Obesity increases the prevalence and severity of focal knee abnormalities diagnosed using 3T MRI in middle-aged subjects--data from the Osteoarthritis Initiative.

OBJECTIVE: To study the effect of BMI on the prevalence, severity, and 36-month progression of early degenerative changes in the knee by using 3T MRI in middle-aged subjects without radiographic osteoarthritis (OA). MATERIALS AND METHODS: We examined baseline and 36-month follow-up MR studies from 137 middle-aged individuals (45-55 years old) with risk factors for knee OA but no radiographic OA from the Osteoarthritis Initiative. Subjects were grouped into three categories: normal BMI (BMI < 25 kg/m(2), n = 38), overweight (BMI 25-29.9 kg/m(2), n = 37), and obese (BMI ≥ 30 kg/m(2), n = 62). Using 3T MRI, cartilage, meniscus, and bone marrow abnormalities were graded using the OA Whole-organ MR Imaging Score (WORMS). The statistical analysis was corrected as necessary for differences in age, sex, and OA risk factors other than BMI. RESULTS: The overall prevalence of lesions was 64% for meniscus and 79% for cartilage (including low grade lesions). At baseline, the prevalence and severity of knee lesions was positively associated with BMI, with a nearly fourfold increase in meniscal tears and more than twofold increase in high-grade cartilage defects in obese individuals relative to normal-weight subjects. Over the 36-month follow-up period, the number of new or worsening cartilage lesions of any grade was significantly higher in obese subjects (p = 0.039), while there was no significant difference in meniscal lesion progression. CONCLUSION: Obesity was associated with both higher prevalence and severity of early degenerative changes in the knee in middle-aged individuals without radiographic OA and with significantly increased cartilage lesion progression (of any grade) over 36 months.

Atherosclerosis and innate immune signaling.

Atherosclerosis, the leading cause of death in developed countries, is characterized by chronic inflammation in the artery wall. It has been appreciated for decades that this disease is linked to hypercholesterolemia and the accumulation of macrophages in the artery wall, yet the exact mechanisms underlying this inflammatory process remain unclear. The role of innate and adaptive immune responses in the pathogenesis of atherosclerosis has been an area of intense study. It now appears that activation of innate immune signaling pathways designed to protect us from microbes may be responsible for initiating and feeding the chronic inflammatory cascade that characterizes this disease. In this review, we discuss the recent identification of Toll-like receptors and their downstream signaling pathways as critical contributors to atherosclerosis. Unraveling the contribution of individual Toll-like receptors and identifying the ligands that activate these pathways will be a central focus of atherosclerosis research in the next few years. The involvement of these pathways in atherogenesis will not only open up new avenues of investigation, but it also provides new targets for therapeutic manipulation that could ameliorate the atherosclerotic inflammatory response directly.

Persistent orthopnea and the prognosis of patients in the heart failure clinic.

Heart failure (HF) is a public health problem with ever-growing costs. Signs such as jugular venous pressure and third heart sound have been associated with disease prognosis. Symptoms of heart failure are frequently subjective, and their real value is often overlooked. The authors aimed to assess the relationship between orthopnea and left ventricular ejection fraction (LVEF) and hospitalization rate in patients referred to the HF clinic. One hundred fifty-three new consecutive patients referred to the HF clinic from September 2001 to July 2002 were reviewed. Information about orthopnea was available at baseline and at a 6-month to 1-year follow-up. One hundred thirty-one patients had a baseline multigated radionuclide ventriculogram scan, and 68 patients had a follow-up multigated radionuclide ventriculogram scan available. The patients were divided into groups by presence of orthopnea and compared with respect to LVEF and hospitalization rate. Patients with or without orthopnea had similar LVEFs at baseline (32%+/-17% vs. 33%+/-15%, respectively; p=NS). However, patients who were orthopnea-free at the follow-up visit had a significant LVEF improvement whereas patients with ongoing orthopnea at follow-up had no LVEF improvement (11%+/-13% vs. -1%+/-6%; p<0.001). Patients who presented with persistent orthopnea had a significantly higher rate of hospitalization (64% vs. 15.3%; p=0.0001). Persistent orthopnea in HF patients is associated with a significantly higher rate of hospitalization and with worsening or no improvement in LVEF. Patients with persistent orthopnea may require a more aggressive approach to improve their outcome. This result may help centers with limited access to LVEF measurements to better stratify HF patients' risk.