Association of kidney function and albuminuria with cardiovascular mortality in older vs younger individuals: The HUNT II Study.

BACKGROUND The cardiovascular risk implications of a combined assessment of reduced kidney function and microalbuminuria are unknown. In elderly persons, traditional cardiovascular risk factors are less predictive, and measures of end organ damage, such as kidney disease, may be needed for improved cardiovascular mortality risk stratification. METHODS The glomerular filtration rate was estimated from calibrated serum creatinine, and the urine albumin-creatinine ratio (ACR) was measured in 3 urine samples in 9,709 participants of the second Nord-Trøndelag Health Study (HUNT II), a Norwegian community-based health study, followed for 8.3 years with a 71% participation rate. RESULTS An estimated glomerular filtration rate (EGFR) at levels of less than 75 mL/min/1.73 m(2) was associated with higher cardiovascular mortality risk, whereas a higher ACR was associated with higher risk with no lower limit. Low EGFR and albuminuria were synergistic cardiovascular mortality risk factors. Compared with subjects with an EGFR greater than 75 mL/min/1.73 m(2) and ACR below the sex-specific median who were at the lowest risk, subjects with an EGFR of less than 45 mL/min/1.73 m(2) and microalbuminuria had an adjusted incidence rate ratio of 6.7 (95% confidence interval, 3.0-15.1; P < .001). The addition of ACR and EGFR improved traditional risk models: 39% of subjects with intermediate risk were reclassified to low- or high-risk categories with corresponding observed risks that were 3-fold different than the original category. Age-stratified analyses showed that EGFR and ACR were particularly strong risk factors for persons 70 years or older. CONCLUSIONS Reduced kidney function and microalbuminuria are risk factors for cardiovascular death, independent of each other and traditional risk factors. The combined variable improved cardiovascular risk stratification at all age levels, but particularly in elderly persons where the predictive power of traditional risk factors is attenuated.

[1]  Jennifer G. Robinson,et al.  Is it Time for a Cardiovascular Primary Prevention Trial in the Elderly? , 2007, Stroke.

[2]  J. Abramson,et al.  Are lipid-lowering guidelines evidence-based? , 2007, The Lancet.

[3]  Tom Greene,et al.  Using Standardized Serum Creatinine Values in the Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate , 2006, Annals of Internal Medicine.

[4]  B. Astor,et al.  Decreased Kidney Function in the Elderly: Clinical and Preclinical, Neither Benign , 2006, Annals of Internal Medicine.

[5]  C. Wanner,et al.  Cross-talk between the kidney and the cardiovascular system. , 2006, Journal of the American Society of Nephrology : JASN.

[6]  N. Powe,et al.  International comparison of the relationship of chronic kidney disease prevalence and ESRD risk. , 2006, Journal of the American Society of Nephrology : JASN.

[7]  G. Curhan,et al.  Screening, monitoring, and treatment of albuminuria: Public health perspectives. , 2006, Journal of the American Society of Nephrology : JASN.

[8]  A. Garg,et al.  Chronic kidney disease and mortality risk: a systematic review. , 2006, Journal of the American Society of Nephrology : JASN.

[9]  E. Steyerberg,et al.  Prediction of mortality risk in the elderly. , 2006, The American journal of medicine.

[10]  B. Astor,et al.  Estimating glomerular filtration rate in the general population: the second Health Survey of Nord-Trondelag (HUNT II). , 2006, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[11]  M. Pfeffer,et al.  Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial , 2006, BMJ : British Medical Journal.

[12]  F. Irie,et al.  The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population. , 2006, Kidney international.

[13]  A. Eggen,et al.  Does implementation of the European guidelines based on the SCORE model double the number of Norwegian adults who need cardiovascular drugs for primary prevention? The Tromsø study 2001. , 2005, European heart journal.

[14]  D. de Zeeuw,et al.  The kidney, a cardiovascular risk marker, and a new target for therapy. , 2005, Kidney international. Supplement.

[15]  V. Salomaa,et al.  The validity of the Finnish Hospital Discharge Register and Causes of Death Register data on coronary heart disease , 2005, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[16]  L. Getz,et al.  Ethical dilemmas arising from implementation of the European guidelines on cardiovascular disease prevention in clinical practice A descriptive epidemiological study , 2004, Scandinavian journal of primary health care.

[17]  G. Bakris Inclusion of albuminuria in hypertension and heart guidelines. , 2004, Kidney international. Supplement.

[18]  Charles E McCulloch,et al.  Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. , 2004, The New England journal of medicine.

[19]  B. Astor,et al.  Evidence for increased cardiovascular disease risk in patients with chronic kidney disease , 2004, Current opinion in nephrology and hypertension.

[20]  G. Mancia,et al.  European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force Of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). , 2004, Archives des maladies du coeur et des vaisseaux.

[21]  Bertram L Kasiske,et al.  Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. , 2003, Circulation.

[22]  Bertram L Kasiske,et al.  Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. , 2003, Hypertension.

[23]  Shah Ebrahim,et al.  European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. , 2003 .

[24]  David R. Anderson,et al.  Model selection and multimodel inference : a practical information-theoretic approach , 2003 .

[25]  H. Tunstall-Pedoe,et al.  Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. , 2003, European heart journal.

[26]  Arnulf Langhammer,et al.  The Nord-Trøndelag Health Study 1995-97 (HUNT 2): Objectives, contents, methods and participation , 2003 .

[27]  G. Eknoyan,et al.  Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[28]  B Waeber,et al.  Practice guidelines for primary care physicians: 2003 ESH/ESC hypertension guidelines. , 2003, Journal of hypertension.

[29]  L. Bouter,et al.  Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study. , 2002, Kidney international.

[30]  R. Stolk,et al.  Primary and secondary prevention in cardiovascular disease: an old‐fashioned concept? , 2002, Journal of internal medicine.

[31]  A. Garg,et al.  Moderate renal insufficiency and the risk of cardiovascular mortality: results from the NHANES I. , 2002, Kidney international.

[32]  Katsuhiko Yano,et al.  Age-related changes in risk factor effects on the incidence of coronary heart disease. , 2002, Annals of epidemiology.

[33]  Ethan M Balk,et al.  K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[34]  Kdoqi Disclaimer K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[35]  G. Dell'omo,et al.  Non-diabetic microalbuminuria, endothelial dysfunction and cardiovascular disease , 2001, Vascular medicine.

[36]  R. D'Agostino,et al.  Prevention Conference V: Beyond secondary prevention: identifying the high-risk patient for primary prevention: medical office assessment: Writing Group I. , 2000, Circulation.

[37]  D. Levy,et al.  Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. , 1999, Kidney international.

[38]  S M Grundy,et al.  Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology. , 1999, Circulation.

[39]  K. Anderson,et al.  Cardiovascular disease risk profiles. , 1991, American heart journal.

[40]  L. Nyström,et al.  A validation of cause of death certification for ischaemic heart disease in two Swedish municipalities. , 1988, Scandinavian journal of primary health care.