Testosterone-to-estradiol ratio and platelet thromboxane release in ischemic heart disease: the EVA project.

BACKGROUND: Data on the interplay between sexual hormones balance, platelet function and clinical outcomes of adults with ischemic heart disease (IHD) are still lacking. OBJECTIVE: To assess the association between the Testosterone (T)-to-Estradiol (E2) Ratio (T/E2) and platelet activation biomarkers in IHD and its predictive value on adverse outcomes. METHODS: The EVA study is a prospective observational study of consecutive hospitalized adults with IHD undergoing coronary angiography and/or percutaneous coronary interventions. Serum T/E2 ratios E2, levels of thromboxane B2 (TxB2) and nitrates (NO), were measured at admission and major adverse events, including all-cause mortality, were collected during a long-term follow-up. RESULTS: Among 509 adults with IHD (mean age 67 ± 11 years, 30% females), males were older with a more adverse cluster of cardiovascular risk factors than females. Acute coronary syndrome and non-obstructive coronary artery disease were more prevalent in females versus males. The lower sex-specific T/E2 ratios identified adults with the highest level of serum TxB2 and the lowest NO levels. During a median follow-up of 23.7 months, the lower sex-specific T/E2 was associated with higher all-cause mortality (HR 3.49; 95% CI 1.24-9.80; p = 0.018). In in vitro, platelets incubated with T/E2 ratios comparable to those measured in vivo in the lowest quartile showed increased platelet activation as indicated by higher levels of aggregation and TxB2 production. CONCLUSION: Among adults with IHD, higher T/E2 ratio was associated with a lower long-term risk of fatal events. The effect of sex hormones on the platelet thromboxane release may partially explain such finding.

Excess psychosocial burden in women with diabetes and premature acute coronary syndrome.

AIM: Diabetes is a stronger risk factor for acute coronary syndrome for women than men. We investigate whether behavioural and psychosocial factors contribute to the disparity in acute coronary syndrome risk and outcomes among women with diabetes relative to women without diabetes and men. METHODS: Among 939 participants in the GENESIS-PRAXY cohort study of premature acute coronary syndrome (age ≤ 55 years), we compared the prevalence of traditional and non-traditional factors by sex and Type 2 diabetes status. In a case-only analysis, we used generalized logit models to investigate the influence of traditional and non-traditional factors on the interaction of sex and diabetes. RESULTS: In 287 women (14.3% with diabetes) and 652 men (10.4% with diabetes), women and men with diabetes showed a heavier burden of traditional cardiac risk factors compared with individuals without diabetes. Women with diabetes were more likely to be the primary earner and have more anxiety relative to women without diabetes, and reported worse perceived health compared with women without diabetes and men with diabetes. The interaction term for sex and diabetes (odds ratio (OR) 1.40, 95% confidence intervals (95% CI) 0.83-2.36) was diminished after additional adjustment for non-traditional factors (OR 1.12, 95% CI 0.54-2.32), but not traditional factors alone (OR 1.41, 95% CI 0.84-2.36). CONCLUSIONS: We observed trends toward a more adverse psychosocial profile among women with diabetes and incident acute coronary syndrome compared with women without diabetes and men with diabetes, which may explain the increased risk of acute coronary syndrome in women with diabetes and may also contribute to worse outcomes.

Omega-3 fatty acids and the genetic risk of early onset acute coronary syndrome.

BACKGROUND AND AIMS: Recent gene-environment interaction studies suggest that diet may influence an individual's genetic predisposition to cardiovascular risk. We evaluated whether omega-3 fatty acid intake may influence the risk for acute coronary syndrome (ACS) conferred by genetic polymorphisms among patients with early onset ACS. METHODS AND RESULTS: Our population consisted of 705 patients of white European descent enrolled in GENESIS-PRAXY, a multicenter cohort study of patients aged 18-55 years and hospitalized with ACS. We used a case-only design to investigate interactions between the omega-3 index (a validated biomarker of omega-3 fatty acid intake) and 30 single nucleotide polymorphisms (SNPs) robustly associated with ACS. We used logistic regression to assess the interaction between each SNP and the omega-3 index. Interaction was also assessed between the omega-3 index and a genetic risk score generated from the 30 SNPs. All models were adjusted for age and sex. An interaction for increased ACS risk was found between carriers of the chromosome 9p21 variant rs4977574 and low omega-3 index (OR 1.57, 95% CI 1.07-2.32, p = 0.02), but this was not significant after correction for multiple testing. Similar results were obtained in the adjusted model (OR 1.55, 95% CI 1.05-2.29, p = 0.03). We did not observe any interaction between the genetic risk score or any of the other SNPs and the omega-3 index. CONCLUSION: Our results suggest that omega-3 fatty acid intake may modify the genetic risk conferred by chromosome 9p21 variation in the development of early onset ACS and requires independent replication.

