Cardiovascular disease in rheumatoid arthritis: Single-center hospital-based cohort study in France

doi:10.1016/j.jbspin.2006.10.001

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Volume 74, Issue 1, January 2007, Pages 66-72

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Abstract

Introduction

Rheumatoid arthritis (RA) was independently associated with cardiovascular events in several studies, most of which were conducted in the US.

Objectives

To estimate the risk of cardiovascular events in a cohort of RA patients recruited at a hospital in France, to identify cardiovascular risk factors, and to measure the severity of cardiovascular events.

Methods

Two hundred and thirty-nine patients admitted between January 1, 1998, and March 31, 1999, for RA meeting American College of Rheumatology criteria, with a negative history for cardiovascular events, were sent a questionnaire in 2004 to evaluate the occurrence of myocardial infarction, stroke, or cardiovascular death.

Results

During the mean follow-up of 5.4 ± 1.8 years, there were 10 cases of myocardial infarction (0.8%/year), 3 cases of stroke (0.2%/year), and 9 cardiovascular deaths (0.7%/year). Of the 10 patients who experienced myocardial infarction, 5 had clinical symptoms of heart failure and 4 died from cardiovascular causes. Independent risk factors for cardiovascular events were older age (relative risk [RR], 2.5/10 years; 95% confidence interval [95%CI], 1.4–4.2), male gender (RR, 5.1; 95%CI, 1.8–14.6), treated hypertension (RR, 4.3; 95%CI, 1.4–13.2), and treated hypercholesterolemia (RR, 6.0; 95%CI, 1.8–20.7).

Conclusion

Our data suggest a higher risk of cardiovascular events in patients with RA compared to the general population in France (0.1–0.5%/year for myocardial infarction and 0.07%/year for stroke in the age group covered by our cohort). Cardiovascular events in the patients with RA seemed unusually severe. Patients with RA should be carefully screened for conventional cardiovascular risk factors.

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease related to dysimmunity. The prevalence of RA among adults ranges from 0.3 to 0.6% [1]. Excess mortality with a 5- to 10-year reduction in life expectancy has been reported in patients with RA [2], [3], [4], [5], [6], [7]. Risk factors for mortality include severe disease (most notably marked functional impairment), positive tests for rheumatoid factors, male gender, and presence of co-morbidities [3], [5], [8], [9]. Cardiovascular events have been shown to contribute about 50% of the excess mortality seen in RA [3], [8]. The relative risk (RR) of myocardial infarction compared to individuals without RA has ranged from 1.4 to 3.9 [2], [3], [4], [5], [7], [10], [11], [12], [13], [14], [15]. Although the mechanisms underlying the increased risk of cardiovascular disease in patients with RA remain unclear, available data incriminate not only conventional cardiovascular risk factors, but also RA-specific factors such as systemic inflammation [16], [17], [18], [19], [20]. In addition, T cells, which contribute to the pathogenesis of RA, may be critically involved in acute coronary syndromes and in plaque instability [21].

The objectives of this study were to evaluate the risk of cardiovascular events in a cohort of patients with RA recruited at a hospital in France, to identify risk factors for cardiovascular disease associated with RA, and to measure the severity of the cardiovascular events in these patients with RA.

Section snippets

Methods

We identified consecutive patients with RA admitted to the rheumatology A (Rheumatology A) department of the Cochin Teaching Hospital, Paris, France, from January 1, 1998 to March 31, 1999. The patients were identified from the hospital database, which lists the main diagnosis and co-morbid conditions determined at discharge by a senior physician in each patient. We reviewed the medical charts of the patients thus identified and selected the patients who met American College of Rheumatology

Statistics

Categorical variables were compared using the chi-square test, or Fisher's exact test where appropriate. Student's t-tests were used for comparing continuous variables. Kaplan–Meier curves analysis was performed to determine the absolute risk of each event. Potential risk factors for myocardial infarction and stroke were evaluated by constructing a Cox model that adjusted for the following factors: age; gender; hypercholesterolemia; arterial hypertension; diabetes mellitus; osteoporosis;

