- Email: [email protected]
Health-related quality of life and long-term mortality in patients treated with percutaneous coronary intervention
Outcomes, Health Policy, and Managed Care
Health-related quality of life and long-term mortality in patients treated with percutaneous coronary intervention Lisanne Schenkeveld, Msc, a Susanne S. Pedersen, PhD, a,b Josephine W.I. van Nierop, Msc, a Mattie J. Lenzen, PhD, a Peter P.T. de Jaegere, MD, PhD, a Patrick W. Serruys, MD, PhD, a and Ron T. van Domburg, PhD a The Netherlands
Background Health status has become increasingly important as an outcome measure in patients with cardiovascular disease. Poor patient-rated health status has been shown to predict mortality in patients with coronary artery disease and heart failure. In patients treated with percutaneous coronary intervention (PCI), we examined whether poor health status predicts 6-year mortality and whether a decline in health status is associated with adverse clinical outcome. Methods
Consecutive patients (N = 872) treated with PCI as part of the RESEARCH registry, completed the 36-item ShortForm Health Survey (SF-36) at 1 and 12 months post-PCI.
Results
The SF-36 domains physical functioning (hazard ratio [HR] 2.59, 95% CI 1.61-4.16), social functioning (HR 2.76, 95% CI 1.74-4.37), role limitations due to physical functioning (HR 2.45, CI 1.52-3.92), mental health (HR 2.12, 95% CI 1.35-3.31), vitality (HR 1.73, 95% CI 1.09-2.74), bodily pain (HR 2.25, 95% CI 1.43-3.54), and general health (HR 2.46, 95% CI 1.57-3.87) were associated with 6-year mortality. A decline in health status was not related with higher 6-year mortality.
Conclusions Health status domains as measured with the SF-36 predicted death at 6-year follow-up in PCI patients treated with drug-eluting stenting, independent of demographic and clinical characteristics. In contrast, a decline in health status between 1 and 12 months post index procedure, as measured with the SF-36, was not associated with 6-year mortality in PCI patients treated with drug-eluting stenting. (Am Heart J 2010;159:471-6.)
Health status has become increasingly important as an outcome measure in patients with cardiovascular disease1 and is frequently used for evaluating the benefits of treatment.2,3 Clinicians and researchers have become more interested in health status because of improved survival. In addition, poor patient-rated health status has been shown to predict adverse clinical outcomes both in patients with coronary artery disease (CAD) and chronic heart failure.3-5 Assessment of health status and its determinants may help bridge the gap between research and clinical practice.1 In a recent systematic review, particularly poor physical health status was shown to be an important predictor for poor prognosis in patients with CAD and heart failure.6 In addition to its prognostic value, patient-rated health status may help optimize the
management of the disease and hence the clinical care of the individual patient.6 A paucity of studies examining the prognostic role of health status in cardiac patients have focused on patients treated with percutaneous coronary intervention (PCI).6 These studies were conducted before the introduction of drug-eluting stents. Moreover, most of these studies only included a single health status assessment,6 whereas only a few studies examining the impact of changes in health status on prognosis with both of these studies focusing on patients with heart failure.7,8 Hence, the aims of this study were to determine (1) whether poor health status, as measured with the 36-item Short-Form Health Survey (SF-36), predicts 6-year mortality in a consecutive series of patients treated with PCI in the drug-eluting stent era, and (2) whether a decline in health status is associated with adverse clinical outcome.
From the aDepartment of Cardiology, Thoraxcenter, Erasmus Medical Center Rotterdam, The Netherlands, and bCoRPS-Center of Research on Psychology in Somatic diseases, Tilburg University, The Netherlands. Submitted October 21, 2009; accepted December 19, 2009.
Methods
Reprint requests: Ron T. van Domburg, PhD, Erasmus Medical Center, Thoraxcenter, Ba-559, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. E-mail: [email protected] 0002-8703/$ - see front matter © 2010, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2009.12.012
The initial study population included 875 consecutive patients (response rate = 71%) treated with PCI with either sirolimuseluting stents (SESs) or bare metal stent implantation between October 16, 2001, and October 15, 2002, as part of the RESEARCH registry who participated in the psychological
Study population
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472 Schenkeveld et al
substudy.9 The design of the RESEARCH registry has been published elsewhere.10 Briefly, the RESEARCH registry is a single-center registry evaluating the safety and efficacy of SES implantation in patients treated in daily clinical practice. Therefore, no clinical and anatomical exclusion criteria were applied. On April 16, 2002, our institution commenced the use of SES (Cypher, Cordis Corporation, Warren, NJ) as the default strategy for every PCI, with the aim of having a patient population representing the “real world.” For the current substudy, all surviving patients were contacted by mail at 1 and 12 months and asked to fill in a self-report questionnaire. A reminder was sent to patients who had not yet returned their questionnaire. Only patients (N = 872) who completed the 36-item Short-Form Health Survey (SF-36) questionnaire at 1 month post-PCI qualified for inclusion for our primary objective. Patients (n = 697) who had a score at 1 and 12 months post-PCI qualified for inclusion for our secondary objective. Assessment at 1 month was chosen to ascertain a stable medical condition. A similar approach has been adopted in other studies of PCI patients.11 Clinical variables were obtained at baseline.
