Abstract
Background
Although the Seattle Angina Questionnaire (SAQ) has been widely used to assess disease-specific health status in patients with ischemic heart disease, it was originally developed in a predominantly male population and its validity in women has been questioned.
Methods
Using data from 8892 men and 4013 women across 2 multicenter trials and 5 registries, we assessed the construct validity, test-retest reliability, responsiveness to clinical change, and predictive validity of the SAQ Summary Score (SS) and its 5 subdomains (Physical Limitation (PL), Anginal Stability (AS), Angina Frequency (AF), Treatment Satisfaction (TS), and Quality of Life (QoL)) separately in men and women.
Results
Comparable correlations of the SAQ SS with Canadian Cardiovascular Society class was demonstrated in both men and women (−0.48 for men, −0.46 for women). Similar correlations between the SAQ PL scale with treadmill exercise duration and Short Form-12 (SF-12) Physical Component Summary were observed in women and men (0.34–0.63 and 0.40–0.63, respectively). SAQ AS scores were significantly lower for both men and women with acute syndromes compared with 1 month later. The SAQ AF scale was strongly correlated with daily angina diaries (0.62 for men and 0.66 for women). The SAQ QoL scores were moderately correlated with the EQ5D visual analog scale and SF-12 general health question in men (0.43 – 0.50) and women (0.33 – 0.39). All SAQ scales demonstrated excellent reliability (intraclass correlation≥0.78) in both men and women with stable CAD and were very sensitive to change after percutaneous coronary intervention (≥15-point difference in scores, standardized response mean ≥0.67). The SAQ SS was similarly predictive of 1-year mortality and cardiac re-hospitalizations for both men and women.
Conclusion
The SAQ demonstrates similar psychometric properties in men and women with CAD. These findings provide evidence for validity of the SAQ in assessing women with IHD.
INTRODUCTION
The primary treatment goals in patients with ischemic heart disease (IHD) are to optimize secondary prevention and to minimize patients’ symptoms of angina, maximize their function, and optimize their quality of life. The 19-item Seattle Angina Questionnaire (SAQ), and its shorter 7-item version,1 have been extensively used in clinical trials and registries to quantify patients’ symptoms, functional status and quality of life.2 Furthermore, it has been endorsed by the International Consortium for Health Outcomes Measurement as a standardized outcome measure for patients with coronary artery disease3 and has been proposed as a performance measure by CMS for percutaneous coronary interventions (PCI) in stable IHD.4 Despite the widespread acceptance of the SAQ, there have been periodic concerns about its validity in women5–7 because it was originally developed in a cohort of patients that was 84% men.8
Although the SAQ was designed to be applicable across sex, race, and socio-economic status,4 there are important differences in the presentation and outcomes of men and women with IHD that could interfere with the psychometrics of the instrument. Women present with IHD at a later age, have a higher prevalence of “atypical” symptoms, and have poorer exercise tolerance as compared with men.9 They also have poorer quality of life and a greater burden of ischemic symptoms for the same degree of obstructive disease in addition to an increased prevalence of non-obstructive coronary disease, which is associated with a greater risk of poor outcomes than men.10, 11 Collectively, these findings suggest a distinct “female pattern” of ischemia7 that could potentially undermine the validity of the SAQ.
Given that the therapeutic goal for both men and women is to maximize function, minimize angina, and optimize patients’ quality of life,12 being able to validly and reliably measure these outcomes in both men and women is important. Because of the differences in pathophysiology, symptoms, presentation and prognosis between men and women with ischemic heart disease, and limited comparisons on the validity of the SAQ between women and men, we sought to explicitly validate the SAQ and its subdomains in women.
Methods
Seattle Angina Questionnaire
The SAQ is a 19-item self-administered questionnaire measuring health status in patients with IHD across 5 domains: physical limitation (PL), angina stability (AS), angina frequency (AF), treatment satisfaction (TS), and quality of life (QoL).8 All domain scores and a summary score (SS; derived from the PL, AF, and QoL domains) range from 0 to 100, with higher scores indicating less angina, fewer physical limitations due to angina, and better QoL. The 7-item version excludes the TS and AS domains.1
Data sources
We used data from 2 trials and 5 longitudinal cohort studies that enrolled patients with IHD and collected the SAQ (Table 1).13–17 These studies included patients with different presentations of IHD; stable ischemic heart disease, patients undergoing coronary revascularization, and acute coronary syndromes (unstable IHD).
Table 1.
