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Comparison of Traditional and Novel Risk Factors

Michael G. Shlipak, MD, MPH; Linda F. Fried, MD, MPH; Mary Cushman, MD, MPH; Teri A. Manolio, MD, PhD; Do Peterson, MS; Catherine Stehman-Breen, MD, MS; Anthony Bleyer, MD; Anne Newman, MD, MPH; David Siscovick, MD, MPH; Bruce Psaty, MD, PhD

JAMA. 2005;293:1737-1745.

Context  Elderly persons with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown.

Objective  To compare traditional and novel risk factors as predictors of cardiovascular mortality.

Design, Setting, and Patients  A total of 5808 community-dwelling persons aged 65 years or older living in 4 communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to June 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up in this longitudinal study was 8.6 years.

Main Outcome Measures  Cardiovascular mortality among those with and without chronic kidney disease. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m².

Results  Among the participants, 1249 (22%) had chronic kidney disease at baseline. The cardiovascular mortality risk rate was 32 deaths/1000 person-years among those with chronic kidney disease vs 16/1000 person-years among those without it. In multivariate analyses, diabetes, systolic hypertension, smoking, low physical activity, nonuse of alcohol, and left ventricular hypertrophy were predictors of cardiovascular mortality in persons with chronic kidney disease (all P values <.05). Among the novel risk factors, only log C-reactive protein (P = .05) and log interleukin 6 (P<.001) were associated with the outcome as linear predictors. Traditional risk factors were associated with the largest absolute increases in risks for cardiovascular deaths among persons with chronic kidney disease: for left ventricular hypertrophy, there were 25 deaths per 1000 person-years; current smoking, 20 per 1000 person-years; physical inactivity, 15 per 1000 person-years; systolic hypertension, 14 per 1000 person-years; diabetes, 14 per 1000 person-years; and nonuse of alcohol, 11 per 1000 person-years vs 5 deaths per 1000 person-years for those with increased C-reactive protein and 5 per 1000 person-years for those with increased interleukin 6 levels. A receiver operating characteristic analysis found that traditional risk factors had an area under the curve of 0.73 (95% confidence interval, 0.70-0.77) among those with chronic kidney disease. Adding novel risk factors only increased the area under the curve to 0.74 (95% confidence interval, 0.71-0.78; P for difference = .15).

Conclusions  Traditional cardiovascular risk factors had larger associations with cardiovascular mortality than novel risk factors in elderly persons with chronic kidney disease. Future research should investigate whether aggressive lifestyle intervention in patients with chronic kidney disease can reduce their substantial cardiovascular risk.

Author Affiliations: General Internal Medicine Section, Veterans Affairs Medical Center, and Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco (Dr Shlipak); Renal-Electrolyte Division, University of Pittsburgh School of Medicine, and the Renal Section, VA Pittsburgh Healthcare System, Pittsburgh, Pa (Dr Fried); Departments of Medicine and Pathology and Biochemistry, the University of Vermont College of Medicine, Colchester (Dr Cushman); Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Manolio); Collaborative Health Studies Coordinating Center, Seattle, Wash (Mr Peterson); Amgen Inc, Thousand Oaks, Calif (Dr Stehman-Breen); Section of Nephrology , Bowman Gray School of Medicine, Winston-Salem, NC (Dr Bleyer); Department of Epidemiology, Graduate School of Public Health and the Division of Geriatric Medicine and School of Medicine, University of Pittsburgh, Pittsburgh, Pa (Dr Newman); and Departments of Medicine and Epidemiology, University of Washington, Seattle (Drs Siscovick and Psaty).

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