Clin Rheumatol DOI 10.1007/s10067-014-2695-y
BRIEF REPORT
The impact of inflammatory rheumatic diseases on the presentation, severity, and outcome of acute coronary syndrome Ilan Ben-Zvi & Ilan Goldenberg & Shlomi Matetzky & Chagai Grossman & Avishay Elis & Natalie Gavrielov-Yusim & Avi Livneh
Received: 15 May 2014 / Accepted: 23 May 2014 # Clinical Rheumatology 2014
Abstract Patients with inflammatory rheumatic diseases (IRD) have a high burden of cardiovascular disease (CVD), leading to increased mortality and morbidity. However, it is not clear whether increased CVD mortality in IRD is due to a higher incidence or worse outcome of cardiovascular events (higher case fatality). In this observational case–control study, we assessed the outcome of acute coronary syndrome (ACS) in patients with IRDs compared to matched controls without IRD, using data from the Acute Coronary Syndrome Israeli Survey (ACSIS), a large, national, real-life registry detailing the extent, severity, and outcome of ACS. Of 2,193 subjects enrolled to the ACSIS, 20 (nine men) were identified with IRD, including 11 patients with rheumatoid arthritis, five patients with systemic lupus erythematosus (SLE), three patients with ankylosing spondylitis (AS), and one patient with psoriatic arthritis (PsA). The study patients were compared to I. Ben-Zvi : C. Grossman : A. Livneh Department of Medicine F and the Rheumatology Unit, Sheba Medical Center, Tel Hashomer, Israel I. Ben-Zvi : I. Goldenberg : S. Matetzky : A. Elis : A. Livneh Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel I. Ben-Zvi (*) The Dr. Pinchas Borenstein Talpiot Medical Leadership Program 2012, Chaim Sheba Medical Center, Tel Hashomer, Israel e-mail: [email protected] I. Goldenberg : S. Matetzky The Leviev Heart Institute, Sheba Medical Center, Tel Hashomer, Israel I. Goldenberg : S. Matetzky : N. Gavrielov-Yusim Neufeld Cardiac Research Institute, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel A. Elis Department of Medicine, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel
120 matched control patients (adjusted for age and risk factors for CVD) without IRD. Compared to controls, IRD patients had similar clinical presentation and similar type of ACS and received identical initial treatment at the ER. The two groups had comparable rates of complications including major adverse cardiovascular events (death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis) (10 vs. 11.7 % in the study and control group, respectively, p>0.05), re-hospitalization (20 vs. 21.1 %, respectively, p>0.05), and severe congestive heart failure (7.7 vs. 6.9 %, respectively, p>0.05) within 30 days. The outcome and prognosis of ACS in patients with IRD is not worse than that of control, supporting the higher prevalence of CVD in this population as the cause for their excess mortality. Keywords Cardiovascular . Coronary syndrome . Inflammation . Rheumatoid arthritis
Background Patients with inflammatory rheumatic diseases (IRD) carry higher risk for cardiovascular disease (CVD), leading to excess premature mortality and morbidity. This risk remains after adjustment for the traditional risk factors and is thought to be mediated by accelerated atherosclerosis. This excess of atherosclerotic CVD in patients with rheumatic diseases was shown mainly for rheumatoid arthritis (RA) [1–3], systemic lupus erythematosus (SLE) [4, 5], psoriatic arthritis (PsA) [6], and ankylosing spondylitis (AS) [7, 8]. Accordingly, the EULAR issued evidence-based recommendations for the management of cardiovascular risk in patients with IRD [9]. Although it is well established that IRD pose a risk for the occurrence of atherosclerotic CVD and for increased CVD mortality, it is not clear whether this increased mortality in
Clin Rheumatol
IRD patients is due to a higher incidence or worse outcome (higher case fatality) of CVD events in this population. Published data on short- and long-term outcomes of acute coronary syndrome (ACS) in IRD is conflicting and scant [3, 10–14]. The Acute Coronary Syndrome Israeli Survey (ACSIS) is a large, national, real-life registry detailing the extent, severity, and outcome of patients with ACS in Israel. This database provides an excellent opportunity to study various aspects of coronary heart disease, including short- and long-term complications and mortality in various subpopulations, including in those with IRD.
