Clinical Briefs in Primary Care
Cholesterol-Lowering, Dietary Treatment, and Psychological Function
Source: Wardle J, et al. Am J Med 2000;108:547-553.
The role of cholesterol lowering for prevention of cardiovascular disease went through a trying period during which there was concern expressed that pharmacologic reduction of cholesterol might have adverse psychological consequences. Some observational studies have found an association between depression, suicide, aggression and hostility, and lower cholesterol levels. This study evaluated the psychological effect of implementing a cholesterol-lowering diet in 176 individuals with cholesterol levels of more than 198 mg/dL.
The group was divided into those receiving a low-fat diet, a Mediterranean diet, and a control diet. Diets were evaluated over a 12-week period, and in addition to physical and laboratory parameters, depression and anger were measured with the Beck Depression Inventory, Profile of Mood States. A variety of other psychometric tests were administered to assess stress, general health perceptions, and even perceptions of partners or close friends were included for analysis.
All groups had stable or improved psychological status throughout the study. Lipid changes were seen in the participants in both the low-fat diet group (5.1% cholesterol reduction) and the Mediterranean diet (10% cholesterol reduction) compared with the control. Wardle and colleagues conclude that their study does not demonstrate any adverse psychological effect from dietary cholesterol reduction. An adverse cognitive effect noted among the cholesterol-lowering diet groups seen during the trial was felt to be a chance event, but it is suggested that future trials seek further demonstration of the effect of cholesterol reduction on cognitive function.
Risk of CHD Events After Menopause
Source: Shlipak MG, et al. JAMA 2000;283:1845-1852.
Debate about the relative risks and benefits of postmenopausal hormone replacement therapy (HRT) continues unabated. The favorable effect of HRT upon traditional lipid fractions HDL and LDL is well established. Lipoprotein(a) [Lp(a)] is known to be an important risk factor for coronary heart disease (CHD), but has been predominantly studied in men, and usually in those without known coronary disease. This study examined the effects of HRT on Lp(a) in participants of the HERS (Heart and Estrogen/Progestin Replacement Study) trial, and the relationship with subsequent CHD end points.
This study evaluated 2763 postmenopausal women, measuring Lp(a) at baseline and at the conclusion of the trial (mean = 4.1 years). At baseline, the Lp(a) level of African American women was almost twice as high as that of other women. Baseline Lp(a) level was linearly associated with risk of subsequent CHD events.
HRT produced a significant reduction in Lp(a), which was most evident in women with the highest levels of Lp(a) prior to treatment at baseline. Although the reduction in Lp(a) achieved with HRT did not reveal a significant association with reduced CHD events, a threshold effect was suggested by the fact that the women in the highest quartile of Lp(a) reduction did have a significantly lower risk of CHD events than those with smaller reductions. Though modulation of Lp(a) is not currently a commonplace therapeutic target, it is encouraging that women with highest deviations of Lp(a) from normal do demonstrate benefit from HRT.
Diagnosing OAD
Source: Straus SE, et al. JAMA 2000;283:1853-1857.
The clinical diagnosis of obstructive airway disease (OAD) has not been systematically evaluated in rigorous blinded trials. Straus and colleagues evaluated 309 patients subgrouped into those with known chronic airway disease, suspected chronic OAD, and those free of either known or suspected OAD (asthma patients were excluded, so this was essentially a group of patients with consequences of chronic smoking). Among this group, they compared sensitivity, specificity, and likelihood ratios for spirometry-defined OAD (gold standard) with nine clinical factors, including history of chronic OAD, smoking history, presence of wheezing, maximum laryngeal height, minimum laryngeal height, and laryngeal descent.
Laryngeal height was measured as the distance from the suprasternal notch and the top of the thyroid cartilage. The difference between laryngeal height at end inspiration and end expiration was considered laryngeal descent.
Of the factors measured, only self-reported smoking history, self-reported history of chronic OAD, age, and maximum laryngeal height proved useful to discriminate OAD. Though previous studies have suggested a role for laryngeal descent, it was not found helpful in this trial, nor was wheezing. Straus et al acknowledge that spirometry should remain the diagnostic tool of choice, but suggest that their four described factors may facilitate a diagnosis of OAD in the absence of availability of spirometry.