Baseline data Demographic variables included sex and age. Information on clinical variables (ie, stent type, dyslipidemia, hypertension, smoking, diabetes mellitus, family history of CAD, renal impairment, indication for PCI, previous myocardial infarction, previous coronary artery bypass graft [CABG], previous PCI, multivessel disease, and left ventricular ejection fraction) were prospectively collected at the time of the procedure and recorded in the institutional database. Dyslipidemia was defined as total cholesterol levels ≥240 mg/dL or on lipid-lowering medication. Hypertension was defined as blood pressure N140/ 90 mm Hg or being treated for hypertension. Diabetes mellitus was defined as being treated for diabetes. Renal impairment was defined as creatinine clearance b60 mL/min.
Health status data Health status was measured with the SF-36.12 The SF-36 assesses 8 health status domains (ie, physical functioning, role physical functioning, role emotional functioning, mental health, vitality, social functioning, bodily pain, and general health). Scale scores are obtained by summing the items together within a domain, dividing this outcome by the range of scores and then transforming the raw scores to a scale from 0 to 100.12 A higher score on the SF-36 subdomains represents a better functioning; a high score on the bodily pain scale indicates the absence of pain. The scale has good reliability, with Cronbach α ranging from 0.65 to 0.96 for all subscales.13 Patients were asked to complete the SF-36 1 and 12 months post-PCI.
Outcome The clinical end point was defined as all-cause mortality at 6-year follow-up. Information about the in-hospital outcomes was obtained from an electronic clinical database maintained at our institution and by review of the hospital records for those discharged to referring hospitals (patients were referred from a total of 14 local hospitals). Post-discharge survival status was obtained from the Municipal Civil Registries. Questionnaires with information about anginal status and medication usage were sent to all living
patients. The referring physicians and institutions were contacted whenever necessary for additional information.
Statistical analysis Discrete variables were compared with the χ2 test and continuous variables with Student t test. Univariable and multivariable Cox proportional hazard regression analyses were used to examine the impact of impaired health status on prognosis. Before these analyses, the health status domains were dichotomized with the lowest tertile indicating poor health status as compared with the other 2 tertiles indicating good health status. This dichotomization was done to enhance clinical interpretability, as advocated by others.3,14 Health status changes were determined based on a difference between the score on the subdomain at 1 and 12 months. To determine whether a decline in health status predicts mortality, we did not dichotomize but used the continuous score. We used Norman's “rule of thumb” to determine the minimal clinical important difference, defined as the smallest change in a patient-reported outcome that is perceived by patients as beneficial or that would result in a change in treatment.15 They found that under many circumstances the threshold of discrimination for changes in HRQL for a chronic disease appears to be approximately half a standard deviation. In multivariable analysis, all specific SF-36 subdomains were adjusted for the following baseline characteristics: gender, age, stent type, previous myocardial infarction, previous CABG, previous PCI, recent event, multivessel disease, dyslipidemia, hypertension, family history of CAD, current smoking, former smoking, diabetes mellitus, renal impairment, indication for PCI, and left ventricular ejection fraction. Kaplan-Meier curves were generated to graphically present the time to death for patients with poor versus good health status. The log-rank test was used to ascertain whether differences between groups were statistically significant. All tests were 2-tailed and a probability value of b.05 was considered statistically significant; for Cox proportional hazard regression analyses, hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) are reported. All data were analyzed using SPSS 15.0 for Windows (SPSS Inc, Chicago, IL). No extramural funding was used to support this work. 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.
Results Baseline characteristics Patient baseline characteristics for the total sample at 6-year follow-up are presented in Table I. Mean age in the population was 62 years and 72% were men. There were 96 deaths during the 6-year follow-up period. The average follow-up time was 6.0 years (range 4-7 years). Nonresponders on the SF-36 at 1 or 12 months were similar divided as compared with responders on most clinical baseline characteristics. Only more previous PCI was present in the nonresponders (32% vs 23%, P = .03).
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Table I. Baseline characteristics
Table II. Impact of poor health status on 6-year mortality Total
No. of patients Male Age ± SD Stent type Sirolimus-eluting stent Cardiovascular history Previous MI Previous CABG Previous PCI Recent event Multi vessel disease Risk factors Dyslipidemia Hypertension Family history Current smoker Former smoker Diabetes mellitus Renal impairment Indication for PCI Stable angina Unstable angina Acute myocardial infarction LVEF Good Impaired Missing
872 627 (72%) 62 ± 11.0 358 (41%) 316 (36%) 101 (12%) 218 (25%) 88 (10%) 457 (52%) 534 279 271 357 140 131 21
(61%) (32%) (31%) (41%) (16%) (15%) (2%)
437 (50%) 306 (35%) 129 (15%) 499 (57%) 98 (11%) 275 (32%)
Univariate
Multivariate⁎
SF-36 domains
HR
95% CI
HR
95% CI
Physical functioning Social functioning Role physical functioning Role emotional functioning Mental health Vitality Bodily pain General health
3.37 2.62 2.82 1.34 1.98 1.79 2.51 2.72
2.20-5.16 1.71-4.01 1.83-4.35 0.85-2.12 1.30-3.01 1.17-2.74 1.67-3.79 1.78-4.14
2.59 2.76 2.45 1.27 2.12 1.73 2.25 2.46
1.61-4.16 1.74-4.37 1.52-3.92 0.76-2.11 1.35-3.31 1.09-2.74 1.43-3.54 1.57-3.87
⁎ Adjusted for the following baseline characteristics: gender, age, stent type, previous MI, previous CABG, previous PCI, recent event, multivessel disease, dyslipidemia, hypertension, family history of CAD, current smoking, former smoking, diabetes mellitus, renal impairment, indication for PCI, and LVEF.
