RESUMO
Through bound apolipoprotein A-I (apoA-I), high-density lipoprotein cholesterol (HDL-C) activates endothelial nitric oxide synthase, inducing vasodilation. Because patients with sickle cell disease (SCD) have low apoA-I and endothelial dysfunction, we conducted a randomized, double-blinded, placebo-controlled trial to test whether extended-release niacin (niacin-ER) increases apoA-I-containing HDL-C and improves vascular function in SCD. Twenty-seven patients with SCD with levels of HDL-C <39 mg/dl or apoA-I <99 mg/dl were randomized to 12 weeks of niacin-ER, increased in 500-mg increments to a maximum of 1,500 mg/day, or placebo. The primary outcome was the absolute change in HDL-C level after 12 weeks, with endothelial function assessed before and at the end of treatment. Niacin-ER-treated patients trended to greater increase in HDL-C level compared with placebo treatment at 12 weeks (5.1 ± 7.7 vs 0.9 ± 3.8 mg/dl, 1-tailed p = 0.07), associated with significantly greater improvements in the ratios of low-density lipoprotein to HDL-C levels (1.24 vs 1.95, p = 0.003) and apolipoprotein B to apoA-I levels (0.46 vs 0.58, p = 0.03) compared with placebo-treated patients. No improvements were detected in 3 independent vascular physiology assays of endothelial function. Thus, the relatively small changes in HDL-C levels achieved by the dose of niacin-ER used in our study are not associated with improved vascular function in patients with SCD with initially low levels of apoA-I or HDL-C.
Assuntos
Anemia Falciforme/tratamento farmacológico , HDL-Colesterol/sangue , Endotélio Vascular/fisiopatologia , Lipídeos/sangue , Niacina/administração & dosagem , Vasodilatação/efeitos dos fármacos , Adolescente , Adulto , Idoso , Anemia Falciforme/sangue , Anemia Falciforme/fisiopatologia , HDL-Colesterol/efeitos dos fármacos , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Método Duplo-Cego , Endotélio Vascular/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Hipolipemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Recurrent foot ulceration is a major cause of morbidity in diabetic patients. Discrepancy between the stiffness of the plantar skin and underlying soft tissues may influence the likelihood of ulceration. Tissue properties change with diabetes primarily due to high blood glucose which promotes intermolecular cross-linking of structural proteins thus leading to altered structure and function of these structural fibers. This study utilizes a non-invasive method for indirectly assessing skin tissue in the context of plantar ulcer formation in diabetic patients' feet. Control (C, n=13), and diabetic subjects with a history of ulceration (n=16) were matched based on gender, age (42-81years old) and BMI. Six subjects re-ulcerated (U) during their 1-year follow-up. At every visit, each subject's plantar skin was excited with a weak laser light (337nm) to induce tissue fluorescence at three locations on each foot. The spectral area under the curve (AUC) was calculated after background subtraction and normalization. The mean AUC was significantly higher for diabetics compared to control subjects, (mean AUC: 145.6+/-7.2, C=112.6+/-8.3, respectively, p=0.006). For those who re-ulcerated (U, n=6), skin site was not a significant factor, but AUC was diminished at the time of re-ulceration (p<0.05). The alteration of intermolecular bonds in diabetic subjects and thinning of skin prior to ulceration could account for these observations. The decrease in AUC prior to an ulcer formation suggests its potential as a marker of tissue changes, which precede ulceration in the diabetic foot.