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Osteoprotegerin concentrations relate independently to established cardiovascular disease in rheumatoid arthritis
Raquel López-Mejias1, Begoña Ubilla1, Fernanda Genre1
1From the Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Department of Internal Medicine, Hospital Universitario Marques de Valdecilla, and the Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and Fundación Instituto de Investigación Marqués de Valdecilla, and Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF), and CIBER Epidemiología y Salud Pública (CIBERESP), Santander; the Rheumatology Division, Hospital Universitario de Canarias, Tenerife; the Cardiology Division, Hospital Lucus Augusti, Lugo, Spain; the Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.P.H. Dessein and M.A. Gonzalez-Gay share senior authorship.R. López-Mejias, PhD; B. Ubilla, BSc; F. Genre, PhD; A. Corrales, MD, PhD; R. Blanco, MD, PhD, Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marques de Valdecilla, IFIMAV; J.L. Hernández, MD, PhD, Department of Internal Medicine, Hospital Universitario Marques de Valdecilla, University of Cantabria, RETICEF, IFIMAV; I. Ferraz-Amaro, MD, Rheumatology Division, Hospital Universitario de Canarias; L. Tsang; P.H. Dessein, MD, FCP(SA), FRCP(UK), PhD, Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand; J. Llorca, MD, PhD, Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBERESP, IFIMAV; C. Gonzalez-Juanatey, MD, PhD, Cardiology Division, Hospital Lucus Augusti; M.A. Gonzalez-Gay, MD, PhD, Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marques de Valdecilla, IFIMAV
Insights
Osteoprotegerin (OPG) levels are linked to cardiovascular disease (CVD) severity in rheumatoid arthritis (RA) patients. Higher OPG concentrations correlate with increased CVD prevalence and disease markers in RA, suggesting OPG
Area of Science:
- Rheumatology
- Cardiology
- Biochemistry
Background:
- Rheumatoid arthritis (RA) is an autoimmune disease associated with increased cardiovascular disease (CVD) risk.
- Biomarkers are needed to assess CVD risk in RA patients.
- Osteoprotegerin (OPG) is a potential mediator in vascular calcification and inflammation.
Purpose of the Study:
- To investigate the association between osteoprotegerin (OPG) concentrations and established cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA).
Main Methods:
- OPG concentrations were measured using ELISA in 151 RA patients (54 with CVD) and 62 controls.
- Established CVD included ischemic heart disease, cerebrovascular disease, and peripheral artery disease.
- Statistical analyses included mixed regression models adjusting for various clinical and demographic factors.
Main Results:
- In RA patients, OPG levels correlated with age, BMI, rheumatoid factor (RF) positivity, anti-CCP antibody positivity, and joint erosion.
- Median OPG concentrations were higher in RA patients with CVD compared to those without CVD and controls (p=0.0002).
- OPG levels remained significantly associated with CVD in RA patients after adjusting for traditional risk factors, RF, anti-CCP, and erosion status (p=0.04).
Conclusions:
- Osteoprotegerin (OPG) concentrations are significantly associated with cardiovascular disease (CVD) prevalence and disease severity in rheumatoid arthritis (RA) patients.
- OPG may serve as a potential biomarker for CVD risk in RA.
- Further longitudinal studies are warranted to evaluate OPG's utility in CVD risk stratification for RA patients.
Objective:
We determined whether osteoprotegerin (OPG) concentrations are associated with established cardiovascular disease (CVD) among patients with rheumatoid arthritis (RA).
Methods:
OPG concentrations were measured by ELISA in 151 patients with RA (54 with CVD) and 62 age-matched control subjects without CVD. Established CVD was composed of documented ischemic heart disease, cerebrovascular disease, and peripheral artery disease.
Results:
In patients with RA, age, body mass index (BMI), rheumatoid factor (RF) positivity, anticyclic citrullinated peptide (anti-CCP) antibody positivity, and joint erosion status were associated with OPG concentrations [partial R (p) = 0.175 (0.03), -0.277 (0.0009), 0.323 (< 0.0001), 0.217 (0.008), and 0.159 (0.05), respectively]. Median (interquartile range) OPG concentrations increased from 6.38 (3.46-9.31) to 7.07 (5.04-10.65) and 8.64 (6.00-11.52) ng/ml in controls and patients with RA who had CVD and those who did not, respectively (p = 0.0002). Upon adjustment for age, sex, traditional risk factors, and BMI in mixed regression models, OPG concentrations remained lower in controls compared to patients with RA without CVD (p = 0.05) and in the latter compared to those with CVD (p = 0.03); the association of OPG concentrations with CVD among patients with RA also persisted after additional adjustment for RF and anti-CCP antibody positivity, and erosion status (p = 0.04).
Conclusion:
OPG concentrations are associated with disease severity and CVD prevalence in patients with RA. Whether consideration of OPG concentrations can improve CVD risk stratification in RA merits future longitudinal investigation.