Inadequate heart rate control despite widespread use of beta-blockers in outpatients with stable CAD: findings from the international prospective CLARIFY registry

Background: To use CLARIFY, a prospective registry of patients with stable CAD (45 countries), to explore heart rate (HR) control and beta-blocker use.<p></p> Methods: We analyzed the CLARIFY population according to beta-blocker use via descriptive statistics with Pearson's χ2 test for comparisons, as well as a multivariable stepwise model.<p></p> Results: Data on beta-blocker use was available for 32,914 patients, in whom HR was 68 ± 11 bpm; patients with angina, previous myocardial infarction, and heart failure had HRs of 69 ± 12, 68 ± 11, and 70 ± 12 bpm, respectively. 75% of these patients were receiving beta-blockers. Bisoprolol (34%), metoprolol tartrate (16%) or succinate (13%), atenolol (15%), and carvedilol (12%) were mostly used; mean dosages were 49%, 76%, 35%, 53%, and 45% of maximum doses, respectively. Patients aged < 65 years were more likely to receive beta-blockers than patients ≥ 75 years (P < 0.0001). Gender had no effect. Subjects with HR ≤ 60 bpm were more likely to be on beta-blockers than patients with HR ≥ 70 bpm (P < 0.0001). Patients with angina, previous myocardial infarction, heart failure, and hypertension were more frequently receiving beta-blockers (all P < 0.0001), and those with PAD and asthma/COPD less frequently (both P < 0.0001). Beta-blocker use varied according to geographical region (from 87% to 67%).<p></p> Conclusions: Three-quarters of patients with stable CAD receive beta-blockers. Even so, HR is insufficiently controlled in many patients, despite recent guidelines for the management of CAD. There is still much room for improvement in HR control in the management of stable CAD

Gender- and age-related differences in clinical presentation and management of outpatients with stable coronary artery disease

<br>Introduction: Contemporary generalizable data on the demographics and management of outpatients with stable coronary artery disease (CAD) in routine clinical practice are sparse. Using the data from the CLARIFY registry we describe gender- and age-related differences in baseline characteristics and management of these patients across broad geographic regions.</br> <br>Methods: This international, prospective, observational, longitudinal registry enrolled stable CAD outpatients from 45 countries in Africa, Asia, Australia, Europe, the Middle East, and North, Central, and South America.</br> <br>Results: Baseline data were available for 33 280 patients. Mean (SD) age was 64 (10.5) years and 22.5% of patients were female. The prevalence of CAD risk factors was generally higher in women than in men. Women were older (66.6 vs 63.4 years), more frequently diagnosed with diabetes (33% vs 28%), hypertension (79% vs 69%), and higher resting heart rate (69 vs 67 bpm), and were less physically active. Smoking and a history of myocardial infarction were more common in men. Women were more likely to have angina (28% vs 20%), but less likely to have undergone revascularization procedures. CAD was more likely to be asymptomatic in older patients perhaps because of reduced levels of physical activity. Prescription of evidence-based medication for secondary prevention varied with age, with patients ≥ 75 years treated less often with beta blockers, aspirin and angiotensin-converting enzyme inhibitors than patients < 65 years.</br> <br>Conclusions: Important gender-related differences in clinical characteristics and management continue to exist in all age groups of outpatients with stable CAD.</br&gt

Heart Rate and Use of Beta-Blockers in Stable Outpatients with Coronary Artery Disease

<p><b>Background:</b> Heart rate (HR) is an emerging risk factor in coronary artery disease (CAD). However, there is little contemporary data regarding HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice. The goal of the present analysis was to describe HR in such patients, overall and in relation to beta-blocker use, and to describe the determinants of HR.</p> <p><b>Methods and Findings:</b> CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis of >50%, or chest pain associated with proven myocardial ischemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, Middle East, and Asia/Pacific were enrolled between November 2009 and July 2010. Most of the 33,177 patients included in this analysis were men (77.5%). Mean (SD) age was 64.2 (10.5) years, HR by pulse was 68.3 (10.6) bpm, and by electrocardiogram was 67.2 (11.4) bpm. Overall, 44.0% had HR≥70 bpm. Beta-blockers were used in 75.1% of patients and another 14.4% had intolerance or contraindications to beta-blocker therapy. Among 24,910 patients on beta-blockers, 41.1% had HR≥70 bpm. HR≥70 bpm was independently associated with higher prevalence and severity of angina, more frequent evidence of myocardial ischemia, and lack of use of HR-lowering agents.</p> <p><b>Conclusions:</b> Despite a high rate of use of beta-blockers, stable CAD patients often have resting HR≥70 bpm, which was associated with an overall worse health status, more frequent angina and ischemia. Further HR lowering is possible in many patients with CAD. Whether it will improve symptoms and outcomes is being tested.</p&gt