Data sources
| Study | Patient Population | Enrollment Time Frame | Number of patients | Time of SAQ assessments |
|---|---|---|---|---|
| MERLIN-TIMI 36 | Multinational Randomized controlled trial of patients with NSTE-ACS | 2004–2007 | 6560 | Baseline, 4, 8, 12 months |
| TERISA | Multinational Randomized Controlled trial of patients with Type 2 Diabetes and chronic stable angina | 2011–2012 | 917 | Baseline, 8 weeks or study termination |
| PRESS | Single-center prospective PCI registry | 1999 | 255 | Baseline, 1, 2, 3, 4, 5, 6 mo |
| OPS | 3-center prospective PCI registry | 2009–2011 | 1901 | Baseline, 6, 12 mo |
| PRISM | 6-center prospective PCI registry | 2010–2011 | 1398 | Baseline, 1, 6, 12 mo |
| PREMIER | 19-center prospective acute MI registry | 2003–2004 | 2498 | Baseline, 1, 6, 12 mo |
| TRIUMPH | 24-center prospective acute MI registry | 2005–2008 | 4340 | Baseline, 1, 6, 12 mo |
MERLIN (Metabolic Efficiency with Ranolazine for Less Ischemia in Non–ST-elevation acute coronary syndromes); TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina); PRESS (Post-Revascularization Recovery and Survival Study); OPS (Outcomes of PCI Study); PRISM (Patient Risk Information Services Manager); PREMIER (Prospective Registry Evaluating Outcomes after Myocardial Infarction: Events and Recovery); TRIUMPH (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients’ Health Status)
Construct Validity
Table 2 summarizes the comparisons used to establish the psychometric properties of the SAQ in men and women. These are further described below.
Table 2.
Analyses, Settings and Cohorts Used for Validation of SAQ
| Objective | Reference measure | Analyses performed | Clinical settings analyzed (study, assessment) |
|---|---|---|---|
| Construct validity | |||
| SAQ summary score | CCSC | Mean ± SD; R2; Kendall Tau-b rank correlation | Stable IHD (PREMIER month 12) |
| SAQ Physical limitation | ETT duration and exercise capacity in METS, SF-12 PCS, CCSC | Mean ± SD; Pearson’s and Kendall Tau-b rank correlation | Stable IHD (MERLIN month 8, TRIUMPH/PREMIER month 12) Unstable IHD (Acute MI-TRIUMPH/PREMIER baseline) |
| SAQ Angina Stability | Difference in the score in unstable disease (PCI, AMI patients) and stable disease (follow-up scores during a stable state) | Paired t-test | Unstable (elective PCI OPS/PRISM baseline with diagnosis of unstable angina and acute MI (TRIUMPH/PREMIER baseline) Stable: scores at month 1 in above patients |
| SAQ Angina Frequency | Angina Diary and Sublingual Nitroglycerin use | Mean ± SD; Spearman’s correlation | Stable IHD (TERISA cross-sectional week 8) |
| SAQ Treatment Satisfaction | Doctor satisfaction questionnaire | Mean ± SD | Stable IHD (TRIUMPH month 6 and 12) |
| SAQ Quality of Life | EQ5D VAS, SF-12 question 1 | Mean ± SD; Pearson’s and Kendall Tau-b rank correlation | Stable IHD (OPS/PRISM and TRIUMPH/PREMIER month 12) |
| Reliability | 1 month change in SAQ scores | Mean ± SD; intraclass-correlation | Stable IHD (PRESS months 5 and 6) |
| Responsiveness to clinical change | 1 month change in SAQ post-PCI | Mean ± SD of change, standardized response mean | Elective PCI (OPS/PRISM baseline, 1 month) |
| Predictive validity | 1 year all-cause mortality, 1 year ACS hospitalization | C statistic | Post-MI (TRIUMPH month 1) |
SAQ Summary Score
The SAQ SS were compared with Canadian Cardiovascular Society classification of angina (CCSC), which is a physician-reported measure of angina-associated limitation with classes ranging 0–IV and higher classes denoting angina with progressively lower degrees of exertion.18 To evaluate this, we assessed the correlation between SAQ summary score and CCSC for both men and women with stable IHD population (PREMIER registry at month 12), using Kendall Tau-b rank correlation coefficient.
