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Title: The prevalence and determinants of subclinical atherosclerosis in an early inflammatory polyarthritis inception cohort
Author: Mirjafari, Hoda
ISNI:       0000 0004 2713 9897
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2011
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Introduction: Patients with inflammatory polyarthritis (IP) have an excess risk of cardiovascular (CVD) mortality due to accelerated atherosclerosis. Markers identifying individuals with subclinical atherosclerosis as measured by carotid intima-medial thickness (cIMT) and plaque may allow for attenuation of CVD risk. The objective of this study was to identify associated risk markers for atheromatous plaque and cIMT in an incident cohort of patients with early IP and to assess the risk markers associated with progression of cIMT and plaque after 2 years of follow-up.Methods: From 2004 to 2008 consecutive patients with early IP (≥2 joints swollen for ≥4 weeks) aged 18-65 years, who were within 24 months of symptom onset (±6 months) were recruited as part of a primary-care-based inception cohort. Apparently healthy controls were recruited on a frequency matched 'buddy' pair system. Patients underwent joint and blood pressure examination. Patients and controls underwent BMI measurement and their medication was recorded. Patients' blood was taken for measurement of rheumatoid factor, anti-citrullinated protein antibody, C reactive protein, glucose, lipids (LDL, HDL, triglycerides, paroxonase 1, apolipoprotein A1 and B) and markers of vascular damage (E-selectin, VCAM) and adipocytokines (leptin and adiponectin). Patients and controls underwent B mode Doppler ultrasound examination of the carotid arteries to assess for cIMT and the presence of plaque. In univariate analyses we identified factors that were associated with cIMT and plaque presence after age and gender adjustment. An additive stepwise multivariable logistic regression model was created to investigate the independence of any associations.Results: The 329 IP subjects had a median (IQR) age of 51 (42-58) years and 96 (29%) were male. IP subjects were more likely to be smokers, have a family history of CVD, have diabetes, higher BP and be overweight than their apparently healthy counterparts. IP subjects with plaque at baseline often did not have prior CVD. Subjects with IP had a 2.87 fold higher plaque frequency at the baseline but a similar median cIMT relative to the controls. Traditional CVD risk markers such as age, systolic BP and LDL were associated with cIMT and plaque at baseline. Adiponectin levels were negatively associated with cIMT and positively associated with plaque. IP subjects had a significant increase in their cIMT in the first 2 years of follow-up. The rate of progression of cIMT was 1.5-2.2 fold greater in IP than reported in the general population. Novel risk factors added to the model above and beyond traditional risk factors in predicting atherosclerosis. Steroid exposure at 2 years was associated with atherosclerosis progression.Conclusion: Markers known to be associated with atherosclerosis in the general population are associated with cIMT and plaque presence in early IP prior to established inflammatory disease and therapy. While cIMT in subjects and controls was the same at baseline there was an accelerated rate of progression of cIMT in IP subjects relative to that reported in the general population.
Supervisor: Symmons, Deborah ; Bruce, Ian Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Cardiovascular disease ; Rheumatoid arthritis