Decline in health status as predictor of 6-year mortality For the univariate and multivariate analyses, we had complete data in 97% of the population. A decline in health status, defined as half a standard deviation, between SF-36 measurements at 1 and 12 months was observed in approximately 13% of the patients. Overall, a decline in health status was not related with 6-year mortality (Table III).
Recent event = MI, CABG, or PCI between 0 and 1 month post-PCI. MI, Myocardial infarction; LVEF, left ventricular ejection fraction.
Discussion
Poor health status as predictor of 6-year mortality The distribution of the patients with poor or good health status on 1 and 12 months post-PCI was as follows: 12% had a good health status at 1 month but a poor health status at 12 months, 9% had a poor health status at 1 month but a good health status at 12 months, 59% had a good health status at both times, and 20% had a poor health status at both times. For the univariate and multivariate analyses, we had complete data in 98% of the population. Unadjusted, poor health status was a predictor of 6-year mortality for all domains except that of role emotional functioning. The HRs associated with poor health status were 1.5- to 3.5fold as compared with normal health status (Table II). Kaplan-Meier survival curves for each of the health status domains are shown in Figure 1. After adjustment for covariates, poor health status remained an independent predictor of 6-year mortality in relation to the domains physical functioning (HR 2.59, 95% CI 1.61-4.16), social functioning (HR 2.76, 95% CI 1.74-4.37), role limitations due to physical functioning (HR 2.45, CI 1.52-3.92), mental health (HR 2.12, 95% CI 1.35-3.31), vitality (HR 1.73, 95% CI 1.09-2.74), bodily pain (HR 2.25, 95% CI 1.43-3.54), and general health (HR 2.46, 95% CI 1.57-3.87) (Table II).
In the current study, we found that poor health status, as measured with the SF-36, is a strong, independent predictor of 6-year mortality in PCI patients treated in the drug-eluting stent era, with the associated adjusted HRs ranging from 1.73 to 2.76. In contrast, we did not find any relation between a decline in health status between 1 and 12 months and mortality at 6 years. Several other studies have shown that poor health status predicts adverse clinical outcome in patients with heart failure and patients with CAD undergoing revascularization with CABG or PCI.5,6,16-20 However, while the duration of the follow-period in most of these studies was restricted to 3 years, the follow-up in the current study extended to 6 years. In addition, to our knowledge this is the first study to examine the predictive validity of the SF36 as a measure of health status in patients treated with PCI in the modern era of drug-eluting stenting. A paucity of studies have examined the impact of a change in health status on mortality in cardiac patients, although preliminary evidence from these studies indicates that a decline in health status increases the risk of poor prognosis.7,8 However, we could not confirm that a decline in health status, as assessed with a generic measure, was associated with a higher risk of 6-year mortality. There are several differences between these previous studies and our study that may explain this differential finding. These include a different population (ie, heart failure vs PCI patients), the type of health status
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474 Schenkeveld et al
Figure 1
Kaplan-Meier survival curves for all SF-36 health status domains.
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Table III. Impact of decline in health status on 6-year mortality Univariate
Multivariate⁎
SF-36 domains
HR
95% CI
HR
95% CI
Physical functioning Social functioning Role physical functioning Role emotional functioning Mental health Vitality Bodily pain General health
0.87 1.56 0.79 1.12 2.08 1.41 1.25 1.16
(0.73-1.93) (0.73-3.31) (0.37-1.68) (0.52-2.41) (0.75-5.79) (0.73-2.69) (0.67-2.33) (0.61-2.22)
0.74 1.33 0.83 1.05 1.48 1.44 0.77 1.33
(0.32-1.72) (0.60-2.95) (0.37-1.83) (0.48-2.31) (0.50-4.44) (0.73-2.84) (0.47-1.76) (0.67-2.62)
⁎ Adjusted for the following baseline characteristics: gender, age, stent type, previous MI, previous CABG, previous PCI, recent event, multivessel disease, dyslipidemia, hypertension, family history of CAD, current smoking, former smoking, diabetes mellitus, renal impairment, indication for PCI, and LVEF.
measure used (ie, disease-specific vs generic), the period between the 2 assessments of health status, and the follow-up period. The follow-up duration in previous studies was 14 months7 and 5 years,8 respectively, and they evaluated a 1- to 3-month change7 and a week change8 in health status, whereas we examined the impact of a 1-year change. In addition, previous studies used a disease-specific measure (ie, the Kansas City Cardiomyopathy Questionnaire),7,8 whereas we used a generic measure. In a recent review of the impact of poor health status on clinical outcome, a disease-specific measure of physical health status was shown to be a stronger predictor of prognosis than a generic.6 An alternative explanation may be the relatively low percentage of patients experiencing a decline in health status between 1 and 12 months of only 13% in the current study, with the possibility that the study might have been insufficiently powered to test this objective. Our study supports the recommendations of Krumholz et al1 and Spertus et al21 to include measurement and integration of health status in clinical practice and clinical trials. Information on health status may help identify patients at risk for poor prognosis and guide the clinical management of these patients, as shown in the COURAGE trial.22 However, more research on health status and its determinants is necessary, including seeking to identify the mechanisms that may be responsible for the link between poor health status and prognosis, which in turn can provide important information for developing interventions to improve health status. Our study has some limitations. First, patients were not randomized to type of stent (ie, BMS vs SES). However, a strength of our study is that the population was representative of the real world of interventional cardiology because no exclusion criteria were applied. It has been advocated that research conducted in realworld settings is a way by which to close the gap between research and clinical practice.1 Second, nonresponders on the SF-36 at 1 or 12 months were similar divided as compared with responders on most baseline character-
istics. Only more previous PCI was present in the nonresponders. Third, we cannot rule out that unknown baseline characteristics such as COPD and PAD will have an influence on the association between quality of life and mortality. However, the HRs are mostly so high, that it will very probably not influence the outcome. Fourth, we used a generic rather a disease-specific measure of health status, which may be less sensitive to tap treatmentrelated changes over time if present. In conclusion, the results of the current study showed that most health status domains as measured with the SF-36 predicted death at 6-year follow-up in PCI patients treated with drug-eluting stenting, independent of demographic and clinical characteristics. By contrast, a decline in health status between 1 and 12 months post index procedure, as measured with the SF-36, was not associated with 6-year mortality in PCI patients treated with drug-eluting stenting. Patientrated health status comprises an important means by which to identify high-risk patients in clinical practice, which cannot be inferred from any other clinical variables standardly assessed.
