Methods

From April 2008 to May 2012, we prospectively studied 712 consecutive patients with CHF who had been admitted for treatment of worsening CHF or for diagnosis and pathophysiologic investigations. The diagnosis of CHF was determined using the generally accepted Framingham criteria and clinical information, including signs of pulmonary congestion or peripheral edema or documentation of left ventricular enlargement or dysfunction on chest x-ray film or echocardiography. The diagnosis of idiopathic dilated cardiomyopathy was determined using the definition of the World Health Organization/International Society and Federation of Cardiology Task Force. Venous blood and urine samples were obtained at admission from all patients. The estimated glomerular filtration rate (eGFR) was calculated from the Japanese Society of Nephrology Chronic Kidney Disease (CKD) Practice Guide as follows: eGFR (ml/min/1.73 m ² ) = 194 × [serum creatinine level (mg/dl)] ^−1.094 × [age (years)] ^−0.287 . The product of this equation was multiplied by a correction factor of 0.739 for women. According to the eGFR values, patients were classified into 5 stages as follows: stage I, eGFR ≥90 ml/min/1.73 m ² ; stage II, eGFR <90 but ≥60 ml/min/1.73 m ² ; stage III, eGFR <60 but ≥30 ml/min/1.73 m ² ; stage IV, eGFR <30 but ≥15 ml/min/1.73 m ² ; and stage V, eGFR <15 ml/min/1.73 m ² . As in a previous study, stages III and V were defined as CKD. Transthoracic echocardiography was performed using an ultrasound instrument (SONOS 7500, Hewlett Packard, Palo Alto, California) equipped with a sector transducer (carrier frequency 2.5 or 3.75 MHz) within 2 days after admission. Optimum medical therapy was determined according to symptom improvement, physical examination findings, and pulmonary congestion on chest x-ray film. Hypertension was defined as blood pressure of ≥140/90 mm Hg or hypertension treatment. Hyperlipidemia was defined as total cholesterol of ≥220 mg/dl, triglycerides of ≥150 mg/dl, or hyperlipidemia treatment. UACR levels of 30 to 300 mg/g × creatinine were defined as microalbuminuria and levels >300 mg/g × creatinine as macroalbuminuria, just as in previous studies.

The patients were prospectively followed up until the occurrence of cardiac events in every case. The end points were cardiac death (defined as death from worsening CHF or sudden cardiac death) and worsening CHF requiring readmission. The exclusion criteria in the present study were acute coronary syndrome within 3 months before admission, renal insufficiency (characterized by a serum creatinine concentration >1.5 mg/dl), active hepatic disease, and active pulmonary disease.

The results are presented as the mean ± SD for continuous variables and the percentage of total patients for categorical variables. Skewed variables are presented as the median and interquartile range. The unpaired Student t test and chi-square test was used for comparison of continuous and categorical variables between the 2 groups, respectively. If the data were not distributed normally, the Mann-Whitney U test was used. Comparisons of the data, including New York Heart Association functional class, CKD, and albuminuria classification, were performed using the Kruskal-Wallis test. Cox proportional hazard regression analysis was performed to evaluate the associations between cardiac events and the measured variables. The cardiac event-free curve was computed using the Kaplan-Meier method and compared using the log-rank test. All p values reported are 2-sided, and p ≤0.05 was considered significant. Statistical analysis was performed with a standard statistical program package (StatView, version 5.0, SAS Institute, Cary, North Carolina).