CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Timothy E. Meyer, PhD,
Sándor J. Kovács, PhD, MD,
Ali A. Ehsani, MD,
Samuel Klein, MD,
John O. Holloszy, MD and
Luigi Fontana, MD, PhD*
* Division of Geriatrics, Washington University School of Medicine, 4566 Scott Avenue, Box 8113, St. Louis, Missouri 63110 (Email: lfontana{at}im.wustl.edu).
We appreciate the views expressed by Dr. Johnson and colleagues regarding our recent study (1) concerning caloric restriction (CR) and diastolic function (DF). We agree that in large population studies, diastolic dysfunction, body mass index (BMI), and adiposity are correlated. It would be ideal to have a BMI and body-fat–matched control group that is healthy and not calorie restricted. However, it is self-evident that such a control group is not readily available. It would be extremely difficult to find healthy individuals, other than extreme endurance athletes, who have a BMI <20 kg/m2 who are not calorie restricted. Individuals with a BMI <20 kg/m2 who are not endurance athletes or calorie restricted are generally in ill-health and frail or heavy smokers. Endurance exercise training causes major cardiovascular adaptations, so athletes are also not an appropriate control group. The control group in our study consisted of individuals typical of the U.S. population, as 78.2% of the men and 68.1% of the women older than 40 years are overweight or obese in the U.S. (2).
In our study (1) we provided evidence that, in humans, long-term CR with optimal nutrition (at least 100% of the recommended daily intake for each nutrient) results in very low levels of inflammation, as demonstrated by low serum C-reactive protein and tumor necrosis factor-alpha concentration, and reduced left ventricular stiffness, indicated by the lower model-based image processing–derived chamber stiffness parameter k and viscoelastic chamber constant c. We also found that CR is associated with low serum concentrations of transforming growth factor-beta, a powerful pro-fibrotic molecule that plays a role in regulating the myocardial composition of the extracellular matrix, thus potentially having salutary effects on k and c (3).
In contrast, individuals who are very thin owing to chronic diseases generally have elevated levels of systemic inflammation and have diastolic dysfunction despite a low BMI (4–6). For the group considered, long-term CR is the cause, and the coexistent low BMI is one effect. Conversely, we are not aware of any mechanism by which a low BMI, as an independent variable, can improve DF. The improved DF observed is mediated by other CR effects, such as lowering blood pressure and decreasing the levels of inflammatory cytokines, hormones, and growth factors that may reduce fibrosis, increase compliance, and improve cardiac efficiency.
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References
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- Meyer TE, Kovacs SJ, Ehsani AA, Klein S, Holloszy JO, Fontana L. Long-term caloric restriction ameliorates the decline in diastolic function in humans J Am Coll Cardiol 2006;47:398-402.[Abstract/Free Full Text]
- Ogden CL, Carroll, MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999–2004 JAMA 2006;295:1549-1555.[Abstract/Free Full Text]
- Brooks WW, Conrad CH. Myocardial fibrosis in transforming growth factor-ß1 heterozygous mice J Mol Cell Cardiol 2000;32:187-195.[CrossRef][ISI][Medline]
- Broekhuizen R, Wouters EF, Creutzberg EC, Schols AM. Raised CRP levels mark metabolic and functional impairment in advanced COPD Thorax 2006;61:17-22.[Abstract/Free Full Text]
- Yilmaz R, Gencer M, Ceylan E, Demirbag R. Impact of chronic obstructive pulmonary disease with pulmonary hypertension on both left ventricular systolic and diastolic performance J Am Soc Echocardiogr 2005;18:873-881.[CrossRef][ISI][Medline]
- Arslan S, Bozkurt E, Ali Sari R, Erol MK. Diastolic function abnormalities in active rheumatoid arthritis evaluation by conventional Doppler and tissue Dopplerrelation with duration of disease. Clin Rheumatol 2006;25:294-299.[CrossRef][ISI][Medline]
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