References 1. Krumholz HM, Peterson ED, Ayanian JZ, et al. Report of the National Heart, Lung, and Blood Institute working group on outcomes research in cardiovascular disease. Circulation 2005;111: 3158-66. 2. van Domburg RT, Daemen J, Pedersen SS, et al. Short- and long- term health related quality-of-life and anginal status after randomisation to coronary stenting versus bypass surgery for the treatment of multivessel disease: results of the Arterial Revascularisation Therapy Study (ARTS). EuroIntervention 2008;3:506-11. 3. Spertus JA, Jones P, McDonell M, et al. Health status predicts longterm outcome in outpatients with coronary disease. Circulation 2002; 106:43-9. 4. Soto GE, Jones P, Weintraub WS, et al. Prognostic value of health status in patients with heart failure after acute myocardial infarction. Circulation 2004;110:546-51. 5. Rumsfeld JS, MaWhinney S, McCarthy Jr M, et al. Health-related quality of life as a predictor of mortality following coronary artery bypass graft surgery. Participants of the Department of Veterans Affairs Cooperative Study Group on Processes, Structures, and Outcomes of Care in Cardiac Surgery. JAMA 1999;281: 1298-303. 6. Mommersteeg PM, Denollet J, Spertus JA, et al. Health status as a risk factor in cardiovascular disease: a systematic review of current evidence. Am Heart J 2009;157:208-18. 7. Kosiborod M, Soto GE, Jones PG, et al. Identifying heart failure patients at high risk for near-term cardiovascular events with serial health status assessments. Circulation 2007;115: 1975-81. 8. Subramanian U, Eckert G, Yeung A, et al. A single health status question had important prognostic value among outpatients with chronic heart failure. J Clin Epidemiol 2007;60:803-11. 9. Pedersen SS, Lemos PA, van Vooren PR, et al. Type D personality predicts death or myocardial infarction after bare metal stent or sirolimus-eluting stent implantation: a Rapamycin-Eluting Stent
476 Schenkeveld et al
10.
11.
12.
13.
14.
15.
Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry substudy. J Am Coll Cardiol 2004;44:997-1001. Lemos PA, Lee CH, Degertekin M, et al. Early outcome after sirolimuseluting stent implantation in patients with acute coronary syndromes: insights from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. J Am Coll Cardiol 2003; 41:2093-9. Poston WS, Haddock CK, Conard MW, et al. Assessing depression in the cardiac patient. When is the appropriate time to assess depression in the patient undergoing coronary revascularization? Behav Modif 2003;27:26-36. Ware Jr JE, Sherbourne CD, The MOS. 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473-83. Smith HJ, Taylor R, Mitchell AA. comparison of four quality of life instruments in cardiac patients: SF-36, QLI, QLMI, and SEIQoL. Heart 2000;84:390-4. Rumsfeld JS, Magid DJ, Plomondon ME, et al. History of depression, angina, and quality of life after acute coronary syndromes. Am Heart J 2003;145:493-9. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care 2003;41:582-92.
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16. Koch CG, Li L, Lauer M, et al. Effect of functional health-related quality of life on long-term survival after cardiac surgery. Circulation 2007; 115:692-9. 17. Faller H, Stork S, Schowalter M, et al. Is health-related quality of life an independent predictor of survival in patients with chronic heart failure? J Psychosom Res 2007;63:533-8. 18. Rodriguez-Artalejo F, Guallar-Castillon P, Pascual CR, et al. Healthrelated quality of life as a predictor of hospital readmission and death among patients with heart failure. Arch Intern Med 2005;165: 1274-9. 19. Lenzen MJ, Scholte op Reimer WJ, Pedersen SS, et al. The additional value of patient-reported health status in predicting 1-year mortality after invasive coronary procedures: a report from the Euro Heart Survey on Coronary Revascularisation. Heart 2007; 93:339-44. 20. Pedersen SS, Martens EJ, Denollet J, et al. Poor health-related quality of life is a predictor of early, but not late, cardiac events after percutaneous coronary intervention. Psychosomatics 2007;48:331-7. 21. Spertus JA. Evolving applications for patient-centered health status measures. Circulation 2008;118:2103-10. 22. Weintraub WS, Spertus JA, Kolm P, et al. Effect of PCI on quality of life in patients with stable coronary disease. N Engl J Med 2008;359: 677-87.