Structure of the Escherichia coli TolB protein determined by MAD methods at 1.95 Å resolution

AbstractBackground: The periplasmic protein TolB from Escherichia coli is part of the Tol–PAL (peptidoglycan-associated lipoprotein) multiprotein complex used by group A colicins to penetrate and kill cells. TolB homologues are found in many Gram-negative bacteria and the Tol–PAL system is thought to play a role in bacterial envelope integrity. TolB is required for lethal infection by Salmonella typhimurium in mice.Results: The crystal structure of the selenomethionine-substituted TolB protein from E. coli was solved using multiwavelength anomalous dispersion methods and refined to 1.95 Å. TolB has a two-domain structure. The N-terminal domain consists of two α helices, a five-stranded β-sheet floor and a long loop at the back of this floor. The C-terminal domain is a six-bladed β propeller. The small, possibly mobile, contact area (430 Å2) between the two domains involves residues from the two helices and the first and sixth blades of the β propeller. All available genomic sequences were used to identify new TolB homologues in Gram-negative bacteria. The TolB structure was then interpreted using the observed conservation pattern.Conclusions: The TolB β-propeller C-terminal domain exhibits sequence similarities to numerous members of the prolyl oligopeptidase family and, to a lesser extent, to class B metallo-β-lactamases. The α/β N-terminal domain shares a structural similarity with the C-terminal domain of transfer RNA ligases. We suggest that the TolB protein might be part of a multiprotein complex involved in the recycling of peptidoglycan or in its covalent linking with lipoproteins

High Prevalence of Hepatitis C Virus Type 5 in Central France Evidenced by a Prospective Study from 1996 to 2002

From 1996 to 2002, hepatitis C virus (HCV) typing was prospectively performed for 1,281 unselected HCV-infected and viremic patients, irrespective of their clinical status. Eighty-three patients (6.5%) were coinfected with human immunodeficiency virus (HIV) and HCV. A total of 1,195 strains were identified by a serotype screening (Murex HCV Serotyping 1-6 assay) and/or genotyping (Inno-LiPA HCV II) test. The distribution of HCV types showed an unusually high rate of type 5 (14.2%) that was stable over time and was the third most frequent type, after type 1 (59.1%) and type 3 (15.1%). HCV type 5 was more frequent in patients who were older than 50 (P = 10(−6)), but its frequency did not differ significantly by gender (P = 0.21). Serotyping was performed for 1,160 strains but failed for 30.2% of them. The efficiency depended on HIV status (for HCV-HIV-coinfected patients, half of the strains were untypeable) and HCV type. Genotyping was performed for 428 samples, with an overall efficiency of 99.3%. It failed in three cases, which were subsequently identified as HCV type 2. Serotyping and genotyping results for 39 patients showed discrepancies between the two methods for 4 patients, who had HCV type 2, type 6, or mixed infections. Thus, HCV type 5 may also be encountered frequently in Western countries. Its apparent confinement to a restricted area raises the question of how it emerged and underscores the need for further studies of HCV type prevalence, routes of transmission, pathogenicity, and responses to treatment

Molecular epidemiology of hepatitis C virus genotype 5a in France (a multicenter ANRS study)

Date du colloque&nbsp;: 10/2009</p

Factors associated with HR≥70 bpm.

<p>BMI, body mass index; CAD, coronary artery disease; CCS, Canadian Cardiovascular Society; CHF, congestive heart failure; CI, confidence interval; COPD, chronic obstructive pulmonary disease; HR, heart rate; OR, odds.</p

Medications of the study population classified according to resting HR by palpation.

<p>ACE, angiotensin-converting enzyme; HR, heart rate; HRT, hormone replacement therapy; IQR, interquartile range.</p

HR distribution in stable CAD patients.

<p>HR distribution in stable CAD patients.</p