Renal Function, Health Outcomes, and Resource Utilization in Acute Heart Failure
2010; Lippincott Williams & Wilkins; Volume: 3; Issue: 6 Linguagem: Inglês
10.1161/circheartfailure.109.920298
ISSN1941-3297
AutoresJaved Butler, Diana Chirovsky, Hemant Phatak, Anne Marie McNeill, Robert Cody,
Tópico(s)Acute Kidney Injury Research
ResumoHomeCirculation: Heart FailureVol. 3, No. 6Renal Function, Health Outcomes, and Resource Utilization in Acute Heart Failure Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBRenal Function, Health Outcomes, and Resource Utilization in Acute Heart FailureA Systematic Review Javed Butler, Diana Chirovsky, Hemant Phatak, Anne McNeill and Robert Cody Javed ButlerJaved Butler From the Cardiology Division (J.B.), Emory University, Atlanta, Ga; the Department of Health Policy and Management (D.C.), University of North Carolina at Chapel Hill, Chapel Hill, NC; Global Outcomes Research and Reimbursement (H.P.), Merck & Co, Inc, Whitehouse Station, NJ; the Epidemiology Department, Merck & Co, Inc (A.M.), Upper Gwynedd, Pa; and Global Scientific Affairs (R.C.), Merck & Co, Inc, Whitehouse Station, NJ. , Diana ChirovskyDiana Chirovsky From the Cardiology Division (J.B.), Emory University, Atlanta, Ga; the Department of Health Policy and Management (D.C.), University of North Carolina at Chapel Hill, Chapel Hill, NC; Global Outcomes Research and Reimbursement (H.P.), Merck & Co, Inc, Whitehouse Station, NJ; the Epidemiology Department, Merck & Co, Inc (A.M.), Upper Gwynedd, Pa; and Global Scientific Affairs (R.C.), Merck & Co, Inc, Whitehouse Station, NJ. , Hemant PhatakHemant Phatak From the Cardiology Division (J.B.), Emory University, Atlanta, Ga; the Department of Health Policy and Management (D.C.), University of North Carolina at Chapel Hill, Chapel Hill, NC; Global Outcomes Research and Reimbursement (H.P.), Merck & Co, Inc, Whitehouse Station, NJ; the Epidemiology Department, Merck & Co, Inc (A.M.), Upper Gwynedd, Pa; and Global Scientific Affairs (R.C.), Merck & Co, Inc, Whitehouse Station, NJ. , Anne McNeillAnne McNeill From the Cardiology Division (J.B.), Emory University, Atlanta, Ga; the Department of Health Policy and Management (D.C.), University of North Carolina at Chapel Hill, Chapel Hill, NC; Global Outcomes Research and Reimbursement (H.P.), Merck & Co, Inc, Whitehouse Station, NJ; the Epidemiology Department, Merck & Co, Inc (A.M.), Upper Gwynedd, Pa; and Global Scientific Affairs (R.C.), Merck & Co, Inc, Whitehouse Station, NJ. and Robert CodyRobert Cody From the Cardiology Division (J.B.), Emory University, Atlanta, Ga; the Department of Health Policy and Management (D.C.), University of North Carolina at Chapel Hill, Chapel Hill, NC; Global Outcomes Research and Reimbursement (H.P.), Merck & Co, Inc, Whitehouse Station, NJ; the Epidemiology Department, Merck & Co, Inc (A.M.), Upper Gwynedd, Pa; and Global Scientific Affairs (R.C.), Merck & Co, Inc, Whitehouse Station, NJ. Originally published1 Nov 2010https://doi.org/10.1161/CIRCHEARTFAILURE.109.920298Circulation: Heart Failure. 2010;3:726–745IntroductionAcute heart failure (AHF) is common and is associated with adverse outcomes among chronic HF patients. According to the US National Discharge Survey, it is estimated that more than 1.1 million hospitalizations with a principal diagnosis of AHF occurred in 2004.1 Data from Europe have also reported high AHF rates.2–5 In patients with chronic HF, hospitalization for AHF is associated with increased mortality.6 AHF patients are also particularly prone to readmission, with reported readmission rates between 44% to 60% within 6 to 9 months of discharge.7,8 AHF hospitalizations account for more than half of the costs of HF treatment,2,9 which in the United States are projected to reach $37 billion in 2009.10Renal impairment (RI) is common in HF and is associated with adverse outcomes in AHF patients.11–14 In addition, approximately 20% to 30% of patients admitted for AHF have worsening renal function (WRF), which further worsens prognosis.15–17 Consistent with these findings, guidelines for HF treatment acknowledge that RI or WRF compromise