Risk of Cataract Among Users of Intranasal Corticosteroids
Source: Derby L, Maier WC. J Allergy Clin Immunol 2000;105:912-916.
Of the single-entity agents available to treat allergic rhinitis, intranasal steroids have been demonstrated to have the highest overall efficacy. Enthusiasm for application of nasal steroids in such settings has been damped by concern for systemic effects, as well as ectopic local effects, such as cataract from nasal steroid instillation. There has been the recent suggestion that inhaled corticosteroids (e.g., antiasthmatic preparations) might be associated with increased risk of cataract, but numerous confounding factors do not allow a definitive conclusion.
The current study investigated, by means of a retrospective observational study, the frequency of cataract among 286,078 patients who were new nasal steroid users, without prior oral or inhaled steroid use. Data were accumulated by general practitioners in the United Kingdom who participated since 1987 in an information system involving 4 million patients.
Of the 88,031 new intranasal corticosteroid users, 70% used beclomethasone dipropionate (marketed in the United States as Beclovent, Beconase, Vancenase, or Vanceril). The incidence rate for new cataract was not significantly different between nasal steroid users and nonusers.
This is the first large-scale retrospective study that examined the incidence rate of cataract among nasal corticosteroid users younger than age 70. Even after correction for age, sex, diabetes, hypertension, or smoking, no increased risk was discernible. These data should provide reassurance about the safety of intranasal steroids in relation to cataract.
Effects of Sildenafil in Men with Severe Coronary Artery Disease
Source: Herrmann HC, et al. N Engl J Med 2000;342:1622-1626.
It is commonly overlooked that the development of sildenafil as an agent for erectile dysfunction (ED) evolved from its initial testing as a potential agent for angina. Many men who suffer ED also suffer other vascular disease, including coronary artery disease. The same risk factors that increase likelihood of ED (e.g., diabetes, hypertension, hyperlipidemia, and advanced age) are also associated with development of coronary artery disease. Since a number of serious cardiovascular events have occurred in men who use sildenafil, temporal association of sildenafil and cardiac events has prompted concern that sildenafil might be causally associated, although it remains uncertain whether acute cardiac events temporally related to sildenafil were due to the medication, the patient’s underlying cardiovascular disease status, stressful physical activity itself, or other factors. This study evaluated the systemic and coronary hemodynamic effects of sildenafil in men with severe coronary artery disease.
Study subjects were men (n = 14) with severe coronary artery stenosis (at least 70%) who were intended to undergo percutaneous coronary revascularization. Measurements were taken at the peak serum concentration of sildenafil (0.8-0.9 hrs post 100-mg dose), and compared with measurements in nonstenotic arteries for comparison.
Sildenafil produced less than 10% change in arterial pressure and had no effect on pulmonary wedge pressure, heart rate, or cardiac output. No adverse effects of sildenafil were detectable when measuring systemic, pulmonary, or coronary hemodynamics. These data support the position that, except for men on nitrates, sildenafil is safe for men with stable coronary artery disease, as proposed by the American College of Cardiology and the American Heart Association.
Using Venlafaxine in Nondepressed Outpatients with GAD
Source: Gelenberg AJ, et al. JAMA 2000;283:3082-3088.
Use of venlafaxine (ven) has been shown to be effective in depression and depression with anxiety. Similarly, VEN has demonstrated short-term benefits (up to 3 months) in generalized anxiety disorder (GAD) in the absence of depression. The current study was undertaken to establish knowledge about the efficacy of VEN in long-term treatment of GAD.
From a multicenter population, 251 patients suffering GAD without depression were treated with VEN in doses ranging from 75 to 225 mg/d (extended release form, once daily) for 28 weeks, in a randomized, double-blind, placebo-controlled, parallel-group trial. Outcome measures included Hamilton Rating Scale for Anxiety score, the Hamilton psychic anxiety factor score, and the Clinical Global Impressions scale Severity of Illness and Global Improvement scores.
The effect of VEN as an anxiolytic was found to be significant and sustained for the duration of the trial. The most common adverse event was nausea, which dissipated over time, so that the long-term phase of the trial demonstrated only a 2% placebo-subtracted incidence of this adversity, some of which may be attributable to the rapid titration schedule used in the trial, and hence avoidable. VEN is a rational therapeutic choice for the long-term management of GAD.
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