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J Am Coll Cardiol, 2006; 47:398-402, doi:10.1016/j.jacc.2005.08.069 (Published online 22 December 2005).
© 2006 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: DIETARY FACTORS AND HEART DISEASE

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

Timothy E. Meyer, PhD*,{dagger}, Sándor J. Kovács, PhD, MD{dagger}, Ali A. Ehsani, MD*,{dagger}, Samuel Klein, MD*, John O. Holloszy, MD* and Luigi Fontana, MD, PhD*,{ddagger},*

* Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, Missouri
{dagger} Cardiovascular Biophysics Laboratory, Washington University School of Medicine, St. Louis, Missouri
{ddagger} Division of Human Nutrition, Istituto Superiore di Sanità, Rome, Italy

Manuscript received April 7, 2005; revised manuscript received July 26, 2005, accepted August 25, 2005.

* Reprint requests and correspondence: Dr. Luigi Fontana, Division of Geriatrics, Washington University School of Medicine, 4566 Scott Avenue, Box 8113, St. Louis, Missouri 63110 (Email: lfontana{at}im.wustl.edu).

OBJECTIVES: We determined whether caloric restriction (CR) has cardiac-specific effects that attenuate the established aging-associated impairments in diastolic function (DF).

BACKGROUND: Caloric restriction retards the aging process in small mammals; however, no information is available on the effects of long-term CR on human aging. In healthy individuals, Doppler echocardiography has established the pattern of aging-associated DF impairment, whereas little change is observed in systolic function (SF).

METHODS: Diastolic function was assessed in 25 subjects (age 53 ± 12 years) practicing CR for 6.5 ± 4.6 years and 25 age- and gender-matched control subjects consuming Western diets. Diastolic function was quantified by transmitral flow, Doppler tissue imaging, and model-based image processing (MBIP) of E waves. C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-{alpha}), and transforming growth factor-beta1 (TGF-ß1) were also measured.

RESULTS: No difference in SF was observed between groups; however, standard transmitral Doppler flow DF indexes of the CR group were similar to those of younger individuals, and MBIP-based, flow-derived DF indexes, reflecting chamber viscoelasticity and stiffness, were significantly lower than in control subjects. Blood pressure, serum CRP, TNF-{alpha}, and TGF-ß1 levels were significantly lower in the CR group (102 ± 10/61 ± 7 mm Hg, 0.3 ± 0.3 mg/l, 0.8 ± 0.5 pg/ml, 29.4 ± 6.9 ng/ml, respectively) compared with the Western diet group (131 ± 11/83 ± 6 mm Hg, 1.9 ± 2.8 mg/l, 1.5 ± 1.0 pg/ml, 35.4 ± 7.1 ng/ml, respectively).

CONCLUSIONS: Caloric restriction 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.

Abbreviations and Acronyms
  BMI = body mass index
  CR = caloric restriction
  CRP = C-reactive protein
  DF = diastolic function
  LV = left ventricle/ventricular
  MBIP = model-based image processing
  SF = systolic function
  TDI = tissue Doppler imaging
  TGF-ß1 = transforming growth factor-beta1
  TNF-{alpha} = tumor necrosis factor-alpha
  WD = Western diet




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