Rheumatoid Arthritis: Avalos I

Avalos I, Rho YH, Chung CP, Stein CM. · Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Boston, MA, USA. · Clin Exp Rheumatol. · Pubmed #19026140 No free full text.

This publication has no abstract.

Chung CP, Avalos I, Raggi P, Stein CM. · Division of Rheumatology, Department of Medicine, Vanderbilt University, 1161 21st Avenue T-3219 MCN, Nashville, TN 37232, USA. · Clin Rheumatol. · Pubmed #17273810 No free full text.

Abstract: Cardiovascular disease is a major health care problem and the most common cause of death among individuals from developed nations. Our understanding of atherosclerosis has evolved from a passive process resulting in narrowing of the lumen and consequent myocardial ischemia to a dynamic process that involves inflammation. The study of atherosclerosis in patients with chronic inflammation, such as rheumatoid arthritis (RA), will provide insights into the relationship between inflammation and atherosclerosis. We review the relationship between atherosclerosis and inflammation within the context of RA, providing evidence that patients with RA have increased cardiovascular morbidity and mortality and accelerated coronary and extra-coronary atherosclerosis. In addition, traditional and novel cardiovascular risk factors are discussed. Finally, actions that a rheumatologist can take to better control this cardiovascular morbidity are suggested. These can be summarized as follows: (1) careful assessment and treatment of cardiovascular risk, (2) better control of inflammation, and (3) individual risk-benefit evaluation of need for cyclo-oxygenase-2 inhibitors, nonsteroidal anti-inflammatory drugs, and high doses of corticosteroids.

Chung CP, Oeser A, Avalos I, Gebretsadik T, Shintani A, Raggi P, Sokka T, Pincus T, Stein CM. · Department of Medicine, Vanderbilt University School of Medicine, 1161 21st Ave, Nashville, TN 37232, USA. · Arthritis Res Ther. · Pubmed #17169159 links to  free full text

Abstract: The prevalence of ischemic heart disease and atherosclerosis is increased in patients with rheumatoid arthritis (RA). In the general population, but not in patients with systemic lupus erythematosus, the Framingham risk score identifies patients at increased cardiovascular risk and helps determine the need for preventive interventions. We examined the hypothesis that the Framingham score is increased and associated with coronary-artery atherosclerosis in patients with RA. The Framingham score and the 10-year cardiovascular risk were compared among 155 patients with RA (89 with early disease, 66 with long-standing disease) and 85 control subjects. The presence of coronary-artery calcification was determined by electron-beam computed tomography. The Framingham score was compared in patients with RA and control subjects, and the association between the risk score and coronary-artery calcification was examined in patients. Patients with long-standing RA had a higher Framingham score (14 [11 to 18]) (median [interquartile range]) compared to patients with early RA (11 [8 to 14]) or control subjects (12 [7 to 14], P < 0.001). This remained significant after adjustment for age and gender (P = 0.015). Seventy-six patients with RA had coronary calcification; their Framingham risk score was higher (14 [12 to 17]) than that of 79 patients without calcification (10 [5 to 14]) (P < 0.001). Furthermore, a higher Framingham score was associated with a higher calcium score (odds ratio [OR] = 1.20, 95% confidence interval [CI] 1.12 to 1.29, P < 0.001), and the association remained significant after adjustment for age and gender (OR = 1.15, 95% CI 1.02 to 1.29, P = 0.03). In conclusion, a higher Framingham risk score is independently associated with the presence of coronary calcification in patients with RA.

Solus J, Chung CP, Oeser A, Avalos I, Gebretsadik T, Shintani A, Raggi P, Sokka T, Pincus T, Stein CM. · Vanderbilt University Medical Center, Nashville, Tennessee. · Arthritis Rheum. · Pubmed #18759301 No free full text.

Abstract: OBJECTIVE: Increased concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality, but little is known about their relationship to chronic inflammation. Patients with rheumatoid arthritis (RA) have chronic inflammation, increased arterial stiffness, and accelerated coronary atherosclerosis. This study was undertaken to test the hypothesis that NT-proBNP concentrations are elevated in patients with RA and are associated with coronary artery calcification and markers of inflammation. METHODS: In 159 patients with RA (90 with early RA and 69 with longstanding RA) without heart failure and 88 control subjects, serum concentrations of NT-proBNP, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFalpha) were measured and coronary calcification was assessed. Associations between NT-proBNP levels and the other parameters were investigated. RESULTS: NT-proBNP concentrations were elevated in patients with longstanding RA (median 142.8 pg/ml [interquartile range 54.8-270.5]) and those with early RA (median 58.1 pg/ml [interquartile range 19.4-157.6]) compared with controls (18.1 [3.2-46.0]) (P < 0.001). In patients with RA, NT-proBNP concentrations were associated with age (rho = 0.35, P < 0.001), levels of IL-6 (rho = 0.33, P < 0.001), TNFalpha (rho = 0.23, P = 0.003), and C-reactive protein (CRP) (rho = 0.21, P = 0.01), coronary calcium score (rho = 0.30, P < 0.001), systolic blood pressure (rho = 0.30, P < 0.001), and disease activity (rho = 0.29, P < 0.001). After adjustment for age, race, and sex, the associations between NT-proBNP concentrations and disease activity, TNFalpha, IL-6, and CRP remained significant, but those with systolic blood pressure and coronary calcium score were attenuated. CONCLUSION: NT-proBNP concentrations are increased in patients with RA without clinical heart failure and may indicate subclinical cardiovascular disease and a chronic inflammatory state.

