Excessive daytime sleepiness, morning tiredness and major adverse cardiovascular events in patients with chronic coronary syndrome.

BACKGROUND: Sleep-related breathing disorders (SRBDs), particularly obstructive sleep apnoea, are associated with increased cardiovascular (CV) risk. However, it is not known whether individual questions used for SRBD screening are associated with major adverse CV events (MACE) and death specifically in patients with chronic coronary syndrome (CCS). METHODS: Symptoms associated with SRBD were assessed by a baseline questionnaire in 15,640 patients with CCS on optimal secondary preventive therapy in the STABILITY trial. The patients reported the frequency (never/rarely, sometimes, often and always) of: 1) loud snoring; 2) more than one awakening/night; 3) morning tiredness (MT); 4) excessive daytime sleepiness (EDS); or 5) gasping, choking or apnoea when asleep. In adjusted Cox regression models, associations between the frequency of SRBD symptoms and CV outcomes were assessed with never/rarely as reference. RESULTS: During a median follow-up time of 3.7 years, 1,588 MACE events (541 CV deaths, 749 nonfatal myocardial infarctions [MI] and 298 nonfatal strokes) occurred. EDS was associated (hazard ratio [HR], 95% confidence interval [CI]) with increased risk of MACE (sometimes 1.14 [1.01-1.29], often 1.19 [1.01-1.40] and always 1.43 [1.15-1.78]), MI (always 1.61 [1.17-2.20]) and all-cause death (often 1.26 [1.05-1.52] and always 1.71 [1.35-2.15]). MT was associated with higher risk of MACE (often 1.23 [1.04-1.45] and always 1.46 [1.18-1.81]), MI (always 1.61 [1.22-2.14]) and all-cause death (always 1.54 [1.20-1.98]). The other SRBD-related questions were not consistently associated with worse outcomes. CONCLUSIONS: In patients with CCS, gradually higher levels of EDS and MT were independently associated with increased risk of MACE, including mortality.

Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease.

OBJECTIVES: Assess the risk of ischaemic events associated with psychosocial stress in patients with stable coronary heart disease (CHD). METHODS: Psychosocial stress was assessed by a questionnaire in 14 577 patients (median age 65.0, IQR 59, 71; 81.6% males) with stable CHD on optimal secondary preventive therapy in the prospective randomized STABILITY clinical trial. Adjusted Cox regression models were used to assess associations between individual stressors, baseline cardiovascular risk factors and outcomes. RESULTS: After 3.7 years of follow-up, depressive symptoms, loss of interest and financial stress were associated with increased risk (hazard ratio, 95% confidence interval) of CV death (1.21, 1.09-1.34; 1.15, 1.05-1.27; and 1.19, 1.08-1.30, respectively) and the primary composite end-point of CV death, nonfatal MI or nonfatal stroke (1.21, 1.13-1.30; 1.19, 1.11-1.27; and 1.17, 1.10-1.24, respectively). Living alone was related to higher risk of CV death (1.68, 1.38-2.05) and the primary composite end-point (1.28, 1.11-1.48), whereas being married as compared with being widowed, was associated with lower risk of CV death (0.64, 0.49-0.82) and the primary composite end-point (0.81, 0.67-0.97). CONCLUSIONS: Psychosocial stress, such as depressive symptoms, loss of interest, living alone and financial stress, were associated with increased CV mortality in patients with stable CHD despite optimal medical secondary prevention treatment. Secondary prevention of CHD should therefore focus also on psychosocial issues both in clinical management and in future clinical trials.

Relationship of QRS duration at baseline and changes over 60 min after fibrinolysis to 30-day mortality with different locations of ST elevation myocardial infarction: results from the Hirulog and Early Reperfusion or Occlusion-2 trial.

OBJECTIVE: To discern if the prognostic meaning of QRS prolongation differs according to the location of ST elevation acute myocardial infarction DESIGN: Measuring QRS duration in patients with normal conduction or right bundle branch block SETTING: HERO-2 trial with prospective collection of electrocardiograms at randomisation and at 60 min after fibrinolytic therapy PATIENTS: 12 456 patients with normal conduction at both randomisation and 60-min time points and 510 with right bundle branch block (RBBB) at both time points MAIN OUTCOME MEASURE: 30-day mortality. RESULTS: On the baseline ECG, there was a positive association between QRS duration and 30-day mortality with anterior acute myocardial infarction (AMI) (p<0.0001 for those with normal conduction and = 0.007 for those with RBBB) but not with inferior AMI (p = 0.29 and p = 0.32, respectively). For anterior AMI, with or without RBBB, an increment of 20 ms increase in QRS duration predicted a significant 30-40% relative increase in 30-day mortality both before and after adjusting for clinical and ECG variables including baseline ST elevation and presence of Q waves. The association was not present for inferior AMI. Changes in QRS duration over 60 min after fibrinolytic therapy were uncommon and unrelated to mortality. CONCLUSION: Baseline QRS duration independently stratifies 30-day mortality in patients with anterior AMI, even when unaccompanied by RBBB, but does not stratify mortality risk in patients with inferior AMI.

B-type natriuretic peptide and left ventricular dysfunction on exercise echocardiography in patients with chronic aortic regurgitation.