Health-related quality of life and long-term mortality in patients treated with percutaneous coronary intervention Lisanne Schenkeveld, Msc, a Susanne S. Pedersen, PhD, a,b Josephine W.I. van Nierop, Msc, a Mattie J. Lenzen, PhD, a Peter P.T. de Jaegere, MD, PhD, a Patrick W. Serruys, MD, PhD, a and Ron T. van Domburg, PhD a The Netherlands
Background Health status has become increasingly important as an outcome measure in patients with cardiovascular disease. Poor patient-rated health status has been shown to predict mortality in patients with coronary artery disease and heart failure. In patients treated with percutaneous coronary intervention (PCI), we examined whether poor health status predicts 6-year mortality and whether a decline in health status is associated with adverse clinical outcome. Methods
Consecutive patients (N = 872) treated with PCI as part of the RESEARCH registry, completed the 36-item ShortForm Health Survey (SF-36) at 1 and 12 months post-PCI.
Results
The SF-36 domains physical functioning (hazard ratio [HR] 2.59, 95% CI 1.61-4.16), social functioning (HR 2.76, 95% CI 1.74-4.37), role limitations due to physical functioning (HR 2.45, CI 1.52-3.92), mental health (HR 2.12, 95% CI 1.35-3.31), vitality (HR 1.73, 95% CI 1.09-2.74), bodily pain (HR 2.25, 95% CI 1.43-3.54), and general health (HR 2.46, 95% CI 1.57-3.87) were associated with 6-year mortality. A decline in health status was not related with higher 6-year mortality.
Conclusions Health status domains as measured with the SF-36 predicted death at 6-year follow-up in PCI patients treated with drug-eluting stenting, independent of demographic and clinical characteristics. In contrast, a decline in health status between 1 and 12 months post index procedure, as measured with the SF-36, was not associated with 6-year mortality in PCI patients treated with drug-eluting stenting. (Am Heart J 2010;159:471-6.)
Health status has become increasingly important as an outcome measure in patients with cardiovascular disease1 and is frequently used for evaluating the benefits of treatment.2,3 Clinicians and researchers have become more interested in health status because of improved survival. In addition, poor patient-rated health status has been shown to predict adverse clinical outcomes both in patients with coronary artery disease (CAD) and chronic heart failure.3-5 Assessment of health status and its determinants may help bridge the gap between research and clinical practice.1 In a recent systematic review, particularly poor physical health status was shown to be an important predictor for poor prognosis in patients with CAD and heart failure.6 In addition to its prognostic value, patient-rated health status may help optimize the
management of the disease and hence the clinical care of the individual patient.6 A paucity of studies examining the prognostic role of health status in cardiac patients have focused on patients treated with percutaneous coronary intervention (PCI).6 These studies were conducted before the introduction of drug-eluting stents. Moreover, most of these studies only included a single health status assessment,6 whereas only a few studies examining the impact of changes in health status on prognosis with both of these studies focusing on patients with heart failure.7,8 Hence, the aims of this study were to determine (1) whether poor health status, as measured with the 36-item Short-Form Health Survey (SF-36), predicts 6-year mortality in a consecutive series of patients treated with PCI in the drug-eluting stent era, and (2) whether a decline in health status is associated with adverse clinical outcome.
From the aDepartment of Cardiology, Thoraxcenter, Erasmus Medical Center Rotterdam, The Netherlands, and bCoRPS-Center of Research on Psychology in Somatic diseases, Tilburg University, The Netherlands. Submitted October 21, 2009; accepted December 19, 2009.
Methods
Reprint requests: Ron T. van Domburg, PhD, Erasmus Medical Center, Thoraxcenter, Ba-559, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. E-mail: [email protected] 0002-8703/$ - see front matter © 2010, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2009.12.012
The initial study population included 875 consecutive patients (response rate = 71%) treated with PCI with either sirolimuseluting stents (SESs) or bare metal stent implantation between October 16, 2001, and October 15, 2002, as part of the RESEARCH registry who participated in the psychological
Study population
American Heart Journal March 2010
472 Schenkeveld et al
substudy.9 The design of the RESEARCH registry has been published elsewhere.10 Briefly, the RESEARCH registry is a single-center registry evaluating the safety and efficacy of SES implantation in patients treated in daily clinical practice. Therefore, no clinical and anatomical exclusion criteria were applied. On April 16, 2002, our institution commenced the use of SES (Cypher, Cordis Corporation, Warren, NJ) as the default strategy for every PCI, with the aim of having a patient population representing the “real world.” For the current substudy, all surviving patients were contacted by mail at 1 and 12 months and asked to fill in a self-report questionnaire. A reminder was sent to patients who had not yet returned their questionnaire. Only patients (N = 872) who completed the 36-item Short-Form Health Survey (SF-36) questionnaire at 1 month post-PCI qualified for inclusion for our primary objective. Patients (n = 697) who had a score at 1 and 12 months post-PCI qualified for inclusion for our secondary objective. Assessment at 1 month was chosen to ascertain a stable medical condition. A similar approach has been adopted in other studies of PCI patients.11 Clinical variables were obtained at baseline.