Methods Study population ACSIS is a biennial national ACS survey, conducted in all 25 operating cardiac departments in Israel since 1992. Details of the nationwide registry have been previously reported [15]. In brief, the ACSIS Registry is a 2-month nationwide survey that prospectively collects data from all acute coronary syndrome admissions from each of the 25 coronary care units and cardiology wards operating in Israel. The parameters for the present study were derived from the ACSIS 2010, which was conducted during a 2-month period (March–April) in 2010. Demographic, historical, clinical data, interventions, and complications were recorded on prespecified forms for all patients admitted with a diagnosis of ACS. Patient management was at the discretion of the attending physicians. Admission and discharge diagnoses were recorded as determined by the attending physicians based on clinical, electrocardiographic, and biochemical (elevated creatine kinase (CK)-MB and/or troponin levels) criteria. Inhospital and 30-day outcome data were ascertained by hospital chart review, telephone contact, and clinical follow-up data. Mortality data during 1 year following enrollment were ascertained through the use of the Israeli National Population Registry. Included in this study were all patients with ACS who had a background diagnosis of an IRD which is known to predispose to the development of CVD (RA, SLE, PsA, and AS). A matched group of patients from the survey, with an episode of ACS and without a background rheumatic disease, served as control. Definitions and outcome measures The composite primary end point was defined as major adverse cardiovascular events (MACE) which include death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis within 30 days of presentation. Secondary end points included: presenting symptoms, severity of
ACS (measured by Killip class), intervention, estimated ejection fraction (EF), in-hospital complications (i.e., arrhythmia, stent thrombosis, sudden death etc.) and 1-year all-cause mortality. Patients of the study and control groups were compared on the primary and various secondary parameters. Statistical analysis For each patient with IRD and ACS, six age-matched and sexmatched controls with ACS but without IRD were randomly selected from the ACSIS database. The patients and controls were also matched for the presence of dyslipidemia, hypertension (HTN), and diabetes mellitus (DM). Comparison of categorical variables was performed with chi-square tests, and comparison of continuous variables was performed using ANOVA and Kruskal–Wallis tests as appropriate. The statistical software used for the analyses was SAS version 9.3 (SAS institute, Cary, NC). A two-sided p value 0.05 IRD inflammatory rheumatic disease, IHD ischemic heart disease, CVD cardiovascular disease, ACS acute coronary syndrome, STEMI ST elevation myocardial infarction, NSTEMI non-STEMI, UAP unstable angina pectoris
heart disease, a family history of CVD, and a history of treatment with antithrombotic or anticoagulation agents, but these differences did not reach statistical significance. There were also no significant differences in the type of ACS (STEMI, NSTEMI, or UAP) between the IRD and control groups, showing that IRD patients do not have a predisposition for a specific type of ACS.
18 (90 %) 1 (5 %) 0
94 (78.3 %) 16 (13.3 %) 2/119 (1.7 %)
1 (5 %) 1 (5 %)
7 (5.8 %) 11 (9.2 %)
17 (85 %) 2 (10 %) 0 0
104 (86.7 %) 6 (5 %) 1 (0.83 %) 5 (4.17 %)
5 (25 %) 7 (35 %) 2 (10 %) 3 (15 %) 1 (5 %) 2 (10 %)
22 (18.3 %) 53 (44.2 %) 15 (12.5 %) 19 (15.8 %) 8 (6.7 %) 3 (2.5 %)
p values for all comparisons are >0.05 IRD inflammatory rheumatic disease, ER emergency room, SCD sudden cardiac death, NSR normal sinus rhythm, AF atrial fibrillation, VT ventricular tachycardia, VF ventricular fibrillation
Initial treatment There were no differences in the initial medical treatment in the ER with antithrombotic agents, anticoagulation, betablockers, statins, or nitrates between the IRD and control groups (Table 3). All five IRD patients with STEMI underwent primary angiography with stent insertion, without complications.
