Background IONA was a randomized trial of nicorandil (20 mg twice daily) versus placebo in 5126 patients with stable angina of effort. We present the characteristics as measured at baseline that were found to be associated with increased risk of major outcomes.Methods The primary end point of the study was coronary heart disease death, nonfatal myocardial infarction (MI), or unplanned hospitalization for cardiac chest pain. The secondary outcome excluded the softer outcome of unplanned hospitalization for chest pain. Potential prognostic factors included nicorandil treatment, sex, smoking, severity of angina (Canadian Cardiovascular Society [CCS] grading), previous MI, coronary artery bypass graft/percutaneous transluminal coronary angioplasty (CABG/PTCA), left ventricular dysfunction, left ventricular hypertrophy (LVH) on electrocardiography (ECG), histories of diabetes or hypertension, baseline cardiovascular drugs, age, blood pressures, heart rate, height, weight, and body mass index.Results A total of 5047 patients hod complete baseline information. There were 724 primary outcomes and 240 secondary outcomes. The strongest determinants of the hard secondary end point were CCS score (hazards ratio [HR] 2.25, 95% confidence intervals [CI] 1.50-3.38) for grades III and IV versus grade 1, age (HR 1.23, 95% Cl I. 13-1.33) for 5-year risk, and previous MI (HR 2.05, 95% CI 1.48-2.85). The results for the primary outcome were similar, with stronger associations with LVH on ECG and smoking, and a weaker association with age.Conclusions We present models of risk factors for coronary outcomes in a population with angina of effort, The strongest risk factors were the CCS score and previous MI.

prospective study of cardiovascular disease

The significant reduction in cardiovascular morbidity and mortality following oestrogen replacement therapy in postmenopausal women is only partly explained by an improved lipid profile. Given acutely, oestradiol causes vasodilatation and increases coronary blood flow and, in large doses, improves treadmill performance in postmenopausal women with coronary artery disease. However, the significance of oestrogen-mediated vasodilatation is unknown since the acute effects of oestradiol in doses and preparations commonly used clinically have not been tested. The aim of this study was to evaluate the acute effects of conventional replacement therapy with 17 beta-oestradiol on treadmill performance in 16 postmenopausal women with angina in a randomized, double-blind, placebo-controlled cross-over trial. Following baseline treadmill testing a transdermal oestrogen patch releasing 50 micrograms oestradiol. 24 h-1 or matching placebo was applied and the exercise test repeated 24 h later. The patch was then removed. Seven to 14 days later the sequence was repeated using the alternative patch. The changes in time to angina, time to 1 mm ST segment depression and total exercise time for each treatment compared with the corresponding baseline test were calculated. Plasma 17 beta-oestradiol increased with active therapy from 56 +/- 30 pmol.l-1 to 204 +/- 90 pmol.l-1, indicating adequate replacement. Compared with their respective baseline exercise tests there were no differences between active and placebo patches for time to angina (active: 13 +/- 55 s vs placebo: 10 +/- 47 s), time to 1 mm ST segment depression (active: -30 +/- 52 s vs placebo: 24 +/- 71 s) or total exercise time (active: 14 +/- 45 s vs placebo: 13 +/- 35 s). Despite the recognized acute vasodilator action of larger doses of oestrogen, doses conventionally used in hormone replacement therapy had no acute effect on treadmill performance in this group of postmenopausal women with coronary artery disease.

Objective: To characterise clinical, investigative, and prognostic features of women referred with chest pain who subsequently underwent coronary angiography. Design: Analysis of all women with angina referred to one consultant during 1987-91 who subsequently underwent coronary angiography, with follow up to present day. Setting: Cardiothoracic centre Subjects: Women with normal coronary arteries; women with coronary artery disease shown on angiography; men with coronary artery disease matched for age; men referred with chest pain during the same period subsequently found to have normal coronary arteries. Main outcome measures: Risk factor analysis; results of exercise testing and coronary angiography; intervention; morbidity and mortality. Results: Women comprised 23% (202/886) of patients referred with chest pain who subsequently underwent angiography. 83/202 women had normal coronary angiograms compared with 55/684 men (41% v 8%, P<0.001). Diabetes mellitus was the only risk factor more frequently encountered in women with coronary artery disease (P=0.001). The specificity and positive predictive value of exercise testing before angiography were significantly lower in women than men (71% v 93%, P<0.001 and 76% v 95%, P<0.001, respectively). Revascularisation procedures were as common in women with coronary artery disease as in men (81 (68%) v 70 (59%)), and there was no difference in event rate during follow up. Many patients with normal coronary arteries, irrespective of sex, had symptoms during follow up (61 (73%) women, 36 (65%) men) and continued to take antianginal drugs (27 (33%) women, 14 (28%) men); 14 (17%) women and six (11%) men required hospital readmission for severe symptoms. Conclusions: In this series, although women comprised the minority of patients referred with chest pain, a diagnosis of normal coronary arteries was five times more common in women than men. Risk factor analysis and exercise testing were of limited value in predicting coronary artery disease in women. There was no sex bias regarding revascularisation procedures, and outcome was similar. A diagnosis of non-cardiac chest pain in patients with normal coronary arteries was of little benefit to the patient with regard to morbidity.

