1. 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,‡‡§§ Michael H. Criqui, MD, MPH†‡ San Diego and San Francisco, California; Seattle, Washington; Pittsburgh, Pennsylvania; and Boston, Massachusetts J Am Coll Cardiol 2009;54:1176–84

2. Background Chronic kidney disease(CKD) and Cardiovascular disease(CVD) –Strongly associated, but not fully explained by traditional CVD risk factors Arterial calcification –One potential mechanism linking CKD and CVD –1. Intimal calcification : asso/w the atherosclerosis –2. Medial arterial calcification Calcification limited to the tunica media Not inflammatory or flow limiting, directly contributes to arterial stiffness Particularly prevalent in DM, CKD patients and the distal arteries of the lower extremities Correlated with higher pulse-wave velocity, left ventricular hypertrophy, and mortality in maintenance dialysis populations

3. Copyright ©1996 American Heart Association Lehto, S. et al. Arterioscler Thromb Vasc Biol 1996;16:978-983 Radiograms show plaque-like intimal-type (left) and medial uniform linear railroad track-ty pe (right) calcification in the femoral artery uniform character resembling a ring in vessel crosssection and tram- tracks in longitudinal view

4. Backgrounds The ankle brachial index (ABI) –Noninvasive measure of arterial disease in the lower limbs –Low ABI (<0.90) Sensitive and specific for ASO of the lower extremities Strongly associated with CVD events and mortality –High ABI (>1.40) Generalized stiffening of the lower limb arteries Specific for medial arterial calcification –U-shaped relationships between ABI and mortality High ABI had nearly equal mortality risk with a low ABI Approximately 2-fold mortality compared to intermediate ABI

5. Objectives High ABI (Medial arterial calcification) High ABI (Medial arterial calcification) Early in the process of Kidney dysfunction CKD Low ABI

6. Methods The Cardiovascular Health study –A community-based cohort of older adults –> 65 years, remain in the area for 3 years after recruitment –5201 participants from U.S.A between 1989 and 1990 –Added, 687 African Americans in 1992 to 1993 Measurements –1. Kidney function : Glomerular filtration rate (GFR) Cystatin C or creatinine, MDRD formula CKD : estimated GFR < 60 ml/min/1.73 m 2 –2. ABI Low (<0.90), low-normal (0.90 to 1.09), normal (1.10 to 1.40), and high (1.40 or incompressible) –3. Secondary predictors By self report HTN, DM, Smoking : current/past/never, Height and weight, Lipid profile, CRP Statistics : Multinomial logistic regression

7. Results – The patient’s characteristics

9. Results – The associations of CKD and ABI

10. Results – The association of GFR and ABI ABI < 0.90 ABI > 1.40

11. Results – The associations of CKD and ABI in DM

12. Conclusions CKD is associated with both the high and the low extremes of ABI in community-living older people.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.