Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Erectile Dysfunction and Subsequent Cardiovascular Disease

The presence of erectile dysfunction (ED) has recently been recognized to commonly be a consequence of endothelial dysfunction. Indeed, some have suggested that ED may be an indicator of existing vasculopathy in the same way angina, intermittent claudication, or TIA reflect vascular compromise.

The Prostate Cancer Prevention Trial population (n = 18,882) was designed to investigate the impact of finasteride upon incidence of prostate cancer in healthy men. As part of the data accrual, assessment of sexual function at baseline and on followup was performed. Because finasteride can affect sexual function, only the placebo group data (n = 9,457) were used for analysis. In this group, 85% were free of cardiovascular disease at baseline.

Although approximately half of the men were free of ED at baseline, by the 5-year mark of the study, 57% of these had developed it. Amongst these men (incident ED), there was a 25% increased hazard ratio for new cardiovascular events. Amongst all men with ED (incident plus present at study initiation), the hazard ratio for a new cardiovascular event was increased by 45%.

ED predicts increased risk of new cardiovascular events. The magnitude of association is as strong as that of cigarette smoking or family history. Men with ED should be encouraged to have close scrutiny and appropriate modification of their cardiovascular risk factors.

Thompson IM, et al. JAMA. 2005;294: 2996-3002.

Oseltamivir Resistance during Influenza A Infection

No one doubts that influenza can extract dread consequences on a grand scale. Some degree of complacency may have been fostered by the development of highly effective oral agents for the treatment of influenza A and B, such as the neuraminidase inhibitors oseltamivir (OTV) and zanamivir. Clinicians share a great respect for the capacity of bacteria to develop resistance to antibiotics; there is little corresponding awareness of the role of viral resistance in antiviral therapeutics.

The H5N1 influenza virus (FLU-H5N1) is particularly ominous in its adverse outcomes and potential for pandemic spread. There has been great hope that agents like OTV might provide adequate treatment or prophylaxis for FLU. Unfortunately, resistance to antivirals, including OTV, might become problematic.

De jong et al provide data from Vietnam about 8 cases of FLU-H5N1. In 2 of the patients, neuraminidase amino acid substitution resulted in OTV resistance; both of these patients died. Amongst the other 6 patients, prompt reductions in FLU-H5N1 viral load was correlated with survival: 2 of 6 patients (without resistance) who failed to evidence a prompt reduction in viral load succumbed.

These sobering data suggest that OTV alone may be insufficient to ensure successful treatment of some evolving strains influenza virus. It may be that a 2-drug regimen will be required to grapple with the potential for emergence of resistant strains, or when failure of monotherapy to promptly reduce viral load occurs.

de Jong MD, et al. N Engl J Med. 2005;353:2667-2672.

Dietary Intake of Antioxidants and AMD

Age-related macular degeneration (AMD) is the most prevalent cause of blindness in first-world nations. Although vitamin and antioxidant supplementation has not fulfilled its blush of initial promise for cardiovascular end points, data on supplements of beta carotene, vitamin C, vitamin E, and zinc indicate a beneficial slowing of AMD progression. Whether dietary intake (apart from supplements) is associated with AMD was the subject of this study.

Rotterdam, the Netherlands was the source of this population-based study (n = 10,725) of socioeconomically middle-class adults older than age 55 (mean age, 68). Early AMD was defined by the presence of drusen (white retinal deposits). All study subjects underwent photographic evaluation of their fundi. All subjects completed food diaries. Follow up was 8 years.

There was an inverse relationship between vitamin E and zinc intake and AMD. Each 1-standard deviation increase in dietary intake was associated with an 8-9% decrease in AMD. Overall intake of vitamin C, E, beta carotene, and zinc above the median was associated with approximately one-third less risk of new AMD. Interestingly, among those in the highest quintile of dietary intake, adding supplements did not appear to affect risk reduction. These observational data suggests that diet may have a meaningful impact upon risk of AMD.

van Leeuwen R, et al. JAMA. 2005;294:3101-3107.