Cardiovascular co-morbidity in rheumatic diseases

Figures & data

Figure 1 Cardiovascular morbidity in a community-based RA sample, compared with the general population. Standardized morbidity ratios; 95% confidence intervals. Based on data from Turesson et al 2004.

Abbreviations: AMI, acute myocardial infarction; RA, rheumatoid arthritis.

Table 1 Shared disease mechanisms in rheumatic diseases and CVD

Mechanism	Pathway in vascular disease	References
Cytokine-induced macrophage migration and activation	Ox-LDL scavenging and formation of vulnerable atherosclerotic plaque	Ross 1999Hansson 2005Dixon and Symmons 2007
Cytokine-induced upregulation of procoagulant factors	Increased systemic thrombodiatesis	McEntegart et al 2001; Sattar et al 2003
Systemic endothelial activation with upregulation of MHC class II molecules	Endothelial dysfunction Increased T-cell migration and activation	Vallbracht et al 2002; Turesson 2004
Clonal expansion and activation of abnormal T-cells	Cytotoxicity leading to plaque damage Local cytokine upregulation	Park et al 1997Liuzzo et al 1999Michel et al 2007
Anti-phospholipid antibodies	Increased arterial and venous thrombodiatesis	Toloza et al 2004

Abbreviations: CVD, cardiovascular disease; LDL, low density lipoprotein; MHC, major hisocompatibility complex

Table 2 Risk factors for cardiovascular disease in patients with rheumatoid arthritis

Risk factor	Predicted outcome	References
Severe extraarticular manifestations	Total mortality and CVD mortality First-ever CVD events New onset PAD or venous thromboembolic events	Gabriel et al 2003Maradit-Kremers et al 2005; Turesson et al 2007; Liang et al 2006
Disability (HAQ score)	Total mortality and CVD mortality First-ever CVD events	Wolfe et al 2003Young et al 2007Jacobsson et al 2005
ESR (≥60 mm/h at least 3 times)	Death from CVD	Maradit-Kremers et al 2005;
	CVD events	Wållberg-Jonsson et al 1999;
Last ESR	Death from CVD	Goodson et al 2005;
CRP	Death from CVD	Maradit-Kremers et al 2005;
Smoking	New onset PAD	Liang et al 2006
Hypertension	Death from CVD	Wållberg-Jonsson et al 1999; Maradit-Kremers et al 2005
Low BMI	Death from CVD	Kremers et al 2004Escalante et al 2005

Abbreviations: CVD, cardiovascular disease; HAQ, health assessment questionnaire; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; BMI, body mass index; PAD, peripheral arterial disease

Table 3 Strategies for prevention of CVD in patients with rheumatic diseases

Preventive strategy	Suggested interventions	References
Achieve target levels for traditional risk factors including blood pressure, glucose, and lipids	Regular screening, counselling and pharmacotherapy according to guidelines	Wajed et al 2004van Doornum et al 2006
Reduce traditional risk factors in high risk individuals	Interventions based on decision algorithms, guided by risk scores	Wilson et al 1998 Yusuf et al 2003
Increase physical exercise	Patient education, physiotherapy and structured rehabilitation	Wikström et al 2005; Turesson et al 2007b
Preventive statin treatment	Statins for patients with severe RA, despite moderate cholesterol levels	McCarey et al 2004; van Doornum et al 2004
Reduce inflammatory burden in patients with RA	Use methotrexate as drug of choice in RA Add TNF inhibitor in refractory patients	Choi et al 2002Jacobsson et al 2005

Abbreviations: CVD, cardiovascular disease; RA, rheumatoid arthritis;TNF, tumor necrosis factor

TuressonCEndothelial expression of MHC class II molecules in autoimmune diseaseCurr Pharm Des2004101294314754393

 PubMed Web of Science ®Google Scholar

RossRAtherosclerosis – an inflammatory diseaseN Engl J Med1999340115269887164

 PubMed Web of Science ®Google Scholar

HanssonGKInflammation, atherosclerosis, and coronary artery diseaseN Engl J Med200535216859515843671

 PubMed Web of Science ®Google Scholar

DixonWGSymmonsDPMWhat effects might anti-TNF[alpha] therapy be expected to have on cardiovascular morbidity and mortality in rheumatoid arthritis? A review of the role of TNF[alpha] in cardiovascular pathophysiologyAnn Rheum Dis20076611323617251223

 PubMed Web of Science ®Google Scholar

McEntegartACapellHACreranDCardiovascular risk factors, including thrombotic variables, in a population with rheumatoid arthritisRheumatology (Oxford)200140640411426020

 PubMed Web of Science ®Google Scholar

SattarNMcCareyDWCapellHExplaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritisCirculation200310829576314676136

