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

OBJECTIVE To compare the incidence of cardiovascular (CV) events in persons with rheumatoid arthritis (RA) with that in people from the general population, adjusting for traditional CV risk factors. METHODS Two hundred thirty-six consecutive patients with RA were assessed for the 1-year occurrence of 1) CV-related hospitalizations, including myocardial infarction, stroke or other arterial occlusive events, or arterial revascularization procedures, or 2) CV deaths. Both outcomes were ascertained by medical records or death certificates. For comparison, we used CV events that occurred during an 8-year period among participants in an epidemiologic study of atherosclerosis and CV disease who were ages 25-65 years at study entry. We calculated the age- and sex-stratified incidence rate ratio (IRR) of CV events between the 2 cohorts and used Poisson regression to adjust for age, sex, smoking status, diabetes mellitus, hypercholesterolemia, systolic blood pressure, and body mass index. RESULTS Of the 236 RA patients, 234 were observed for 252 patient-years, during which 15 CV events occurred. Of these, 7 incident events occurred during the 204 patient-years contributed by patients ages 25-65 years, for an incidence of 3.43 per 100 patient-years. In the comparison cohort, 4,635 community-dwelling persons were followed up for 33,881 person-years, during which 200 new events occurred, for an incidence of 0.59 per 100 person-years. The age- and sex-adjusted IRR of incident CV events associated with RA was 3.96 (95% confidence interval [95% CI] 1.86-8.43). After adjusting for CV risk factors using Poisson regression, the IRR decreased slightly, to 3.17 (95% CI 1.33-6.36). CONCLUSION The increased incidence of CV events in RA patients is independent of traditional CV risk factors. This suggests that additional mechanisms are responsible for CV disease in RA. Physicians who provide care to individuals with RA should be aware of their increased risk of CV events and implement appropriate diagnostic and therapeutic measures.

[1]  U. Ikeda Inflammation and coronary artery disease. , 2003, Current vascular pharmacology.

[2]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[3]  C. Mulrow,et al.  Symptoms of depression and psychological distress among Hispanics with rheumatoid arthritis. , 2000, Arthritis care and research : the official journal of the Arthritis Health Professions Association.

[4]  M. Wasko,et al.  Inflammation-mediated rheumatic diseases and atherosclerosis. , 2000, Annals of the rheumatic diseases.

[5]  S. Jacobsen [Use of glucocorticoids in rheumatoid arthritis]. , 2000, Ugeskrift for laeger.

[6]  R. Frye,et al.  Perturbation of the T-cell repertoire in patients with unstable angina. , 1999, Circulation.

[7]  C. Suh,et al.  Lipid profiles in untreated patients with rheumatoid arthritis. , 1999, The Journal of rheumatology.

[8]  A. Escalante,et al.  How much disability in rheumatoid arthritis is explained by rheumatoid arthritis? , 1999, Arthritis and rheumatism.

[9]  S. Haffner,et al.  Rapid rise in the incidence of type 2 diabetes from 1987 to 1996: results from the San Antonio Heart Study. , 1999, Archives of internal medicine.

[10]  A. Escalante,et al.  HLA-DRB1 alleles associated with susceptibility or resistance to rheumatoid arthritis, articular deformities, and disability in Mexican Americans. , 1999, Arthritis and rheumatism.

[11]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[12]  H. Aoshima,et al.  Serum lipoprotein(a) and apolipoprotein(a) phenotypes in patients with rheumatoid arthritis. , 1999, Arthritis and rheumatism.

[13]  A. Döring,et al.  C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. , 1999, Circulation.

[14]  W. Koenig,et al.  C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[15]  J. Loscalzo,et al.  Homocysteine and atherothrombosis. , 1998, The New England journal of medicine.

[16]  A. Escalante What do self-administered joint counts tell us about patients with rheumatoid arthritis? , 1998, Arthritis care and research : the official journal of the Arthritis Health Professions Association.

[17]  G. Alarcón,et al.  Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. , 1998, The Journal of rheumatology.

[18]  J. A. Calvin Regression Models for Categorical and Limited Dependent Variables , 1998 .

[19]  J L Witztum,et al.  Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. , 1997, The Journal of clinical investigation.

