Atherosclerotic cardiovascular disease (ASCVD) is a leading contributor to the high morbidity and mortality among end-stage renal disease (ESRD) patients, accounting for 36 percent of ESRD deaths (total annual mortality of 23 percent). This application tests the hypothesis that higher levels of several novel risk factors (Lp(a) levels and apo(a) isoforms; homocysteine and related vitamins; Chlamydia pneumoniae and cytomegalovirus; and C-reactive protein and fibrinogen) and traditional risk factors predict higher risk of ASCVD in a prospective study of 925 incident dialysis patients recruited within three months of starting dialysis. Although these factors have been implicated in the etiology of ASCVD in ESRD patients, little prospective data exist. Cross-sectional studies are susceptible to large survival bias because of the high mortality of patients with renal disease. This cohort has already been recruited through a collaboration between Johns Hopkins and 80 Dialysis Clinics Incorporated (DCI) clinics; many of the important predictors and possible confounders have been measured. This application proposes to obtain long term followup (extending mean followup of 2.4 years by four more years) and conduct laboratory assays. The investigators will: 1) extend specimen collection, and follow-up, and institute standardized review of ASCVD events; 2) characterize baseline associations of novel and traditional factors with each other, dialysis modality and dose, nutritional status, and ASCVD prevalence in the full cohort using a cross-sectional design; 3) determine whether baseline levels of risk factors predict subsequent incidence of ASCVD events, and total mortality using a prospective cohort study design and test a priori hypothesized interactions between risk factors and the risk of ASCVD; 4) study the variability of risk factors over time using annual measurements in a random subset of 180 patients (subcohort) using a longitudinal design; and lastly, 5) use a case-cohort design, utilizing the subcohort, to test whether the most recent level before an ASCVD event, the baseline level, or the mean level of each risk factor is most predictive of ASCVD risk. Baseline data collection will include a patient health questionnaire and a standardized review of comorbidity using dialysis chart records. Serum, plasma and DNA will be stored at -80 degrees C. from patient visits at recruitment (month 0), and followup (months 1,2,3,6,12,8,24, etc.). ASCVD will be assessed by review of hospital charts, patients and care providers questionnaires, and HCFA death forms. The investigators state that this study will use state-of-the-art epidemiologic and laboratory methods to identify modifiable risk factors, answer the call of an NKF task force for prospective studies of risk factors for ASCVD in the dialysis population, and lay the essential groundwork for future preventive interventions to reduce the burden of ASCVD in persons with ESRD.
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