The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia

OBJECTIVES

The goal of this study was to determine the long-term effects of statins and antioxidant vitamins on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia.

BACKGROUND

Lipid-lowering therapy and antioxidant vitamins improve endothelium-dependent vasodilation in young and middle-aged adults with hypercholesterolemia, but their effects in older adults are not known.

METHODS

Two double-blind, placebo-controlled studies were performed in individuals ≥70 years old with low-density lipoprotein cholesterol (LDL-C) ≥140 mg/dl. In the first study, 37 subjects were randomized to receive (group 1) pravastatin for six months then pravastatin and vitamin E for six additional months or (group 2) vitamin E for six months, then pravastatin and vitamin E for six additional months. In the second study, additional 17 subjects sequentially received simvastatin for six months, then simvastatin and vitamins C and E for six additional months. Flow-mediated vasodilation of the brachial artery was measured by high-resolution ultrasound.

RESULTS

At baseline, subjects in both studies were similar in age (mean ± SD, 75.8 ± 4.2 years), gender, systolic blood pressure, total cholesterol (261.6 ± 37.4 mg/dl), LDL-C (180.3 ± 28.1 mg/dl), high-density lipoprotein cholesterol and triglycerides levels. Flow-mediated vasodilation was severely impaired (2.2 ± 3.9%). Both statins reduced total and LDL-C levels (p < 0.001); however, neither statin, antioxidant vitamin regimen nor the combination of statins and antioxidant vitamins improved flow-mediated vasodilation of the brachial artery. At baseline, nitroglycerin-mediated vasodilation also was impaired (10.7 ± 5.6%) and did not change in either study.

CONCLUSIONS

Older adults with hypercholesterolemia have impaired flow-mediated vasodilation of the brachial artery that does not improve after one year of therapy with statins and antioxidant vitamins, despite significant lipid-lowering.     

Efficacy of NVC‐422 in the treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model

Objectives Dermatophytes, belonging to genera including Trichophyton, Epidermophyton, and Microsporum, are the causative agents of superficial fungal infections, prevalences of which are estimated to be as high as 25% in the worldwide population. This study evaluated the activity of topical formulations of NVC‐422 (sodium 2‐[dichloroamino]‐2‐methylpropane‐1‐sulfonate), the lead compound in a new class of antimicrobials that consist of broad‐spectrum, fast‐acting, nonantibiotic antimicrobial molecules based on the endogenously produced N‐chlorotaurines. Methods The antifungal efficacy of NVC‐422 was investigated using a guinea pig model of infection with Trichophyton mentagrophytes. Infected guinea pigs were randomly assigned to four treatment and two control groups. The efficacy of the treatments was assessed clinically and mycologically at 72 hours after the final topical dose. Results The test compound 2% NVC‐422 in 1% Noveon Gel demonstrated the highest level of clinical efficacy. Outcomes of treatment with all other test compounds differed significantly from outcomes in the untreated control group (P = 0.003, P = 0.029, P = 0.012, and P < 0.0001, respectively). Fungal elements were detectable in skin sections from untreated guinea pigs but not in skin sections obtained from any of the treatment groups. Conclusions Evaluation of the efficacy of NVC‐422 in the treatment of dermatophytosis using an experimental guinea pig model showed that this compound possesses potent antifungal efficacy as measured by mycological and clinical endpoints. The highest degree of clinical and mycological efficacy was demonstrated by 2% NVC‐422 in 1% Noveon Gel. These data show that NVC‐422 has potent antifungal activity in vivo. Clinical evaluation of NVC‐422 in the treatment of superficial infections caused by dermatophytes, including onychomycosis, is warranted.