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Patients with osteoarthritis have elevated concentrations of high-sensitivity C-reactive protein (hsCRP) in their sera. It is not known, however, whether comorbidities such as osteoarthritis or ethnicity affect the overall ability of hsCRP measurements to predict the risk of cardiovascular disease.The objective of this study was to investigate the association between hsCRP concentrations and the incidence of osteoarthritis, in order to determine whether or not hsCRP levels can predict risk of cardiovascular disease.This study was a population-based analysis of patients from the Johnston County Osteoarthritis Project. Participants were selected using a stratified simple random sampling method, aiming for an overall balance of general demographic characteristics and presence of knee osteoarthritis. All participants had to have undergone bilateral anteroposterior weight-bearing radiography of both knees, and were also required to have available serum sample data. Patients included in the study also had either a grade 0 level of osteoarthritis on the Kellgren-Lawrence scale in both knees, or grade ≥2 in at least one knee. Patients were interviewed to determine their status for other conditions, including chronic pulmonary disease, cardiovascular disease (using the Framingham risk factor algorithm), high blood pressure and diabetes or high blood sugar. Serum natural-log-transformed hsCRP (ln-hsCRP) was calculated for all patients. Participants who reported a diagnosis of cancer, rheumatoid arthritis or gout were not included in the study.There were no outcome measures in this study.A total of 662 patients-48% black, 58% female, mean age (±SD) 61.4 years (±10.3 years)-participated in this study. The authors found that ln-hsCRP was significantly increased in the black population of patients (P<0.0001) and in women (P<0.0001). Similarly, ln-hsCRP was increased in those patients who had chronic pulmonary disease (P = 0.01), hypertension (P<0.0001), or had reported use of pain medications (P = 0.004), and correlated with BMI (r = 0.40, P<0.0001) and waist circumference (r = 0.33, P<0.0001). Age, reported cardiovascular disease and smoking were not associated with increased ln-hsCRP. A positive association with all definitions of radiographic osteoarthritis was reported (P<0.0001), but this association was not independent of BMI. Although 183 participants reported no cardiovascular disease and were classified as low-risk by the Framingham score, 61% were classified as moderate-risk or high-risk for cardiovascular disease according to hsCRP levels.The authors conclude that the prognostic significance of increased ln-hsCRP levels in the studied patients is unclear, but that obesity, ethnicity, sex and other comorbidities confound the use of hsCRP for determining risk of cardiovascular disease.