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J Am Coll Cardiol, 2003; 41:47-55
© 2003 by the American College of Cardiology Foundation
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CLINICAL STUDY: CHRONIC CORONARY ATHEROSCLEROSIS

Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community

Guruprasad Manjunath, MD*, Hocine Tighiouart, MS{dagger}, Hassan Ibrahim, MD{ddagger}, Bonnie MacLeod, BS{dagger}, Deeb N. Salem, MD§, John L. Griffith, PhD{dagger}, Josef Coresh, MD, PhD||, Andrew S. Levey, MD* and Mark J. Sarnak, MD*,*

* Division of Nephrology, Boston, Massachusetts, USA
{dagger} Division of Clinical Care Research, Boston, Massachusetts, USA
§ Division of Cardiology, Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
{ddagger} Division of Nephrology and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
|| Johns Hopkins School of Medicine and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

Manuscript received June 21, 2002; revised manuscript received September 12, 2002, accepted September 26, 2002.

* Reprint requests and correspondence: Dr. Mark J. Sarnak, Box 391, New England Medical Center, 750 Washington Street, Boston, Massachusetts 02111, USA.
msarnak{at}lifespan.org

OBJECTIVES: The goal of this study was to determine whether the level of kidney function is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) outcomes in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of subjects aged 45 to 64 years.

BACKGROUND: The level of kidney function is now recognized as a risk factor for ASCVD outcomes in patients at high risk for ASCVD, but it remains unknown whether the level of kidney function is a risk factor for ASCVD outcomes in the community.

METHODS: Cox proportional-hazards regression was used to evaluate the association of glomerular filtration rate (GFR) with ASCVD after adjustment for the major ASCVD risk factors in 15,350 subjects. We searched for nonlinear relationships between GFR and ASCVD.

RESULTS: During a mean follow-up time of 6.2 years, 965 (6.3%) of subjects had ASCVD events. Subjects with GFR of 15 to 59 ml/min/1.73 m2 (n = 444, hazard ratio 1.38 [1.02, 1.87]) and 60 to 89 ml/min/1.73 m2 (n = 7,665, hazard ratio 1.16 [1.00, 1.34]) had an increased adjusted risk of ASCVD compared with subjects with GFR of 90 to 150 ml/min/1.73 m2. Each 10 ml/min/1.73 m2 lower GFR was associated with an adjusted hazard ratio of 1.05 (1.02, 1.09), 1.07 (1.01, 1.12), and 1.06 (0.99, 1.13) for ASCVD, de novo ASCVD, and recurrent ASCVD, respectively. A nonlinear model did not fit the data better than a linear model.

CONCLUSIONS: The level of GFR is an independent risk factor for ASCVD and de novo ASCVD in the ARIC study.

Abbreviations and Acronyms
  ARIC
  Atherosclerosis Risk in Communities Study
  ASCVD
  atherosclerotic cardiovascular disease
  CHD
  coronary heart disease
  CVD
  cardiovascular disease
  GFR
  glomerular filtration rate
  HDL
  high-density lipoprotein
  K/DOQI
  Kidney Disease Outcomes Quality Initiative
  LDL
  low-density lipoprotein
  LVH
  left ventricular hypertrophy
  MDRD
  Modification of Diet in Renal Disease
  NHANES
  National Health and Nutrition Examination Survey
  NKF
  National Kidney Foundation




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Revascularization in patients with chronic kidney disease: the state of the ARTS
Eur. Heart J., August 1, 2005; 26(15): 1456 - 1457.
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 HypertensionHome page
K. P. Klausen, H. Scharling, G. Jensen, and J. S. Jensen
New Definition of Microalbuminuria in Hypertensive Subjects: Association With Incident Coronary Heart Disease and Death
Hypertension, July 1, 2005; 46(1): 33 - 37.
[Abstract] [Full Text] [PDF]