Physical Limitation scale
The SAQ PL scale assesses the degree of physical limitation over the past 4 weeks due to various activities representing mild, moderate and severe exertion.8 We assessed the correlation of SAQ PL scores with exercise treadmill test duration and exercise capacity using Pearson’s correlation in patients enrolled in the MERLIN trial where the patients’ 8-month exercise treadmill tests were used to capture a stable IHD population. We also assessed the cross-sectional correlation of the SAQ PL scale with other assessments of physical capacity –the Physical Component Summary score (PCS) of the Short-Form 12 (SF-12) and the Canadian Cardiovascular Society classification of angina (CCSC)– in patients with stable and unstable IHD (AMI) (Table 2), using Pearson’s correlation and Kendall Tau-b rank correlation.
Angina Stability Scale
The SAQ AS scale assesses the change in patient symptoms over the past 4 weeks, with a score of 50 representing no change and lower scores indicating a recent worsening of patients’ angina, while higher scores indicate fewer symptoms compared with 4 weeks ago. We compared mean SAQ AS scores between patients with unstable IHD (unstable angina patients undergoing PCI in PRISM, AMI patients in TRIUMPH and PREMIER registries) and patients with stable IHD (follow-up scores 1 month later), using paired t-tests both for men and women. We hypothesized that scores in stable IHD patients would be higher than scores in unstable patients.
Angina Frequency Scale
The SAQ AF scale measures the frequency of angina symptoms over the past 4 weeks with higher scores representing lesser angina burden. This domain has been previously validated against daily angina and sublingual nitroglycerin use with no difference between sexes.19 TERISA trial included patients with type 2 diabetes and stable angina wherein SAQ questionnaires and electronic angina diary responses were collected at study entry and 8 weeks (study end) or study withdrawal. The responses to the 2 SAQ angina frequency questions were correlated with angina diary responses of angina frequency and sublingual nitroglycerin use over previous 4 weeks at study end or week 8 using Spearman’s correlation coefficient. The results of correlation stratified by sex are reproduced here.19
Treatment Satisfaction Scale
The SAQ TS scale evaluates the level of satisfaction with the treatment of the patient’s angina. We compared SAQ TS scores with a separately-administered patient satisfaction questionnaire. Patients with AMI who were enrolled in the TRIUMPH registry were asked the following questions at 12 months: “Q1: How well does your doctor or care provider know you and your medical condition?” and “Q2: How good is your doctor or care provider or his or her staff at following up with you on appointment and test results?” Patients’ responses were captured on a 5-point Likert scale, and dichotomized as “satisfied” (extremely well, fairly well) and “not satisfied” (somewhat well, not very well, not at all). For both men and women, SAQ TS scores were compared between those patients who were and were not satisfied using two-tailed t-tests.
Quality of Life scale
The SAQ QoL scale assesses how the patient perceives their CAD to be impacting his or her QoL. The SAQ QoL was compared with the general health question of the SF-12 (“how well is your general health?”) and the Euro-Quality of Life Visual Analog Scale (EQ-5D VAS). We assessed these correlations separately for men and women, in different CAD states (stable CAD and elective PCI population) using Kendall Tau-b rank and Pearson’s correlation coefficient.
Construct validity for patients with Myocardial infarction with non-obstructive coronary arteries (MINOCA)
Women are more likely to present with a distinct phenotype of non-obstructive ischemic heart disease, including Myocardial Infarction with non-obstructive coronary arteries (MINOCA).20, 21 To assess the construct validity of the SAQ in this population, we conducted a sub-analysis of patients presenting with myocardial infarction with absence of obstructive coronary artery disease (<50% left main or <70% any epicardial coronary stenosis) enrolled in the TRIUMPH and PREMIER AMI registries. We compared baseline SAQ PL, SAQ QoL and SAQ summary scores with SF-12 PCS, SF-12 general health question and CCSC using Pearson’s correlation and Kendall Tau-b rank correlation coefficient.
Predictive Validity
Predictive validity was assessed by comparing the associations in men and women of SAQ scores (SS, AF, PL, and QOL domains) 1 month after an AMI with 12-month mortality and rehospitalization for acute coronary syndromes in the TRIUMPH study. Hazard ratios and 95% confidence intervals were calculated for ranges of the SAQ Scores; 0–49 (poor to fair), 50–74 (fair to good) and 75–100 (good to excellent)) using Cox proportional hazards models. C-statistics were calculated to assess discrimination for each subdomain in men and women.