Adjusted prognostic association of depression following myocardial infarction with mortality and cardiovascular events: individual patient data meta-analysis.

BACKGROUND: The association between depression after myocardial infarction and increased risk of mortality and cardiac morbidity may be due to cardiac disease severity. AIMS: To combine original data from studies on the association between post-infarction depression and prognosis into one database, and to investigate to what extent such depression predicts prognosis independently of disease severity. METHOD: An individual patient data meta-analysis of studies was conducted using multilevel, multivariable Cox regression analyses. RESULTS: Sixteen studies participated, creating a database of 10 175 post-infarction cases. Hazard ratios for post-infarction depression were 1.32 (95% CI 1.26-1.38, P<0.001) for all-cause mortality and 1.19 (95% CI 1.14-1.24, P<0.001) for cardiovascular events. Hazard ratios adjusted for disease severity were attenuated by 28% and 25% respectively. CONCLUSIONS: The association between depression following myocardial infarction and prognosis is attenuated after adjustment for cardiac disease severity. Still, depression remains independently associated with prognosis, with a 22% increased risk of all-cause mortality and a 13% increased risk of cardiovascular events per standard deviation in depression z-score.

Sex differences in young patients with acute myocardial infarction.

AIMS: To identify sex differences in risk factors, presenting symptoms and outcomes of young patients with acute myocardial infarction. METHODS: We adopted a comprehensive approach and performed two parallel studies: (1) using provincial administrative databases from Quebec, Canada from 2000 to 2007, we identified baseline characteristics and post-acute myocardial infarction survival of patients aged < 50 years (n = 10,619); (2) to overcome the lack of clinical data in the administrative databases, a medical chart review was performed on 215 patients < 50 years of age with an acute myocardial infarction between April 2000 and August 2006 from our institution. RESULTS: Administrative cohort: fewer women than men sought medical attention for retrosternal chest pain 1-month pre-acute myocardial infarction (P = 0.035). Diabetes and hypertension were more prevalent in women, and patients equally received interventional procedures post-infarction. Diabetes significantly reduced post-infarction survival in men and women [HR = 2.02 (95% CI 1.21-3.36) and HR = 2.25 (95% CI 1.06-4.80), respectively]. However, young women had greater post-infarction mortality in-hospital and up to 1 year after discharge (4.23% vs. 2.21%, respectively; P = 0.005). Medical chart review: diabetes and hypertension were more prevalent in women, while men were more obese. There were no significant sex differences in typical presenting symptoms, or in interventional procedures post-infarction. CONCLUSIONS: Young men and women with acute myocardial infarctions equally presented with retrosternal chest pain, although fewer women sought medical attention for retrosternal chest pain before admission. Diabetes and hypertension were more prevalent in young women, and mortality was higher in young female patients. Our results highlight the continued need for diabetes prevention and control in young patients, especially women.

The effect of smoking cessation counselling in pregnant women: a meta-analysis of randomised controlled trials.

BACKGROUND: Pregnant smokers are often prescribed counselling as part of multicomponent cessation interventions. However, the isolated effect of counselling in this population remains unclear, and individual randomised controlled trials (RCTs) are inconclusive. OBJECTIVE: To conduct a meta-analysis of RCTs examining counselling in pregnant smokers. SEARCH STRATEGY: We searched the CDC Tobacco Information and Prevention, Cochrane Library, EMBASE, Medline and PsycINFO databases for RCTs evaluating smoking cessation counselling. SELECTION CRITERIA: We included RCTs conducted in pregnant women in which the effect of counselling could be isolated and those that reported biochemically validated abstinence at 6 or 12 months after the target quit date. DATA COLLECTION AND ANALYSIS: Overall estimates were derived using random effects meta-analysis models. MAIN RESULTS: Our search identified eight RCTs (n = 3290 women), all of which examined abstinence at 6 months. The proportion of women that remained abstinent at the end of follow up was modest, ranging from 4 to 24% among those randomised to counselling and from 2 to 21% among control women. The absolute difference in abstinence reached a maximum of only 4%. Summary estimates are inconclusive because of wide confidence intervals, albeit with little evidence to suggest that counselling is efficacious at promoting abstinence (odds ratio 1.08, 95% confidence interval 0.84-1.40). There was no evidence to suggest that efficacy differed by counselling type. CONCLUSIONS: Available data from RCTs examining the isolated effect of smoking cessation counselling in pregnant women are limited but sufficient to rule out large treatment effects. Future RCTs should examine pharmacological therapies in this population.

