Cystatin C and Sudden Cardiac Death Risk in the Elderly

Methods and Results: The study was a longitudinal analysis among 4465 participants from the Cardiovascular Health Study without prevalent cardiovascular disease at baseline. Cystatin C and creatinine were measured from baseline sera. Sudden cardiac death (SCD) was defined as a sudden pulseless condition from a cardiac origin in a previously stable individual that occurred out of the hospital or in the emergency room. The association between cystatin C tertiles and SCD was determined with multivariate Cox proportional hazards. A similar analysis compared SCD incidence across creatinine-based estimated glomerular filtration rate (eGFR) tertiles. Over a median follow-up of 11.2 years, 91 adjudicated SCD events occurred. The annual incidence of SCD events increased across cystatin C tertiles: 10 events per 10000 person years in tertile 1, 25 events per 10000 person years in tertile 2, and 32 events per 10000 person-years in the highest cystatin C tertile. These associations persisted after multivariate adjustment: hazards ratio=2.72; 95% confidence interval, 1.44 to 5.16 in tertile 2 and hazards ratio=2.67; 95% confidence interval, 1.33 to 5.35 in tertile 3. After multivariate adjustment, the rate of SCD also increased in a linear distribution across creatinine-based eGFR tertiles: 15 events per 10000 person-years in tertile 1, 22 events per 10000 person-years in tertile 2, and 27 events per 10000 person-years in tertile 3. No significant associations, however, remained between creatinine-based eGFR and SCD after multivariable adjustment.

Conclusions: Impaired kidney function, as measured by cystatin C, has an independent association with SCD risk among elderly persons without clinical cardiovascular disease.

Rajat Deo, MD; Nona Sotoodehnia, MD, MPH; Ronit Katz, DPhil; Mark J. Sarnak, MD, MS; Linda F. Fried, MD, MPH; Michel Chonchol, MD; Bryan Kestenbaum, MD; Bruce M. Psaty, MD, PhD; David S. Siscovick, MD, MPH and Michael G. Shlipak, MD, MPH
From the Division of Cardiology (R.D.), University of Pennsylvania, Philadelphia;

the Division of Cardiology (N.S.), University of Washington, Seattle; Collaborative Health Studies Coordinating Center (R.K.), University of Washington, Seattle; the Division of Nephrology (M.J.S.), Tufts Medical Center, Boston, Mass;

The Renal-Electrolyte Division (L.F.F.), University of Pittsburgh School of Medicine, and the Renal Section, VA Pittsburgh Healthcare System, Pittsburgh, Pa; the Division of Renal Diseases and Hypertension (M.C.), University of Colorado Health Sciences Center, Denver; the Division of Nephrology (B.K.), University of Washington, Veterans Affairs Puget Sound Health Care System, Seattle, Wash; the Cardiovascular Health Research Unit (B.M.P., D.S.S.), Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle; Center for Health Studies, Group Health, Seattle, Wash; and General Internal Medicine Section (M.G.S.), Veterans Affairs Medical Center, San Francisco, Calif, and Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco.

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