Test-retest Reliability
Reliability was assessed in the PRESS study, where SAQ scores were collected monthly for 6 months after PCI. We compared the change in SAQ scores and the intraclass correlation coefficient between months 5 and 6 among clinically stable patients (defined as no ACS or repeat revascularization between months 5 and 6). Intra-class correlations describe the proportion of variability in scores due to between-patient differences compared to within-patient differences and range from 0–1 and higher intra-class correlations indicate greater reliability. Angina Stability scores were not compared for test-retest reliability as this metric represents a change in patient angina burden over the past 4 weeks and is therefore not appropriate for longitudinal analysis.
Responsiveness to Clinical Change
Responsiveness was assessed by comparing SAQ scores before and 1 month after PCI in the PRISM study, as this is a period where significant gains in health status are expected. As above, Angina Stability scores were not analyzed for this psychometric property, as changes in change scores are not readily interpretable. We calculated the mean (SD) change in scores and standardized response means (SRM; mean change/SD of change) for both men and women. Larger SRMs indicated greater responsiveness and an SRM > 0.8 is considered a large clinical change.
The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper and its final contents. No extramural funding was used to support this work.
RESULTS
Our analytic cohort was derived from 2 multinational clinical trials (MERLIN-TIMI 36 and TERISA) and 5 prospective registries (PRESS, OPS, PRISM, PREMIER, and TRIUMPH; Table 1). These studies included 8729 patients who were hospitalized with an acute coronary syndrome (5913 men and 2816 women), 2736 patients who underwent PCI (1964 men and 772 women) and 917 patients with stable angina (563 men and 354 women). Across all data sources, SAQ scores were available for 8440 men and 3952 women.
Construct Validity
SAQ Summary score
The SAQ SS showed strong correlations with CCS class in 1878 patients with stable IHD for both men and women, with correlations of −0.48 and −0.46, respectively (Table 3).
Table 3.
Sex-specific construct validity of SAQ summary score
| Stable IHD (PREMIER mo 12) SAQ summary score |
||
|---|---|---|
| CCSC class | Men (n=1276) Mean ± SD |
Women (n=602) Mean ± SD |
| 0 | 95 ± 7 | 94 ± 8 |
| I | 76 ± 14 | 72 ± 17 |
| II | 71 ± 15 | 67 ± 22 |
| III | 56 ± 16 | 57 ± 18 |
| IV | 54 ± 22 | 49 ± 19 |
| Kendall Tau-b rank correlation coefficient | −0.48 P<0.0001 |
−0.46 P <0.0001 |
SAQ Physical Limitation
For 1902 patients with stable IHD, the cross-sectional correlations between SAQ PL scores and both exercise duration and exercise capacity (METs) were moderately strong and similar for men and women (exercise duration correlations: men=0.40 vs. women=0.34; exercise capacity: men=0.35 vs. women=0.28; Table 4). The correlations between SAQ PL and the SF-12 PCS and CCSC were also moderately strong (correlation ranging from 0.51 to 0.63 for men and 0.59 to 0.63 for women) and similar for both men and women in stable and unstable (AMI) IHD settings (Table 4).
Table 4.
Sex-specific construct validity of the SAQ Physical Limitation (PL) subdomain
| Men | Women | ||||
|---|---|---|---|---|---|
| Setting | Mean ± SD SAQ PL score | Correlation coefficient (N) | Mean ± SD SAQ PL score | Correlation coefficient (N) | |
| Exercise treadmill duration | Stable IHD (MERLIN mo 8) | 79.5 ±21.2 | 0.40 (N=1339) | 80.0 ±22.5 | 0.34 (N=563) |
| Exercise capacity (METs) | Stable IHD (MERLIN mo 8) | 79.5±21.2 | 0.35 (N=1339) | 80.0 ±22.5 | 0.28 (N=563) |
| SF-12 PCS | Stable IHD (TRIUMPH/PREMIER 12m) | 94.6 ± 5.1 | 0.51 (N=2506) | 90.7 ±19.6 | 0.59 (N=932) |
| SF-12 PCS | Unstable IHD (Acute MI-TRIUMPH/PREMI ER BL) | 87.2 ±21.3 | 0.63 (N=3988) | 79.3 ± 6.6 | 0.63 (N=1708) |
| CCSC | Stable IHD (PREMIER 12m) | 95.8 ±12.9 | −0.55 (N=1047) | 93.5 ± 6.9 | −0.56 (N=384) |
p-values for all correlations <0.0001;
SF-12 PCS: Short Form-12 Physical Component Summary, CCSC: Canadian Cardiovascular Society Classification, METs: Metabolic Equivalents
SAQ Angina Stability
Patients with unstable disease (i.e., presenting with MI or unstable angina) had significantly lower SAQ AS scores than the same patients 1 month later, and these differences were similar between men and women (men (n=3652): 43.2 ± 23.7 vs. 55.8 ± 18.6; p <0.0001; women (n=1751): 41.4 ± 24.4 vs. 55.7 ± 19.7, p<.0001).
