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Background Whereas there exists a direct relationship between glycated hemoglobin and cardiovascular disease (CVD), clinical trials targeting glycated hemoglobin to near-normal levels using intensive therapy have failed to prevent CVD and have even increased mortality, making clinical decision making difficult. A common polymorphism at the haptoglobin (Hp) genetic locus is associated with CVD, especially coronary heart disease, in the setting of hyperglycemia. Objectives This study sought to determine whether the treatment difference of intensive versus standard glucose-lowering therapy on risk of CVD events in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study depended on Hp phenotype. Methods Hp phenotype was measured within 5,806 non-Hispanic white ACCORD participants using a validated assay. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) estimated from stratified Cox regression models were used to quantify the association between intensive therapy and incident CVD for the 2 different Hp phenotype groups (Hp2-2, Hp1 carriers). Results Compared with standard therapy, intensive therapy was associated with a lower risk of incident coronary heart disease among participants with the Hp2-2 phenotype (n = 2,133; aHR: 0.71; 95% CI: 0.55 to 0.91; p = 0.006), but not among the other 2 phenotypes (Hp1 allele carriers) (n = 3,673; aHR: 0.95; 95% CI: 0.79 to 1.13; p = 0.550). The same pattern was observed for CVD. Conversely, intensive therapy was associated with an increased risk of fatal CVD (aHR: 1.50; 95% CI: 1.00 to 2.25; p = 0.049) and total mortality (aHR: 1.40; 95% CI: 1.08 to 1.81; p = 0.011) among the Hp1 carriers, whereas this risk was not increased in the Hp2-2 phenotype (fatal CVD: aHR: 1.02; 95% CI: 0.59 to 1.77; p = 0.931; total mortality: aHR: 0.98; 95% CI: 0.68 to 1.41; p = 0.908). Conclusions Intensive glucose-lowering therapy was effective at preventing incident coronary heart disease and CVD events in ACCORD study participants with the Hp2-2 phenotype but not in Hp1 carriers, who had increased mortality risk from intensive therapy. more...

The Beta-Blocker Heart Attack Trial was a placebo-controlled, randomized, double-blind clinical trial of the long-term administration of propranolol hydrochloride to patients who had had at least one myocardial infarction. Among 3,837 patients followed up for an average of 25 months, 3,290 (85.7%) had 24 hour ambulatory electrocardiograms performed at the baseline examination. Four classifications of arrhythmia were examined. One of these, the presence of complex ventricular arrhythmias (at least 10 ventricular premature beats/h, or at least one pair or run of ventricular premature beats or multiform ventricular premature beats) was the subgroup of major interest. Regardless of the classification, the presence of arrhythmia identifies a group of patients with a higher risk of total mortality, coronary heart disease mortality, sudden cardiac death and instantaneous cardiac death. The a priori subgroup hypothesis that sudden death would be preferentially reduced by propranolol in patients with complex ventricular arrhythmias was not supported. The relative benefit of propranolol in reducing sudden death for this subgroup was 28 versus 16% for the subgroup without ventricular arrhythmia (relative risk of 0.72 versus 0.84, a nonsignificant relative difference of 14%). There were similar findings for two of the three other classifications of arrhythmia and for the other response variables. Although propranolol does not appear to be of special relative benefit in patients with ventricular arrhythmia, the presence of the arrhythmia does identify a high-risk group. The mechanism by which propranolol reduces mortality is still unclear, but is probably not solely an antiarrhythmic one. more...

Twenty-four hour ambulatory electrocardiography was performed on 3,290 survivors of acute myocardial infarction participating in the Beta-Blocker Heart Attack Trial (BHAT). History of myocardial infarction before the qualifying event, congestive heart failure and age were independently associated with the frequency and complexity of ventricular premature beats. Of the 1,640 patients randomized to placebo therapy, 163 died (76 suffered sudden death) during a 25 month average follow-up period. Ventricular ectopic activity was an independent predictor of total mortality after taking into consideration 16 other prognostic factors describing past history, risk factors, physical examination and laboratory investigations. Seven categoric definitions of ventricular ectopic activity predicted mortality, with similar odds ratios ranging from 2.27 to 2.69. A reciprocal relation of the sensitivity and specificity of each definition in predicting mortality was observed. Three clinical criteria (ST depression, cardiomegaly and prior infarction) allowed stratification of patients into four subsets with respective mortality rates of 35.5% (three criteria present), 19.0% (two criteria), 11.5% (one criterion) and 4.7% (none). Presence of ventricular ectopic activity (greater than or equal to 10 ventricular premature beats/h or pairs, ventricular tachycardia or multiform complexes) was associated with higher mortality rates in all four risk strata. The relative risk was higher (3.86) in the lowest risk stratum (mortality 2.4% without and 9.1% with ventricular ectopic activity). Thus, in survivors of acute myocardial infarction, ventricular ectopic activity was more pronounced in patients with prior myocardial infarction and congestive heart failure. It predicted mortality independently of other factors. Although mortality ratios were similar for all seven arrhythmia definitions, a reciprocal relation between sensitivity and specificity of the definitions in predicting mortality existed; ventricular ectopic activity was associated with increased mortality in all risk strata, but with a higher risk ratio in the numerically larger, low risk subset. more...

angiopl~sty (36%), acute myocardial infaretion (23%), or acids myocardial tschemla (15%), D~t~ were collected by medical record review to assess tnt0rventions eroded hl the hospital, nnd nn intenriew, physical oxamlnntton, and blood samptn was obtalnod ,~t tn,~st si~ months ~ftnr discha~e to essess which interventlena wore s~ibsoqtlentty IniIIsfed and whether goals were attained, Substantial pmv~ioncas of smoking, elevated blood pressure (~-t40/90 remHg,), nnd 0tnv¢lted LDL ehoiostnret (-.100 mg/dl) were still absented Six months nft0r discharge, Aspirin usage was widespread, but substantial numbom of patients were still not receiving beta blockers, ltpi,~. lowering agents, or estrogen tin women), Missed opportunities to implement the AHAIACC guidelines were identified at inpatient, ambulaton/care, and patient levels, Ft,lhor analysis of ACCEPT data will identily barriers which, it rectified, will serve to optimize cardlologlc care in those high risk patients. more...