OBJECTIVE: To determine whether plasma levels of B-type natriuretic peptide (BNP) predict left ventricular (LV) dysfunction on exercise echocardiography in patients with moderate to severe aortic regurgitation (AR). DESIGN: Case-control study. SETTING: Outpatient cardiology departments. PATIENTS: 39 asymptomatic or mildly symptomatic patients with chronic moderate to severe AR and a normal LV ejection fraction (>50%), and 10 normal controls. MAIN OUTCOME MEASURES: Plasma level of BNP and echocardiographic measures of LV function at rest and immediately after treadmill exercise. RESULTS: LV end systolic volume index (LVESVI) was significantly increased in AR patients with normal BNP (0.05 for all). However, there were modest but statistically significant associations between the plasma level of BNP and severity of AR indicated by a greater AR:LV outflow tract width ratio (r = 0.37, p = 0.02) and lower diastolic blood pressure (r = -0.44, p = 0.004). Increased BNP was also associated with a greater LVESVI (r = 0.33, p = 0.04) and lower LV longitudinal strain rate (r = -0.037, 0.02) on echocardiography after exercise. CONCLUSIONS: In moderate to severe AR compensatory LV remodelling can occur with no increase in plasma BNP. Increased BNP is associated with more severe regurgitation and changes consistent with early LV dysfunction on exercise echocardiography.

Variations in the use of emergency PCI for the treatment of re-infarction following intravenous fibrinolytic therapy: impact on outcomes in HERO-2.

BACKGROUND: Patients who suffer re-infarction during initial hospitalization for ST-elevation myocardial infarction (STEMI) have decreased survival compared to patients without re-infarction, so treatment of re-infarction may influence survival. METHODS AND RESULTS: To determine whether the utilization of reperfusion therapies varied within 12 h of re-infarction and was associated with 30-day mortality, we studied 552 patients with re-infarction of 17,073 patients with STEMI enrolled in HERO-2 in five regions (Russia, Eastern Europe, Western Countries, Asia, and Latin America). Patients presenting within 6 h of symptom-onset were randomized to receive either bivalirudin or unfractionated heparin intravenously just prior to streptokinase. Re-infarction occurred in 2.8 and 3.6% of bivalirudin and heparin treated patients, respectively (P = 0.004), but treatment assignment did not influence mortality after re-infarction. Patients with re-infarction had a higher 30-day mortality than those without re-infarction (24 vs. 10%; P < 0.001 by Cox model). Within 12 h of re-infarction, fibrinolytic therapy was administered to 12.0 and 8.2% underwent percutaneous coronary intervention (PCI); these two treatments were more frequently utilized in patients from Western countries (n = 112), compared to patients from other countries (n = 440) (34.8 and 16.1% compared to 6.1 and 6.1%, respectively, P < 0.001). Mortality was 15% in patients receiving reperfusion therapy for re-infarction and 27% for those with conservative management, hazard ratio (HR) 0.53 (95% CI 0.32-0.88), P = 0.01. In multiple Cox regression analysis which included adjustment for clinical variables and randomized treatment assignment, 30-day mortality after re-infarction varied by region (highest Latin America 29%, lowest Western countries 15%; P = 0.01). Other independent prognostic factors included age, time from randomization to re-infarction, and Killip class at randomization. The HR for PCI treatment of re-infarction was 0.18 [(95% CI 0.04-0.76), P = 0.02] in analyses which excluded deaths within 12 h. CONCLUSION: Treatment of re-infarction with reperfusion therapies was markedly under-utilized, especially in non-western countries. PCI for re-infarction, in particular, was associated with a lower 30-day mortality, which may reflect both patient selection and effects of treatment.

Lack of association between baseline plasma homocysteine concentrations and restenosis rates after a first elective percutaneous coronary intervention without stenting.

OBJECTIVE: To evaluate the association between baseline homocysteine concentrations and restenosis rates in patients electively undergoing their first percutaneous coronary intervention (PCI) without stenting. DESIGN: Prospective, single centre, observational study. SETTING AND PATIENTS: Patients electively undergoing their first PCI without stenting at a tertiary referral centre between 1990 and 1998. METHODS: Blood samples were collected from all patients at baseline and assayed to determine the patients' homocysteine concentrations. Patients whose PCI was successful underwent repeat angiography at a median of 6.4 (interquartile range 6-6.8) months. Their baseline and follow up angiograms were compared by quantitative coronary angiography to assess the incidence of restenosis. For the analysis, the patients were divided into two groups based on whether their baseline homocysteine concentrations were above or below the median value. These two groups were compared to determine whether there was any association between their baseline homocysteine concentrations and the incidence of restenosis at six months. RESULTS: 134 patients had a successful first PCI without stenting (involving 200 lesions). At six month angiography, restenosis was observed in 33 patients (49.3%) with baseline homocysteine concentrations above the median value and in 31 patients (46.3%) with concentrations below the median value (p = 0.74). There was no difference in the percentage of lesions developing restenosis (38 (39.6%) v 40 (38.5%), respectively, p = 0.87) or late lumen loss (0.40 mm v 0.31 mm, respectively, p = 0.24). On multivariable analysis, there was no association between homocysteine concentrations and late lumen loss (r = -0.11, p = 0.11) or the percentage diameter stenosis at follow up (r = -0.07, p = 0.32). CONCLUSION: Baseline homocysteine concentrations were not associated with six month restenosis rates in patients electively undergoing their first PCI without stenting.