SAQ Anginal Frequency
SAQ AF domain was previously validated in patients with stable angina in the TERISA trial, which enrolled 563 men and 354 women.19 The SAQ AF question responses were strongly correlated with daily angina diaries (correlation= 0.62 for men and 0.66 for women) and SL nitroglycerin use (0.67 for men and 0.73 for women).19
SAQ Treatment Satisfaction
Patients with stable IHD who reported being unsatisfied on the generic questions had lower SAQ TS scores than those who reported being satisfied, with similar differences in men and women (men (n=1568): Q1 89.5 ± 16.7 vs. 94.9 ± 10.3, p= 0.0004; Q2: 85.7 ± 18.1 vs. 95.1 ± 10.1, p <0.0001; women (n=782) Q1: 83.7 ± 18.9 vs. 93.5 ± 12.4, p <0.0001; Q2: 80.5 ± 24.8 vs. 93.6 ± 11.43, p <0.0001).
SAQ Quality of Life
In patients with stable IHD, SAQ QoL scores had moderately strong correlations with the EQ5D visual analog scale and the SF-12 general health question (men: 0.50 and 0.43; women: 0.34 and 0.33; Table 5). The statistically significant correlations between the SAQ QoL scale and these general QoL scales were lower in women compared with men.
Table 5.
Sex-specific construct validity of SAQ Quality of Life (QOL) subdomain
| Men | Women | ||||
|---|---|---|---|---|---|
| Settings | Mean ± SD SAQ QOL scores | Pearson’s correlation coefficient (N) | Mean ± SD SAQ QOL scores | Pearson’s correlation coefficient (N) | |
| EQ5D VAS | Stable IHD (OPS/PRISM 12m) | 81.8 ± 18.6 | 0.50 (N=1557) | 77.9 ± 19.4 | 0.34 (N=607) |
| SF-12 question 1 | Stable IHD (TRIUMPH/PREMIER 12m) | 84.2 ± 19.0 | 0.43 (N= 3034) | 80.4 ± 21.4 | 0.33 (N=1477) |
p-values for all correlations <0.0001
EQ5D VAS: Euro QOL 5 Dimension Visual Analog Scale; SF-12: Short Form-12 Q1: “how well is your general health?”, CCSC: Canadian Cardiovascular Society Classification of angina
Myocardial infarction with non-obstructive coronaries (MINOCA)
In patients presenting with myocardial infarction but no evidence of obstructive coronaries on angiography, SAQ PL score, SAQ QoL score and SAQ summary scores showed moderately strong correlation which were similar in men and women with SF-12 PCS score (men: 0.63 and women: 0.64), SF-12 general health question (men: 0.41 and women: 0.42) and CCSC class (men: −0.55 and women: −0.52) respectively.
Predictive validity
The SAQ SS, AF, PL, and QoL domain scores demonstrated a graded inverse relationship with 12-month mortality and acute coronary syndrome rehospitalization for both men and women (Table 7). The PL scale was most strongly associated with 12-month mortality, particularly for women (c=0.57 for men and 0.77 for women), whereas all 3 domains and the summary score with similarly associated with risk of cardiac rehospitalization (c=0.59 to 0.60).
Table 7.
