Publications (2)11.65 Total impact
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Article: Risk of cardiac events in patients with asthma and long-QT syndrome treated with beta(2) agonists.
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ABSTRACT: The clinical course and risk factors associated with beta(2)-agonist therapy for asthma have not been investigated previously in patients with the long-QT syndrome (LQTS). The risk of a first LQTS-related cardiac event due to beta(2)-agonist therapy was examined in 3,287 patients enrolled in the International LQTS Registry with QTc > or = 450 ms. The Cox proportional hazards model was used to assess the independent contribution of clinical factors for first cardiac events (syncope, aborted cardiac arrest, or sudden death) from birth through age 40. Time-dependent beta(2)-agonist therapy for asthma was associated with an increased risk for cardiac events (hazard ratio [HR] = 2.00, 95% confidence interval 1.26 to 3.15, p = 0.003) after adjustment for relevant covariates including time-dependent beta-blocker use, gender, QTc, and history of asthma. This risk was augmented within the first year after the initiation of beta(2)-agonist therapy (HR = 3.53, p = 0.006). The combined use of beta(2)-agonist therapy and anti-inflammatory steroids was associated with an elevated risk for cardiac events (HR = 3.66, p <0.01); beta-blocker therapy was associated with a reduction in cardiac events in those using beta(2) agonists (HR = 0.14, p = 0.05). In conclusion, beta(2)-agonist therapy was associated with an increased risk for cardiac events in patients with asthma with LQTS, and this risk was diminished in patients receiving beta blockers.The American Journal of Cardiology 10/2008; 102(7):871-4. · 3.37 Impact Factor -
Article: Peroxisome proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes.
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ABSTRACT: Dysregulation of fatty acid metabolism is important in the pathogenesis of type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR)alpha is a master regulator of fatty acid catabolism, and PPARalpha activators delay the onset of type 2 diabetes. We examined association between three PPARalpha gene polymorphisms (an A-->C variant in intron 1, the L162V variant, and the intron 7 G-->C variant) and age at diagnosis of type 2 diabetes in 912 Caucasian type 2 diabetic subjects. Individually, PPARalpha gene variants did not influence age at diagnosis, but in combination, the rare alleles of both the intron 1 A-->C (P < 0.001) and intron 7 G-->C (P = 0.025) variants synergistically lowered age at diagnosis (interaction P < 0.001). Overall, the PPARalpha haplotype signficantly influenced age at diagnosis (P = 0.027), with the C-L-C and C-V-C haplotypes (intron 1-L162V-intron 7) accelerating onset of diabetes by 5.9 (P = 0.02) and 10 (P = 0.03) years, respectively, as compared with the common A-L-G haplotype, and was associated with an odds ratio for early-onset diabetes (age at diagnosis </=45 years) of 3.75 (95% CI 1.65-8.56, P = 0.002). Intron 1 C-allele carriers also progressed more rapidly to insulin monotherapy (AA 9.4 +/- 1.5 and AC + CC 5.3 +/- 1.1 years, P = 0.002). These data indicate that PPARalpha gene variation influences the onset and progression of type 2 diabetes.Diabetes 03/2005; 54(2):582-6. · 8.29 Impact Factor