A Phase II trial of 8 weeks of degarelix for prostate volume reduction: Efficacy and hormonal recovery.

PURPOSE: The purpose of this study was to determine the efficacy of 8 weeks of degarelix for prostate downsizing before interstitial brachytherapy. We also report associated toxicity and the time course of endocrine recovery over the following 12 months. METHODS AND MATERIALS: Fifty patients were accrued to an open-label Phase II clinical trial (www.clinicaltrials.gov ID NCT01446991). Baseline prostate transrectal ultrasound (TRUS) was performed on all patients followed by degarelix administration and a repeat TRUS at Week 8. Brachytherapy was performed within 4 weeks of the 8-week TRUS for all patients who achieved suitable downsizing. RESULTS: The median prostate volume was reduced from 65.0 cc (interquartile range [IQR]: 55.2-80.0 cc) to 48.2 cc at 8 weeks (IQR: 41.2-59.3 cc), representing a median decrease of 26.2% (IQR: 21-31%). Functional recovery of testosterone within an age-adjusted normal range occurred at a median of 34.1 weeks (IQR: 28.2-44.5 weeks) from the date of the final injection. Despite this recovery, follicle-stimulating hormone and luteinizing hormone levels remained abnormally elevated throughout 12 months. Quality-of-life implications are discussed. CONCLUSIONS: Degarelix is effective for prostate downsizing before prostate brachytherapy with a median volume decrease of 26.2% by 8 weeks. Despite the short course of treatment and eventual testosterone recovery, follicle-stimulating hormone and luteinizing hormone remain elevated beyond 12 months. Further investigation with randomized comparisons to other hormonal agents is warranted.

Better functional status in American than Canadian patients with heart disease: an effect of medical care?

OBJECTIVES: This study compared functional status in Americans and Canadians with and without prior symptoms of heart disease to separate the effects of medical care from nonmedical factors. BACKGROUND: Coronary angiography and revascularization are used more often in the United States than in Canada, yet rates of mortality and myocardial infarction are similar in the two countries. Recent data suggest that functional status after myocardial infarction is better among Americans than Canadians, but it is uncertain whether this difference is due to medical care or nonmedical factors. METHODS: Quality of life was measured in patients enrolled in seven American and one Canadian site in the Bypass Angioplasty Revascularization Investigation. Prior symptoms of heart disease were defined as angina, myocardial infarction or congestive heart failure before the episode of illness leading to randomization. Functional status was measured with the Duke Activity Status Index and overall emotional and social health using Medical Outcome Study measures on the basis of patient status before the index episode of acute ischemic heart disease. RESULTS: Quality of life was generally better in the 934 Americans than in the 278 Canadians, with overall health rated as excellent or very good in 30% of Americans versus 20% of Canadians (p = 0.0001), higher median Duke Activity Status Index scores (16 vs. 13.5, p = 0.03) but equivalent emotional health (76 vs. 76, p = 0.74) and social health scores (100 vs. 80, p = 0.07). Among the 350 patients without prior symptoms of heart disease, Americans and Canadians had similar overall health, Duke Activity Status Index and emotional and social health scores. However, of the 860 patients with previous symptoms of heart disease, Americans had higher overall health (p = 0.0001) and Duke Activity Status Index scores (p = 0.0008) but similar emotional and social health scores. The results were essentially unchanged after statistical adjustment for potential confounding factors. CONCLUSIONS: The functional status of patients without prior symptoms of heart disease is similar in Americans and Canadians. However, among patients with previous symptomatic heart disease, functional status is higher in Americans than in Canadians. This difference may be due to different patterns of medical management of heart disease in the two countries.

High resolution crystal structures of recombinant human renin in complex with polyhydroxymonoamide inhibitors.