Sex-specific predictive validity of SAQ
| 12-month mortality | 12-month Cardiac Rehospitalization | |||
|---|---|---|---|---|
|
| ||||
| Men (N=1956) | Women (N=984) | Men (N=1703) | Women (N=855) | |
|
| ||||
| Physical limitation | ||||
| Poor to fair (0 to <50) | 3.1 (1.3, 7.0) | 9.1 (3.5, 23.7) | 2.4 (1.5, 4.0) | 2.7 (1.6, 4.8) |
| Good (50 to <75) | 1.4 (0.6, 3.5) | 1.2 (0.3, 6.1) | 2.1 (1.4, 3.1) | 1.4 (0.7, 2.7) |
| Excellent (75 to100) | Ref | Ref | Ref | Ref |
| C statistic | 0.57 | 0.77 | 0.60 | 0.64 |
|
| ||||
| Anginal frequency | ||||
| Poor to fair (0 to <50) | 1.9 (0.6, 6.1) | 2.4 (0.9, 6.8) | 2.5 (1.2, 5.0) | 3.6 (1.8, 7.2) |
| Good (50 to <75) | 1.3 (0.6, 2.6) | 0.9 (0.4, 2.2) | 2.3 (1.6, 3.4) | 1.9 (1.2, 3.0) |
| Excellent (75 to100) | Ref | Ref | Ref | Ref |
| C statistic | 0.53 | 0.52 | 0.59 | 0.60 |
|
| ||||
| Quality of life | ||||
| Poor to fair (0 to <50) | 1.8 (0.9, 3.5) | 1.0 (0.5, 2.3) | 2.8 (1.9, 4.1) | 2.1 (1.3, 3.4) |
| Good (50 to <75) | 1.3 (0.7, 2.3) | 1.1 (0.5, 2.2) | 1.3 (0.9, 1.8) | 1.4 (0.9, 2.3) |
| Excellent (75 to100) | Ref | Ref | Ref | Ref |
| C statistic | 0.52 | 0.54 | 0.59 | 0.59 |
|
| ||||
| SAQ Summary score | ||||
| Poor to fair (0 to <50) | 2.4 (1.1, 5.2) | 2.0 (0.9, 4.6) | 2.9 (1.8, 4.8) | 3.1 (1.8, 5.2) |
| Good (50 to <75) | 1.3 (0.7, 2.5) | 1.5 (0.8, 2.9) | 2.0 (1.4, 2.9) | 1.8 (1.2, 2.8) |
| Excellent (75 to100) | Ref | Ref | Ref | Ref |
| C statistic | 0.56 | 0.59 | 0.61 | 0.62 |
Numbers in each cell represent Hazard Ratios for the outcome (95% confidence intervals) with excellent health status (SAQ summary and subdomain scores between 75–100) as the reference. SAQ scores used were collected 1 month post-AMI as we wanted scores representing stable disease.
Test-retest Reliability
Among patients with stable IHD, the reliability of the SAQ domain and summary scores was excellent (ICC≥0.78, mean change of < 2.5 points for all scores) in both men and women (Table 8).
Table 8.
Reliability and responsiveness of SAQ to clinical change, according to patient sex.
| Reliability (change from 5m to 6m in stable patients) | ||||
|---|---|---|---|---|
| Men (n=115) | Women (n=50) | |||
| SAQ domain | Mean change ± SD | ICC1 | Mean change ± SD | ICC1 |
| Physical limitation | −0.1 ± 10.8 | 0.88 | −0.3 ± 14.4 | 0.82 |
| Angina frequency | 0.6 ± 13.1 | 0.78 | 1.2 ± 14.2 | 0.79 |
| Treatment satisfaction | 0.1 ± 10.7 | 0.80 | 1.1 ± 10.4 | 0.84 |
| Quality of life | −0.6 ± 11.7 | 0.84 | 2.3 ± 12.1 | 0.88 |
| Summary score | 0.1 ± 9.7 | 0.86 | 1.5 ± 10.1 | 0.88 |
| Responsiveness to change (change from before PCI to 1m after PCI) | ||||
| Men (n=770) | Women (n=277) | |||
| SAQ domain | Mean change ± SD | SRM2 | Mean change ± SD | SRM2 |
| Physical limitation | 17.5 ± 22.7 | 0.77 | 24.6 ± 28.6 | 0.86 |
| Angina frequency | 21.3 ± 25.4 | 0.84 | 21.0 ± 24.7 | 0.85 |
| Treatment satisfaction | −0.2 ± 11.6 | −0.02 | 0.8 ± 13.9 | 0.06 |
| Quality of life | 21.6 ± 27.0 | 0.80 | 19.6 ± 29.4 | 0.67 |
| Summary score | 20.0 ± 20.6 | 0.97 | 19.8 ± 22.2 | 0.89 |
ICC (Intraclass correlation) = variability in scores due to between-patient differences (higher=more reliable).
SRM (Standardized response mean) = mean change divided by SD of change (higher = more responsive).