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 Nephrol Dial TransplantHome page
R. Vanholder, Z. Massy, A. Argiles, G. Spasovski, F. Verbeke, N. Lameire, and for the European Uremic Toxin Work Group (EUTox)
Chronic kidney disease as cause of cardiovascular morbidity and mortality
Nephrol. Dial. Transplant., June 1, 2005; 20(6): 1048 - 1056.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
L. A. Stevens and A. S. Levey
Chronic Kidney Disease in the Elderly -- How to Assess Risk
N. Engl. J. Med., May 19, 2005; 352(20): 2122 - 2124.
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 ANN INTERN MEDHome page
M. J. Sarnak, R. Katz, C. O. Stehman-Breen, L. F. Fried, N. S. Jenny, B. M. Psaty, A. B. Newman, D. Siscovick, M. G. Shlipak, and and the Cardiovascular Health Study*
Cystatin C Concentration as a Risk Factor for Heart Failure in Older Adults
Ann Intern Med, April 5, 2005; 142(7): 497 - 505.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
R. N. Foley, A. M. Murray, S. Li, C. A. Herzog, A. M. McBean, P. W. Eggers, and A. J. Collins
Chronic Kidney Disease and the Risk for Cardiovascular Disease, Renal Replacement, and Death in the United States Medicare Population, 1998 to 1999
J. Am. Soc. Nephrol., February 1, 2005; 16(2): 489 - 495.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
P. Muntner, J. He, B. C. Astor, A. R. Folsom, and J. Coresh
Traditional and Nontraditional Risk Factors Predict Coronary Heart Disease in Chronic Kidney Disease: Results from the Atherosclerosis Risk in Communities Study
J. Am. Soc. Nephrol., February 1, 2005; 16(2): 529 - 538.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
L. G. Bongartz, M. J. Cramer, P. A. Doevendans, J. A. Joles, and B. Braam
The severe cardiorenal syndrome: 'Guyton revisited'
Eur. Heart J., January 1, 2005; 26(1): 11 - 17.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
M. P. Tokmakova, H. Skali, S. Kenchaiah, E. Braunwald, J. L. Rouleau, M. Packer, G. M. Chertow, L. A. Moye, M. A. Pfeffer, and S. D. Solomon
Chronic Kidney Disease, Cardiovascular Risk, and Response to Angiotensin-Converting Enzyme Inhibition After Myocardial Infarction: The Survival And Ventricular Enlargement (SAVE) Study
Circulation, December 14, 2004; 110(24): 3667 - 3673.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
S. J. Cameron and G. B. Green
Cardiac Biomarkers in Renal Disease: The Fog Is Slowly Lifting
Clin. Chem., December 1, 2004; 50(12): 2233 - 2235.
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 Eur Heart JHome page
C. M. Gibson, R. L. Dumaine, E. V. Gelfand, S. A. Murphy, D. A. Morrow, S. D. Wiviott, R. P. Giugliano, C. P. Cannon, E. M. Antman, E. Braunwald, et al.
Association of glomerular filtration rate on presentation with subsequent mortality in non-ST-segment elevation acute coronary syndrome; observations in 13307 patients in five TIMI trials
Eur. Heart J., November 2, 2004; 25(22): 1998 - 2005.
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 J Am Coll CardiolHome page
R. Mehran, E. D. Aymong, E. Nikolsky, Z. Lasic, I. Iakovou, M. Fahy, G. S. Mintz, A. J. Lansky, J. W. Moses, G. W. Stone, et al.
A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: Development and initial validation
J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1393 - 1399.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
N. S. Anavekar, J. J.V. McMurray, E. J. Velazquez, S. D. Solomon, L. Kober, J.-L. Rouleau, H. D. White, R. Nordlander, A. Maggioni, K. Dickstein, et al.
Relation between Renal Dysfunction and Cardiovascular Outcomes after Myocardial Infarction
N. Engl. J. Med., September 23, 2004; 351(13): 1285 - 1295.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
A. S. Go, G. M. Chertow, D. Fan, C. E. McCulloch, and C.-y. Hsu
Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization
N. Engl. J. Med., September 23, 2004; 351(13): 1296 - 1305.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
K. Klausen, K. Borch-Johnsen, B. Feldt-Rasmussen, G. Jensen, P. Clausen, H. Scharling, M. Appleyard, and J. S. Jensen
Very Low Levels of Microalbuminuria Are Associated With Increased Risk of Coronary Heart Disease and Death Independently of Renal Function, Hypertension, and Diabetes
Circulation, July 6, 2004; 110(1): 32 - 35.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
V. Franco, S. Oparil, and O. A. Carretero
Hypertensive Therapy: Part II
Circulation, June 29, 2004; 109(25): 3081 - 3088.
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 J. Am. Soc. Nephrol.Home page
J. Segura, C. Campo, P. Gil, C. Roldan, L. Vigil, J. L. Rodicio, and L. M. Ruilope
Development Of Chronic Kidney Disease and Cardiovascular Prognosis in Essential Hypertensive Patients
J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1616 - 1622.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
D. E. Weiner, H. Tighiouart, M. G. Amin, P. C. Stark, B. MacLeod, J. L. Griffith, D. N. Salem, A. S. Levey, and M. J. Sarnak
Chronic Kidney Disease as a Risk Factor for Cardiovascular Disease and All-Cause Mortality: A Pooled Analysis of Community-Based Studies
J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1307 - 1315.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
J. A. Joles and H. A. Koomans
Causes and Consequences of Increased Sympathetic Activity in Renal Disease
Hypertension, April 1, 2004; 43(4): 699 - 706.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
F. A. McAlister, J. Ezekowitz, M. Tonelli, and P. W. Armstrong
Renal Insufficiency and Heart Failure: Prognostic and Therapeutic Implications From a Prospective Cohort Study
Circulation, March 2, 2004; 109(8): 1004 - 1009.
[Abstract] [Full Text] [PDF]