 PubMed Web of Science ®Google Scholar

VallbrachtKBSchwimmbeckPLSeebergBEndothelial dysfunction of peripheral arteries in patients with immunohistologically confirmed myocardial inflammation correlates with endothelial expression of human leukocyte antigens and adhesion molecules in myocardial biopsiesJ Am Coll Cardiol2002405152012142120

 PubMed Web of Science ®Google Scholar

ParkWWeyandCMSchmidtDCo-stimulatory pathways controlling activation and peripheral tolerance of human CD4+CD28- T cellsEur J Immunol1997271082909174596

 PubMed Web of Science ®Google Scholar

LiuzzoGKopeckySLFryeRLPerturbation of the T-cell repertoire in patients with unstable anginaCirculation19991002135910571971

 PubMed Web of Science ®Google Scholar

MichelJJTuressonCLemsterBCD56-expressing T cells that have senescent features are expanded in rheumatoid arthritisArthritis Rheum200756435717195207

 PubMedGoogle Scholar

TolozaSMUribeAGMcGwinGJrSystemic lupus erythematosus in a multiethnic US cohort (LUMINA). XXIII. Baseline predictors of vascular eventsArthritis Rheum20045039475715593203

 PubMed Web of Science ®Google Scholar

GabrielSECrowsonCSKremersHMSurvival in rheumatoid arthritis: a population- based analysis of trends over 40 yearsArthritis Rheum20034854812528103

 PubMed Web of Science ®Google Scholar

Maradit-KremersHMNicolaPJCrowsonCSCardiovascular death in rheumatoid arthritis: a population-based studyArthritis Rheum2005527223215751097

 PubMed Web of Science ®Google Scholar

TuressonCMcClellandRLChristiansonTJSevere extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritisAnn Rheum Dis200766596416901955

 PubMed Web of Science ®Google Scholar

LiangKPLiangKVMattesonELIncidence of noncardiac vascular disease in rheumatoid arthritis and relationship to extra-articular disease manifestationsArthritis Rheum200654642816447212

 PubMed Web of Science ®Google Scholar

WolfeFMichaudKGefellerOPredicting mortality in patients with rheumatoid arthritisArthritis Rheum20034815304212794820

 PubMed Web of Science ®Google Scholar

YoungAKoduriGBatleyMMortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosisRheumatology (Oxford)2007463505916908509

 PubMed Web of Science ®Google Scholar

JacobssonLTTuressonCGülfeALow incidence of first cardiovascular event in rheumatoid arthritis patients treated with TNF-blockersJ Rheumatol20053212131815996054

 PubMed Web of Science ®Google Scholar

Wållberg-JonssonSJohanssonHÖhmanM-LExtent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis. A retrospective cohort study from disease onsetJ Rheumatol19992625627110606363

 PubMed Web of Science ®Google Scholar

GoodsonNJSymmonsDPMScottDGBaseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohortArthritis Rheum2005522293916052597

 PubMed Web of Science ®Google Scholar

KremersHMNicolaPJCrowsonCSPrognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritisArthritis Rheum2004503450715529378

 PubMed Web of Science ®Google Scholar

EscalanteAHaasRWdel RinconIParadoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammationArch Intern Med20051651624916043681

 PubMedGoogle Scholar

WajedDAhmadYDurringtonPNPrevention of cardiovascular disease in systemic lupus erythematosus. Proposed guidelines for risk factor managementRheumatology (Oxford)20044371212867578

 PubMed Web of Science ®Google Scholar

van DoornumSJenningsGLRWicksIPReducing the cardiovascular disease burden in rheumatoid arthritisMed J Aust20061842879016548834

 PubMed Web of Science ®Google Scholar

WilsonPWD’AgostinoRBLevyDPrediction of coronary heart disease using risk factor categoriesCirculation1998971837479603539

 PubMed Web of Science ®Google Scholar

WikströmIJacobssonLTChange in and predictors of leisure activities among patients with rheumatoid arthritis: a prospective studyScand J Rheumatol2005343677116296568

 PubMed Web of Science ®Google Scholar

TuressonCMattesonELCardiovascular risk factors, fitness and physical activity in rheumatic diseasesCurr Opin Rheumatol200719190617278937

 PubMed Web of Science ®Google Scholar

McCareyDWMcInnesIBMadhokRTrial of atorvastatin in rheumatoid arthritis (TARA): double blind, placebo-controlled trialLancet200436320152115207950

 PubMed Web of Science ®Google Scholar

van DoornumSMcCollGWicksIPAtorvastatin reduces arterial stiffness in patients with rheumatoid arthritisAnn Rheum Dis20046315717515547080

 PubMed Web of Science ®Google Scholar

ChoiHKHernanMASeegerJDMethotrexate and mortality in patients with rheumatoid arthritis: a prospective studyLancet20023591173711955534

 PubMed Web of Science ®Google Scholar