Polymorphisms of the beta(2)-adrenergic receptor determine exercise capacity in patients with heart failure.

The beta(2)-adrenergic receptor (beta(2)AR) exists in multiple polymorphic forms with different characteristics. Their relevance to heart failure (HF) physiology is unknown. Cardiopulmonary exercise testing was performed on 232 compensated HF patients with a defined beta(2)AR genotype. Patients with the uncommon Ile164 polymorphism had a lower peak VO(2) (15.0+/-0.9 mL. kg(-1). min(-1)) than did patients with Thr164 (17.9+/-0.9 mL. kg(-1). min(-1), P<0.0001). The percentage achieved of predicted peak VO(2) was also lower in patients with Ile164 (62. 3+/-4.5% versus 71.5+/-5.1%, P=0.045). The relative risk of a patient having a VO(2)

The Ile164 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure.

The beta2-adrenergic receptor (beta2AR), an important modulator of cardiac inotropy and chronotropy, has significant genetic heterogeneity in the population. Because dysfunctional betaARs play a role in the pathogenesis of the failing ventricle, we tested the hypothesis that beta2AR polymorphisms alter the outcome of congestive heart failure. 259 patients with NYHA functional class II-IV heart failure due to ischemic or dilated cardiomyopathy were genotyped and prospectively followed, with the endpoint defined as death or cardiac transplantation. The allele frequencies between this group and those of 212 healthy controls also were compared and did not differ between the groups. However, those with the Ile164 polymorphism displayed a striking difference in survival with a relative risk of death or cardiac transplant of 4.81 (P < 0.001) compared with those with the wild-type Thr at this position. Age, race, gender, functional class, etiology, ejection fraction, and medication use did not differ between these individuals and those with the wild-type beta2AR, and thus the beta2AR genotype at position 164 was the only clear distinguishing feature between the two groups. The 1-yr survival for Ile164 patients was 42% compared with 76% for patients harboring wild-type beta2AR. In contrast, polymorphisms at amino acid positions 16 (Arg or Gly) or 27 (Gln or Glu), which also alter receptor phenotype, did not appear to have an influence on the course of heart failure. Taken together with cell-based and transgenic mouse results, this study establishes a paradigm whereby genetic variants of key signaling elements can have pathophysiologic consequences within the context of a disease. Furthermore, patients with the Ile164 polymorphism and heart failure may be candidates for earlier aggressive intervention or cardiac transplantation.

Effect of weight loss and refeeding diet composition on anaerobic performance in wrestlers.

Collegiate wrestlers (N = 12) consumed a formula, hypoenergy diet (18 kcal.kg-1, 60% carbohydrate) without dehydration for 72 h. For the next 5 h, the athletes were fed either a 75% (HC) or a 47% (MC) carbohydrate formula diet of 21 kcal.kg-1. Each wrestler performed three anaerobic arm ergometer performance tests (TEST1, before weight loss; TEST2, after weight loss; TEST3, after refeeding). Blood withdrawn just before and after each test was analyzed for pH, bicarbonate, base excess, glucose, and lactate. Both groups had a similar significant reduction in total work done during TEST2 (92.4% of TEST1). Work done in TEST3 by HC was 99.1% of TEST1 while MC did 91.5% of their initial work (P = 0.1). Peak power was unaffected by the treatment. Plasma lactate significantly increased during the performance test from 1.72 to 21.91 mmol.l-1 as did plasma glucose from 4.88 to 5.25 mmol.l-1 when groups and trials were collapsed. Lactate accumulation was diminished during TEST2 compared with the other tests. Although the exercise bout reduced pH, bicarbonate, and base excess, there was no difference in the effect by group. In conclusion, weight loss by energy restriction significantly reduced anaerobic performance of wrestlers. Those on a high carbohydrate refeeding diet tended to recover their performance while those on a moderate carbohydrate diet did not. The changes in performance were not explained by the acid/base parameters measured.