Results

Of the 285 patients listed in the hospital database as having RA, 245 (84.5%) met ACR criteria for RA. A history of cardiovascular disease was noted in 6 (2.5%) patients. Thus, 239 (239/285, 82.4%) patients were included in the study. Fig. 1 shows the patient flow chart. Mean age was 56.3 ± 15.7 years, 82% of patients were women, and mean disease duration was 11.6 ± 8.8 years. Table 1 lists the main patient characteristics. Mean follow-up was 5.4 ± 1.8 years. Nine patients either declined to

Discussion

In this historical cohort of patients admitted in France for RA, annual risks over a mean follow-up of 5.4 ± 1.8 years were 0.8%, 0.2%, and 1.3% for myocardial infarction, stroke, and major cardiovascular events, respectively. In addition, nearly 40% of deaths were related to cardiovascular disease, in keeping with earlier data [3], [4], [5], [6], [7], [8]. We are not aware of previous studies of the risk of cardiovascular events in RA patients having a low overall risk of cardiovascular disease.

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Prevalence of ischemic heart disease and associated factors in patients with rheumatoid arthritis in Southern Brazil
2017, Revista Brasileira de Reumatologia
Estimar a prevalência da doença isquêmica cardíaca e os fatores associados em pacientes com artrite reumatoide.
Estudo transversal que usou o critério diagnóstico do Colégio Americano de Reumatologia para selecionar pacientes atendidos nas unidades de saúde da atenção primária ou secundária em Blumenau, Santa Catarina, sul do Brasil, em 2014. A presença de doença cardíaca isquêmica foi definida com infarto agudo do miocárdio com intervenção coronariana percutânea ou cirurgia de revascularização do miocárdio que tenha ocorrido depois do diagnóstico. Para testar as associações usou‐se o teste exato de Fischer, o teste de tendência linear de Wald e a análise de regressão logística multivariada.
Entre 296 pacientes, 83,1% de mulheres, com média de 56,6 anos, tempo médio de artrite reumatoide de 11,3 anos, 13 relatam ter tido infarto agudo do miocárdio que necessitou de procedimento de reperfusão percutânea ou cirúrgica, prevalência de 4,4% (IC 95% 2,0‐6,7). O diabetes melittus (razão de chance de 4,9 [IC 95% 1,6‐13,8]) e o tempo de doença maior do que 10 anos (razão de chance de 8,2 [IC 95% 1,8‐39,7]) foram os únicos fatores associados com a doença isquêmica que permaneceram no modelo final após análise multivariada.
A prevalência de infarto agudo do miocárdio foi semelhante com a observada em outros estudos. Entre os fatores de risco tradicionais e entre os fatores relacionados à artrite reumatoide, o diabetes melittus e o tempo de doença foram as variáveis associadas à comorbidade
To estimate the prevalence of ischemic heart disease and associated factors in patients with rheumatoid arthritis.
A cross‐sectional study using the American College of Rheumatology diagnostic criteria in order to select patients seen at primary or secondary health care units in Blumenau, Santa Catarina, Southern Brazil, in 2014. The presence of ischemic heart disease was defined as an acute myocardial infarction with percutaneous coronary intervention or coronary artery bypass graft surgery that has occurred after diagnosis. Fischer's exact test, Wald's linear trend test, and multivariate logistic regression analysis were used to test the associations.
Among 296 patients (83.1% female) with a mean age of 56.6 years and a mean rheumatoid arthritis duration of 11.3 years, 13 reported having acute myocardial infarction requiring a percutaneous or surgical reperfusion procedure, a prevalence of 4.4% (95% CI 2.0‐6.7). Diabetes Mellitus (odds ratio [OR] 4.9 (95% CI 1.6‐13.8) and disease duration >10 years (OR 8.2 [95% CI 1.8‐39.7]) were the only factors associated with an ischemic disease that remained in the final model, after the multivariate analysis.
The prevalence of acute myocardial infarction was similar to that observed in other studies. Among the traditional risk factors, Diabetes Mellitus, and among the factors related to rheumatoid arthritis, disease duration, were the variables associated with comorbidity.
Lipid profile in adult patients with idiopathic juvenile arthritis
2013, Revista Brasileira de Reumatologia
