11/6/2011. Abnormal Concentric Ventricular Remodeling in Rheumatoid Arthritis. Disclosure. Background. Purpose. Rationale

Transcription

1 Disclosure Abnormal Ventricular Remodeling in Rheumatoid Arthritis John M. Davis, III, Veronique L. Roger, Cynthia S. Crowson, Terry M. Therneau, Eric L. Matteson, and Sherine E. Gabriel We have no financial or other relationship to disclose. From the Division of Rheumatology, the Division of Cardiovascular Diseases, and the Department of Health Sciences Research Mayo Clinic, Rochester, Minnesota, USA Background Supported By U.S. Department of Health and Human Services National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases Heart failure (HF) is an important complication of rheumatoid arthritis () Significantly increased incidence in 1 Unexplained by traditional risk factors HF-related mortality is high in 2 Preserved systolic function 2 LV diastolic dysfunction 3 1 Nicola PJ et al. Arthritis Rheum 5;52:412-2 Davis JM et al. Arthritis Rheum 8;58: Liang KP et al. Ann Rheum Dis ; 69: Rationale Purpose Distinct pathogenesis of HF complicating? Inflammatory immune mechanisms Structural changes in the myocardium Analysis of left ventricular geometry elucidates patterns of remodeling. To compare left ventricular geometry between patients with and subjects without any history of arthritis from the same community. New mechanistic insights 1 Prognostic & therapeutic implications 2 1 Velagaleti RS et al. Circulation 8; 118: Rosen BD et al. Circulation 5; 112:

2 Design: Cross-sectional study Population-based cohorts vs. non- Study population: Olmsted County, MN residents Age 5 years No history of clinical heart failure Data collection: BMI, CV risk factors, data Lab: CRP, RF, ACPA 2D/Doppler echocardiography NIA/NIH Key Parameters of LV Geometry Posterior wall thickness Left ventricle internal diameter Posterior wall thickness Septal wall thickness Left ventricle internal diameter ized to body surface area Relative wall thickness (RWT) (LVMI) remodeling 2

3 Statistical analysis: Contingency tables Chi square tests Logistic regression models Model 1: fit all adjustors Model 2: assess variable of interest holding the adjustors constant Reduce overfitting bias Covariates: Age (per years) Male sex Systolic blood pressure Diastolic blood pressure Body mass index Waist circumference Ischemic heart disease Current smoking Use of lipid-lowering drugs Use of antihypertensives Use of insulin/oral hypoglycemics Abnormal egfr Characteristics of the Cohort (N = 2) Disease duration, yrs.1 ± 7. Rheumatoid factor or ACPA positive 69% Pain, mm VAS ( ) 29.7 ± 24.1 HAQ disability index ( 3).6 ±.6 C-reactive protein, mg/l (<3. 8.) 4.4 ± 6.8 Methotrexate use 56% Biologic use 14% Prednisone use 29% Comparison of and non- subjects N = 2 DBP, mm Hg 71 ± 9 68 ± <.1, g/m 2 85 ± ± 22 <.1 Comparison of and non- subjects N = 2 DBP, mm Hg 71 ± 9 68 ± <.1, g/m 2 85 ± ± 22 <.1 Comparison of and non- subjects N = 2 DBP, mm Hg 71 ± 9 68 ± <.1, g/m 2 85 ± ± 22 <.1 Comparison of and non- subjects N = 2 DBP, mm Hg 71 ± 9 68 ± <.1, g/m 2 85 ± ± 22 <.1 3

4 % Abnormal % Abnormal % Abnormal 11/6/11 Abnormal LV geometry in and non- 5 remodeling in and non- 5 Overall Abnormal geometry remodeling. * 31 remodeling Adjusted OR = 1.3 (95% CI:.9, 1.8), p=.13 *Adjusted OR = 3.8 (95% CI: 2.6 to 5.6) p<.1 remodeling in and non Patients with abnormal geometry 27 * 72 remodeling *Adjusted OR = 6.7 (95% CI: 3.8 to 11.9), p<.1 Predictors of Abnormal LV Geometry in Abnormal LV Geometry Odds Ratio 95% CI duration.99.94, 1.4 RF , 2.61 ACPA , 2.85 CRP >8 mg/l 2..88, 6.2* Pain score , 2.26 HAQ disability index , 3.12 MTX , 4.34 Anti-TNF 1..99, 1. Prednisone.94.47, 1.88 *P =.88. P =.58. P =.19. Odds ratios are adjusted for all covariates. Summary is associated with abnormal LV geometry remodeling, in particular Significant after adjustment for CV risk factors Association with markers of severity Possible Implications Pathogenesis -associated remodeling suggests a distinct pathogenesis of heart failure remodeling is related to aging, obesity, and metabolic syndrome 1-3 New hypotheses? Clinical management Screening for ventricular remodeling? Different approach to prevention of HF? 1 Woodiwiss et al. Am J Hypertension 8; 21: Mahmud, A. et al. J Cardiometab Syndr 9; 4: Puchades, R. et al. Rev Exp Cardiol ; 63:

5 Conclusions is associated with concentric remodeling Further research is necessary to understand: Biological mechanisms involved Impact on diagnosis and treatment Impact on cardiovascular outcomes Acknowledgments Our patients! Mayo Rheumatology clinicians Research study team: Nurse Abstractors Margaret R. Donohue, RN Julie A. Gingras, RN Denise M. Herman, RN Constance A. Neuman, RN Cynthia L. Nosek, RN Deborah C. Olson, RN Lorna N. Stevens, RN Diane K. Wilke, RN Study Coordinators Jeaneen J. Alcorn Konnie B. Bicknese Penelope Davidson Cynthia J. Stoppel Admin Assistants Donette M. Adler Darcy L. Jacobson Sherry L. Kallies Melissa Schuh Immune Signatures John M. Davis III, MD Keith L. Knutson, PhD Larry R. Pease, PhD Michael A. Strausbauch, BS Peter J. Wettstein, PhD Minzhi Zhang, BS CV / Echo Daniel D. Borgeson, MD Jo-Ellen Ehrsam, RDCS My (Tammy) D. Green, RDCS Mary (Libby) E. Hagen, RN Barry L. Karon, MD Edward Mendrick, RDCS Richard J. Rodeheffer, MD Veronique L. Roger, MD, MSc Mary J. Wenzel, RDCS Heart Disease in Rheumatoid Arthritis Epidemiology Sherine E. Gabriel, MD, MSc Hilal Maradit Kremers, MD, MSc Eric L. Matteson, MD, MPH Biostatistics Karla V. Ballman, PhD Cynthia S. Crowson, MS Patrick D. Fitz-Gibbon, BS Abigail B. Green, BS Megan S. Reinalda, BS Ruchi G. Sharma, MS Terry M. Therneau, PhD Fellows A. Kirstin Bacani, MD Angel Gonzalez, MD Kimberly P. Liang, MD Elena Myasoedova, MD, PhD Paulo J. Nicola, MD 5