Cardiovascular risk at the extremes of body composition
Article Outline
Abbreviations: AN, Anorexia nervorvosa, apo, Apolipoprotein, HOMA-IR, Homeostasis model assessment, IL, Interleukin
Prevalence estimates for anorexia nervosa (AN) range from 0.1% to 1% in the general population, with an average prevalence of approximately 0.29% in girls.1 The mortality rate associated with this condition is high (5.9%-18%),1 and death is mainly attributed to cardiac events stemming from electrical abnormalities such as prolonged QT interval. Individuals with AN also demonstrate cardiac systolic2 and diastolic3 dysfunction and adverse myocardial remodeling.2 Many of these problems are corrected or improved with weight regain.4, 5
See related article, p 763
The limited data that exist suggest that, similar to AN in adults, AN in adolescents is associated with cardiac structural (decreased left-ventricular mass and wall thickness),3, 4, 5 functional (diastolic dysfunction),3 and electrical (prolonged QT interval and bradycardia) abnormalities.4, 6 Like in adults, in adolescents most of these abnormalities seem to be reversible or improved with re-feeding and weight regain.4, 5, 6 Little is known about the presence of the traditional risk factors for atherosclerotic cardiovascular disease in AN. Reports from the adult literature are mixed. Some studies show that AN is associated with lipid derangements and increased levels of inflammatory cytokines, and others show that these variables are not altered. There are currently no reports in the literature addressing this question in adolescents.
In this issue of The Journal, Misra et al7 report the findings of a small study comparing traditional and emerging markers of cardiovascular risk in adolescent girls with AN and healthy control subjects. In this study, as expected, girls with AN demonstrated hormonal dysregulation compared with healthy control subjects. However, girls with AN had a striking discordance in cardiovascular risk markers. They found that apolipoprotein-B (apo-B), apo-B/HDL, apo-B/LDL, and interleukin-6 (IL-6) levels were increased in girls with AN compared with control subjects, suggesting elevated cardiovascular risk; however, fasting insulin, homeostasis model assessment insulin resistance (HOMA-IR), triglycerides, leptin, and C-reactive protein levels were lower than in control subjects, suggesting decreased cardiovascular risk. The cardiovascular risk factors reported in this study behaved somewhat erratically; the interrelationships observed were very different from the traditional associations reported in other populations.
Although the associations among traditional cardiovascular risk factors for atherosclerotic disease are complicated in patients with AN, the main message of the study by Misra et al7 is that markers of cardiovascular risk are uncoupled in relation to body fatness in this condition. It is clear that AN is not simply an extreme form of healthy leanness, but rather a complicated pathophysiological state with a number of severe metabolic and hormonal disturbances that are difficult to interpret from the standpoint of traditional atherosclerotic cardiovascular risk. Current views on the role of adiposity on subclinical inflammation suggest that increased body fatness has a central role in the increased levels of cytokines such as IL-6 and tumor necrosis factor-α. In contrast, it is likely that in patients with AN, hormonal imbalances and other less well understood factors, but not body fat, are driving the uncharacteristic relationships among many of the cardiovascular risk factors measured in this study. Insulin resistance, an established cardiovascular disease risk factor, was decreased in patients with AN. One can speculate that this reduction in insulin resistance might be related to the abnormally low levels of fat mass and the known delay in pubertal maturation associated with AN and may not reflect reduced cardiovascular risk as observed in healthy populations.
Another important message of this study is that many markers of cardiovascular risk, in particular inflammatory factors, improve with weight gain in patients with AN. For example, IL-6 levels decreased with weight gain, paralleled by increases in the levels of estradiol, leptin, and T3 and decreases in the level of cortisol. These improvements in hormone levels with weight gain do not explain all the changes in cardiovascular risk factors, because no differences were noted for apo-B and other lipid variables.
Thus, it appears that at the extremes of body composition, whether referring to anorexia or obesity, there is an increase in cardiovascular disease risk burden, although by different mechanisms. Even modest improvements in these conditions can significantly decrease cardiovascular risk. As shown in the study by Misra et al,7 when patients with AN move toward a more healthy body weight with modest weight gain (10% increase in body mass index), improvements occur in both hormone and inflammatory cytokine levels. Similarly, on the other end of the spectrum, moderate weight loss in overweight adolescents results in improvements in many components of the cardiovascular risk factor profile, such as dyslipidemia and insulin resistance.8 By understanding the reversibility of the cardiovascular burden, one can advocate that early and aggressive intervention toward reaching a healthier weight should be undertaken in these patients. This is of particular importance in the current era of obesity and disordered eating behaviors.
References
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- Uncoupling of cardiovascular risk markers in adolescent girls with anorexia nervosa. J Pediatr. 2006;149:763
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PII: S0022-3476(06)00981-4
doi:10.1016/j.jpeds.2006.10.050
© 2006 Mosby, Inc. All rights reserved.
Refers to article:
- Uncoupling of cardiovascular risk markers in adolescent girls with anorexia nervosa
