Cholesterol induced heart valve inflammation and injury: efficacy of cholesterol lowering treatment

BACKGROUND: Heart valves often undergo a degenerative process leading to mechanical dysfunction that requires valve replacement. This process has been compared with atherosclerosis because of shared pathology and risk factors. In this study, we aimed to elucidate the role of inflammation triggered by cholesterol infiltration and cholesterol crystals formation causing mechanical and biochemical injury in heart valves. METHODS: Human and atherosclerotic rabbit heart valves were evaluated. New Zealand White male rabbits were fed an enriched cholesterol diet alone or with simvastatin and ezetimibe simultaneous or after 6 months of initiating cholesterol diet. Inflammation was measured using C-reactive protein (CRP) and RAM 11 of tissue macrophage content. Cholesterol crystal presence and content in valves was evaluated using scanning electron microscopy. RESULTS: Cholesterol diet alone induced cholesterol infiltration of valves with associated increased inflammation. Tissue cholesterol, CRP levels and RAM 11 were significantly lower in simvastatin and ezetimibe rabbit groups compared with cholesterol diet alone. However, the treatment was effective only when initiated with a cholesterol diet but not after lipid infiltration in valves. Aortic valve cholesterol content was significantly greater than all other cardiac valves. Extensive amounts of cholesterol crystals were noted in rabbit valves on cholesterol diet and in diseased human valves. CONCLUSIONS: Prevention of valve infiltration with cholesterol and reduced inflammation by simvastatin and ezetimibe was effective only when given during the initiation of high cholesterol diet but was not effective when given following infiltration of cholesterol into the valve matrix

Determining early referral criteria for patients with suspected inflammatory arthritis presenting to primary care physicians: a cross-sectional study

Hani Almoallim,1–3 Nahid Janoudi,2 Suzan M Attar,4 Mohammed Garout,5 Shereen Algohary,3 Muhammad Irfanullah Siddiqui,5 Hanan Alosaimi,3 Ashraf Ibrahim,3 Amira Badokhon,6 Zaki Algasemi7 1Department of Medicine, Medical College, Umm Alqura University, Makkah, 2Department of Medicine, Dr. Soliman Fakeeh Hospital, Jeddah, 3Alzaidi Chair of Research in Rheumatic Diseases, Medical College, Umm Alqura University, Makkah, 4Department of Medicine, King Abdulaziz University, Jeddah, 5Department of Community Medicine and Public Health, Umm Alqura University, Makkah, 6Administration of Public Health, Ministry of Health, Jeddah, 7Joint Program of Family and Community Medicine, Ministry of Health, Jeddah, Kingdom of Saudi Arabia Objective: Early diagnosis and initiation of treatment for inflammatory arthritis can greatly improve patient outcome. We aimed to provide standardized and validated criteria for use by primary care physicians (PCPs) in the identification of individuals requiring referral to a rheumatologist. Patients and methods: We analyzed the predictive value of a wide variety of demographic variables, patient-reported complaints, physical examination results, and biomarkers in order to identify the most useful factors for indicating a requirement for referral. Patients for this cross-sectional study were enrolled from various centers of the city of Jeddah, Saudi Arabia, if they were ≥18 years of age and presented to a PCP with small joint pain that had been present for more than 6 weeks. A total of 203 patients were enrolled, as indicated by the sample size calculation. Each patient underwent a standardized physical examination, which was subsequently compared to ultrasound findings. Biomarker analysis and a patient interview were also carried out. Results were then correlated with the final diagnosis made by a rheumatologist. Results: A total of 9 variables were identified as having high specificity and good predictive value: loss of appetite, swelling of metacarpophalangeal joint 2 or 5, swelling of proximal inter-phalangeal joint 2 or 3, wrist swelling, wrist tenderness, a positive test for rheumatoid factor, and a positive test for anti-citrullinated protein antibodies. Conclusion: Nine variables should be the basis of early referral criteria. It should aid PCPs in making appropriate early referrals of patients with suspected inflammatory arthritis, accelerating diagnosis and initiation of treatment. Keywords: inflammatory arthritis, rheumatoid, diagnosis, primary care, early referral criteri