Chung CP, Oeser A, Solus JF, Gebretsadik T, Shintani A, Avalos I, Sokka T, Raggi P, Pincus T, Stein CM. · Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA. · Arthritis Rheum. · Pubmed #18576352 links to  free full text

Abstract: OBJECTIVE: Insulin resistance is increased by inflammation, but the mechanisms are unclear. The present study was undertaken to test the hypothesis that decreased insulin sensitivity is differentially associated with mediators of inflammation by studying 2 chronic inflammatory diseases of different pathogenesis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: We measured fasting insulin, glucose, and lipid levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and coronary artery calcification in 103 patients with SLE and in 124 patients with RA. Insulin sensitivity was measured using the homeostasis model assessment (HOMA) index. RESULTS: The HOMA value was higher in RA patients (median 2.05 [interquartile range (IQR) 1.05-3.54]) than in SLE patients (1.40 [0.78-2.59]) (P = 0.007). CRP and ESR did not differ significantly in RA and SLE patients. Body mass index (BMI) was significantly correlated with the HOMA index in both RA (rho = 0.20) and SLE (rho = 0.54), independently of age, sex, race, and current use of corticosteroids. In RA patients, the HOMA index was also significantly positively correlated with IL-6 (rho = 0.63), TNFalpha (rho = 0.50), CRP (rho = 0.29), ESR (rho = 0.26), coronary calcification (rho = 0.26), and Disease Activity Score in 28 joints (rho = 0.21); associations adjusted for age, sex, race, BMI, and current use of corticosteroids remained significant (P < 0.05). In SLE patients, the HOMA index was also significantly correlated with ESR (rho = 0.35) and CRP (rho = 0.25), but not with other variables. The association between the ESR and the HOMA value in patients with SLE remained significant after adjustment for confounding covariates (P = 0.008). In multivariable models, the major contributing factors to the HOMA index were the BMI in SLE patients, and IL-6 and TNFalpha levels in RA patients. CONCLUSION: The pathogenesis of insulin resistance and its contribution to atherogenesis varies in different inflammatory settings.

Avalos I, Chung CP, Oeser A, Gebretsadik T, Shintani A, Kurnik D, Raggi P, Sokka T, Pincus T, Stein CM. · Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2681, USA. · J Rheumatol. · Pubmed #18050386 No free full text.

Abstract: OBJECTIVE: Arterial stiffness, assessed by the augmentation index and pulse wave velocity, is an independent risk factor for cardiovascular disease. Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular mortality. We examined the hypothesis that augmentation index and pulse wave velocity are increased in RA, and are related to coronary artery atherosclerosis. METHODS: We measured augmentation index and brachial pulse wave velocity in 117 patients with RA [57 with early (< 6 yrs) and 60 with late disease (> 10 yrs)] and 65 healthy controls. Coronary artery calcification was measured by electron beam computed tomography. Augmentation index and pulse wave velocity were compared in patients with early RA, late RA, and controls, and the association with coronary atherosclerosis was examined. RESULTS: Patients with late RA had a higher augmentation index (median 33.8%, interquartile range 27.5% 37.0%) than those with early disease (median 27.5%, IQR 21.0% 34.0%) (p = 0.008) and controls (median 27.0%, IQR 20.4% 33.0%) (p < 0.001). After adjusting for height and cardiovascular risk factors, the association between late disease and augmentation index remained significant (p = 0.02). Augmentation index was associated with coronary calcification score (rs = 0.19, p = 0.046), and the association was marginal after adjustment for cardiovascular risk factors, disease status, and disease activity (p = 0.09). There was no significant difference in brachial pulse wave velocity among patients with late (9.2 +/- 1.7 m/s) and early RA (9.1 +/- 1.6 m/s) and controls (8.9 +/- 1.5 m/s) (p = 0.78). CONCLUSION: Patients with RA have increased augmentation index independent of cardiovascular risk factors. Augmentation index was associated with coronary artery calcification in patients with RA; this was attenuated after adjusting for cardiovascular risk factors.