Baseline data Demographic variables included sex and age. Information on clinical variables (ie, stent type, dyslipidemia, hypertension, smoking, diabetes mellitus, family history of CAD, renal impairment, indication for PCI, previous myocardial infarction, previous coronary artery bypass graft [CABG], previous PCI, multivessel disease, and left ventricular ejection fraction) were prospectively collected at the time of the procedure and recorded in the institutional database. Dyslipidemia was defined as total cholesterol levels ≥240 mg/dL or on lipid-lowering medication. Hypertension was defined as blood pressure N140/ 90 mm Hg or being treated for hypertension. Diabetes mellitus was defined as being treated for diabetes. Renal impairment was defined as creatinine clearance b60 mL/min.
Health status data Health status was measured with the SF-36.12 The SF-36 assesses 8 health status domains (ie, physical functioning, role physical functioning, role emotional functioning, mental health, vitality, social functioning, bodily pain, and general health). Scale scores are obtained by summing the items together within a domain, dividing this outcome by the range of scores and then transforming the raw scores to a scale from 0 to 100.12 A higher score on the SF-36 subdomains represents a better functioning; a high score on the bodily pain scale indicates the absence of pain. The scale has good reliability, with Cronbach α ranging from 0.65 to 0.96 for all subscales.13 Patients were asked to complete the SF-36 1 and 12 months post-PCI.
Outcome The clinical end point was defined as all-cause mortality at 6-year follow-up. Information about the in-hospital outcomes was obtained from an electronic clinical database maintained at our institution and by review of the hospital records for those discharged to referring hospitals (patients were referred from a total of 14 local hospitals). Post-discharge survival status was obtained from the Municipal Civil Registries. Questionnaires with information about anginal status and medication usage were sent to all living
patients. The referring physicians and institutions were contacted whenever necessary for additional information.
Statistical analysis Discrete variables were compared with the χ2 test and continuous variables with Student t test. Univariable and multivariable Cox proportional hazard regression analyses were used to examine the impact of impaired health status on prognosis. Before these analyses, the health status domains were dichotomized with the lowest tertile indicating poor health status as compared with the other 2 tertiles indicating good health status. This dichotomization was done to enhance clinical interpretability, as advocated by others.3,14 Health status changes were determined based on a difference between the score on the subdomain at 1 and 12 months. To determine whether a decline in health status predicts mortality, we did not dichotomize but used the continuous score. We used Norman's “rule of thumb” to determine the minimal clinical important difference, defined as the smallest change in a patient-reported outcome that is perceived by patients as beneficial or that would result in a change in treatment.15 They found that under many circumstances the threshold of discrimination for changes in HRQL for a chronic disease appears to be approximately half a standard deviation. In multivariable analysis, all specific SF-36 subdomains were adjusted for the following baseline characteristics: gender, age, stent type, previous myocardial infarction, previous CABG, previous PCI, recent event, multivessel disease, dyslipidemia, hypertension, family history of CAD, current smoking, former smoking, diabetes mellitus, renal impairment, indication for PCI, and left ventricular ejection fraction. Kaplan-Meier curves were generated to graphically present the time to death for patients with poor versus good health status. The log-rank test was used to ascertain whether differences between groups were statistically significant. All tests were 2-tailed and a probability value of b.05 was considered statistically significant; for Cox proportional hazard regression analyses, hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) are reported. All data were analyzed using SPSS 15.0 for Windows (SPSS Inc, Chicago, IL). No extramural funding was used to support this work. 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.
Results Baseline characteristics Patient baseline characteristics for the total sample at 6-year follow-up are presented in Table I. Mean age in the population was 62 years and 72% were men. There were 96 deaths during the 6-year follow-up period. The average follow-up time was 6.0 years (range 4-7 years). Nonresponders on the SF-36 at 1 or 12 months were similar divided as compared with responders on most clinical baseline characteristics. Only more previous PCI was present in the nonresponders (32% vs 23%, P = .03).
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Table I. Baseline characteristics
Table II. Impact of poor health status on 6-year mortality Total
No. of patients Male Age ± SD Stent type Sirolimus-eluting stent Cardiovascular history Previous MI Previous CABG Previous PCI Recent event Multi vessel disease Risk factors Dyslipidemia Hypertension Family history Current smoker Former smoker Diabetes mellitus Renal impairment Indication for PCI Stable angina Unstable angina Acute myocardial infarction LVEF Good Impaired Missing
872 627 (72%) 62 ± 11.0 358 (41%) 316 (36%) 101 (12%) 218 (25%) 88 (10%) 457 (52%) 534 279 271 357 140 131 21
(61%) (32%) (31%) (41%) (16%) (15%) (2%)
437 (50%) 306 (35%) 129 (15%) 499 (57%) 98 (11%) 275 (32%)
Univariate
Multivariate⁎
SF-36 domains
HR
95% CI
HR
95% CI
Physical functioning Social functioning Role physical functioning Role emotional functioning Mental health Vitality Bodily pain General health
3.37 2.62 2.82 1.34 1.98 1.79 2.51 2.72
2.20-5.16 1.71-4.01 1.83-4.35 0.85-2.12 1.30-3.01 1.17-2.74 1.67-3.79 1.78-4.14
2.59 2.76 2.45 1.27 2.12 1.73 2.25 2.46
1.61-4.16 1.74-4.37 1.52-3.92 0.76-2.11 1.35-3.31 1.09-2.74 1.43-3.54 1.57-3.87
⁎ Adjusted for the following baseline characteristics: gender, age, stent type, previous MI, previous CABG, previous PCI, recent event, multivessel disease, dyslipidemia, hypertension, family history of CAD, current smoking, former smoking, diabetes mellitus, renal impairment, indication for PCI, and LVEF.