The crystal structures of recombinant glycosylated human renin in complex with several polyhydroxymonoamide inhibitors have been determined at up to 1.8 A resolution. The high resolution structures permit a detailed analysis of the conformation of renin, the interactions between the inhibitors and renin, and the network of ordered water molecules. The polyhydroxymonoamide inhibitors are bound with their backbones in an extended conformation, and with their side-chains occupying the S3 to S1 pockets. The inhibited renin molecules are shown to exist in both the closed and the open conformations. Inhibitors bound to the two distinct forms of renin can assume different conformations at the P3 position.

Impact of diabetes on 12-month outcomes following coronary artery bypass graft surgery: results from the ROSETTA-CABG Registry.

BACKGROUND: Diabetes mellitus is associated with poorer long-term outcomes following coronary artery bypass graft (CABG) surgery. However, little is known about the impact of diabetes mellitus on outcomes during the first 12 months following CABG. OBJECTIVES: To examine the relationship between diabetes mellitus and outcomes during the 12 months following CABG. METHODS: The Routine versus Selective Exercise Treadmill Testing after Coronary Artery Bypass Grafting (ROSETTA-CABG) Registry is a prospective, multicentre study examining the use of functional testing after CABG surgery. A total of 398 patients who were enrolled in the ROSETTA-CABG Registry were examined. Diabetic status was defined by medication use at discharge. Only patients undergoing a first successful CABG (all ischemic areas thought to be revascularized) were included. RESULTS: Among the 398 patients, 37 (9.3%) were receiving insulin, 67 (16.8%) were receiving oral hypoglycemic agents, and 294 (73.9%) were not receiving insulin or oral hypoglycemic agents. Insulin-treated patients had a higher 12-month incidence of composite clinical events consisting of readmission for unstable angina, myocardial infarction or death than did oral hypoglycemic-treated patients and nondiabetic patients (21.6% versus 4.5% and 6.0%, respectively; P=0.0003). Insulin-treated patients were also more likely to undergo repeat cardiac catheterization than were oral hypoglycemic-treated patients and nondiabetic patients (18.9% versus 8.8% and 7.9%, respectively; P=0.03). After controlling for other variables, use of insulin was independently associated with a composite of adverse clinical events (OR 3.80, 95% CI 1.5 to 9.6, P=0.005). CONCLUSIONS: During the 12-month period after a successful CABG, insulin-treated patients had a higher rate of adverse cardiac events than did patients receiving oral hypoglycemic agents and nondiabetic patients. These results suggest that diabetic patients may benefit from more aggressive surveillance during the first year after CABG surgery.

Differences in the treatment of myocardial infarction in the United States and Canada. A comparison of two university hospitals.

OBJECTIVE: To compare practice patterns and clinical outcomes for a costly yet common condition, acute myocardial infarction. DESIGN: Retrospective cohort study in two university hospitals (Stanford [Calif] University and McGill University, Montreal, Quebec) and a patient survey. PATIENTS: All consecutive patients (n = 518) treated for acute myocardial infarction in the coronary care unit of those two hospitals over 2 years. MEASURES: Rates of diagnostic and therapeutic procedures, mortality, reinfarction, and level of functional status (by chart review and patient survey). RESULTS: Demographic and clinical characteristics were similar for the two groups. Noninvasive tests were more common at McGill (exercise tests, 56% vs 20%; tests of left ventricular function, 86% vs 59%; P < .0001 for both). In contrast, invasive procedures were more common at Stanford (angiography, 55% vs 34%; angioplasty, 30% vs 13%; and bypass surgery, 10% vs 4%; P < .0001). At a median follow-up of 20 months, reinfarction and mortality rates were similar at Stanford and McGill (13% vs 8% and 28% vs 27%, respectively; P > .05 for both). In contrast, the angina rate was slightly lower at Stanford (33% vs 40%; P = .15), and the functional status of Stanford patients was better than that of McGill patients (mean Duke Activity Status Index score, 28.8 and 22.9, respectively; P = .006). This functional status difference persisted after adjustment for differences in clinical factors, including coronary revascularization. CONCLUSION: The aggressive treatment of the American patients with myocardial infarction did not improve reinfarction and mortality rates compared with the conservative treatment of the Canadian patients. The superior functional status of the American patients merits further investigation.

Adherence to isoniazid prophylaxis in the homeless: a randomized controlled trial.

