calculated from a curve fit of the diastolic portion of the pressure-volume curve. The strongest clinical predictors of lipid content were body mass index (β=+0.03; 95% confidence interval, 0.001-0.06) and peak oxygen uptake (β=-0.02; 95% confidence interval, -0.03 to -0.009; R(2)=0.14; P<0.001). Subjects in the highest quintile had smaller LV end-diastolic volumes (68±13 versus 58±12 mL/m(2); P<0.01) and decreased peak early mitral annular and increased peak late mitral inflow velocities. There were no differences in LV stiffness, but a leftward shift in the pressure-volume curve suggested a less distensible ventricle with increasing myocardial lipid levels. After adjusting for age, fitness, and body mass index, echocardiographic and morphometric differences among groups were attenuated and no longer significant.

Conclusions: Body mass index and fitness levels are the strongest predictors of myocardial lipid content in nonobese humans. Cardiac lipid content is associated with decreased ventricular distensibility, and it may provide a causal mechanism linking changes in LV function related to age and fitness.

Keywords: aging; exercise; ventricular remodeling.

Figure 1. Localized Cardiac ¹H Magnetic Resonance Spectroscopy

Representative ¹H spectra from a subject with high (5^th Q) and low (1^st Q) cardiac lipid % with peak signal intensity at 1.4 ppm. Myocardial triglyceride content was calculated as a percentage of area relative to myocardial water intensity at 4.8 ppm.

Figure 2. Peak VO₂ by Cardiac Lipid Quintile

Distribution of peak VO₂ by lipid quintiles with 1^st quintile containing subjects with lowest levels of cardiac lipid. Solid boxes represent interquartile (25–75%) range and solid line represents median value within quintile. Error bars encompass 5–95% range and outliers beyond this range are signified by solid black dots.

Figure 3. End-diastolic pressure volume relationship in lowest (Q1) and highest (Q5) quintiles of cardiac lipid content

End diastolic volumes (EDV) were obtained from 3-dimensional echocardiography and indexed to BSA. Stiffness constants (s) were derived from an exponential curve fit. While LV stiffness for subjects in the highest and lowest quintiles were similar, indexed EDV for the highest quintile was smaller under varying preloads (main effect by lipid quintile p<0.01; 2 way repeated measures ANOVA) suggesting a less distensible LV with increasing myocardial lipid content. There were no differences in PCWP between quintiles. PCWP – pulmonary capillary wedge pressure. Values are mean ± SE.