Felipe N. Albuquerque

Adverse Effects of Testosterone Therapy in Adult Men: A Systematic Review and Meta-Analysis

CONTEXT The risks of testosterone therapy in men remain poorly understood. OBJECTIVE The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men. DATA SOURCES We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies. STUDY SELECTION Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility. DATA EXTRACTION Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data. DATA SYNTHESIS The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin [weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14] and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, -0.49 mg/dl; 95% CI, -0.85 to -0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes. CONCLUSIONS The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.

Aspirin for the Primary Prevention of Cardiovascular Events: A systematic review and meta-analysis comparing patients with and without diabetes

OBJECTIVE The negative results of two randomized controlled trials (RCTs) have challenged current guideline recommendations for using aspirin for primary prevention of cardiovascular events among patients with diabetes. We therefore sought to determine if the effect of aspirin for primary prevention of cardiovascular events and mortality differs between patients with and without diabetes. RESEARCH DESIGN AND METHODS We conducted a systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus since their inceptions until November 2008 for RCTs of aspirin for primary prevention of cardiovascular events. Blinded pairs of reviewers evaluated studies and extracted data. Random-effects meta-analysis and Bayesian logistic regression were used to estimate the ratios of relative risks (RRs) of outcomes of interest among patients with and without diabetes. A 95% CI that crosses 1.00 indicates that the effect of aspirin does not differ between patients with and without diabetes. RESULTS Nine RCTs with moderate to high methodological quality contributed data to the analyses. The ratios of RRs comparing the benefit of aspirin among patients with diabetes compared with patients without diabetes for mortality, myocardial infarction, and ischemic stroke were 1.12 (95% CI 0.92–1.35), 1.19 (0.82–1.17), and 0.70 (0.25–1.97), respectively. CONCLUSIONS Whereas estimates of benefit among patients with diabetes remain imprecise, our analysis suggests that the relative benefit of aspirin is similar in patients with and without diabetes.

Adult Height in Patients with Congenital Adrenal Hyperplasia: A Systematic Review and Metaanalysis

CONTEXT Treatment for patients with congenital adrenal hyperplasia (CAH) may affect the final height of these patients. OBJECTIVE Our objective was to determine the distribution of achieved height in patients with classic CAH diagnosed at infancy or early childhood and treated with glucocorticoids. DATA SOURCES We searched MEDLINE, EMBASE, Cochrane Library, ISI Web of Science, and Scopus through September 2008; the reference sections of included studies; and expert files. STUDY SELECTION Eligible studies included patients diagnosed with CAH before age 5 and followed to final height. DATA EXTRACTION Reviewers working in duplicate independently extracted data on study characteristics and outcomes and determined each studys risk of bias. DATA SYNTHESIS The sd score (SDS) for final height and corrected height (defined as final height SDS - midparental height SDS) were estimated from each study and pooled using random-effects metaanalysis. The I(2) statistic was used to assess inconsistency in results across studies. RESULTS We found 35 eligible studies, most of which were retrospective single-cohort studies. The final height SDS achieved by CAH patients was -1.38 (-1.56 to -1.20; I(2) = 90.2%), and the corrected height SDS was -1.03 (-1.20 to -0.86; I(2) = 63.1%). This was not significantly associated with age at diagnosis, gender, type and dose of steroid, and age of onset of puberty. Mineralocorticoid users had a better height outcome in comparison with the nonusers (P = 0.02). CONCLUSION Evidence derived from observational studies suggests that the final height of CAH patients treated with glucocorticoids is lower than the population norm and is lower than expected given parental height.

Outcomes of surgical treatment for nonfunctioning pituitary adenomas: a systematic review and meta-analysis

Background  Surgery is commonly used in the management of pituitary nonfunctioning adenomas (NFPA). The goal of this systematic review and meta‐analysis is to evaluate the effect of surgery on mortality, surgical complications, pituitary function and vision.

Outcomes of surgical treatment for nonfunctioning pituitary adenomas

Background  Surgery is commonly used in the management of pituitary nonfunctioning adenomas (NFPA). The goal of this systematic review and meta‐analysis is to evaluate the effect of surgery on mortality, surgical complications, pituitary function and vision.

