Angina is a common symptom in patients with coronary artery disease (CAD); however, its impact on patients’ quality of life over time is not well understood. We sought to determine the longitudinal association of angina frequency with quality of life and functional status over a 5-year period. We used data from the Heart and Soul Study, a prospective cohort study of 1,023 outpatients with stable CAD. Participants completed the Seattle Angina Questionnaire (SAQ) at baseline and annually for 5 years. We evaluated the population effect of angina frequency on disease-specific quality of life (SAQ Disease Perception), physical function (SAQ Physical Limitation), perceived overall health, and overall quality of life, with adjusted models. We evaluated these associations within the same year and with a time-lagged association between angina and quality of life reported 1 year later. Generalized estimating equation models were used to account for repeated measures and within-subject correlation of responses. Over 5 years of follow-up, patients with daily or weekly angina symptoms had lower quality of life scores (52 vs 89, p <0.001) and greater physical limitation (61 vs 86, p <0.001) after adjustment. Compared with patients with daily or weekly angina symptoms, those with no angina symptoms had 2-fold greater odds of better quality of life (odds ratio 2.39, 95% confidence interval 1.76 to 3.25) and 5-fold greater odds of better perceived overall health (odds ratio 5.45, 95% confidence interval 3.85 to 7.73). In conclusion, angina frequency is strongly associated with quality of life and physical function in patients with CAD. Even after modeling to adjust for both clinical risk factors and repeated measures within subjects, we found that less frequent angina symptoms were associated with better quality of life.
In the United States, more than 8 million people per year experience chronic stable angina pectoris. Angina has been associated with worse quality of life and greater health care spending in previous cohorts, but its longitudinal effects on quality of life and functional status have not been well quantified. Angina has been associated with greater cardiovascular (CV) events in some studies, whereas others have shown that asymptomatic patients are at equal or higher risk of CV events. However, effective antianginal treatment has consistently shown improved symptom burden and overall quality of life even when subsequent myocardial infarction (MI) or CV deaths are not reduced. Previous investigations of the Heart and Soul Study cohort have found that angina was not associated with inducible ischemia on treadmill exercise echocardiography, but it was associated with lower exercise capacity and more nitrate use. Angina was also associated with higher rates of recurrent CV events and death, independent of other markers of cardiac disease severity. To better understand the longitudinal impact of angina pectoris on quality of life and functional status, accounting for changes in both over time, we sought to determine the longitudinal association of angina frequency with quality of life and functional status over a 5-year period.
Methods
The Heart and Soul Study is a prospective cohort study that was originally designed to investigate the effects of psychosocial factors on health outcomes in patients with stable coronary artery disease (CAD). Methods have been previously described. Patients were eligible if they had at least one of the following: history of MI, angiographic evidence of ≥50% stenosis in ≥1 coronary arteries, evidence of exercise-induced ischemia by treadmill electrocardiography or stress nuclear perfusion imaging, a history of coronary revascularization, or a diagnosis of CAD. Patients were excluded if they were unable to walk at least 1 block, had an acute coronary syndrome within the previous 6 months, or were likely to move from the area within 3 years. Institutional review boards at each site approved this study protocol. All participants provided written informed consent.
Between September 2000 and December 2002, 1,024 subjects were recruited from 12 outpatient clinics in the San Francisco Bay Area, including 549 with a history of MI (54%), 237 with a history of revascularization but not MI (23%), and 238 with a diagnosis of coronary disease (23%) that was documented by their physician, based on a positive angiogram or treadmill test in more than 98% of cases. All participants completed a full-day evaluation including medical history and physical examination, health status questionnaires, and an exercise treadmill test with baseline and stress echocardiograms. The analytic cohort for this study included the 1,023 participants who completed the Seattle Angina Questionnaire (SAQ) angina frequency domain.