Decline in health status as predictor of 6-year mortality For the univariate and multivariate analyses, we had complete data in 97% of the population. A decline in health status, defined as half a standard deviation, between SF-36 measurements at 1 and 12 months was observed in approximately 13% of the patients. Overall, a decline in health status was not related with 6-year mortality (Table III).
Recent event = MI, CABG, or PCI between 0 and 1 month post-PCI. MI, Myocardial infarction; LVEF, left ventricular ejection fraction.
Discussion
Poor health status as predictor of 6-year mortality The distribution of the patients with poor or good health status on 1 and 12 months post-PCI was as follows: 12% had a good health status at 1 month but a poor health status at 12 months, 9% had a poor health status at 1 month but a good health status at 12 months, 59% had a good health status at both times, and 20% had a poor health status at both times. For the univariate and multivariate analyses, we had complete data in 98% of the population. Unadjusted, poor health status was a predictor of 6-year mortality for all domains except that of role emotional functioning. The HRs associated with poor health status were 1.5- to 3.5fold as compared with normal health status (Table II). Kaplan-Meier survival curves for each of the health status domains are shown in Figure 1. After adjustment for covariates, poor health status remained an independent predictor of 6-year mortality in relation to the domains physical functioning (HR 2.59, 95% CI 1.61-4.16), social functioning (HR 2.76, 95% CI 1.74-4.37), role limitations due to physical functioning (HR 2.45, CI 1.52-3.92), mental health (HR 2.12, 95% CI 1.35-3.31), vitality (HR 1.73, 95% CI 1.09-2.74), bodily pain (HR 2.25, 95% CI 1.43-3.54), and general health (HR 2.46, 95% CI 1.57-3.87) (Table II).
In the current study, we found that poor health status, as measured with the SF-36, is a strong, independent predictor of 6-year mortality in PCI patients treated in the drug-eluting stent era, with the associated adjusted HRs ranging from 1.73 to 2.76. In contrast, we did not find any relation between a decline in health status between 1 and 12 months and mortality at 6 years. Several other studies have shown that poor health status predicts adverse clinical outcome in patients with heart failure and patients with CAD undergoing revascularization with CABG or PCI.5,6,16-20 However, while the duration of the follow-period in most of these studies was restricted to 3 years, the follow-up in the current study extended to 6 years. In addition, to our knowledge this is the first study to examine the predictive validity of the SF36 as a measure of health status in patients treated with PCI in the modern era of drug-eluting stenting. A paucity of studies have examined the impact of a change in health status on mortality in cardiac patients, although preliminary evidence from these studies indicates that a decline in health status increases the risk of poor prognosis.7,8 However, we could not confirm that a decline in health status, as assessed with a generic measure, was associated with a higher risk of 6-year mortality. There are several differences between these previous studies and our study that may explain this differential finding. These include a different population (ie, heart failure vs PCI patients), the type of health status
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Figure 1
Kaplan-Meier survival curves for all SF-36 health status domains.
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Table III. Impact of decline in health status on 6-year mortality Univariate
Multivariate⁎
SF-36 domains
HR
95% CI
HR
95% CI
Physical functioning Social functioning Role physical functioning Role emotional functioning Mental health Vitality Bodily pain General health
0.87 1.56 0.79 1.12 2.08 1.41 1.25 1.16
(0.73-1.93) (0.73-3.31) (0.37-1.68) (0.52-2.41) (0.75-5.79) (0.73-2.69) (0.67-2.33) (0.61-2.22)
0.74 1.33 0.83 1.05 1.48 1.44 0.77 1.33
(0.32-1.72) (0.60-2.95) (0.37-1.83) (0.48-2.31) (0.50-4.44) (0.73-2.84) (0.47-1.76) (0.67-2.62)
⁎ Adjusted for the following baseline characteristics: gender, age, stent type, previous MI, previous CABG, previous PCI, recent event, multivessel disease, dyslipidemia, hypertension, family history of CAD, current smoking, former smoking, diabetes mellitus, renal impairment, indication for PCI, and LVEF.
measure used (ie, disease-specific vs generic), the period between the 2 assessments of health status, and the follow-up period. The follow-up duration in previous studies was 14 months7 and 5 years,8 respectively, and they evaluated a 1- to 3-month change7 and a week change8 in health status, whereas we examined the impact of a 1-year change. In addition, previous studies used a disease-specific measure (ie, the Kansas City Cardiomyopathy Questionnaire),7,8 whereas we used a generic measure. In a recent review of the impact of poor health status on clinical outcome, a disease-specific measure of physical health status was shown to be a stronger predictor of prognosis than a generic.6 An alternative explanation may be the relatively low percentage of patients experiencing a decline in health status between 1 and 12 months of only 13% in the current study, with the possibility that the study might have been insufficiently powered to test this objective. Our study supports the recommendations of Krumholz et al1 and Spertus et al21 to include measurement and integration of health status in clinical practice and clinical trials. Information on health status may help identify patients at risk for poor prognosis and guide the clinical management of these patients, as shown in the COURAGE trial.22 However, more research on health status and its determinants is necessary, including seeking to identify the mechanisms that may be responsible for the link between poor health status and prognosis, which in turn can provide important information for developing interventions to improve health status. Our study has some limitations. First, patients were not randomized to type of stent (ie, BMS vs SES). However, a strength of our study is that the population was representative of the real world of interventional cardiology because no exclusion criteria were applied. It has been advocated that research conducted in realworld settings is a way by which to close the gap between research and clinical practice.1 Second, nonresponders on the SF-36 at 1 or 12 months were similar divided as compared with responders on most baseline character-
istics. Only more previous PCI was present in the nonresponders. Third, we cannot rule out that unknown baseline characteristics such as COPD and PAD will have an influence on the association between quality of life and mortality. However, the HRs are mostly so high, that it will very probably not influence the outcome. Fourth, we used a generic rather a disease-specific measure of health status, which may be less sensitive to tap treatmentrelated changes over time if present. In conclusion, the results of the current study showed that most health status domains as measured with the SF-36 predicted death at 6-year follow-up in PCI patients treated with drug-eluting stenting, independent of demographic and clinical characteristics. By contrast, a decline in health status between 1 and 12 months post index procedure, as measured with the SF-36, was not associated with 6-year mortality in PCI patients treated with drug-eluting stenting. Patientrated health status comprises an important means by which to identify high-risk patients in clinical practice, which cannot be inferred from any other clinical variables standardly assessed.