Clinical presentation of ACS Complications Most patients with IRD had typical chest pain at presentation (90 %), without rhythm abnormalities on ECG (85 %) (Table 2). There were no significant differences between the groups in the presenting symptoms, ECG rhythm or ischemic changes at the time of presentation to the emergency department. None of the IRD patients had ventricular fibrillation/tachycardia or a high-degree AV block at presentation. The most common ischemic change on ECG in the IRD group was ST segment elevation (35 %), compared to 44.2 % in the control group. In terms of ACS severity, there were no significant differences in the Killip class between the groups at presentation (10 vs. 15 % of patients with Killip class 2 or higher in the IRD and control groups, respectively, p>0.05).
The rates of significant congestive heart failure, rehospitalization, and MACE at 30 days were comparable between the groups (Fig. 1). None of the patients in the IRD group had early complications of ACS, including pulmonary edema, cardiogenic shock, high-degree AV block, primary ventricular fibrillation, atrial fibrillation, asystole, acute renal failure, major bleeding, or infection, compared to 4.2, 2.5, 4.2, 2.5, 6.7, 0.8, 4.2, 8.3, and 8.3 % in the control group, respectively (p>0.05 for all comparisons). There was also no event of re-infarction or mortality at 30 days in the IRD group, compared to 0.8 and 4.2 % in the control group, respectively (p>0.05). All IRD patients with ACS were alive after 1 year, compared to a rate of 12.2 % of all-cause mortality in the control group.
Clin Rheumatol Table 3 Comparison between IRD and control groups of initial medical and reperfusion treatments IRD group (n=20)
Control group (n=120)
Medical treatment in the ER Aspirin 12 (60 %) Heparin 3 (15.8 %) LMWH 0
81 (67.5 %) 31 (25.8 %) 5 (4.2 %)
Clopidogrel Beta-blockers Statins Nitrates Primary reperfusion Angiography Thrombolysis Stent insertion
26 (21.7 %) 36 (30 %) 36 (30.5 %) 21 (18.8 %) 40/109 (36.7 %) 37 (30.8 %) 1 (2.5 %) 34/37 (91.9 %)
4 (20 %) 6 (30 %) 7 (35 %) 4 (21.1 %) 5 (25 %) 5 (100 %) 0 5 (100 %)
p values for all comparisons are >0.05 IRD inflammatory rheumatic disease, ER emergency department, LMWH low molecular weight heparin
Discussion In this small, observational case–control study, IRD did not carry an additional adverse effect on the extent, characteristics, and outcome of ACS. Compared to controls, IRD patients had similar clinical presentation, similar type of ACS (STEMI, NSTEMI, or UAP), received identical initial treatment at the ER, and had comparable rates of complications at 30 days following the ACS. It is well established that IRD leads to an increase in cardiovascular mortality. This can be attributed to a higher prevalence of CVD in this population or to a worse case fatality of ACS. Our data supports the higher prevalence of CVD as the cause for excess mortality in this population. Fig. 1 The rate of significant congestive heart failure, rehospitalization, and MACE at 30 days in the IRD and control groups. p values for all comparisons are >0.05. MACE major adverse cardiovascular events (including death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis), IRD inflammatory rheumatic disease, EF ejection fraction
The data on the outcome of IRD patients after ACS is scarce. In one study, by Douglas et al., RA patients with a first episode of ACS were shown to have higher rates of recurrent ACS and death, compared to controls [3]. The differences in our results might stem from differences in the rate of previous ischemic heart disease, IRD type (RA only vs. heterogeneous IRD in our study), length of follow-up (longer in Douglas et al. study), accounting for troponin for the definition of the study population (troponin was not used in Douglas et al. study), and rate of baseline treatment with antithrombotic agents, anticoagulation agents, and statins, probably because of higher rates of previous ischemic heart disease in our cohort (70 % vs. none in Douglas’ cohort). Another study, by Desai et al., showed similar clinical characteristics, presentation, severity, and outcome of coronary artery disease between RA patients and controls, resembling our results [10]. However, this study was limited to RA only and included a population with less severe (subacute) coronary disease. Looking at outcomes of ACS in RA at much longer periods, Sodergren et al. found no increased mortality at 5-year interval following acute myocardial infarction (AMI) [16]. However, survival after 10 years was lower for RA patients compared to controls. In our study, there was no difference in all-cause mortality at 1 year following ACS. A longer follow-up is needed in order to assess the long-term outcome in our cohort. It is worth pointing out that Sodergren’s study was an observational study, on a cohort of patients presenting with AMI between the years 1980–1997. Today, there is more awareness to the need of aggressive primary and secondary prevention treatments for CVD in patients with IRD, which might lead to the better outcome of their ACS, compared to older cohorts. Also, earlier and more aggressive treatment of IRDs with diseases modifying antirheumatic drugs (DMARDs) is the state-of-the-art today, leading to a better control of inflammation and possibly to a lower burden of CVD in these patients.