O processo inflamatório articular de uma criança com artrite idiopática juvenil (AIJ) pode persistir na vida adulta. A inflamação tem sido ligada a distorções do perfil lipídico e à aterogênese acelerada. Neste trabalho, estudou-se o perfil lipídico de indivíduos adultos com AIJ, comparando-o ao de pessoas saudáveis. Foram recrutados 54 adultos com AIJ (57,3% poliarticular, 37% oligoarticular, 1,9% do subtipo entesítica e 3,7% do subtipo sistêmica) e 54 indivíduos saudáveis para comparação de perfil lipídico. Nos adultos AIJ, coletaram-se dados sobre sexo, idade e idade de início da doença, presença de fator reumatoide (FR) e fator antinuclear (FAN), HAQ (Health Assessment Questionnaire) e tempo de doença. Observou-se que hipercolesterolemia, aumento de LDL e diminuição de HDL foram mais comuns em pacientes com AIJ do que nos controles (com P = 0,016; P < 0,0001 e P = 0,0008, respectivamente). Alterações no colesterol total (CT) e no LDL foram mais comuns em indivíduos com início de doença mais tardio (P = 0,0017 para CT e P = 0,023 para LDL). Em todo o grupo de pacientes com AIJ nenhuma outra variável pode ser ligada à dislipidemia tal como presença de FR, FAN, duração de doença e HAQ (P = ns). Concluiu-se que pacientes adultos com AIJ apresentam um perfil lipídico com aumento de CT e de LDL, e diminuição de HDL em relação aos controles. Nenhuma característica clínica pode ser ligada a essa alteração, exceto idade de início da doença.
The inflammatory processes in the joints of a child with juvenile idiopathic arthritis (JIA) can persist into adulthood. Inflammation has been linked to distortions of the lipid profile and accelerated atherogenesis. In the present study, we examined the lipid profiles of adults with JIA compared with those of healthy people. A lipid profile of a sample of 54 adults with JIA (57.3% with polyarticular JIA, 37.0% with oligoarticular JIA, 1.9% with enthesitis-related JIA and 3.7% with systemic onset JIA) and 54 healthy subjects were compared. In the adults with JIA, data on gender, age, age at disease onset, the presence of rheumatoid factor (RF) and antinuclear antibodies (ANA), a Health Assessment Questionnaire (HAQ) and the disease duration were collected. We found that hypercholesterolaemia, increased low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) were more common in patients with JIA than the controls (P = 0.016, P < 0.0001 and P = 0.0008, respectively). Changes in the levels of total cholesterol (TC) and LDL were more common in the individuals who had a later onset of disease (P = 0.0017 for TC and P = 0.023 for LDL). In the entire JIA group, no other variable, such as RF, ANA, disease duration or responses to the HAQ, could be linked to dyslipidaemia (P = non-significant). We concluded that the adult patients with JIA have a lipid profile with increased TC and LDL levels and decreased levels of HDL compared to the controls. No clinical feature could be correlated with this change except for the age at disease onset.
Cardiovascular Risk in Rheumatic Disease
2012, Kelley's Textbook of Rheumatology: Volume 1-2, Ninth Edition
High risk of clinical cardiovascular events in rheumatoid arthritis: Levels of associations of myocardial infarction and stroke through a systematic review and meta-analysis
2010, Archives of Cardiovascular Diseases
While there are convergent data suggesting that overall cardiovascular mortality is increased in patients with rheumatoid arthritis, the relative contributions of myocardial infarction and stroke remain unclear.
We sought to clarify this issue by conducting a meta-analysis of cohort studies on myocardial infarction and stroke in patients with rheumatoid arthritis.
A MEDLINE search from January 1960 to September 2009 and abstracts from international conferences from 2007 to 2009 were searched for relevant literature. All cohort studies reporting on standardized mortality ratio or incidence rate ratio of myocardial or stroke associated with rheumatoid arthritis, with available crude numbers, were included. STATA meta-analysis software was used to calculate pooled risk estimates.
Seventeen papers fulfilled the inclusion criteria, corresponding to a total of 124,894 patients. Ten studies reported on standardized mortality ratio for fatal myocardial infarction, which ranged from 0.99 to 3.82. The overall pooled estimate was 1.77 (95% confidence interval [CI] 1.65–1.89). Incidence rate ratio for myocardial infarction was reported in five studies; the pooled estimate was 2.10 (95% CI 1.52–2.89). Nine studies reported on fatal stroke, with standardized mortality ratio ranging from 1.08 to 2.00; the pooled estimate was 1.46 (95% CI 1.31–1.63). The pooled incidence rate ratio for stroke (three studies) was 1.91 (95% CI 1.73–2.12).
Our results show that risks of myocardial infarction and stroke are increased in patients with rheumatoid arthritis. In addition, both account for the observed increased mortality in individuals with rheumatoid arthritis.
La mortalité cardiaque globale est augmentée au cours de la polyarthrite rhumatoïde, mais le niveau de risque de survenue d’un infarctus du myocarde et d’un accident vasculaire cérébral demeurent incertains.
Préciser ce niveau de risque à l’aide d’une méta-analyse.