[20]  A. Silman,et al.  Blood transfusion, smoking, and obesity as risk factors for the development of rheumatoid arthritis: results from a primary care-based incident case-control study in Norfolk, England. , 1997, Arthritis and rheumatism.

[21]  J. Danesh,et al.  Chronic infections and coronary heart disease: is there a link? , 1997, The Lancet.

[22]  L H Kuller,et al.  Relationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the Cardiovascular Health Study and the Rural Health Promotion Project. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[23]  P. Ridker,et al.  Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. , 1997, The New England journal of medicine.

[24]  E. Bramucci,et al.  Tissue-factor antigen and activity in human coronary atherosclerotic plaques , 1997, The Lancet.

[25]  S. R. Dahlqvist,et al.  Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden. , 1997, The Journal of rheumatology.

[26]  R. D'Agostino,et al.  Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. , 1997, American journal of epidemiology.

[27]  S. Thompson,et al.  Production of C-reactive protein and risk of coronary events in stable and unstable angina , 1997, The Lancet.

[28]  S. Haffner,et al.  Effects of cigarette smoking, diabetes, high cholesterol, and hypertension on all-cause mortality and cardiovascular disease mortality in Mexican Americans. The San Antonio Heart Study. , 1996, American journal of epidemiology.

[29]  L. Kuller,et al.  Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple Risk Factor Intervention Trial. , 1996, American journal of epidemiology.

[30]  E. Vartiainen,et al.  Symptoms of chronic bronchitis and the risk of coronary disease , 1996, The Lancet.

[31]  A. Silman,et al.  Cigarette smoking increases the risk of rheumatoid arthritis. Results from a nationwide study of disease-discordant twins. , 1996, Arthritis and rheumatism.

[32]  I. Sartori Hemostatic Factors and the Risk of Myocardial Infarction or Sudden Death in Patients with Angina Pectoris , 1996 .

[33]  K. Aho,et al.  Mortality in rheumatoid arthritis. , 1995, Seminars in arthritis and rheumatism.

[34]  H. Kautiainen,et al.  Cardiovascular mortality in women with rheumatoid arthritis. , 1995, The Journal of rheumatology.

[35]  H. Kautiainen,et al.  Shortening of life span and causes of excess mortality in a population-based series of subjects with rheumatoid arthritis. , 1995, Clinical and experimental rheumatology.

[36]  T. Koepsell,et al.  Smoking, Obesity, Alcohol Consumption, and the Risk of Rheumatoid Arthritis , 1994, Epidemiology.

[37]  Alexander Rw Inflammation and Coronary Artery Disease , 1994 .

[38]  A. Rebuzzi,et al.  The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. , 1994, The New England journal of medicine.

[39]  M. Tikly,et al.  Interleukin 1 beta, hand and foot bone mineral content and the development of joint erosions in rheumatoid arthritis. , 1994, Annals of the rheumatic diseases.

[40]  T. Pincus,et al.  Prediction of Long-Term Mortality in Patients with Rheumatoid Arthritis according to Simple Questionnaire and Joint Count Measures , 1994, Annals of Internal Medicine.

[41]  S. Pillemer,et al.  Rheumatoid arthritis and mortality. A longitudinal study in Pima Indians. , 1993, Arthritis and rheumatism.

[42]  A. Silman,et al.  Factors predicting death, survival and functional outcome in a prospective study of early rheumatoid disease over fifteen years. , 1993, British journal of rheumatology.

[43]  R. Ross The pathogenesis of atherosclerosis: a perspective for the 1990s , 1993, Nature.

[44]  E. Thonar,et al.  Levels of circulating tumor necrosis factor alpha and interleukin-6 in patients with rheumatoid arthritis. Relationship to serum levels of hyaluronan and antigenic keratan sulfate. , 1993, Arthritis and rheumatism.

[45]  Harry,et al.  C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. , 1993, Blood.

[46]  R. Roubenoff,et al.  Rheumatoid cachexia: depletion of lean body mass in rheumatoid arthritis. Possible association with tumor necrosis factor. , 1992, The Journal of rheumatology.

[47]  J. Ilonen,et al.  No association between rheumatoid arthritis and insulin dependent diabetes mellitus: an epidemiologic and immunogenetic study. , 1992, The Journal of rheumatology.