Angina frequency was measured using the SAQ, which is a 19-item, self-administered questionnaire previously validated for use in patients with CAD. The questionnaire is divided into several domains, which we used to assess 3 components of health status including angina frequency (2-item angina frequency scale), functional status (9-item physical limitation scale), and disease-specific quality of life (3-item disease perception scale). , The angina frequency domain includes 2 questions with Likert-scale responses including, “Over the past 4 weeks, on average, how many times have you had chest pain, chest tightness, or angina pectoris?” and “How many times have you had to take nitroglycerin for your chest pain, chest tightness, or angina pectoris?” Scores for angina frequency are translated into a score on a 100-point scale, with 100 representing no angina and 0 representing angina occurring 4 or more times per day.
Participants were categorized into 3 groups of angina frequency based on their score from the corresponding domain defined as no angina (score 100), monthly angina (score 61 to 99), weekly (score 31 to 60), and daily (score 0 to 30). Because only 10 participants reported daily angina, participants with daily or weekly angina were combined into a single category for analysis. Changes in angina from 1 year to the next were categorized into 3 groups defined as (1) those who reported the same category of angina in the following year, (2) those who reported an improved angina, and (3) those who reported their angina was worse.
Functional status was assessed using the SAQ domain regarding physical limitation, and scores were calculated on a 100-point scale, with 100 representing no limitation and 0 representing severe physical limitations due to angina. Quality of life was assessed using the SAQ domain regarding disease perception, and scores were also calculated on a 100-point scale, with 100 representing no concern about angina to 0 representing extreme concern about angina. Annual changes in functional status and quality of life were calculated by subtracting the score of the preceding year from the current year, such that a positive change score indicated an improvement and a negative change score indicated a decline (range: −100, 100).
As a measure of overall perceived health status, participants were asked, “Compared with other people your age, how would you rate your overall health?” , As an additional measure of quality of life, participants were also asked, “Compared with other people your age, how would you rate your overall quality of life?” For both questions, participants chose from responses of “poor,” “fair,” “good,” “very good,” or “excellent.” Annual changes in these measures were created by first assigning a numeric value from 1 to 5 for “poor” to “excellent.” We then calculated the change score by subtracting the value for the measure in the preceding year from the current year (range: −4, 4).
Demographic characteristics, medical history, and smoking status were assessed by self-report questionnaire. Participants were asked to bring their medication bottles to the study appointment, and research personnel recorded all current medications. Medications were categorized using ePocrates Rx (San Mateo, California). To assess depressive symptoms, all participants completed the 9-item Patient Health Questionnaire. , Patients were categorized as “depressed” if they scored a 10 or greater on the 9-item Patient Health Questionnaire, which represented an estimate of the burden of depressive symptoms.
Assessment of functional status was performed using a scale combining elements of the New York Heart Association functional classification and the Canadian Cardiovascular Society angina score, which are both well-established prognostic tools in patients with CV disease. Participants were asked to grade the severity of their cardiac symptom burden, which could include chest discomfort, dyspnea, or fatigue, ranging from minimal (I) to mild (II), moderate (III), or severe (IV).
Baseline characteristics were compared across categories of angina frequency using the chi-square test for categoric variables and one-way analysis of variance for continuous variables. We evaluated the longitudinal association of angina frequency with quality of life and functional status in patients who completed the SAQ at baseline and annually for 5 years.
We examined the longitudinal associations of the SAQ domains for quality of life and physical functioning between groups of angina severity using linear regression models fitted with generalized estimating equations. We estimated the adjusted means and 95% confidence intervals (CIs) for each measure by groups of angina severity. We also used a 1-year lag of angina severity to predict quality of life and functional status the following year. We repeated these analyses using the continuous measure of angina frequency and estimated changes in quality of life and physical functioning per 10-unit increment of angina on the SAQ angina scale. We estimated the odds of improved overall health and quality of life as predicted by groups of angina severity and the continuous measure of angina frequency as before, using multinomial logistic mixed regression models. The proportional odds assumption was not violated, and therefore, we report 1 odds ratio (OR) for the multilevel outcome using the ordinal logistic mixed model. We repeated these analyses using the 1-year lagged measures of angina severity. To evaluate the relation between changes in angina severity predicting the change scores in quality of life and physical functioning from the SAQ domains, we fit linear regression models using generalized estimating equations. We estimated means and 95% CIs of change scores by groups of change in angina frequency. These analyses were repeated using the change scores for the overall quality of life rating and overall health rating as the outcome. Statistical significance was set a priori at p <0.05. All analyses were performed using Stata (version 15.1; College Station, Texas).