La recherche a été effectuée sur Medline, de janvier 1960 à septembre 2009 et à partir des abstracts des conférences internationales de 2007 à 2009. Les études de cohorte rapportant les risques de mortalité (SMR) et les taux d’incidence (IRR) d’infarctus du myocarde ou d’accident vasculaire cérébral au cours de la polyarthrite rhumatoïde ont été inclues.
Dix-sept articles et/ou abstracts ont été retenus, ce qui correspond à une population totale de 124 894 patients. Dix études rapportent le SMR pour l’infarctus du myocarde fatal; il varie entre 0,99 et 3,82 selon les études. Le SMR global calculé est de 1,77 (IC 95 % : 1,65–1,89). Le risque de survenue d’infarctus du myocarde total a été rapporté dans cinq études ; le risque global calculé est de 2,10 (IC 95 % : 1,52–2,89). Neuf études ont rapporté le risque d’accident vasculaire cérébral fatal avec des SMR compris entre 1,08 et 2,00 ; le SMR global est de 1,46 (IC 95 % : 1,31–1,63). Le risque d’accident vasculaire cérébral total est de 1,91 (IC 95 % : 1,73–2,12).
Nos résultats montrent qu’il existe un sur-risque d’infarctus du myocarde et d’accident vasculaire cérébral au cours de la polyarthrite rhumatoïde ; tous deux contribuent à la surmortalité observée au cours de la polyarthrite rhumatoïde.
The importance of systematic electrocardiogram in the screening of heart attack during spondyloarthropathy and rheumatoid arthritis
2010, Revue du Rhumatisme (Edition Francaise)
L’objectif était d’évaluer l’intérêt de l’électrocardiogramme (ECG) systématique, comme outil de détection des anomalies cardiaques au cours des spondylarthropathies (SPA) et de la polyarthrite rhumatoïde (PR).
Des malades consécutifs atteints de SPA, PR ou maladies articulaires dégénératives (considérés comme témoins) hospitalisés sur une période de six mois et indemnes d’évènement cardiovasculaire ont été inclus. Un ECG – 12 dérivations – était réalisé et interprété par un cardiologue en insu du diagnostic.
Au total, 108 patients avec SPA (durée moyenne 11 ± dix ans), 106 malades avec PR (durée moyenne 12 ± neuf ans) et 74 témoins ont été inclus. Ceux-ci étaient asymptomatiques sur le plan cardiaque et sans antécédent cardiovasculaire. Les populations étaient homogènes, concernant la présence des facteurs de risque cardiovasculaire, hormis pour le diabète, plus fréquent dans les groupes PR et témoin. Les proportions d’extrasystoles, de blocs auriculoventriculaires (2,8 % dans le groupe SPA ; 1,9 % dans le groupe PR ; 2,7 % chez les témoins), de bloc de branche gauche complet ou incomplet (respectivement : 0,9 % ; 0,9 % ; 2,7 %), de bloc de branche droit complet ou de bloc de branche gauche (respectivement : 0,9 % ; 4,7 % ; 4,1 %) et d’anomalie évocatrice d’ischémie myocardique (10,2 % ; 19,8 % ; 17,6 %) étaient similaires chez les patients atteints de PR ou de SPA par comparaison à la population témoin.
Chez les patients sans antécédent cardiovasculaire, asymptomatiques, la réalisation d’un ECG systématique ne permet pas de mettre en évidence le risque accru de complications cardiaques spécifiques liées à ces pathologies, chez les patients atteints de SPA et PR.
Usefulness of routine electrocardiography for heart disease screening in patients with spondyloarthropathy or rheumatoid arthritis
2010, Joint Bone Spine
To assess the usefulness of routine electrocardiography for heart disease screening in patients with spondyloarthropathy (SpA) or rheumatoid arthritis (RA).
We included consecutive patients with SpA or RA or with degenerative joint disease (control group) admitted over a 6-month period and free of cardiovascular events. A 12-lead electrocardiogram (ECG) was obtained and was interpreted by a cardiologist who was unaware of the diagnosis.
We included 108 patients with SpA (mean duration, 11 ± 10 years), 106 with RA (mean duration, 12 ± 9 years), and 74 with degenerative joint disease (controls). No patient had cardiovascular symptoms or a prior history of cardiovascular disease. The only difference in cardiovascular risk factors across the three populations was a higher prevalence of diabetes in the RA and control groups. We found no differences between the SpA or RA groups and the control group regarding the rates of the following ECG findings: premature beats, atrioventricular block (2.8% in the SpA group, 1.9% in the RA group, and 2.7% in the control group), complete or incomplete left bundle branch block (0.9%, 0.9%, and 2.7%, respectively), complete right bundle branch bloc or left bundle branch block (0.9%, 4.7%, and 4.1%, respectively); and abnormalities suggesting myocardial ischemia (10.2%, 19.8%, and 17.6%, respectively).
In patients with SpA or RA who have no cardiovascular symptoms or history of cardiovascular disease, a routine ECG shows no increase in the cardiac abnormalities specifically associated with these joint diseases, compared to controls with degenerative joint disease.

