Long-Term Caloric Restriction Ameliorates the Decline in Diastolic Function in Humans

Study subjects

Twenty-five subjects practicing CR for 3 to 15 years (mean age 53 ± 12 years; range 35 to 82 years; 21 men, 4 women) were compared with 25 age- and gender-matched subjects eating typical Western diets (WD) using a cross-sectional design. None of the subjects had evidence of chronic disease or smoked. None of the subjects were taking lipid-lowering or antihypertensive agents or other medications. All participants were weight stable (<2 kg weight change in the preceding six months) and did not perform more than 20 min of vigorous exercise twice per week. The Human Studies Committee of Washington University School of Medicine approved the study, and all subjects gave informed consent before their participation.

Anthropometrics and body composition

Body weight was obtained in the morning after an overnight fast. Body fat mass was determined by dual-energy X-ray absorptiometry (DXA) (QDR 1000/w, Hologic, Waltham, Massachusetts).

Dietary assessment

Subjects recorded all food and beverages consumed and portion sizes for seven consecutive days. Food records were analyzed using the NDS-R program (version 4.03_31), which is the Nutrition Data System for research from the Nutrition Coordinating Center at the University of Minnesota (5).

Laboratory analyses

Commercial ELISA kits were used to measure serum TNF-α (Quantakine High Sensitive, R&D Systems, Minneapolis, Minnesota), high-sensitivity CRP and TGF-β₁(American Laboratory Products Company Diagnostics, Windham, New Hampshire).

Echocardiography

A standard two-dimensional Doppler echocardiographic examination was performed with an echocardiographic imaging system (Hewlett-Packard SONOS 5500, Andover, Massachusetts) (6). Doppler transmitral flow velocity images were acquired in the apical four-chamber view according to American Society of Echocardiography criteria (6). Mitral annular velocities were recorded via pulsed wave tissue Doppler imaging (TDI) technique (7,8). For technical reasons, Doppler flow and TDI measurements were not made in all subjects.

Data analysis

Left ventricular SF was determined from fractional shortening (systolic shortening) calculated via the conventional equation (8). Standard DF indexes were measured from the transmitral Doppler E- and A-wave contours (8). Additional DF indexes were obtained by subjecting E- and A-waves to model-based image processing (MBIP) on the basis of a kinematic model of filling that was previously validated via simultaneous cardiac catheterization and echocardiography (9–11). Three mathematically independent parameters (x_o, c, k) were determined from the clinical Doppler E-wave by MBIP. The parameters account for the amplitude (load), decay rate (viscosity/relaxation), and width (average chamber stiffness) of the E-wave contour, respectively (Fig. 1)(9–11).

• Download figure
• Open in new tab
• Download powerpoint

Figure 1

The model-based image processing (MBIP) method of quantitative diastolic function assessment using the Doppler image as input. MSE = mean square error; MVE = maximum velocity envelope; PDF = parameterized diastolic filling.

Statistical analysis

A Student ttest was used to evaluate the significance of differences between groups when variables were normally distributed with approximately equal standard deviations. For variables not normally distributed or with unequal standard deviations, the Mann-Whitney test was used. Statistical significance was set a priori at p < 0.05 for all tests. All data were analyzed with a commercially available statistical package (SPSS FOR WINDOWS version 10.0, SPSS Inc., Chicago, Illinois). Data are expressed as means ± SD.

Study participants

The characteristics of the study subjects are shown in Table 1.Values for body mass index (BMI) in the WD group were similar to the mean range for middle-aged people in the U. S. (12). Values for body weight, BMI, and blood pressure for 18 CR subjects before they began CR are shown along with their current values in Table 2.

Nutrient intake

The WD group ate a typical WD providing approximately 2,445 ± 470 kcal/day, approximately 17% protein, approximately 52% carbohydrates, approximately 31% fat, approximately 11% saturated fat. The CR subjects ate a nutritionally balanced diet (4) (at least 100% of the Recommended daily intake for each nutrient) providing approximately 1,671 ± 294 kcal/day (p = 0.0001 vs. WD group), approximately 23% protein, (p = 0.0001 vs. WD group), approximately 49% complex carbohydrates, approximately 28% fat, approximately 6% saturated fat. Daily salt intake was lower in the CR group compared with the WD group (2.6 ± 1.3 g vs. 3.4 ± 1.0 g; p = 0.007).

Cardiac function

No difference in LV fractional shortening was detected between the two groups (Table 3).Although E-wave peak was not different between groups, early filling fraction was greater in the CR group (Table 3). A waves of the CR group had less evidence of aging-related changes than those of the WD group. As a result, the peak E-wave to peak A-wave (E/A) ratio was greater in the CR group than in the WD group. Deceleration time was increased in the WD group, trending toward the “delayed relaxation pattern” of filling. The increased E-wave duration was solely due to increased deceleration time, because acceleration time was not different between groups.

The velocity assessed at the mitral annulus from both the lateral and septal aspects during early LV filling (E′) was significantly higher in the CR group than in the WD group (Table 3), and cand kwere lower in the CR group than in the WD group (Table 3).

Blood analyses

Serum CRP, TNF-α, and TGF-β₁concentrations were lower in the CR group than in the WD group (p < 0.05) (Table 1).

Study limitations

Because our study was not randomized, our cross-sectional study design does not allow us to assign causation, although the observed significant differences on the basis of cross-sectional data are an important first-step in elucidating the effects of long-term CR in humans. Another minor limitation is that some echocardiographic parameters were not obtained in all subjects for technical reasons.

Conclusions

We conclude that CR has cardiac-specific effects that ameliorate aging-associated changes in DF. These beneficial effects on cardiac function might be mediated by the effect of CR on blood pressure, systemic inflammation, and myocardial fibrosis.