Responsiveness to clinical change
Among patients undergoing PCI, all SAQ domains, except TS, were highly responsive to the improvements in patients’ health status after PCI in both men and women. A ≥ 15-point mean difference in scores (SRM ≥0.67; Table 8) was seen for all domains, although women had a greater change in SAQ PL score after PCI as compared with men (24.6 ± 28.6 vs. 17.5 ± 22.7). SAQ TS scores were high for both men and women at baseline (men= 93.7 ± 10.9, women= 92.5 ± 11.5), as would be expected before and after revascularization.
The psychometric properties and results of the shorter version of SAQ, SAQ-7 were similar in men and women, and are presented in Supplement Tables 2–6.
DISCUSSION
Cardiovascular disease in women has historically received less attention7, 22, despite the increased cost, morbidity, and mortality associated with it.11, 23, 24 As the health care landscape moves towards rewarding value, quality, and patient-centered care, patient-reported outcomes are becoming increasingly important. Instruments, such as the SAQ, that assess the impact of ischemic heart disease on patient’s symptoms, function, and quality of life are ideally suited to become performance measures and tools to improve the quality of clinical care. However, the psychometric validation studies for the SAQ were performed in a predominantly male population primarily enrolled from Veteran’s Affairs hospitals.8, 25 As such, even though the SAQ has been widely used to measure patient’s health-related quality of life in multiple trials, registries, and clinical practice, a lack of explicit validation of the SAQ in women has been perceived as a weakness.7 While there has been some prior work with factor-analysis in 175 women with stable angina showing good internal consistency and reliability of the SAQ in women, there has never been a comprehensive comparison of the psychometric properties of the SAQ between men and women.5 In the current study, we explicitly examined the psychometric properties of the SAQ, using patient data from multiple trials and prospective registries representing various different presentations of IHD, and found comparable performance in both men and women.
Women with cardiovascular disease have several notable differences in their presentation, symptoms, time to diagnosis, functional status and prognosis as compared with men.7, 9, 11 Anginal symptoms in women are often “atypical,” defined by lack of exertional component or unusual prodromal symptoms such as fatigue, sleep problems and shortness of breath.26, 27 Women have also been described to have a greater symptom burden, present more often for evaluation of their symptoms, but to be at a higher risk for delayed and under-diagnosis of their disease, although a recent study did not identify sex to be a significant predictor of under-recognition in a stable outpatient cohort with known IHD.9, 28 Thus, it is critically important to identify tools that could standardize angina symptom reporting by women and accurately quantify changes in symptoms with treatment. We found that the SAQ is not only good at identifying angina-related symptom severity, frequency, and the stability in women, but it was also highly reproducible in women with stable disease and highly sensitive to change when a clinical change occurs.
In examining the construct validity of the different SAQ scales, only the SAQ QoL score showed lower correlations with the selected criterion standards in women compared to men. In both the TRIUMPH and PRISM studies, used for these comparisons, the burden of comorbid conditions was greater in women than in men. Thus the generic health status questionnaires may be capturing the impact of these comorbidities in women, thus decreasing the strength of the associations between disease-specific and overall health status in women. Nevertheless, the SAQ QoL domain had similar reproducibility, responsiveness to change, and predictive validity between men and women, which suggests that it is a very good measure of the impact of IHD on women’s health status.
Patient-reported outcomes, such as the SAQ, are increasingly being advocated for use to measure the patient-centeredness and quality of care.2, 3 Accordingly, the 7-item version of SAQ has been proposed as a performance measure by CMS for PCI in stable IHD.4 Our study provides comprehensive evidence that the SAQ is a valid patient-reported instrument that reliably helps capture the symptoms, functional status and quality of life related to angina, while also providing useful prognostic information in women with CAD. The SAQ can be a used as a quick, inexpensive, and reliable instrument to assess the sex-related disparities in symptoms, presentation, management, and outcomes related to ischemic heart disease in a standardized manner.