Results
At baseline, in 1,023 participants, baseline SAQ scores were 90 ± 17 for angina frequency, 73 ± 23 for physical limitation, and 74 ± 23 for quality of life. In addition, 633 participants reported no angina (62%), 279 reported monthly angina (27%), 101 reported weekly angina (10%), and 10 reported daily angina (1%). The mean age was 67 years, 82% were men, and 60% were Caucasian ( Table 1 ). The majority of patients had hypertension (71%) and previous coronary revascularization (59%). Self-reported ratings for overall quality of life and overall health rating were well distributed. Most patients were New York Heart Association functional Class I to II. Participants with daily or weekly angina were less likely to be male; a current smoker; to have a history of hypertension or heart failure; to have depressive symptoms; and to take β-blockers, calcium channel blockers, and nitrates.
| Baseline angina frequency | ||||
|---|---|---|---|---|
| Variable | Absent | Monthly | Daily or weekly | p Value |
| (n = 633) | (n = 279) | (n = 111) | ||
| Age (years), mean ± SD | 67.9 ± 10.6 | 64.7 ± 11.1 | 66.2 ± 11.7 | <0.001 |
| Men | 534 (84%) | 221 (79%) | 85 (77%) | 0.048 |
| White | 391 (62%) | 156 (56%) | 67 (60%) | 0.28 |
| Smoker | 100 (16%) | 67 (24%) | 34 (31%) | <0.001 |
| Hypertension | 421 (67%) | 213 (76%) | 89 (80%) | 0.001 |
| Myocardial infarction | 330 (52%) | 151 (54%) | 66 (59%) | 0.28 |
| Heart failure | 89 (52%) | 63 (23%) | 27 (24%) | 0.001 |
| Diabetes mellitus | 155 (24%) | 81 (29%) | 29 (26%) | 0.37 |
| Coronary revascularization | 382 (60%) | 155 (56%) | 65 (59%) | 0.42 |
| Physical inactivity | 199 (31%) | 115 (41%) | 57 (51%) | <0.001 |
| Depressive symptoms | 79 (12%) | 75 (27%) | 45 (41%) | <0.001 |
| Medications | ||||
| ACE inhibitors or ARBs | 319 (50%) | 139 (50%) | 66 (59%) | 0.19 |
| Aspirin | 449 (71%) | 206 (74%) | 86 (77%) | 0.34 |
| β-blockers | 352 (56%) | 162 (58%) | 79 (71%) | 0.01 |
| Calcium channel blockers | 146 (23%) | 64 (23%) | 37 (33%) | 0.06 |
| Nitrates | 116 (18%) | 103 (37%) | 78 (70%) | <0.001 |
| Statins | 421 (67%) | 168 (60%) | 68 (61%) | 0.12 |
| Seattle Angina Questionnaire | ||||
| Angina frequency, median (IQR) | 100 | 80 (80 to 90) | 50 (40 to 60) | <0.001 |
| Quality of life, median (IQR) | 92 (75 to 100) | 67 (50 to 75) | 42 (25 to 58) | <0.001 |
| Physical limitation, median (IQR) | 86 (67 to 100) | 67 (50 to 86) | 50 (33 to 67) | <0.001 |
| Overall quality of life | <0.001 | |||
| Excellent | 94 (15%) | 21 (8%) | 7 (6%) | |
| Very good | 221 (35%) | 72 (26%) | 19 (17%) | |
| Good | 204 (32%) | 109 (39%) | 34 (31%) | |
| Fair | 94 (15%) | 59 (21%) | 43 (39%) | |
| Poor | 20 (3%) | 18 (6%) | 8 (7%) | |
| New York Heart Association functional class | <0.001 | |||
| I | 306 (48%) | 61 (22%) | 10 (9%) | |
| II | 246 (39%) | 132 (47%) | 37 (33%) | |
| III | 67 (11%) | 67 (24%) | 47 (42%) | |
| IV | 13 (2%) | 19 (7%) | 17 (15%) | |
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