Clinical Briefs in Primary Care
November 1, 2002 6 minutes read
Source: Heart Protection Study Collaborative Group. Lancet. 2002;360:23-33.
Observational studies have indicated that intake of antioxidant vitamins (AOV), such as vitamins E, C, and beta-carotene, is inversely related to incidence of vascular disease. It has been postulated that this favorable relationship might be mediated, at least in part, through the demonstrated in vitro inhibition of LDL oxidation afforded by AOV. Oxidized LDL is known to be more atherogenic than native LDL. Though the positive potential for AOV benefits is intellectually appealing, want of a randomized, placebo-controlled interventional trial confirming AOV benefit has limited the enthusiasm of the scientific community. The Heart Protection Study Collaborative Group performed such a trial in the largest ever prospective randomized trial of antioxidants (n = 20,536).
Subjects in the trial were at high risk for vascular disease end points, since all had suffered either previous vascular morbidity or were diabetic. The AOV regimen was 600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily for 5 years.
There was no significant effect of AOV on any measured end point. To the contrary, there was a small increase in LDL and triglyceride levels in persons receiving AOV compared to placebo recipients. This study concluded that recommendation of AOV supplementation is not justified.
Prolonged Erections Produced by Dihydrocodeine & Sildenafil
Source: Goldmeier D, Lamba H. BMJ. 2002;324:1555.
Unless used concomitantly with nitrates, the clinical safety profile of the PDE5 inhibitor sildenafil has been generally very good. Another popular method of erectile dysfunction (ED) treatment, intracavernosal injection, has been associated not uncommonly with the adverse effect of priapism, but this adversity has been noted only in anecdotal case reports with sildenafil. Goldmeier and Lamba report on 2 cases of patients with prolonged erections associated with the combination of dihydrocodeine and sildenafil.
In case 1, a man treated for ED with sildenafil 100 mg had been achieving adequate erections that detumesced appropriately with orgasm. After a minor shoulder injury, for which he was prescribed dihydrocodeine 30 mg, administration of the same sildenafil dose resulted in an erection that persisted 5 hours post-ejaculation. Four days later the patient experienced a 4-hour erection with the same combination. Omission of the dihydrocodeine subsequently restored his previous pattern of appropriate detumescence.
Case 2 describes a patient receiving 100 mg sildenafil for psychogenic ED, who also received dihydrocodeine for soft tissue injury. During the first week of narcotic administration, the patient experienced erections persisting 2-3 hours postejaculation, but this effect disappeared in the next 2 weeks, despite continued concomitant sildenafil-opioid administration. Goldmeier and Lamba state that acute opiate intake heightened cyclic GMP concentrations, resulting in prolonged erections. They suggest that persons receiving sildenafil be cautioned regarding this potential interaction.
Effect of Magnesium Supplementation of Blood Pressure
Source: Jee SH, et al. Am J Hypertens. 2002;15:691-696.
Magnesium (MAG) participates in vascular tone and reactivity by its involvement in Na-K transport. Parenteral high-dose MAG has been shown to reduce blood pressure (BP) in eclampsia and glomerulonephritis. Whether dietary intake of magnesium effects BP in healthy populations remains uncertain, since interventional trials have produced conflicting results. Jee and colleagues performed a meta-analysis of interventional MAG supplementation trials (n = 20 trials, with 1220 total subjects) to seek further clarification of the relationship between MAG and blood pressure.
Overall, MAG supplementation reduced BP by 0.6/0.8 mm Hg. There was a dose-response relationship, however, with BP reductions of 4.3/2.3 for each 10-mmol increase/day in MAG dose. This meta-analysis encourages the performance of an adequately powered interventional trial for ultimate confirmation of the potential role of MAG supplementation.
Homocysteine-Lowering Therapy with Folic Acid, Vitamins, and Clinical Outcome after Percutaneous Coronary Intervention
Source: Schnyder G, et al. JAMA. 2002;288:973-979.
Homocysteine (HCST) has recently obtained substantial attention as a modifiable cardiovascular risk factor. Elevated levels of HCST have been associated with adverse cardiovascular outcome in a linear fashion, similar to cholesterol. It is suggested that elevations of HCST alter patterns of vascular smooth muscle cell growth and migration, endothelial function, lipoproteins, and coagulability. Hence, modification of HCST might favorably affect outcomes in high-risk CAD patients, such as those undergoing coronary angioplasty.
Schnyder and associates studied patients who underwent PCTA on at least 1 vessel for underlying stenosis > 50%, evaluating the effect of treatments known to reduce HCST: a combination of folic acid, vitamin B12, and vitamin B6. After PCTA, subjects were randomly assigned to the supplements or placebo, administered for 6 months. The primary study outcome was a composite of death, MI, and need for repeat revascularization for as long as 6 months after administration of the supplements.
At baseline, no patients had severe elevations of HCST, but mild-moderate increases were found in 29% of subjects. HCST-lowering therapy was associated with a risk reduction of 32% in the composite end point, mostly due to a 38% relative reduction in need for revascularization. This inexpensive multiple vitamin intervention holds promise in reducing cardiovascular risk among persons undergoing PCTA.
Effect of Cataract Surgery on Motor Vehicle Accidents in Older Adults
Source: Owsley C, et al. JAMA. 2002;288:841-849.
Older adults suffer visual impairment due to cataract (CAT) more often than any other single cause. More than half of adults older than age 65 have cataract, which is slightly more frequent in African Americans. Retrospective reviews have shown that among older drivers, presence of CAT was associated with an increased frequency of a recent motor vehicle accident (MVA) when compared with persons free of CAT.
The per capita MVA rate in older licensed drivers (40/1000) is substantially less than in persons younger than 25 (140/1000), but this is largely a result of the many fewer miles driven by older persons than younger. Hence, the per-mile driven rate of MVA among older drivers is actually comparable to that of the highest risk younger drivers. Whether correction of CAT results in improvements of MVA risk was the subject of this report.
Owsley et al prospectively compared patients (n = 277) with CAT who underwent intraocular lens implantation after CAT excision to untreated CAT patients, followed 4-6 years. During follow-up, the MVA rate/million miles traveled in the surgically treated group was less than half that seen in the untreated group. Though the trial was not randomized, the data are highly supportive of the potential favorable effect of CAT surgery on highway safety.
Inflammatory Biomarkers, Hormone Replacement Therapy, and Incident Coronary Heart Disease
Source: Pradhan AD, et al. JAMA. 2002;288:980-987.
The role of hormone replacement therapy (HRT) in menopausal women is an area of current controversy, primarily due to the discordance between observational data that suggested cardiovascular benefits associated with HRT, and recently completed interventional trials that have shown increases in venous and arterial thrombotic end points early after HRT initiation. Among the possible mechanisms for deleterious effects of HRT upon cardiovascular risk, changes in C-reactive protein (CRP) and interleukin (IL-6) might play a role.
Pradhan and associates studied subjects from the Women’s Health Initiative (n = 75,343) who had suffered an incident coronary heart disease event (n = 304). In their analysis, they compared CRP and IL-6 levels in persons with incident CHD vs. controls.
Although both baseline CRP and IL-6 were found to predict (independently) CHD events, only CRP levels were increased by the use of HRT. Comparatively, baseline CRP and IL-6 levels demonstrated greater effect on subsequent CHD events than did use or nonuse of HRT. Pradhan et al observe that it is the CRP level, rather than use of HRT, which is the primary determinant of subsequent risk for CHD events.
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