Clin Rheumatol
Indeed, it was shown that there is a decline in mortality rate from AMI in RA patients according to the year of incidence of coronary events [17]. Most of the studies assessing cardiovascular outcomes in IRD have evaluated mainly RA patients with myocardial infarction [11–14]. As aforementioned, there are conflicting results, which may be attributed to the difference in previous studies in the rate of reperfusion and of secondary prevention treatment in RA patients compared to controls. In our study, patients with IRD had similar medical and reperfusion treatments for their ACS as the controls, by that neutralizing this potential confounder affecting previous studies. The major limitation of our study is the small cohort size (n=140). This is due to the low incidence of patients with IRD and ACS, affecting previous studies as well. The prevalence of patients with ACS and IRD was approximately 1 % (of 2,193 patients), which is the expected prevalence of these diseases in the general population. Another caveat is the variety of IRDs in our group, as opposed to studying a single disease. Since IRDs are rare, it is difficult to assemble a large cohort of patients with a single IRD that suffers from ACS. However, it is reasonable to assume that different IRDs will have a similar effect on the outcome of ACS, because of the similar underlying pathophysiology, which is continuous exposure to active systemic inflammation. Further studies are needed to evaluate a possible differential effect of each IRD separately. Also, this study is a retrospective analysis, based on medical records’ review; therefore, IRD activity scores were not routinely collected in the setting of ACS hospitalization and were not available to us. In summary, we found in a small heterogeneous population with IRDs that the presentation, extent and outcome of ACS are similar to a matched group of patients without IRD. Disclosures None.
References 1. Avina-Zubieta JA et al (2008) Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 59(12):1690–1697
2. del Rincon ID et al (2001) High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 44(12):2737–2745 3. Douglas KM et al (2006) Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome. Ann Rheum Dis 65(3):348–353 4. Esdaile JM et al (2001) Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 44(10):2331–2337 5. Manzi S et al (1997) Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol 145(5): 408–415 6. Gladman DD et al (2009) Cardiovascular morbidity in psoriatic arthritis. Ann Rheum Dis 68(7):1131–1135 7. Peters MJ et al (2004) Cardiovascular risk profile of patients with spondylarthropathies, particularly ankylosing spondylitis and psoriatic arthritis. Semin Arthritis Rheum 34(3):585–592 8. Peters MJ et al (2010) Signs of accelerated preclinical atherosclerosis in patients with ankylosing spondylitis. J Rheumatol 37(1):161–166 9. Peters MJ et al (2010) EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 69(2): 325–331 10. Desai SP et al (2010) Comparison of symptoms, treatment, and outcomes of coronary artery disease among rheumatoid arthritis and matched subjects undergoing percutaneous coronary intervention. Semin Arthritis Rheum 40(3):215–221 11. Francis ML et al (2010) Outcomes in patients with rheumatoid arthritis and myocardial infarction. Am J Med 123(10):922–928 12. McCoy SS et al (2013) Longterm outcomes and treatment after myocardial infarction in patients with rheumatoid arthritis. J Rheumatol 40(5):605–610 13. Van Doornum S et al (2006) Increased case fatality rates following a first acute cardiovascular event in patients with rheumatoid arthritis. Arthritis Rheum 54(7):2061–2068 14. Van Doornum S et al (2010) Rheumatoid arthritis patients receive less frequent acute reperfusion and secondary prevention therapy after myocardial infarction compared with the general population. Arthritis Res Ther 12(5):R183 15. Ben-Dor I et al (2006) Prognostic implications of increased cardiac biomarkers and ST segment depression in non-ST elevation acute coronary syndromes: lessons from the acute coronary syndrome Israeli survey (ACSIS) 2002. Heart 92(4):547–548 16. Sodergren A et al (2007) Increased incidence of and impaired prognosis after acute myocardial infarction among patients with seropositive rheumatoid arthritis. Ann Rheum Dis 66(2): 263–266 17. Krishnan E, Lingala VB, Singh G (2004) Declines in mortality from acute myocardial infarction in successive incidence and birth cohorts of patients with rheumatoid arthritis. Circulation 110(13):1774–1779