Asanuma Y, Chung CP, Oeser A, Solus JF, Avalos I, Gebretsadik T, Shintani A, Raggi P, Sokka T, Pincus T, Stein CM. · Saitama Medical University, Saitama, Japan. · Atherosclerosis. · Pubmed #17570371 links to  free full text

Abstract: Osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor kappaB ligand, is implicated in the pathogenesis of atherosclerosis. Patients with rheumatoid arthritis (RA) have inflammation and increased atherosclerosis. We examined the hypothesis that OPG concentrations are increased in patients with RA and are associated with coronary-artery atherosclerosis. Serum OPG concentrations were measured by ELISA and coronary-artery calcification by electron-beam computer tomography in 157 patients with RA and 87 control subjects. OPG concentrations were higher in patients with long-standing RA (n=67) [median (interquartile range)]: [1895 (1337-2847) pg/mL, and early RA (n=90): [1340 (1021-1652) pg/mL, than controls 1068 (692-1434) pg/mL; (p<0.001)]. In patients with RA, OPG concentrations were associated with erythrocyte sedimentation rate (p<0.001), homocysteine (p=0.001), disease duration (p=0.02), coronary calcium score (p=0.03), and cumulative dose of corticosteroids (p=0.04) after adjustment for age and sex. In patients with long-standing RA, OPG was associated with coronary-artery calcification independently of cardiovascular risk factors and disease activity [OR for every increase in 500 pg/mL of OPG=2.22 (1.43-3.34), p<0.001]. In conclusion, OPG concentrations are increased in patients with RA and are associated with inflammation. In patients with long-standing disease, OPG is independently associated with coronary-artery calcification.

Chung CP, Oeser A, Solus JF, Avalos I, Gebretsadik T, Shintani A, Raggi P, Sokka T, Pincus T, Stein CM. · Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA. · Atherosclerosis. · Pubmed #17266963 No free full text.

Abstract: Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis. The metabolic syndrome, a cluster of cardiovascular risk factors, identifies cardiovascular risk. We tested the hypotheses that patients with RA have a higher prevalence of the metabolic syndrome, particularly the WHO-defined syndrome that requires insulin resistance, and that this is associated with coronary atherosclerosis. The prevalence of the metabolic syndrome was determined using the modified WHO and NCEP III criteria in 154 patients with RA (88 with early RA and 66 with long-standing RA) and 85 control subjects. Coronary-artery atherosclerosis was detected by electron beam computed tomography. The WHO-defined metabolic syndrome was present in 42% of patients with long-standing RA, 31% with early RA and 11% of controls (P<0.001); the NCEP-defined metabolic syndrome was present in 42% of patients with long-standing RA, 30% with early RA and 22% of controls (P=0.03). Patients with the WHO-defined metabolic syndrome had an increased risk of having higher coronary-artery calcification scores, independent of age and sex (OR=2.02, 95% CI: 1.03-3.97, P=0.04). In conclusion, patients with RA have a higher prevalence of the metabolic syndrome than control subjects. Inflammation-associated metabolic syndrome is a mechanism that may contribute to increased coronary-artery atherosclerosis in RA.

Chung CP, Oeser A, Raggi P, Gebretsadik T, Shintani AK, Sokka T, Pincus T, Avalos I, Stein CM. · Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA. · Arthritis Rheum. · Pubmed #16200609 links to  free full text

Abstract: OBJECTIVE: To compare the prevalence and severity of coronary-artery atherosclerosis in patients with early and established rheumatoid arthritis (RA) and controls. METHODS: Electron-beam computed tomography was used to measure the extent of coronary-artery calcification in 227 subjects, of whom 70 had early RA, 71 had established RA, and 86 were controls. Coronary-artery calcification calculated according to the Agatston calcium score was compared in patients and controls, and its relationship to clinical characteristics was examined. Adjusted odds ratios (ORs) were obtained with the use of proportional odds logistic regression models to determine independent associations of early and established RA and coronary-artery calcification. RESULTS: Calcium scores were higher in patients with established RA (median 40.2, interquartile range [IQR] 0-358.8) compared with those with early disease (median 0, IQR 0-42.6) and controls (median 0, IQR 0-19.2) (P = 0.001). Coronary-artery calcification occurred more frequently in patients with established RA (60.6%) than in patients with early RA (42.9%) and control subjects (38.4%) (P = 0.016) The OR for the likelihood of having more severe coronary-artery calcification (defined as an Agatston score >109) in patients with established disease was 3.42 (P = 0.002) after adjusting for cardiovascular risk factors. Among patients with RA, smoking (OR 1.02, P = 0.04) and an elevated erythrocyte sedimentation rate (OR 1.02, P = 0.05) were associated with more severe coronary-artery calcification after adjustment for age and sex. CONCLUSION: The prevalence and severity of coronary calcification is increased in patients with established RA and is related, in part, to smoking and an increased erythrocyte sedimentation rate.