OBJECTIVES: To test 2 interventions to improve adherence to isoniazid preventive therapy for tuberculosis in homeless adults. We compared (1) biweekly directly observed preventive therapy using a $5 monetary incentive and (2) biweekly directly observed preventive therapy using a peer health adviser, with (3) usual care at the tuberculosis clinic. METHODS: Randomized controlled trial in tuberculosis-infected homeless adults. Outcomes were completion of 6 months of isoniazid treatment and number of months of isoniazid dispensed. RESULTS: A total of 118 subjects were randomized to the 3 arms of the study. Completion in the monetary incentive arm was significantly better than in the peer health adviser arm (P = .01) and the usual care arm (P = .04), by log-rank test. Overall, 19 subjects (44%) in the monetary incentive arm completed preventive therapy compared with 7 (19%) in the peer health adviser arm (P = .02) and 10 (26%) in the usual care arm (P = .11). The median number of months of isoniazid dispensed was 5 in the monetary incentive arm vs 2 months in the peer health adviser arm (P = .005) and 2 months in the usual care arm (P = .04). In multivariate analysis, independent predictors of completion were being in the monetary incentive arm (odds ratio, 2.57; 95% CI, 1.11-5.94) and residence in a hotel or other stable housing at entry into the study vs residence on the street or in a shelter at entry (odds ratio, 2.33; 95% CI, 1.00-5.47). CONCLUSIONS: A $5 biweekly cash incentive improved adherence to tuberculosis preventive therapy compared with a peer intervention or usual care. Living in a hotel or apartment at the start of treatment also predicted the completion of therapy.

Tuberculosis prophylaxis in the homeless. A trial to improve adherence to referral.

BACKGROUND: Adherence to tuberculosis evaluation is poor in a high-risk population such as the homeless. OBJECTIVE: To test two interventions aimed at improving adherence to tuberculosis evaluation and to identify predictors of adherence. METHODS: We conducted a randomized clinical trial in shelters and food lines in the inner city of San Francisco, Calif. We randomized 244 eligible subjects infected with tuberculosis to (1) peer health adviser (assistance by a peer [n = 83]), (2) monetary incentive ($5 payment [n = 82]), or (3) usual care (referral slips and bus tokens only [n = 79]). The primary outcome of the study was adherence to a first follow-up appointment at the tuberculosis clinic, where subjects were evaluated for active tuberculosis and the need for isoniazid prophylaxis. RESULTS: Of the subjects assigned to a monetary incentive, 69 (84%) completed their first follow-up appointment, compared with 62 subjects (75%) assigned to a peer health adviser and 42 subjects (53%) assigned to usual care. Adherence was higher in the monetary incentive and peer health adviser groups than in the usual care group (P < .001 and P = .004, respectively). Patients not using intravenous drugs and patients 50 years of age or older were more likely to adhere to a first follow-up appointment (odds ratios [95% confidence intervals], 2.5 [1.3 to 5.0] and 3.3 [1.2 to 8.8], respectively). Among the 173 tuberculosis-infected subjects who completed their appointment, isoniazid therapy was started for 72 individuals, and three cases of active tuberculosis were identified. CONCLUSION: A monetary incentive or a peer health adviser is effective in improving adherence to a first follow-up appointment in homeless individuals infected with tuberculosis. A monetary incentive appears to be superior. Intravenous drug users and young individuals are at high risk for poor adherence to referral.

Clinical yield and cost of exercise treadmill testing to screen for coronary artery disease in asymptomatic adults.

Exercise treadmill testing is frequently performed to screen for coronary artery disease (CAD) in asymptomatic individuals; however, its clinical value is unclear. We examined a consecutive cohort of asymptomatic adults undergoing exercise treadmill testing at the Cleveland Clinic Foundation between September 1990 and December 1993. End points included (1) identification of subjects with severe CAD and (2) performance of any second diagnostic study within 90 days of the index exercise treadmill test. Screening exercise treadmill testing was performed in 4,334 adults (median age 51, 89% men); only 34% had > or = 1 cardiac risk factor and 15% exhibited an abnormal response to exercise. A second test after treadmill testing was performed in 215 patients (in 110, coronary angiography; in 105, stress thallium scintigraphy, followed by coronary angiography in 16). The strongest predictor of referral for a second test was an ischemic ST-segment response (adjusted odds ratio [OR] 34, 95% confidence intervals [Cl] 24 to 47, p < 0.0001). The only clinical variable independently associated with referral for a second test was female gender (adjusted OR 0.35, 95% CI 0.21 to 0.60, p <0.0001). Of the 126 patients who underwent coronary angiography, severe CAD was identified in only 19 individuals (10.44% of the original cohort, 95% CI 0.26% to 0.62%); coronary artery bypass grafting was performed in 14 of these patients. The estimated cost of exercise treadmill testing to identify 1 case of severe CAD for which surgical revascularization may provide a survival benefit was $39,623. The estimated cost per year of life saved was at least $55,274. Thus, as used in actual practice in 1 center, screening exercise treadmill testing has a low yield and is costly. This is perhaps in part because of the low-risk population that was selected and the failure to incorporate pretest variables, increasing probability of disease into post-test clinical decision making.