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 Nephrol Dial TransplantHome page
L. M. Ruilope
New European guidelines for management of hypertension: what is relevant for the nephrologist
Nephrol. Dial. Transplant., March 1, 2004; 19(3): 524 - 528.
[Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
T. Pinkau, K. F. Hilgers, R. Veelken, and J. F. E. Mann
How Does Minor Renal Dysfunction Influence Cardiovascular Risk and the Management of Cardiovascular Disease?
J. Am. Soc. Nephrol., March 1, 2004; 15(3): 517 - 523.
[Abstract] [Full Text] [PDF]

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 JAMAHome page
C. S. Fox, M. G. Larson, E. P. Leip, B. Culleton, P. W. F. Wilson, and D. Levy
Predictors of New-Onset Kidney Disease in a Community-Based Population
JAMA, February 18, 2004; 291(7): 844 - 850.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
J. Segura, C. Campo, C. Roldan, H. Christiansen, L. Vigil, R. Garcia-Robles, J. L. Rodicio, and L. M. Ruilope
Hypertensive Renal Damage in Metabolic Syndrome Is Associated with Glucose Metabolism Disturbances
J. Am. Soc. Nephrol., January 1, 2004; 15(90010): S37 - 42.
[Abstract] [Full Text]

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 HypertensionHome page
A. V. Chobanian, G. L. Bakris, H. R. Black, W. C. Cushman, L. A. Green, J. L. Izzo Jr, D. W. Jones, B. J. Materson, S. Oparil, J. T. Wright Jr, et al.
Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
Hypertension, December 1, 2003; 42(6): 1206 - 1252.
[Abstract] [Full Text] [PDF]

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 Nephrol Dial TransplantHome page
H. Reinecke and R. M. Schaefer
Percutaneous coronary interventions in patients with mild to moderate chronic renal failure: to dilate or not to dilate?
Nephrol. Dial. Transplant., November 1, 2003; 18(11): 2218 - 2221.
[Full Text] [PDF]


 
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