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The HUNT II Study

Stein Hallan, MD, PhD; Brad Astor, MPH, PhD; Solfrid Romundstad, MD, PhD; Knut Aasarød, MD, PhD; Kurt Kvenild, MD; Josef Coresh, MD, PhD

Arch Intern Med. 2007;167(22):2490-2496.

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 9709 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 m² 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 m² 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 m² 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.

Author Affiliations: Departments of Cancer Research and Molecular Medicine (Drs Hallan, Romundstad, and Aasarød) and Community Medicine (Dr Kvenild), Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Medicine, Division of Nephrology, St Olav University Hospital, Trondheim (Drs Hallan, Romundstad, and Aasarød); and Welch Center for Prevention, Epidemiology, and Clinical Research, Department of Epidemiology, Bloomberg School of Public Health, and Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland (Drs Astor and Coresh).

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