Introduction 1 2 3 4 6 7 8 9 10 13 14 21 22 23 24 22 23 Methods Patient population n P P n 10 25 26 27 28 27 Classification of anemia Patients were classified as being anemic or not based upon their hemoglobin at the time of study enrollment. Thus, the patients’ hemoglobin value at baseline determined their anemia status throughout the remainder of the study. The World Health Organization (WHO) definition of anemia was used (hemoglobin <13 g/dl for men, <12 g/dl for women). Statistical analysis t To evaluate the construct validity of the KCCQ in anemic and nonanemic patients, comparisons across NYHA classifications from the baseline interviews were conducted. A two-way ANOVA with KCCQ overall summary score as the dependent variable and baseline anemia classification, NYHA, and an anemia-by-NYHA interaction term as independent variables was constructed to establish whether the association of NYHA and KCCQ was different in patients with and without anemia. t 10 P  Results Patient characteristics 1 P P P P 2 P P P P P P Table 1 Baseline clinical characteristics of the population Characteristic n n P Age (mean +/− SD) 67.0 +/− 13.1 62.9 +/− 13.5 <0.001 n 105 (39.2%) 239 (44.0%) 0.190 n 80 (29.9%) 123 (22.7%) 0.026 n 6 (2.2%) 19 (3.5%) 0.329 n   0.038     Hypertensive  49 (18.3%) 92 (17.0%)      Ischemic 124 (46.3%) 208 (38.4%)      Other 95 (35.4%) 242 (44.6%)  Mean left ventricular ejection fraction (mean +/− SD) 36.4 +/− 15.9 35.9 +/− 16.2 0.742 n 125 (46.8%) 185 (34.1%) <0.001 n 51 (19.1%) 87 (16.0%) 0.273 n 89 (33.3%) 82 (15.1%) <0.001 n 17 (6.3%) 61 (11.2%) 0.026 Body mass index (mean +/− SD) 30.3 +/− 7.3 31.1 +/− 7.4 0.181 n   0.001      I 35 (13.1%) 99 (18.2%)      II 116 (43.3%) 268 (49.4%)      III 105 (39.2%) 169 (31.1%)      IV 12 (4.5%) 7 (1.3%)  Mean KCCQ overall summary score (mean +/− SD) 60.8 +/− 22.8 65.3 +/− 23.2 0.009 n     ACE inhibitor/ARB 232 (86.6%) 486 (89.5%) 0.217     ß-blocker 222 (82.8%) 446 (82.1%) 0.806     Diuretic 240 (89.6%) 458 (84.3%) 0.044     Spironolactone 76 (28.4%) 132 (24.3%) 0.214     Digoxin 126 (47.0%) 245 (45.1%) 0.610 Mean hemoglobin (mean +/− SD) 11.4 +/− 1.1 14.1 +/− 1.3 <0.001 Mean creatinine (mean +/− SD) 1.7 +/− 1.5 1.3 +/− 1.2 <0.001 2 50.8 +/− 24.6 63.9 +/− 23.1 <0.001 * Modification of diet in renal disease (MDRD) abbreviated formula 1 P P Construct validity 1 P n n P Fig. 1 KCCQ overall summary score by NYHA class in anemic and nonanemic patients  Reliability The internal consistency reliability (Cronbach’s alpha) of the KCCQ overall summary score for the entire population was 0.93. In patients who were anemic and nonanemic, the Cronbach alphas were 0.92 and 0.93, respectively. n n n P P Responsiveness 2 P P Fig. 2 Three-month KCCQ change by reported health change and anemia status  Discussion We report empirical evidence to support the reliability and validity (including responsiveness) of the KCCQ in HF patients with anemia. We found similar associations between the KCCQ overall summary score and NYHA classification, similar internal consistency and test–retest reliability in stable patients, and similar responsiveness of the KCCQ to patients’ perceptions of 3-month clinical change. In light of the potential overlap in symptoms between anemia and HF, we tested and rejected the hypothesis that the psychometric properties of the KCCQ might differ between HF patients with and without anemia. Thus, the KCCQ could be a valid, reliable, and responsive outcome for clinical trials of anemia treatment in HF. To date, there has been a paucity of literature examining attribution of symptoms to one of a spectrum of potentially co-occurring diseases in patient-reported health status assessments. A common recommendation for the design of clinical trials is to include both disease-specific and generic measures of health status. These recommendations are predicated upon the desire to capture the impact of treatments on a specific disease of interest, as well as the overall impact of treatment on patients’ health outside the condition of interest. The latter intended to capture side effects or other unanticipated complications of therapy. 29 30 31 32 35 36 37 28 global 10 10 28 In summary, we provide empirical evidence to support the ability of a disease-specific measure of heart failure patients’ health status, the KCCQ, regardless of the presence of anemia. As such, we believe that patient-reported health status outcomes are a valid, reliable, and sensitive means to quantify the impact of anemia treatment on HF-specific outcomes. Given that the improvement in patients’ health status is a primary goal of treatment, being able to accurately capture HF patients’ health status in trials of anemia therapy are important. The KCCQ should be a valid and sensitive measure for accomplishing these goals.