Iron stores and coronary artery disease: a clinical application of a method to incorporate measurement error of the exposure in a logistic regression model.

Rates of coronary artery disease (CAD) increase sharply after menopause. We examined the hypotheses that high iron stores, as measured by plasma ferritin levels, are a risk factor for CAD and that the increase in iron stores after menopause is at least in part responsible for the rise in CAD in women. We also investigated measurement error of plasma ferritin using a Bayesian conditional independence model and incorporated it into the estimation of the odds ratio (OR) for males. Cases had >/=1 coronary artery stenosis >/=70%. Controls had no visible coronary lesions on angiography. The median plasma ferritin level was 48 mg/L (interquartile range: 28 to 86) among 244 cases and 45 mg/l (24 to 85) among 140 controls. The multivariate analyses among females, males, and females and males combined did not support an association between plasma ferritin levels and CAD (OR for one unit change in log ferritin 1.01, 95% CI 0.71-1.44, OR 0.95, 95% CI 0.66-1.37 and OR 0.95, 95% CI 0.75-1.21, respectively). Accounting for the measurement error of ferritin in males slightly improved the precision of the estimate of the OR but did not unmask an association (OR: 0.94, 95% CI 0.69-1.30). We conclude that high ferritin levels before or after menopause are not associated with CAD. Measurement error might be considered in situations where a one-time measurement is assumed to be representative of long-term exposure.

Stiff left atrial syndrome.

A 67-year-old female presented seven years after insertion of a mitral prosthesis with mild to moderate pulmonary edema and severe right heart failure with pulmonary and tricuspid insufficiency. Clinical examination and noninvasive tests did not demonstrate prosthetic valve dysfunction. Cardiac catheterization revealed a marked V wave but no mitral regurgitation and no significant mitral diastolic gradient. A clinical diagnosis of a stiff left atrium was made and confirmed at autopsy. The pathophysiology of the syndrome is discussed.

Discharge prescriptions following admission for acute myocardial infarction at tertiary care and community hospitals in Quebec.

BACKGROUND: Many physicians are not adhering to the recommendations found in evidence-based guidelines for the treatment of acute myocardial infarction (AMI). Physicians who practise in tertiary care settings may show better adherence to guideline recommendations than physicians who practise in other settings. OBJECTIVE: To determine whether there is an association between the practice setting of admission for AMI and discharge prescriptions for cardiac drugs recommended in evidence-based guidelines. PATIENTS AND METHODS: Discharge prescription data from a prospective cohort of patients with AMI admitted at five tertiary care (n=250) and five community hospitals (n=331) in Quebec from December 1996 to November 1998 were examined. RESULTS: The proportions of patients who were prescribed recommended drugs at tertiary care hospitals compared with those at community hospitals were as follows: beta-blockers (78% versus 74%, respectively; 95% CI around the difference - 4% to 11%), lipid-lowering drugs (45% versus 39%, respectively; 95% CI - 2% to 15%) and angiotensin-converting enzyme (ACE) inhibitors (44% versus 57%, respectively; 95% CI - 22% to - 5%). In adjusted analyses, practice setting was not associated with the prescription of beta-blockers (odds ratio [OR] for tertiary care 1.36; 95% CI 0.82 to 2.24) or lipid-lowering drugs (OR for tertiary care 1.06; 95% CI 0.67 to 1.68). However, tertiary care admission reduced the likelihood of ACE inhibitor prescription (OR 0.50; 95% CI 0.32 to 0.77). This association may have been due to the increased likelihood of ACE inhibitor prescription for patients with hypertension at community hospitals (OR 2.13; 95% CI 1.23 to 3.67). The results also showed that older patients were less likely to be prescribed beta-blockers or lipid-lowering drugs, women were less likely to be prescribed beta-blockers and patients with diabetes mellitus were less likely to be prescribed lipid-lowering drugs (OR 0.45; 95% CI 0.23 to 0.89). CONCLUSION: No strong association was found between the practice setting of admission for AMI and discharge prescriptions for cardiac drugs recommended in evidence-based guidelines. Prescription rates for recommended drugs were high, yet results suggest that there is room for improvement with regard to patients with diabetes, women and older patients.

