Salvatore Mottillo

The Metabolic Syndrome and Cardiovascular Risk : A Systematic Review and Meta-Analysis

OBJECTIVES We sought to conduct a systematic review and meta-analysis of the cardiovascular risk associated with the metabolic syndrome as defined by the 2001 National Cholesterol Education Program (NCEP) and 2004 revised National Cholesterol Education Program (rNCEP) definitions. BACKGROUND Numerous studies have investigated the cardiovascular risk associated with the NCEP and rNCEP definitions of the metabolic syndrome. There is debate regarding the prognostic significance of the metabolic syndrome for cardiovascular outcomes. METHODS We searched the Cochrane Library, EMBASE, and Medline databases through June 2009 for prospective observational studies investigating the cardiovascular effects of the metabolic syndrome. Two reviewers extracted data, which were aggregated using random-effects models. RESULTS We identified 87 studies, which included 951,083 patients (NCEP: 63 studies, 497,651 patients; rNCEP: 33 studies, 453,432 patients). There was little variation between the cardiovascular risk associated with NCEP and rNCEP definitions. When both definitions were pooled, the metabolic syndrome was associated with an increased risk of cardiovascular disease (CVD) (relative risk [RR]: 2.35; 95% confidence interval [CI]: 2.02 to 2.73), CVD mortality (RR: 2.40; 95% CI: 1.87 to 3.08), all-cause mortality (RR: 1.58; 95% CI: 1.39 to 1.78), myocardial infarction (RR: 1.99; 95% CI: 1.61 to 2.46), and stroke (RR: 2.27; 95% CI: 1.80 to 2.85). Patients with the metabolic syndrome, but without diabetes, maintained a high cardiovascular risk. CONCLUSIONS The metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality. Studies are needed to investigate whether or not the prognostic significance of the metabolic syndrome exceeds the risk associated with the sum of its individual components. Furthermore, studies are needed to elucidate the mechanisms by which the metabolic syndrome increases cardiovascular risk.

Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials

Background: Many placebo-controlled trials have demonstrated the efficacy of individual pharmacotherapies approved for smoking cessation. However, few direct or indirect comparisons of such interventions have been conducted. We performed a meta-analysis to compare the treatment effects of 7 approved pharmacologic interventions for smoking cessation. Methods: We searched the US Centers for Disease Control and Preventions Tobacco Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo-controlled, double-blind randomized controlled trials of pharmacotherapies for smoking cessation. We included studies that reported biochemically validated measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random-effects model to summarize the results for each intervention. Results: We identified 70 published reports of 69 trials involving a total of 32 908 patients. Six of the 7 pharmacotherapies studied were found to be more efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible interval [CrI] 1.91–3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12–5.13), bupropion (OR 2.07, 95% CrI 1.73–2.55), transdermal nicotine (OR 2.07, 95% CrI 1.69–2.62), nicotine tablet (OR 2.06, 95% CrI 1.12–5.13) and nicotine gum (OR 1.71, 95% CrI 1.35–2.21). Similar results were obtained regardless of which measure of abstinence was used. Although the point estimate favoured nicotine inhaler over placebo (OR 2.17), these results were not conclusive because the credible interval included unity (95% CrI 0.95–5.43). When all 7 interventions were included in the same model, all were more efficacious than placebo. In our analysis of data from the varenicline trials that included bupropion control arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09–4.08). Interpretation: Varenicline, bupropion and the 5 nicotine replacement therapies were all more efficacious than placebo at promoting smoking abstinence at 6 and 12 months.

Addition of Frailty and Disability to Cardiac Surgery Risk Scores Identifies Elderly Patients at High Risk of Mortality or Major Morbidity

Background— Cardiac surgery risk scores perform poorly in elderly patients, in part because they do not take into account frailty and disability which are critical determinants of health status with advanced age. There is an unmet need to combine established cardiac surgery risk scores with measures of frailty and disability to provide a more complete model for risk prediction in elderly patients undergoing cardiac surgery. Methods and Results— This was a prospective, multicenter cohort study of elderly patients (≥70 years) undergoing coronary artery bypass and/or valve surgery in the United States and Canada. Four different frailty scales, 3 disability scales, and 5 cardiac surgery risk scores were measured in all patients. The primary outcome was the STS composite end point of in-hospital postoperative mortality or major morbidity. A total of 152 patients were enrolled, with a mean age of 75.9±4.4 years and 34% women. Depending on the scale used, 20–46% of patients were found to be frail, and 5–76% were found to have at least 1 disability. The most predictive scale in each domain was: 5-meter gait speed ≥6 seconds as a measure of frailty (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.17–5.90), ≥3 impairments in the Nagi scale as a measure of disability (OR, 2.98; 95% CI, 1.35–6.56) and either the Parsonnet score (OR, 1.08; 95% CI, 1.04–1.13) or Society of Thoracic Surgeons Predicted Risk of Mortality or Major Morbidity (STS-PROMM) (OR, 1.05; 95% CI, 1.01–1.09) as a cardiac surgery risk score. Compared with the Parsonnet score or STS-PROMM alone, (area under the curve, 0.68–0.72), addition of frailty and disability provided incremental value and improved model discrimination (area under the curve, 0.73–0.76). Conclusions— Clinicians should use an integrative approach combining frailty, disability, and risk scores to better characterize elderly patients referred for cardiac surgery and identify those that are at increased risk.