BRIEF REPORT
The impact of inflammatory rheumatic diseases on the presentation, severity, and outcome of acute coronary syndrome Ilan Ben-Zvi & Ilan Goldenberg & Shlomi Matetzky & Chagai Grossman & Avishay Elis & Natalie Gavrielov-Yusim & Avi Livneh
Received: 15 May 2014 / Accepted: 23 May 2014 # Clinical Rheumatology 2014
Abstract Patients with inflammatory rheumatic diseases (IRD) have a high burden of cardiovascular disease (CVD), leading to increased mortality and morbidity. However, it is not clear whether increased CVD mortality in IRD is due to a higher incidence or worse outcome of cardiovascular events (higher case fatality). In this observational case–control study, we assessed the outcome of acute coronary syndrome (ACS) in patients with IRDs compared to matched controls without IRD, using data from the Acute Coronary Syndrome Israeli Survey (ACSIS), a large, national, real-life registry detailing the extent, severity, and outcome of ACS. Of 2,193 subjects enrolled to the ACSIS, 20 (nine men) were identified with IRD, including 11 patients with rheumatoid arthritis, five patients with systemic lupus erythematosus (SLE), three patients with ankylosing spondylitis (AS), and one patient with psoriatic arthritis (PsA). The study patients were compared to I. Ben-Zvi : C. Grossman : A. Livneh Department of Medicine F and the Rheumatology Unit, Sheba Medical Center, Tel Hashomer, Israel I. Ben-Zvi : I. Goldenberg : S. Matetzky : A. Elis : A. Livneh Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel I. Ben-Zvi (*) The Dr. Pinchas Borenstein Talpiot Medical Leadership Program 2012, Chaim Sheba Medical Center, Tel Hashomer, Israel e-mail: [email protected] I. Goldenberg : S. Matetzky The Leviev Heart Institute, Sheba Medical Center, Tel Hashomer, Israel I. Goldenberg : S. Matetzky : N. Gavrielov-Yusim Neufeld Cardiac Research Institute, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel A. Elis Department of Medicine, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel
120 matched control patients (adjusted for age and risk factors for CVD) without IRD. Compared to controls, IRD patients had similar clinical presentation and similar type of ACS and received identical initial treatment at the ER. The two groups had comparable rates of complications including major adverse cardiovascular events (death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis) (10 vs. 11.7 % in the study and control group, respectively, p>0.05), re-hospitalization (20 vs. 21.1 %, respectively, p>0.05), and severe congestive heart failure (7.7 vs. 6.9 %, respectively, p>0.05) within 30 days. The outcome and prognosis of ACS in patients with IRD is not worse than that of control, supporting the higher prevalence of CVD in this population as the cause for their excess mortality. Keywords Cardiovascular . Coronary syndrome . Inflammation . Rheumatoid arthritis
Background Patients with inflammatory rheumatic diseases (IRD) carry higher risk for cardiovascular disease (CVD), leading to excess premature mortality and morbidity. This risk remains after adjustment for the traditional risk factors and is thought to be mediated by accelerated atherosclerosis. This excess of atherosclerotic CVD in patients with rheumatic diseases was shown mainly for rheumatoid arthritis (RA) [1–3], systemic lupus erythematosus (SLE) [4, 5], psoriatic arthritis (PsA) [6], and ankylosing spondylitis (AS) [7, 8]. Accordingly, the EULAR issued evidence-based recommendations for the management of cardiovascular risk in patients with IRD [9]. Although it is well established that IRD pose a risk for the occurrence of atherosclerotic CVD and for increased CVD mortality, it is not clear whether this increased mortality in