References 1. Krumholz HM, Peterson ED, Ayanian JZ, et al. Report of the National Heart, Lung, and Blood Institute working group on outcomes research in cardiovascular disease. Circulation 2005;111: 3158-66. 2. van Domburg RT, Daemen J, Pedersen SS, et al. Short- and long- term health related quality-of-life and anginal status after randomisation to coronary stenting versus bypass surgery for the treatment of multivessel disease: results of the Arterial Revascularisation Therapy Study (ARTS). EuroIntervention 2008;3:506-11. 3. Spertus JA, Jones P, McDonell M, et al. Health status predicts longterm outcome in outpatients with coronary disease. Circulation 2002; 106:43-9. 4. Soto GE, Jones P, Weintraub WS, et al. Prognostic value of health status in patients with heart failure after acute myocardial infarction. Circulation 2004;110:546-51. 5. Rumsfeld JS, MaWhinney S, McCarthy Jr M, et al. Health-related quality of life as a predictor of mortality following coronary artery bypass graft surgery. Participants of the Department of Veterans Affairs Cooperative Study Group on Processes, Structures, and Outcomes of Care in Cardiac Surgery. JAMA 1999;281: 1298-303. 6. Mommersteeg PM, Denollet J, Spertus JA, et al. Health status as a risk factor in cardiovascular disease: a systematic review of current evidence. Am Heart J 2009;157:208-18. 7. Kosiborod M, Soto GE, Jones PG, et al. Identifying heart failure patients at high risk for near-term cardiovascular events with serial health status assessments. Circulation 2007;115: 1975-81. 8. Subramanian U, Eckert G, Yeung A, et al. A single health status question had important prognostic value among outpatients with chronic heart failure. J Clin Epidemiol 2007;60:803-11. 9. Pedersen SS, Lemos PA, van Vooren PR, et al. Type D personality predicts death or myocardial infarction after bare metal stent or sirolimus-eluting stent implantation: a Rapamycin-Eluting Stent
476 Schenkeveld et al
10.
11.
12.
13.
14.
15.
Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry substudy. J Am Coll Cardiol 2004;44:997-1001. Lemos PA, Lee CH, Degertekin M, et al. Early outcome after sirolimuseluting stent implantation in patients with acute coronary syndromes: insights from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. J Am Coll Cardiol 2003; 41:2093-9. Poston WS, Haddock CK, Conard MW, et al. Assessing depression in the cardiac patient. When is the appropriate time to assess depression in the patient undergoing coronary revascularization? Behav Modif 2003;27:26-36. Ware Jr JE, Sherbourne CD, The MOS. 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473-83. Smith HJ, Taylor R, Mitchell AA. comparison of four quality of life instruments in cardiac patients: SF-36, QLI, QLMI, and SEIQoL. Heart 2000;84:390-4. Rumsfeld JS, Magid DJ, Plomondon ME, et al. History of depression, angina, and quality of life after acute coronary syndromes. Am Heart J 2003;145:493-9. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care 2003;41:582-92.
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16. Koch CG, Li L, Lauer M, et al. Effect of functional health-related quality of life on long-term survival after cardiac surgery. Circulation 2007; 115:692-9. 17. Faller H, Stork S, Schowalter M, et al. Is health-related quality of life an independent predictor of survival in patients with chronic heart failure? J Psychosom Res 2007;63:533-8. 18. Rodriguez-Artalejo F, Guallar-Castillon P, Pascual CR, et al. Healthrelated quality of life as a predictor of hospital readmission and death among patients with heart failure. Arch Intern Med 2005;165: 1274-9. 19. Lenzen MJ, Scholte op Reimer WJ, Pedersen SS, et al. The additional value of patient-reported health status in predicting 1-year mortality after invasive coronary procedures: a report from the Euro Heart Survey on Coronary Revascularisation. Heart 2007; 93:339-44. 20. Pedersen SS, Martens EJ, Denollet J, et al. Poor health-related quality of life is a predictor of early, but not late, cardiac events after percutaneous coronary intervention. Psychosomatics 2007;48:331-7. 21. Spertus JA. Evolving applications for patient-centered health status measures. Circulation 2008;118:2103-10. 22. Weintraub WS, Spertus JA, Kolm P, et al. Effect of PCI on quality of life in patients with stable coronary disease. N Engl J Med 2008;359: 677-87.