prognosis in AHF and recommend regular monitoring of renal function in these patients.18–21 However, despite its importance, there is no clear consensus on how RI and WRF should be defined and to what extent these conditions affect outcomes in AHF specifically.22Two recent systematic reviews and meta-analyses have evaluated the association of RI and long-term mortality in HF23 as well as the association of WRF and mortality and readmission risk.17,23 Smith et al,23 in a meta-analysis of 7 chronic HF (n=16 106) and 2 AHF (n=54 305) studies found a 56% increase in long-term mortality risk with severe renal impairment; moreover, WRF was associated with a 47% increase in the risk of 6-month mortality, but there was only marginal association with readmissions in AHF patients.23 Damman et al17 reported a 61% increase in risk of mortality and 30% risk of all-cause readmission associated with WRF after 2 to 6 months of follow-up. Although these studies provide valuable insights, they were not designed to assess outcomes specifically in AHF and did not address short-term health and health care resource outcomes such as in-hospital mortality, risk of complications, and length of stay (LOS), which are uniquely relevant to AHF patients.17,23 The objective of this systematic review was to enumerate the range of studies that have assessed the impact of RI and WRF on short- and long-term health outcomes and health care resource use in adult AHF patients. We also describe the range of definitions for RI and WRF as well as compare the associations of these definitions with relevant outcomes in AHF.Literature SearchA MEDLINE (PubMed) literature search was performed to identify peer-reviewed studies that assessed the association between RI or WRF and health outcomes and health care resource use in adult AHF patients (Figure). Because WRF epidemiology has been mainly defined after the Evaluation of Losartan in the Elderly (ELITE) trial was published in 1997,24 we limited the search to studies published after 1995. Only English-language, full-text, peer-reviewed articles were considered. Studies including HF patients who were not hospitalized for AHF were excluded. Prior systematic review and meta-analyses were not included; they served as sources for potentially relevant articles.17,23,25 According to the above-mentioned criteria, 33 original studies were considered relevant to the aims of this literature review.11–16,26–52 The references of these studies were cross-checked to ensure a comprehensive evaluation of all relevant studies, which yielded 28 additional articles.53–80 We excluded studies that assessed primarily pediatric populations51 or cohorts with <100 patients.50,76 Studies that did not provide multivariate-adjusted assessments were excluded16,78,80; however, certain univariate analyses of LOS were included because there were no consistent methods to evaluate this outcome. Studies that did not define RI/WRF using specific laboratory measures and cut points,48,74,75,79 focused on combined measures of RI/WRF with other risk factors,52 or did not measure RF at baseline but at discharge were excluded.77 Last, to avoid multiple obsolete reports of the same cohort, the most recent publication was considered. As such, earlier reports of the same cohort49,68–71 were excluded because of later follow-up studies or studies with revised methodologies.12–14,58,60 However, in cases in which 2 studies of the same cohort reported results for different outcomes, both studies were included.45,47,63,64Download figureDownload PowerPointFigure. Literature search and selection strategy. Flow chart describes the literature search and selection strategy used to select the 42 published reports that were included in this review.Overall, 42 studies met all the inclusion and exclusion criteria.11–15,26–47,53–67 All studies were grouped according to the outcomes assessed, which included inpatient mortality, follow-up mortality (all-cause mortality after discharge; HF-related where noted), risk of complications (in-hospital), readmission (all-cause; HF-related where noted) or composite end point of readmission or all-cause