Isolated aerobic exercise and weight loss: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND Aerobic exercise is a common nonpharmacological intervention for the management of obesity. However, the efficacy of isolated aerobic exercise at promoting weight loss is unclear. We conducted a systematic review and meta-analysis to evaluate the efficacy of isolated aerobic exercise programs in overweight and obese populations. METHODS We searched for published randomized controlled trial reports of aerobic exercise through January 20, 2010. Trials with an isolated aerobic exercise intervention were included. A random-effect model was used to synthesize the results of each intervention. RESULTS We identified 14 trials involving 1847 patients. The duration of aerobic exercise programs ranged from 12 weeks to 12 months. Results were pooled for programs with 6-month duration and programs with 12-month duration. Six-month programs were associated with a modest reduction in weight (weighted mean difference [WMD]=-1.6 kg; 95% confidence interval [CI], -1.64 to -1.56) and waist circumference (WMD=-2.12 cm; 95% CI, -2.81 to -1.44). Twelve-month programs also were associated with modest reductions in weight (WMD=-1.7 kg; 95% CI, -2.29 to -1.11) and waist circumference (WMD=-1.95 cm; 95% CI, -3.62 to -0.29). CONCLUSION Moderate-intensity aerobic exercise programs of 6-12 months induce a modest reduction in weight and waist circumference in overweight and obese populations. Our results show that isolated aerobic exercise is not an effective weight loss therapy in these patients. Isolated aerobic exercise provides modest benefits to blood pressure and lipid levels and may still be an effective weight loss therapy in conjunction with diets.

Meta-analysis of usefulness of d-dimer to diagnose acute aortic dissection.

Numerous studies have examined whether plasma D-dimer (DD) can be used to identify patients with acute aortic dissection (AAD). These studies have been inconclusive because of their limited sample sizes and the different cut-off values employed. We aimed to conduct a systematic review and meta-analysis to examine the utility of plasma DD as a screening tool for AAD. We systematically searched EMBASE and MEDLINE and hand-searched relevant articles to identify studies investigating plasma DD as a screening tool for AAD. A value of 500 ng/ml was defined as the threshold for a positive plasma DD finding because it is widely used for ruling out pulmonary emboli. Using DerSimonian-Laird random-effects models we pooled data across studies to estimate sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (LRs). We identified 7 studies involving 298 subjects with AAD and 436 without. When data were pooled across studies, sensitivity (0.97, 95% confidence interval [CI] 0.94 to 0.99) and negative predictive value (0.96, 95% CI 0.93 to 0.98) were high. Specificity (0.56, 95% CI 0.51 to 0.60) and positive predictive value (0.60, 95% CI 0.55 to 0.66) were low. Negative LR showed an excellent discriminative ability (0.06, 95% CI 0.03 to 0.12), whereas positive LR did not (2.43, 95% CI 1.89 to 3.12). In conclusion, our meta-analysis suggests that plasma DD <500 ng/ml is a useful screening tool to identify patients who do not have AAD. Plasma DD may thus be used to identify subjects who are unlikely to benefit from further aortic imaging.

Coronary Artery Perforation During Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis

Numerous studies have examined the incidence, predictors, outcomes, and management strategies of coronary artery perforation (CAP). Individually, these studies have been inconclusive because of their limited sample sizes and/or single-centre designs. We conducted a systematic review and meta-analysis of studies pertaining to CAP in order to estimate its incidence and outcomes and to critically review its risk factors and treatment. We systematically searched the literature to identify all registry studies investigating CAP. Data were pooled by means of the random-effects model. In 16 studies involving 197,061 percutaneous coronary interventions, the pooled incidence of CAP was 0.43% (95% confidence interval, 0.35%-0.52%). The most reproducible risk factors were treatment of complex lesions and use of atheroablative devices. A variety of major management strategies for CAP were used, in particular, observation, heparin reversal, prolonged balloon inflation, covered stent implantation, pericardiocentesis, and surgery. In a hierarchical Bayesian random-effects model, the pooled tamponade rates were 0.4% (95% credible interval [CrI], 0.0%-5.7%), 3.3% (95% CrI, 0.0%-11.4%), and 45.7% (95% CrI, 34.9%-57.5%) for patients with Ellis class I, II, and III CAP, respectively. Pooled mortality rates were 0.3% (95% CrI, 0.0%-4.4%), 0.4% (95% CrI, 0.0%-2.8%), and 21.2% (95% CrI, 12.0%-31.4%) for patients with Ellis class I, II, and III CAP respectively. CAP complicating percutaneous coronary intervention is rare, and its morbidity and mortality vary directly with Ellis classification. Management discrepancies highlight the need to establish a uniform treatment paradigm for CAP.

Alternative Smoking Cessation Aids: A Meta-analysis of Randomized Controlled Trials

BACKGROUND Acupuncture, hypnotherapy, and aversive smoking are the most frequently studied alternative smoking cessation aids. These aids are often used as alternatives to pharmacotherapies for smoking cessation; however, their efficacy is unclear. METHODS We carried out a random effect meta-analysis of randomized controlled trials to determine the efficacy of alternative smoking cessation aids. We systematically searched the Cochrane Library, EMBASE, Medline, and PsycINFO databases through December 2010. We only included trials that reported cessation outcomes as point prevalence or continuous abstinence at 6 or 12 months. RESULTS Fourteen trials were identified; 6 investigated acupuncture (823 patients); 4 investigated hypnotherapy (273 patients); and 4 investigated aversive smoking (99 patients). The estimated mean treatment effects were acupuncture (odds ratio [OR], 3.53; 95% confidence interval [CI], 1.03-12.07), hypnotherapy (OR, 4.55; 95% CI, 0.98-21.01), and aversive smoking (OR, 4.26; 95% CI, 1.26-14.38). CONCLUSION Our results suggest that acupuncture and hypnotherapy may help smokers quit. Aversive smoking also may help smokers quit; however, there are no recent trials investigating this intervention. More evidence is needed to determine whether alternative interventions are as efficacious as pharmacotherapies.

Defining optimal activated clotting time for percutaneous coronary intervention: A systematic review and Bayesian meta-regression

Guidelines recommend routine monitoring of unfractionated heparin (UFH) with activated clotting time (ACT) during percutaneous coronary intervention (PCI). However, the optimal ACT for patients undergoing PCI is unclear.

Should family members witness cardiopulmonary resuscitation

CLINICAL QUESTION What is the effect of family presence during cardiopulmonary resuscitation on family members and the medical team? ARTICLE CHOSEN Jabre P, Belpomme V, Azoulay E, et al. Family presence during cardiopulmonary resuscitation. N Engl J Med 2013;368:1008-18. OBJECTIVE The authors sought to determine whether systematically offering relatives the option to be present during cardiopulmonary resuscitation increases the proportion of relatives with posttraumatic stress disorder-related symptoms after 90 days. Secondary outcomes included the presence of anxiety and depression symptoms in relatives, the effect of family presence on medical efforts at resuscitation, the well-being of the medical team, and the occurrence of medicolegal claims.

A National Survey of Mentoring Practices for Young Investigators in Circulatory and Respiratory Health

Background. Improving mentorship may help decrease the shortage of young investigators (graduate students, postdoctoral fellows, and new investigators) available to work as independent researchers in cardiovascular and respiratory health. Objectives. To determine (1) the mentoring practices for trainees affiliated with the Canadian Institutes of Health Research (CIHR), Institute of Circulatory and Respiratory Health (ICRH), (2) the positive attributes of mentors, and (3) the recommendations regarding what makes good mentorship. Methods. We conducted a survey and descriptive analysis of young investigators with a CIHR Training and Salary Award from 2010 to 2013 or who submitted an abstract to the ICRH 2014 Young Investigators Forum. Clinicians were compared to nonclinicians. Results. Of 172 participants, 7.0% had no mentor. Only 43.6% had defined goals and 40.7% had defined timelines, while 54.1% had informal forms of mentorship. A significant proportion (33.1%) felt that their current mentorship did not meet their needs. Among clinicians, 22.2% would not have chosen the same mentor again versus 11.4% of nonclinicians. All participants favored mentors who provided guidance on career and work-life balance. Suggestions for improved mentoring included formal mentorship, increased networking, and quality assurance. Conclusion. There is an important need to improve mentoring in cardiovascular and respiratory health.