Obesity and C-reactive protein in various populations: a systematic review and meta-analysis.

Obesity has been associated with elevated levels of C-reactive protein (CRP), a marker of inflammation and predictor of cardiovascular risk. The objective of this systematic review and meta-analysis was to estimate the associations between obesity and CRP according to sex, ethnicity and age. MEDLINE and EMBASE databases were searched through October 2011. Data from 51 cross-sectional studies that used body mass index (BMI), waist circumference (WC) or waist-to-hip ratio (WHR) as measure of obesity were independently extracted by two reviewers and aggregated using random-effects models. The Pearson correlation (r) for BMI and ln(CRP) was 0.36 (95% confidence interval [CI], 0.30-0.42) in adults and 0.37 (CI, 0.31-0.43) in children. In adults, r for BMI and ln(CRP) was greater in women than men by 0.24 (CI, 0.09-0.37), and greater in North Americans/Europeans than Asians by 0.15 (CI, 0-0.28), on average. In North American/European children, the sex difference in r for BMI and ln(CRP) was 0.01 (CI, -0.08 to 0.06). Although limited to anthropometric measures, we found similar results when WC and WHR were used in the analyses. Obesity is associated with elevated levels of CRP and the association is stronger in women and North Americans/Europeans. The sex difference only emerges in adulthood.

Reporting on sex-based analysis in clinical trials of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker efficacy.

BACKGROUND: Clinical practice recommendations for hypertension do not make recommendations specific to men or women. However, the sex hormones appear to modulate differently the renin-angiotensin system (RAS), which plays a central role in the regulation of blood pressure. Today, little is known about the effects of sex on the efficacy of therapies that antagonize the RAS, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). OBJECTIVE: To identify randomized controlled trials evaluating the efficacy of ACEIs and ARBs in preventing major cardiovascular outcomes, determine what proportion of the trial participants were female, and evaluate whether there was any evidence of a sex difference in the efficacy of these agents. METHODS: A systematic review of the literature was conducted to identify randomized controlled trials that used either ACEIs or ARBs for the treatment of hypertension. RESULTS: Thirteen ACEI trials and nine ARB trials were identified. Sex-specific outcome data were available in six of the ACEI trials and three of the ARB trials. These trials enrolled 74,105 patients; 39.1% were women. Seven of the nine trials indicated that ACEIs or ARBs may be slightly more beneficial in men. The magnitude of these differences, in most trials, was small. CONCLUSIONS: Sex-specific data are reported in 43% of large hypertension clinical trials. Review of the trials reporting sex-specific effect sizes indicates that ACEIs and ARBs may be more effective in men.

Effectiveness of antiresorptive agents in the prevention of recurrent hip fractures.

UNLABELLED: Hip fracture is associated with recurrent fractures and increased mortality. The results of our retrospective cohort study support the use of antiresorptive agents to prevent recurrent hip fractures in this population. INTRODUCTION: Hip fracture, the most serious consequence of osteoporosis, is associated with recurrent fractures and increased mortality. Antiresorptive therapy has proven efficacy in the prevention of fractures after vertebral fractures. It is unknown if it can prevent recurrent fractures after a hip fracture. METHODS: We designed a population based, retrospective cohort study, using administrative databases and identified patients hospitalized for a hip fracture between 1996 and 2002. The exposure was defined as being dispensed a prescription for an antiresorptive agent at any time following discharge. Multivariate Cox regression models were used to estimate the hazard ratio of recurrent hip fracture. Subgroup and propensity score analyses were performed. RESULTS: A total of 20,644 patients were identified; 6,779 filled a prescription for antiresorptive agents. There were 992 recurrent hip fractures. Patients exposed to antiresorptives had a 26% reduction in the rate of recurrent fractures (adjusted hazard ratio 0.74; 95% CI, 0.64-0.86) compared to patients who were not. All subgroups experienced a reduction in recurrent fracture, except the very elderly. Propensity score analyses were consistent with the main analysis. CONCLUSIONS: Antiresorptive therapy reduces the risk of recurrent hip fractures in elderly patients. These results provide evidence that this therapy should be considered for secondary prevention of hip fractures.