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CLINICAL RESEARCH: PERIPHERAL VASCULAR DISEASE

Association of Chronic Kidney Disease With the Spectrum of Ankle Brachial Index

The CHS (Cardiovascular Health Study)

Joachim H. Ix, MD, MAS^_*,,,_*, Ronit Katz, DPhil^||, Ian H. De Boer, MD, MS^¶,#, Brian R. Kestenbaum, MD, MS^¶, Matthew A. Allison, MD, MPH, David S. Siscovick, MD, MPH^||, Anne B. Newman, MD, MPH^_**, Mark J. Sarnak, MD, MS, Michael G. Shlipak, MD, MPH^, and Michael H. Criqui, MD, MPH^,

^_* Division of Nephrology, Department of Medicine, University of California San Diego, San Diego, California
Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California San Diego, San Diego, California
Division of Cardiology, Department of Medicine, University of California San Diego, San Diego, California
Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California
^|| Collaborative Health Studies Coordinating Center, Department of Biostatistics, University of Washington, Seattle, Washington
^¶ Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
^# Nephrology Section, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington
^_** Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
Division of Nephrology, Department of Medicine, Tufts-New England Medical Center, Boston, Massachusetts
Department of Medicine, University of California San Francisco, San Francisco, California
General Medicine Section, San Francisco Veterans Affairs Medical Center, San Francisco, California

Manuscript received February 7, 2009; revised manuscript received May 11, 2009, accepted June 16, 2009.

^_* Reprint requests and correspondence: Dr. Joachim H. Ix, Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, 3350 La Jolla Village Drive, Mail Code 111-H, San Diego, California 92161 (Email: joeix{at}ucsd.edu).

Objectives: This study sought to determine the association of chronic kidney disease (CKD) with high ankle brachial index (ABI) measurement and to compare its strength with that of CKD with a low ABI.

Background: CKD is an important risk factor for cardiovascular disease (CVD) events. A high ABI, a marker of lower extremity arterial stiffness, is associated with CVD events and mortality. The association between CKD and high ABI is unknown.

Methods: The CHS (Cardiovascular Health Study) enrolled community-living people >65 years of age and measured kidney function and ABI. Glomerular filtration rate (GFR) was estimated using equations that incorporated either cystatin C or creatinine, and CKD was defined by estimated GFR <60 ml/min/1.73 m². The ABI was categorized as low (<0.90), low-normal (0.90 to 1.09), normal (1.10 to 1.40), and high (>1.40 or incompressible). Multinomial logistic regression was used to evaluate the associations of CKD with ABI categories.

Results: Among 4,513 participants, 23% had CKD, 13% had a low ABI, and 3% had a high ABI. In models adjusted for age, sex, race, hypertension, diabetes, smoking, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and C-reactive protein, cystatin C-based CKD was associated with both low ABI (relative risk [RR]: 2.0; 95% confidence interval [CI]: 1.6 to 2.5; p <0.001) and high ABI (RR: 1.6; 95% CI: 1.0 to 2.3; p = 0.03). Results were similar when CKD was defined by creatinine.

Conclusions: CKD is associated with both the high and the low extremes of ABI in community-living older people. Future studies should evaluate whether arterial stiffness is an important mechanism leading to CVD in people with CKD.

Key Words: kidney disease • chronic • atherosclerosis • calcium • cardiovascular disease • arterial stiffness

Abbreviations and Acronyms   ABI = ankle brachial index   CKD = chronic kidney disease   CRP = C-reactive protein   CVD = cardiovascular disease   eGFR = estimated glomerular filtration rate   HDL = high-density lipoprotein   PAD = peripheral arterial disease

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