Clin Rheumatol
IRD patients is due to a higher incidence or worse outcome (higher case fatality) of CVD events in this population. Published data on short- and long-term outcomes of acute coronary syndrome (ACS) in IRD is conflicting and scant [3, 10–14]. The Acute Coronary Syndrome Israeli Survey (ACSIS) is a large, national, real-life registry detailing the extent, severity, and outcome of patients with ACS in Israel. This database provides an excellent opportunity to study various aspects of coronary heart disease, including short- and long-term complications and mortality in various subpopulations, including in those with IRD.
Methods Study population ACSIS is a biennial national ACS survey, conducted in all 25 operating cardiac departments in Israel since 1992. Details of the nationwide registry have been previously reported [15]. In brief, the ACSIS Registry is a 2-month nationwide survey that prospectively collects data from all acute coronary syndrome admissions from each of the 25 coronary care units and cardiology wards operating in Israel. The parameters for the present study were derived from the ACSIS 2010, which was conducted during a 2-month period (March–April) in 2010. Demographic, historical, clinical data, interventions, and complications were recorded on prespecified forms for all patients admitted with a diagnosis of ACS. Patient management was at the discretion of the attending physicians. Admission and discharge diagnoses were recorded as determined by the attending physicians based on clinical, electrocardiographic, and biochemical (elevated creatine kinase (CK)-MB and/or troponin levels) criteria. Inhospital and 30-day outcome data were ascertained by hospital chart review, telephone contact, and clinical follow-up data. Mortality data during 1 year following enrollment were ascertained through the use of the Israeli National Population Registry. Included in this study were all patients with ACS who had a background diagnosis of an IRD which is known to predispose to the development of CVD (RA, SLE, PsA, and AS). A matched group of patients from the survey, with an episode of ACS and without a background rheumatic disease, served as control. Definitions and outcome measures The composite primary end point was defined as major adverse cardiovascular events (MACE) which include death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis within 30 days of presentation. Secondary end points included: presenting symptoms, severity of
ACS (measured by Killip class), intervention, estimated ejection fraction (EF), in-hospital complications (i.e., arrhythmia, stent thrombosis, sudden death etc.) and 1-year all-cause mortality. Patients of the study and control groups were compared on the primary and various secondary parameters. Statistical analysis For each patient with IRD and ACS, six age-matched and sexmatched controls with ACS but without IRD were randomly selected from the ACSIS database. The patients and controls were also matched for the presence of dyslipidemia, hypertension (HTN), and diabetes mellitus (DM). Comparison of categorical variables was performed with chi-square tests, and comparison of continuous variables was performed using ANOVA and Kruskal–Wallis tests as appropriate. The statistical software used for the analyses was SAS version 9.3 (SAS institute, Cary, NC). A two-sided p value 0.05 IRD inflammatory rheumatic disease, IHD ischemic heart disease, CVD cardiovascular disease, ACS acute coronary syndrome, STEMI ST elevation myocardial infarction, NSTEMI non-STEMI, UAP unstable angina pectoris
heart disease, a family history of CVD, and a history of treatment with antithrombotic or anticoagulation agents, but these differences did not reach statistical significance. There were also no significant differences in the type of ACS (STEMI, NSTEMI, or UAP) between the IRD and control groups, showing that IRD patients do not have a predisposition for a specific type of ACS.
