From March 2002 to December 2002, 3779 patients with stable angina were enrolled into the study. Vital status during follow-up was ascertained in 3259 (86%) patients, and data were suitable for survival analysis for the primary outcome of interest, which included non-fatal myocardial infarction, in 3031. The median duration of follow-up was 13 (interquartile range 12-15) months. No substantial differences existed between the patients with and without follow-up information in terms of clinical characteristics () or regional distribution. Thus the survival analysis results, which are based on the 3031 patients with follow-up data, can be treated as indicative of the overall survival experience. The population was relatively young—mean age 61 years—and 58% were male. Most patients had mild to moderate symptoms of angina for six months or less before presentation to a cardiologist, although only 48 (1.7%) patients had symptoms for less than one month before cardiology assessment.
Baseline clinical characteristics of patients with and without completed clinical follow-up. Values are numbers (percentages) unless stated otherwise
Confirmation of coronary disease
Coronary angiography was done at least once during follow-up in 1253 (41%) patients. At the end of the follow-up period, approximately one third (n = 994) of patients had had coronary disease confirmed angiographically and a further third (n = 1023) had negative investigations. One sixth of patients had no definitive diagnostic test to confirm the presence or absence of coronary disease ().
Coronary disease status according to level of diagnostic investigation completed at end of follow-up (n=3031).
Clinical events during follow-up
shows the numbers of individual clinical events and the annual rates of clinical events in the overall study population and the subgroup with confirmed coronary disease. The incidence of death or infarction was significantly greater (P < 0.001) in patients with confirmed coronary disease than in those with negative investigations or positive non-invasive tests without angiographic confirmation of disease (). However, patients who had no investigation, or inconclusive results on non-invasive investigation that were not pursued further, had a rate of death or infarction—4.1/100 patient years (95% confidence interval 2.7 to 6.0)—that was similar to that in the population with confirmed coronary disease. Non-cardiovascular death did not seem to contribute a disproportionate number of these deaths, accounting for only 7/21 (33%) deaths. This was a similar proportion to that seen in the group with positive non-invasive tests (1/3, 33%) and less than the proportion seen in the group with negative investigations (4/7, 57%), although it was higher than the proportion seen in the group with confirmed coronary artery disease (2/19, 11%).
Major clinical events occurring during follow-up in the overall population and in patients with confirmed coronary disease
Cumulative probability of death or non-fatal myocardial infarction during follow-up in patients with stable angina, according to diagnostic level of confirmation of coronary disease
Clinical and investigative factors predictive of adverse outcome
shows the risk of death or myocardial infarction associated with baseline clinical characteristics and results of investigations. Previous myocardial infarction, signs of heart failure, or a past history of diabetes, hypertension, or any comorbidity were significant predictors of adverse outcome, as were increasing severity of symptoms and shorter duration of symptoms. Resting electrocardiographic abnormalities (Q wave or ST/T wave changes) were associated with approximately double the risk of death or myocardial infarction, but positive non-invasive stress test results were not significantly associated with adverse outcome. As the numbers of patients with stress imaging techniques were small, we created a new indicator to summarise the information on all forms of functional assessment (exercise electrocardiogram, stress echocardiogram, or perfusion). Not having had any functional assessment was an indicator of substantially increased risk, as was abnormal left ventricular function assessed by echocardiography.
Unadjusted hazard ratio of death or myocardial infarction associated with clinical and investigative parameters in general population with stable angina (n=3031)
Stepwise regression selected comorbidity, diabetes, recent onset of symptoms, more severe symptoms, ST or T wave abnormalities on the resting electrocardiogram, not having any stress test done, and abnormal ventricular function as the variables most predictive of outcome (). Age and sex were not significant predictors when forced into the model. Although age had a linear effect that was significant when examined on its own (), its strong association with most of the other variables led to its lack of significance in the multivariate model (highly significant association with all variables except “ST or T wave change”).
Clinical and investigative parameters independently predictive of death or myocardial infarction, determined by using stepwise selection procedures in general population with stable angina
Development of a clinical risk score for patients with stable angina
As non-performance of a test is not an objective measure of a patient but can be influenced by many physician related and non-clinical factors, we used a further stepwise selection process to consider only the results of non-invasive investigations that had been done. A positive versus negative or inconclusive non-invasive stress test result was not selected as a significant predictor of outcome when combined with information from echocardiography and resting electrocardiography. Thus in the model developed to derive the clinical risk score the final predictors of death or myocardial infarction were comorbidity, diabetes, severity of symptoms, duration of symptoms, resting electrocardiogram abnormalities, and abnormal ventricular function. Using each of these parameters a risk score can be calculated according to the weighted scores shown in . This score can then be used to estimate visually the probability of death or myocardial infarction from the plot in or (using the closest rounded figure) to read the estimated probability from . Applying the model developed on 75% of the population to the remaining 25% of the population gave a C-statistic for the angina score to predict outcome of 0.74.
Score sheet to calculate risk score for patients presenting with stable angina
Fig 2 Plot to assign estimated probability of death or non-fatal myocardial infarction within one year of presentation according to combination of clinical and investigative features in patients with stable angina (corresponding to scoring system in (more ...)
Estimated probability of death or non-fatal myocardial infarction over one year corresponding to selected values of the individual scores