June 16, 2007 – Milan, Italy – A substudy of the Nordic trial with diltiazem has shown that microalbuminuria (MA+) is a risk factor for cardiovascular (CV) disease, independent of classical risk factors, independent of diabetes. Further, that estimated glomerular filtration rate (GFR) is also an independent risk factor for CV disease. Importantly, the presence of both MA+ and GFR has a synergistic effect and represents an even further increase in CV disease risk.

The Nordic Diltiazem (NORDIL) study randomized 10,881 Swedish and Norwegian patients with a diastolic blood pressure >100 mmHg to treatment with either a beta blocker and diuretic (n=5471) or with diltiazem (n=5410), who were followed for a mean of 4.5 years. The primary endpoint was fatal and nonfatal myocardial infarction (MI) and stroke and other CV disease death. The patients were about 60 years old, and 48% were men with a baseline blood pressure of 173/104 mmHg, and fairly normal renal function [Modification of Diet in Renal Disease (MDRD) 74.1 ml/min/1.72 m3 body surface and Cockcroft-Gault formula (CRG) 92.9 ml/min/1.72 m3 body surface)]. Twenty-two percent were smokers, 4% had a history of CV disease, and BMI was 27.8 kg/m2 at baseline.

MA+ was measured using the Micral dipstick for a morning urine spot test, which was repeated if the clinical significance was doubtful, for example, because of fever or exercise. MA+ was defined as a value ≥20 mg/dL. Estimated GFR was calculated by creatinine, Cockcroft-Gault formula, and MDRD. The hazard ratios were adjusted for age, sex, systolic blood pressure, smoking, cholesterol, previous CVD, diabetes, and treatment allocation.

CV disease risk was increased by:

9% (crude) and 20% (adjusted) with each 10 micromolar/L increase in creatinine, with a clear linear increase in CV risk as creatinine increased.

13% (crude) and 6% (adjusted) for CRG, with each 10 ml/min/1.73 m3 decrease in body surface, with a linear increase in CV risk in step with change in CRG.

5% (crude) and 7% (adjusted) in association with MDRD, with each 10 mil/min/1.73 m3 decrease in body surface area.

Overall, microalbuminuria was a strong predictor of CV disease risk, with a 35% increase in CV disease risk (adjusted; p<0.0001). A primary endpoint was experienced in 20% of the patients with MA+, versus 10% MA-, at the end of the study.

The results of the substudy were presented by Dr. P. Färborm, Lund University, Malmo, Sweden, and the 17th European Meeting on Hypertension, held in Milan from June 15-19, 2007.