18 (90 %) 1 (5 %) 0
94 (78.3 %) 16 (13.3 %) 2/119 (1.7 %)
1 (5 %) 1 (5 %)
7 (5.8 %) 11 (9.2 %)
17 (85 %) 2 (10 %) 0 0
104 (86.7 %) 6 (5 %) 1 (0.83 %) 5 (4.17 %)
5 (25 %) 7 (35 %) 2 (10 %) 3 (15 %) 1 (5 %) 2 (10 %)
22 (18.3 %) 53 (44.2 %) 15 (12.5 %) 19 (15.8 %) 8 (6.7 %) 3 (2.5 %)
p values for all comparisons are >0.05 IRD inflammatory rheumatic disease, ER emergency room, SCD sudden cardiac death, NSR normal sinus rhythm, AF atrial fibrillation, VT ventricular tachycardia, VF ventricular fibrillation
Initial treatment There were no differences in the initial medical treatment in the ER with antithrombotic agents, anticoagulation, betablockers, statins, or nitrates between the IRD and control groups (Table 3). All five IRD patients with STEMI underwent primary angiography with stent insertion, without complications.
Clinical presentation of ACS Complications Most patients with IRD had typical chest pain at presentation (90 %), without rhythm abnormalities on ECG (85 %) (Table 2). There were no significant differences between the groups in the presenting symptoms, ECG rhythm or ischemic changes at the time of presentation to the emergency department. None of the IRD patients had ventricular fibrillation/tachycardia or a high-degree AV block at presentation. The most common ischemic change on ECG in the IRD group was ST segment elevation (35 %), compared to 44.2 % in the control group. In terms of ACS severity, there were no significant differences in the Killip class between the groups at presentation (10 vs. 15 % of patients with Killip class 2 or higher in the IRD and control groups, respectively, p>0.05).
The rates of significant congestive heart failure, rehospitalization, and MACE at 30 days were comparable between the groups (Fig. 1). None of the patients in the IRD group had early complications of ACS, including pulmonary edema, cardiogenic shock, high-degree AV block, primary ventricular fibrillation, atrial fibrillation, asystole, acute renal failure, major bleeding, or infection, compared to 4.2, 2.5, 4.2, 2.5, 6.7, 0.8, 4.2, 8.3, and 8.3 % in the control group, respectively (p>0.05 for all comparisons). There was also no event of re-infarction or mortality at 30 days in the IRD group, compared to 0.8 and 4.2 % in the control group, respectively (p>0.05). All IRD patients with ACS were alive after 1 year, compared to a rate of 12.2 % of all-cause mortality in the control group.