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Original articleCardiovascular disease in rheumatoid arthritis: Single-center hospital-based cohort study in France

Abstract

Introduction

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Statistics

Results

Discussion

Am J Cardiol

Mayo Clin Proc

Lancet

Prevalence of rheumatoid arthritis and spondyloarthropathy in Brittany, France. Société de Rhumatologie de l'Ouest

J Rheumatol

Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden

J Rheumatol

All-cause mortality and vascular events among patients with rheumatoid arthritis, osteoarthritis, or no arthritis in the UK General Practice Research Database

J Rheumatol

Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis

Circulation

Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years

Arthritis Rheum

Cardiovascular death in rheumatoid arthritis

Arthritis Rheum

Cardiovascular mortality in women with rheumatoid arthritis

J Rheumatol

Association of mortality with disease severity in rheumatoid arthritis, independent of comorbidity

Arthritis Rheum

Predicting mortality in patients with rheumatoid arthritis

Arthritis Rheum

Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis

J Rheumatol

High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors

Arthritis Rheum

Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis

Arthritis Rheum

Increased incidence of cardiovascular disease in patients with rheumatoid arthritis: results from a community based study

Ann Rheum Dis

Decreasing mortality in patients with rheumatoid arthritis: results from a large population based cohort in Sweden, 1964–95

J Rheumatol

Cardiovascular risks in women with and without rheumatoid arthritis

Arthritis rheum

Traditional and nontraditional cardiovascular risks factors are associated with atherosclerosis in rheumatoid arthritis

J Rheumatol

Original article
Cardiovascular disease in rheumatoid arthritis: Single-center hospital-based cohort study in France