BACKGROUND/RATIONALE:
The incidence of cardiovascular disease (CVD) is 3 times higher in patients with chronic kidney disease (CKD) compared to the general population. CKD disproportional affects African Americans who make up a third of the population that needs renal replacement therapy (dialysis or transplant). There are several novel cardiovascular risk factors whose profile worsens as CKD progresses such as proteinuria, elevated lipoprotein (a) [Lp(a)] and homocysteine. Because CKD patients are at high risk for cardiovascular disease, it is important to screen for CVD. Carotid intima-media thickness (IMT) measured by ultrasound has been shown to assess the extent and severity of atherosclerosis. CKD is common among veterans increasing the morbidity and mortality.
OBJECTIVE(S):
The proposed study will examine prospectively patients with CKD and determine if traditional and non-traditional risk factors such as Lp(a), homocysteine, and C-reactive protein are independent risk factor for progression of subclinical CVD as measured by IMT.
METHODS:
The study population will include patients 18 to 74 years of age who come in to Philadelphia Veteran Administration Medical Center (PVAMC) for their primary or nephrology care during the study's recruitment period. The subjects have been recruited as part of an ancillary study to the Chronic Renal Insufficiency Cohort (CRIC) that will determine associations between IMT and chronic kidney disease. This award will allow us to perform baseline and three-year follow-up IMT in the VA subjects subjects to assess progression and determine risk factors for progression in this high-risk population. Patients will be eligible to participate if they have an estimated glomerular filtration rate (eGFR) between 20 and 70 ml/min/1.73 m2. The tool of analysis will be multiple linear regression for baseline associations. A change will be measured by the difference in IMT measurements. Models using standard mixed effects growth curves will be used to allow both the estimation of individual subjects' slopes and intercepts and for the comparison of groups defined by baseline or time-varying covariates.
FINDINGS/RESULTS:
Recruitment for this ancillary study to the Chronic Renal Insufficiency Cohort (CRIC) was completed in December 2006. Four hundred and fifty subjects have consented to this study. Approximately a hundred are veterans.
In a preliminary cross-sectional univariate analysis(n=331), increasing age, homocysteine, history of cardiovascular disease, and diabetes were associated with increasing IMT. In a multivariate analysis, age (p=0.03) and diabetes(p=0.02) were independent predictors of IMT. There was a borderline association with homocysteine.
IMPACT:
Because half of all cardiovascular events occur in patients without any known traditional risk factors, it is important to screen for CVD in an effort to identify high-risk individuals. The optimal evaluation for the presence of cardiovascular disease in particular coronary artery disease in patients with CKD is unknown. Carotid intima-media thickness (IMT) measured by ultrasound has been shown to assess the extent and severity of atherosclerosis in the general population. We propose to utilize this promising new non-invasive technique for the quantitative assessment of CVD in CKD veteran patients. Identifying modifiable risk factors for the progression of cardiovascular disease may lead to targeted medical interventions for easily identifiable high-risk groups to decrease disease progression.
PUBLICATIONS:
Journal Articles
- Israni AK, Li N, Sidhwani S, Rosas S, Kong X, Joffe M, Rebbeck T, Feldman HI. Association of hypertension genotypes and decline in renal function after kidney transplantation. Transplantation. 2007; 84(10): 1240-7.
- Kamoun M, Israni AK, Joffe MM, Hoy T, Kearns J, Mange KC, Feldman D, Goodman N, Rosas SE, Abrams JD, Brayman KL, Feldman HI. Assessment of differences in HLA-A, -B, and -DRB1 allele mismatches among African-American and non-African-American recipients of deceased kidney transplants. Transplantation Proceedings. 2007; 39(1): 55-63.