Clin Rheumatol Table 3 Comparison between IRD and control groups of initial medical and reperfusion treatments IRD group (n=20)
Control group (n=120)
Medical treatment in the ER Aspirin 12 (60 %) Heparin 3 (15.8 %) LMWH 0
81 (67.5 %) 31 (25.8 %) 5 (4.2 %)
Clopidogrel Beta-blockers Statins Nitrates Primary reperfusion Angiography Thrombolysis Stent insertion
26 (21.7 %) 36 (30 %) 36 (30.5 %) 21 (18.8 %) 40/109 (36.7 %) 37 (30.8 %) 1 (2.5 %) 34/37 (91.9 %)
4 (20 %) 6 (30 %) 7 (35 %) 4 (21.1 %) 5 (25 %) 5 (100 %) 0 5 (100 %)
p values for all comparisons are >0.05 IRD inflammatory rheumatic disease, ER emergency department, LMWH low molecular weight heparin
Discussion In this small, observational case–control study, IRD did not carry an additional adverse effect on the extent, characteristics, and outcome of ACS. Compared to controls, IRD patients had similar clinical presentation, similar type of ACS (STEMI, NSTEMI, or UAP), received identical initial treatment at the ER, and had comparable rates of complications at 30 days following the ACS. It is well established that IRD leads to an increase in cardiovascular mortality. This can be attributed to a higher prevalence of CVD in this population or to a worse case fatality of ACS. Our data supports the higher prevalence of CVD as the cause for excess mortality in this population. Fig. 1 The rate of significant congestive heart failure, rehospitalization, and MACE at 30 days in the IRD and control groups. p values for all comparisons are >0.05. MACE major adverse cardiovascular events (including death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis), IRD inflammatory rheumatic disease, EF ejection fraction
The data on the outcome of IRD patients after ACS is scarce. In one study, by Douglas et al., RA patients with a first episode of ACS were shown to have higher rates of recurrent ACS and death, compared to controls [3]. The differences in our results might stem from differences in the rate of previous ischemic heart disease, IRD type (RA only vs. heterogeneous IRD in our study), length of follow-up (longer in Douglas et al. study), accounting for troponin for the definition of the study population (troponin was not used in Douglas et al. study), and rate of baseline treatment with antithrombotic agents, anticoagulation agents, and statins, probably because of higher rates of previous ischemic heart disease in our cohort (70 % vs. none in Douglas’ cohort). Another study, by Desai et al., showed similar clinical characteristics, presentation, severity, and outcome of coronary artery disease between RA patients and controls, resembling our results [10]. However, this study was limited to RA only and included a population with less severe (subacute) coronary disease. Looking at outcomes of ACS in RA at much longer periods, Sodergren et al. found no increased mortality at 5-year interval following acute myocardial infarction (AMI) [16]. However, survival after 10 years was lower for RA patients compared to controls. In our study, there was no difference in all-cause mortality at 1 year following ACS. A longer follow-up is needed in order to assess the long-term outcome in our cohort. It is worth pointing out that Sodergren’s study was an observational study, on a cohort of patients presenting with AMI between the years 1980–1997. Today, there is more awareness to the need of aggressive primary and secondary prevention treatments for CVD in patients with IRD, which might lead to the better outcome of their ACS, compared to older cohorts. Also, earlier and more aggressive treatment of IRDs with diseases modifying antirheumatic drugs (DMARDs) is the state-of-the-art today, leading to a better control of inflammation and possibly to a lower burden of CVD in these patients.
Clin Rheumatol
Indeed, it was shown that there is a decline in mortality rate from AMI in RA patients according to the year of incidence of coronary events [17]. Most of the studies assessing cardiovascular outcomes in IRD have evaluated mainly RA patients with myocardial infarction [11–14]. As aforementioned, there are conflicting results, which may be attributed to the difference in previous studies in the rate of reperfusion and of secondary prevention treatment in RA patients compared to controls. In our study, patients with IRD had similar medical and reperfusion treatments for their ACS as the controls, by that neutralizing this potential confounder affecting previous studies. The major limitation of our study is the small cohort size (n=140). This is due to the low incidence of patients with IRD and ACS, affecting previous studies as well. The prevalence of patients with ACS and IRD was approximately 1 % (of 2,193 patients), which is the expected prevalence of these diseases in the general population. Another caveat is the variety of IRDs in our group, as opposed to studying a single disease. Since IRDs are rare, it is difficult to assemble a large cohort of patients with a single IRD that suffers from ACS. However, it is reasonable to assume that different IRDs will have a similar effect on the outcome of ACS, because of the similar underlying pathophysiology, which is continuous exposure to active systemic inflammation. Further studies are needed to evaluate a possible differential effect of each IRD separately. Also, this study is a retrospective analysis, based on medical records’ review; therefore, IRD activity scores were not routinely collected in the setting of ACS hospitalization and were not available to us. In summary, we found in a small heterogeneous population with IRDs that the presentation, extent and outcome of ACS are similar to a matched group of patients without IRD. Disclosures None.
References 1. Avina-Zubieta JA et al (2008) Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 59(12):1690–1697
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