Treatment of both stable and unstable angina depends on initially defining the pathophysiological mechanisms. The goal of treatment is to prevent the development of angina pectoris and possibly also to improve the prognosis. beta-blockade is effective in treating effort-related angina, as are calcium antagonists, which are also effective in treating coronary spasm. Combination therapy may be synergistic, but evidence to support this is controversial. In unstable angina the main goal of treatment is the prevention of myocardial infarction and death. While calcium antagonists have not been shown to improve the prognosis, there is more evidence to support the use of beta-blockers, particularly in combination with a calcium antagonist. Aspirin and possibly heparin should be considered as routine treatment.

Many studies have confirmed a peak in the onset of acute myocardial infarction, sudden cardiac death and ischemic activity in the morning waking hours in patients with coronary artery disease. Factors potentially relevant to this observed surge in activity include marked increases in heart rate, blood pressure, catecholamine release, coronary artery tone and platelet aggregability, and a trough in the fibrinolytic state at this time. 1 Various studies have shown that β-adrenergic blockade is effective in blunting particularly the morning surge in ischemic activity,2,3 onset of acute myocardial infarction, 4 and sudden cardiac death5; however, despite the powerful coronary vasodilating and afterload-reducing properties of calcium antagonists, they have not been shown to alter the morning surge in ischemia2,6 (except in high doses7), or the morning peak in onset of myocardial infarction.4 Although the recently published nifedipine Gastrointestinal Therapeutic System (GITS) study showed an overall modification of the circadian pattern of ischemia with nifedipine GITS as monotherapy, there appeared to be no difference in circadian patterns during such active therapy and subsequent placebo withdrawal.8 It is possible that previous studies of calcium antagonists without either a 24-hour profile or chronotropic control have resulted in (1) the morning waking period being “unprotected” regarding efficacious plasma levels of drug on waking, and/or (2) an absence of modification of the heart rate response to increasing and commencing activity, a mechanism by which β blockers may, at least partially, exert their effects.

This paper is a summary of present practices in the investigation and management of angina. The mechanism, incidence, and prevalence of angina are reviewed, the roles of invasive and non-invasive investigations assessed, and the indications for coronary angioplasty and coronary bypass grafting discussed. Basic audit data sets for primary, secondary, and tertiary care are proposed and potential audit initiatives suggested.

Spontaneous, sustained low frequency oscillations of pulmonary arterial pressure were observed in 8 patients with moderate to severe chronic heart failure during recordings of pulmonary arterial pressure of 8.6 to 48 hours duration. The oscillations (frequency range 0.015 to 0.035 Hz) had a distinct peak from and lower frequency range than respiration (0.2 to 0.6 Hz) and heart rate (0.8 to 1.9 Hz). They were present from 42% to 82% of the recording time with an amplitude varying from undetectable to a maximum range from 5.3 mm Hg to 19.7 mm Hg. When detectable, the mean amplitude of the low frequency oscillations of pulmonary arterial pressure ranged from 1.2 +/- 1.2(SD) mm Hg to 4.3 +/- 3.3 mm Hg. These oscillations are lower in frequency than the low frequency component usually described in recordings of systemic arterial pressure and heart rate in normal subjects, and are closer to the very low frequency rhythms described in severe chronic heart failure and Cheyne Stokes respiration.

Objective—To develop a complete system for the measurement, recording, and analysis of ambulatory pulmonary artery pressure. Design—The new system consists of a pulmonary artery catheter, an ambulatory recorder, and a desktop computer. Pulmonary artery pressure is measured by a micromanometer tipped catheter with an in vivo calibration system to allow correction for zero drift. This catheter is plugged into a small battery powered recorder. The recorder has two input channels, one for pressure and one for an event marker. The pressure wave is sampled 32 times/s, processed by an in built computer, compressed, and stored in semiconductor memory. On completion of a recording, data is transferred from the ambulatory recorder through a serial data link to an Acorn Archimedes desktop computer on which further data processing, statistical analysis, graphics, and printouts can be obtained. Results—The system has been used in 18 patients, with technically successful recording in 14, less than 15 minutes of data loss in three, and 12 hours of data loss in one. Conclusions—A new system for ambulatory pulmonary artery monitoring has been developed and used clinically with success. It may provide new perspectives on the pathophysiology of disease as it applies to everyday life.