Sleep-Disordered Breathing and Excessive Daytime Sleepiness in Patients With Atrial Fibrillation

BACKGROUND An important consequence of sleep-disordered breathing (SDB) is excessive daytime sleepiness (EDS). EDS often predicts a favorable response to treatment of SDB, although in the setting of cardiovascular disease, particularly heart failure, SDB and EDS do not reliably correlate. Atrial fibrillation (AF) is another highly prevalent condition strongly associated with SDB. We sought to assess the relationship between EDS and SDB in patients with AF. METHODS We conducted a prospective study of 151 patients referred for direct current cardioversion for AF who also underwent sleep evaluation and nocturnal polysomnography. The Epworth Sleepiness Scale (ESS) was administered prior to polysomnography and considered positive if the score was ≥ 11. The apnea-hypopnea index (AHI) was tested for correlation with the ESS, with a cutoff of ≥ 5 events/h for the diagnosis of SDB. RESULTS Among the study participants, mean age was 69.1 ± 11.7 years, mean BMI was 34.1 ± 8.4 kg/m(2), and 76% were men. The prevalence of SDB in this population was 81.4%, and 35% had EDS. The association between ESS score and AHI was low (R(2) = 0.014, P = .64). The sensitivity and specificity of the ESS for the detection of SDB in patients with AF were 32.2% and 54.5%, respectively. CONCLUSIONS Despite a high prevalence of SDB in this population with AF, most patients do not report EDS. Furthermore, EDS does not appear to correlate with severity of SDB or to accurately predict the presence of SDB. Further research is needed to determine whether EDS affects the natural history of AF or modifies the response to SDB treatment.

Sleep-disordered breathing, hypertension, and obesity in retired National Football League players.

To the Editor: In 1994, the Centers for Disease Control and Prevention conducted a study evaluating retired National Football League (NFL) players. Linemen were 3 times more likely than other position players to die of heart disease and had a 52% higher risk of cardiovascular death than the

Usefulness of Epicardial Adipose Tissue as Predictor of Cardiovascular Events in Patients With Coronary Artery Disease

Several studies have suggested that epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD). However, the role of EAT as a potential risk factor for, and predictor of, long-term cardiovascular outcomes in patients with CAD requires additional investigation. We investigated the relation among EAT, cardiovascular events, and measures of adiposity in patients with CAD. The study was a prospective cohort study of 194 consecutive patients with CAD who entered a phase II cardiac rehabilitation program at the Mayo Clinic. EAT was measured using echocardiography. The primary outcome was the long-term recurrence of major adverse cardiovascular events (MACE). The outcomes were assessed using the Mayo Clinic electronic medical records. The mean age was 59.4 ± 10.8 years, the body mass index was 28.7 ± 4.6 kg/m(2), 80% were men, and 21% of the patients underwent coronary artery bypass grafting. The mean follow-up period was 3.6 ± 1.3 years, and 52 MACE occurred. EAT was not a predictor of MACE (hazard ratio 1.32, 95% confidence interval 0.75 to 2.31; p = 0.33) when used as a continuous variable and correlated poorly with the measures of adiposity. However, a nonsignificant trend was seen for a greater incidence of cardiovascular events when EAT was stratified by tertile (hazard ratio for third tertile 1.77, 95% confidence interval 0.84 to 3.32; p = 0.11), after statistical adjustments for age, gender, body mass index, and other covariates. In conclusion, the results of the present longitudinal study suggest that EAT, as measured using echocardiography, does not strongly predict for MACE and is poorly associated with measures of obesity in patients with CAD.

Decreased exercise capacity and sleep-disordered breathing in patients with hypertrophic cardiomyopathy.

BACKGROUND Mechanisms of decreased exercise capacity in patients with hypertrophic cardiomyopathy (HCM) are not well understood. Sleep-disordered breathing (SDB) is a highly prevalent but treatable disorder in patients with HCM. The role of comorbid SDB in the attenuated exercise capacity in HCM has not been studied previously. METHODS Overnight oximetry, cardiopulmonary exercise testing, and echocardiographic studies were performed in consecutive patients with HCM seen at the Mayo Clinic. SDB was considered present if the oxygen desaturation index (number of ≥ 4% desaturations/h) was ≥ 10. Peak oxygen consumption (VO2 peak) (the most reproducible and prognostic measure of cardiovascular fitness) was then correlated with the presence and severity of SDB. RESULTS A total of 198 patients with HCM were studied (age, 53 ± 16 years; 122 men), of whom 32% met the criteria for the SDB diagnosis. Patients with SDB had decreased VO2 peak compared with those without SDB (16 mL O2/kg/min vs 21 mL O2/kg/min, P < .001). SDB remained significantly associated with VO2 peak after accounting for confounding clinical variables (P < .001) including age, sex, BMI, atrial fibrillation, and coronary artery disease. CONCLUSIONS In patients with HCM, the presence of SDB is associated with decreased VO2 peak. SDB may represent an important and potentially modifiable contributor to impaired exercise tolerance in this unique population.

Erratum. Aspirin for the Primary Prevention of Cardiovascular Events. A Systematic Review and Meta-Analysis Comparing Patients With and Without Diabetes. Diabetes Care 2009;32:2300–2306

In the article cited above, Fig. 2 should have shown the pooled relative risks and 95% CI for the effect of aspirin versus control on death, myocardial infarction, and ischemic stroke, respectively, stratified by diabetes status of the trial participants. The published version of the manuscript incorrectly labeled the …