death, and LOS. The studies were further organized by specific laboratory measures used to evaluate RI or WRF (serum creatinine [SCr], estimated glomerular filtration rate [eGFR], creatinine clearance [CrCl], blood urea nitrogen [BUN], BUN-to-SCr ratio [BUN/SCr]), and last, by study design (prospective observational, post hoc analysis of a clinical trial, and retrospective observational).Considering that the focus of this review was to assess the importance of renal function on outcomes, the tables were constructed using the following algorithm. Studies were first stratified in the tables by the various definitions of renal insufficiency and worsening renal function. Within each renal function definition, the studies were then divided on the basis of study design with prospective observational studies first followed by post hoc analysis of clinical trials (PHC) and last, retrospective observational studies. Finally, within this framework, rather than citing the data based on year of publication or author name, we choose to serially cite on the basis of the number of patients in the study from highest to lowest. This scheme provides a solid rationale of data display, focusing on the central issue (ie, renal function) with highest level of evidence (study type and number of patients).Because of the lack of a standard definition for RI or WRF and differences in study design and populations, pooling the data for a meta-analysis study was deemed unfeasible. Thus, a qualitative approach was taken. For each outcome and definition of RI and WRF, the number of studies that found a significant association out of the total number of studies identified was counted and reported. In general, the association between RI or WRF and mortality and/or readmission was assessed using logistic or Cox proportional hazards regression (odds ratio, risk ratio, or hazards ratio, 95% confidence interval, and/or probability value). Differences in LOS outcomes among patients at various levels of renal function with and without RI or WRF were primarily expressed as mean (SD) values or median (90% range), with probability values for univariate comparisons. Four studies provided multivariate assessments using logistic regression according to predefined LOS categories38,42 or continuously using linear regression.27,43 Few studies assessed the association of RI or WRF with the risk of in-hospital complications, and all results were summarized separately. Study analyses were considered to show a significant association between RI or WRF and each outcome if P<0.05 and/or if the 95% confidence interval did not include 1.0.Literature OverviewWe identified 42 relevant studies, including a total of 275 832 AHF patients that evaluated the association between RI and/or WRF and health/health care resource use outcomes. Of these, 20 were prospective observational,26–38,53–59 5 were post hoc analyses of clinical trials,12,13,39–41 and 17 were retrospective observational studies.11,14,15,42–47,60–67 Only 1 study focused exclusively on new-onset AHF patients without a prior diagnosis of HF.56 Thirty-six studies (n=271 702) provided analyses of RI and its effect on health and/or health care resource use outcomes11–15,30–41,44–47,53–67 (Table 1), and 11 studies (n=12 482) examined the effect of WRF on these outcomes12,13,15,26–30,39,42,77 (Table 2). Among studies that assessed RI and long-term health and resource use outcomes, the duration of follow-up ranged from 1 month61 to 8 years,46,58 with most studies reporting a 1-year follow-up.11,30,32,34,35,40,44,53,54,59,60,64,67 In contrast, most studies that evaluated the impact of WRF and long-term outcomes reported a 6-month follow-up,12,26,27,29,39,43 with a range of 1 month26,43 to approximately 5 years.15Table 1. Definitions and Frequency of Renal Insufficiency and Stratifications of Renal FunctionStudy (Trial/ Registry), YearDesignOrigin, CountryFollow-Up, moPopulation (% Men)*AHF DiagnosisAge: Mean† (SD/Range), yDefinition/ Stratification of RIEstimated Frequency, %Mean Level† (SD or IQR) for CohortSCr, mg/dL§ Tavazzi et al,36 2005PO206 centers, Italy…2807 (60.5)ESC Guidelines