[48]  S. Rantapää-Dahlqvist,et al.  Lipoprotein (a), lipids, and lipoproteins in patients with rheumatoid arthritis. , 1991, Annals of the rheumatic diseases.

[49]  S. Haffner,et al.  Myocardial infarction in Mexican-Americans and non-Hispanic whites. The San Antonio Heart Study. , 1991, Circulation.

[50]  J P Vandenbroucke,et al.  Lifestyle and the risk of rheumatoid arthritis: cigarette smoking and alcohol consumption. , 1990, Annals of the rheumatic diseases.

[51]  Vittorio,et al.  Tumour necrosis factor in serum and synovial fluid of patients with active and severe rheumatoid arthritis. , 1990, Annals of the rheumatic diseases.

[52]  F. Arnett Revised criteria for the classification of rheumatoid arthritis. , 1990, Orthopedic nursing.

[53]  W. Weintraub,et al.  Elevation of C-reactive protein in "active" coronary artery disease. , 1990, The American journal of cardiology.

[54]  M. Laakso,et al.  Cardiovascular mortality in patients with rheumatoid arthritis. , 1989, Cardiology.

[55]  D. Heinegård,et al.  Detection of tumor necrosis factor alpha but not tumor necrosis factor beta in rheumatoid arthritis synovial fluid and serum. , 1988, Arthritis and rheumatism.

[56]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[57]  D. Symmons Mortality in rheumatoid arthritis. , 1988, British journal of rheumatology.

[58]  H. Lithell,et al.  Serum lipoprotein in active rheumatoid arthritis and other chronic inflammatory arthritides. II. Effects of anti-inflammatory and disease-modifying drug treatment. , 1987, Archives of internal medicine.

[59]  H. Lithell,et al.  Serum lipoprotein in active rheumatoid arthritis and other chronic inflammatory arthritides. I. Relativity to inflammatory activity. , 1987, Archives of internal medicine.

[60]  T. Pincus,et al.  Taking mortality in rheumatoid arthritis seriously--predictive markers, socioeconomic status and comorbidity. , 1986, The Journal of rheumatology.

[61]  J. Fries,et al.  Survival, prognosis, and causes of death in rheumatoid arthritis. , 1986, Arthritis and rheumatism.

[62]  T. Pincus,et al.  Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. , 1984, Arthritis and rheumatism.

[63]  A. Cats,et al.  Survival and cause of death in rheumatoid arthritis: a 25-year prospective followup. , 1984, The Journal of rheumatology.

[64]  D. Spodick,et al.  Association of acute respiratory symptoms with onset of acute myocardial infarction: prospective investigation of 150 consecutive patients and matched control patients. , 1984, The American journal of cardiology.

[65]  J. Relethford,et al.  Prevalence of Diabetes in Mexican Americans: Relationship to Percent of Gene Pool Derived from Native American Sources , 1984, Diabetes.

[66]  C. Werning [Rheumatoid arthritis]. , 1983, Medizinische Monatsschrift fur Pharmazeuten.

[67]  J. Pugh,et al.  Knowledge, attitudes, and behavior related to obesity and dieting in Mexican Americans and Anglos: the San Antonio Heart Study. , 1982, American journal of epidemiology.

[68]  P. Allebeck Increased Mortality in Rheumatoid Arthritis: The Use of a Medical Information System for Assessment of Death Risks , 1982 .

[69]  P. Allebeck Increased mortality in rheumatoid arthritis. , 1982, Scandinavian Journal of Rheumatology.

[70]  R. Hanka,et al.  Cause of death in patients with rheumatoid arthritis with particular reference to azathioprine. , 1980, Annals of the rheumatic diseases.

[71]  R. Monson,et al.  Mortality among arthritics. , 1976, Journal of chronic diseases.

[72]  F. Eulderink [Cause of death: rheumatoid arthritis]. , 1976, Nederlandsch tijdschrift voor geneeskunde.

[73]  H. Mcdevitt,et al.  Adrenocortical steroid treatment of rheumatic diseases. Effects on lipid metabolism. , 1973, Archives of internal medicine.

[74]  W. Haenszel,et al.  Statistical aspects of the analysis of data from retrospective studies of disease. , 1959, Journal of the National Cancer Institute.