Our study should be interpreted in the context of the following potential limitations. First, there is no gold standard for quantifying the impact of IHD on patients’ symptoms, function, and QoL. We therefore had to rely on other measures, such as the SF-12 and physician-assigned CCSC, as our comparison standards. As such, it is important to note that we do not expect perfect correlations of the SAQ with these measures, as the SAQ is capturing something distinct from these measures. Second, the SAQ only includes questions regarding angina symptoms, while women are more likely to present with shortness of breath or silent ischemia and therefore might respond differently to these questions. However, despite this theoretical concern, we were able to demonstrate that the SAQ performs similarly well in men and women across multiple different clinical settings. Nevertheless, we cannot exclude the possibility that the inclusion of other questions might further improve the performance of a disease-specific health status measure in women, although it would also have to be proven to similarly quantify the impact of IHD on men. There is increasing data supporting a distinct phenotype of ischemic heart disease in women, one associated with increased cardiovascular risk despite non-obstructive coronary disease,21 which might not have been captured in its entirety in the registries and trials used in this study. For example, we were able to identify a population of patients with MINOCA, but did not have data on patients with stable chest pain considered to be myocardial ischemia who were documented to not have obstructive coronary disease. Ongoing studies, such as the CIAO (NCT02347215) and the WARRIOR (NCT03417388) will provide additional opportunities to validate the SAQ in more stable patients without obstructive coronary disease. Nevertheless, a large recent study of young men and women with myocardial infarction showed that men and women present in a similar manner with chest pain as the predominant symptom, with women having greater non-chest pain symptoms in addition.29 Also, our analyses showing comparable validity in MINOCA patients suggests that it works well in this population.
In conclusion, across a large number of patients with IHD in a broad range of clinical settings, analyses we found comparable psychometric performance of the SAQ in both men and women with CAD. These findings provide evidence for validity of the SAQ in assessing women with CAD and support its use in observational studies, clinical trials and for quality assessment.
Supplementary Material
Table 6.
Sex-specific construct validity of SAQ in patients presenting with myocardial infarction with non-obstructive coronaries (MINOCA) enrolled in the TRIUMPH/PREMIER myocardial infarction registries at baseline
| SAQ | Reference measure | Men | Women | ||
|---|---|---|---|---|---|
| Mean ± SD SAQ score | Correlation coefficient (N) | Mean ± SD SAQ PL score | Correlation coefficient (N) | ||
| SAQ PL | SF-12 PCS | 82.74 ± 24.54 | 0.63 (N=146) | 85.73 ± 24.07 | 0.64 (N=174) |
| SAQ QOL | SF-12 question1 | 59.48 ± 25.27 | 0.41 (N=146) | 61.30 ± 23.11 | 0.42 (N=174) |
| SAQ SS | CCSC | 75.76 ± 18.79 | −0.55* (N=159) | 77.90 ± 18.04 | −0.52* (N=214) |
p-values for all correlations <0.0001;
SF-12 PCS: Short Form-12 Physical Component Summary, SF-12: Short Form-12 Q1: “how well is your general health?”, CCSC: Canadian Cardiovascular Society Classification. Correlations assessed using Pearson’s correlation except * where Kendall Tau-b rank correlation was used.
Acknowledgments
Sources of Funding:
The Prospective Registry Evaluating Outcomes After Myocardial Infarction: Events and Recovery (PREMIER) study was funded by CV Therapeutics, Palo Alto, California. The Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients’ Health Status (TRIUMPH) study was funded by grant P50 HL 077113 from the National Heart, Lung and Blood Institute. This study was also funded in part by CV Outcomes, Inc, Kansas City, Missouri. The MERLIN-TIMI 36 Trial was funded by a grant from CV Therapeutics. The Outcomes of PCI Study (OPS) was supported by an American Heart Association Outcomes Research Center grant (0875149N), and the Personalized Risk Information Services Manager™ (PRISM) study was supported by a grant from the National Heart Lung and Blood Institute (R01-HL096624). This current study was self-funded, and therefore the funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Drs. Patel and Qintar are supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL110837. Dr. Chan is supported by funding (R01HL123980) from the National Heart Lung and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Footnotes
Disclosures:
Dr. Spertus owns copyright for the Seattle Angina Questionnaire. He serves as a consultant to United Healthcare, Bayer and Novartis (modest). He has research grants from Abbott Vascular, Novarits and is the PI of an analytic center for the American College of Cardiology (significant). He has an equity interest in Health Outcomes Sciences (significant).
Dr Morrow has research grants from Abbott Laboratories, Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GlaxoSmithKline, Merck, Novartis, Roche Diagnostics, Takeda. He serves as a consultant or on the advisory board of Abbott Laboratories, Aralez, Bayer, Merck, Peloton, Roche Diagnostics, and Verseon.
The other authors report no conflicts.
Author Contributions: Drs. Patel and Spertus had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Patel, Arnold, Jones, Spertus.
Acquisition, analysis, or interpretation of data: All authors
Drafting of initial manuscript: Patel.
Critical revision of the manuscript for important intellectual content: All authors
Statistical analysis: Patel, Tang, Guo, Jones.
Administrative, technical, or material support: Spertus.
Study supervision: Spertus.
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