criteria9173 (11) 2.513.3 Rohde et al,33 2006PO1 center, Brazil…779 (50)Remes et al (Boston criteria)9267 (14)>1.4 (mean value)…1.4 (0.8) Siirilä-Waris et al (FINN-AKVA),35 2006PO14 centers, Finland12620 (50)ESC Guidelines criteria9175 (10)>1.36 (120 μmol/L)28.9… Zannad et al (EFICA),59 2006PO60 centers, France12581 (59)Clinical opinion73 (13)>2.26 (200 μmol/L)53.0… Nohria et al,53 2003PO1 center, United States12452 (69)Clinical opinion55.4 (14.2)per 1 mg/dL increment…∼1.39 (…) Formiga et al,31 2007PO1 center, Spain…414 (43)Criteria from Fonarow et al5276 (10)>2.26 (200 μmol/L)11.4Patients died: 1.78 (0.78)Patients survived: 1.45 (0.75) Alla et al (EPICAL),54 2000PO35 centers, France12401 (79.8)Prespecified criteriaDilated cardiomyopathy: 64>2.04 (180 μmol/L)11.7…Ischemic heart disease: 66 Cowie et al,55 2002PO1 hospital and 1 clinic, Bromley, United KingdomMean: 19332 (54)Clinical opinion75 (56–89)Per 0.11 (10 μmol/L) increment…1.26 (0.76–2.29) Cowie et al,56 2000PO1 hospital and 1 clinic, Hillington, United KingdomMean: 16 (6–26)220 (53.6)Clinical opinionMedian (IQR) = 76 (67–83)Per log 0.01 (1 μmol/L) increment…1.27 (1.04–1.62) Aronson et al (PRECEDENT),40 2004PHC66 centers, United StatesMean: ∼12541 (∼70)Prespecified criteria and clinical opinion93,94∼63 (…)Q1: 1.8 Akhter et al (VMAC),39 2004PHC55 centers, United States6481 (70)Prespecified criteria95∼62 (…)>1.5 (RI)44.7… Nohria et al (ESCAPE),12 2008PHC26 centers, United States6373 (…)Prespecified criteria9656 (14)Per 0.3-mg/dL increment…1.5 (0.6) Filippatos et al (ACTIV in CHF),41 2007PHC45 centers, United States and Argentina2302 (53)Prespecified criteria9762 (…)Per 1-mg/dL increment…1.4 (…) Smith et al (National Heart Care Project),60 2006ROMedicare data base, United States1256 652 (41.9)Discharge diagnosis79 (8)D1: ≤0.810.0Median (IQR): 1.3 (1.0–1.7)D2: >0.8–0.910.0D3: >0.9–1.012.0D4: >1.0–1.15.5D5: >1.1–1.214.0D6: >1.2–1.48.4D7: >1.4–1.59.1D8: >1.5–1.89.4D9: >1.8–2.38.0D10: >2.313.5‡ Abraham et al (OPTIMIZE-HF),45 2008RO259 centers, United States…37 548 (48)Discharge diagnosis73 (14)Per 0.3-mg/dL increment up to 3.5…1.8 (1.6) O'Connor et al (OPTIMIZE-HF),47 2008RO259 centers, United States2–3Follow-up cohort: 5791 (51.2)Discharge diagnosisFollow-up cohort: 72.1 (13.7)Per 1-mg/dL increment up to 4…1.3 (1.0–1.8) Rosenthal et al,61 2000RO30 centers, United States113 834 (41.7)Discharge diagnosis78.9 (7.7) 1.44 (127 μmol/L)32…Women: >1.21 (107 μmol/L) Owan et al,15 2006ROMayo Clinic hospitals, United States3, Median: 586440 (56.2)Discharge diagnosis and Framingham criteria98,99∼73 (…)Per 1 mg/dL increment…… Lee et al (EFFECT),67 2003RO34 centers, Ontario, Canada1 and 122624 (50)Discharge diagnosis and Framingham criteria98,99∼76 (…)>2.0…1.45 (0.96) Goldberg et al,63 2005RO11 centers, United States…2604 (43.3)Discharge diagnosis and Framingham criteria98,99Median: 79 (…)1.022.7 (584/2570)‡1.6 (…)1.0–1.119.81.2–1.730.4≥1.827.0 Goldberg et al,64 2007RO11 centers, United States3, 12, and 602445 (43.5)Discharge diagnosis and Framingham criteria98,99∼76.8 (…)Per 1-mg/dL increment…Patients died: 1.7 (1.2)Patients survived: 1.4 (1.2) McClellan et al,11 2002RO120 centers, United States12665 (40)Discharge diagnosis76 (11)Women: >1.438.01.46 (0.78)Men: >1.5 (CKD) Parkash et al,65 2005RO1 center, United States60478 (53)Discharge diagnosis and Framingham criteria98,9974 (13)>2.0…1.23 (0.5) Sosin et al,46 2004RO1 center, United Kingdom96214 (51)ESC guidelines criteria91∼74 (…)>1.36 (120 μmol/L)57.5…eGFR (mL/min per 1.73 m2) Tavazzi et al,36 2005POSee above>60∥40.9 (1115/2728) 46.7…30–6012.4<30 van Kimmenade et al,37 2006PO4 centers, multinational2720 (51)ESC guidelines criteria9175 (…)<60∥51.860.4 (…) O'Connor et. al (IMPACT-HF),57 2005PO30 centers, United States2567 (52)Clinical opinion71 (12)<60∥23.5… Komukai et al,30 2008PO1 center, Japan∼12 (0–122)109 (67)Framingham criteria98,9972 (1)<45 (decreased renal function)∥38.553.5 (2.4) Klein et al (OPTIME-CHF),13 2008PHC80 centers, United States…949 (66)Prespecified criteria100∼67 (…)Q1: not defined∥25.0 (234/937)‡Median (IQR):Q2: not defined25.151 (37–70)Q3: not defined25.0Q4: not defined25.0 50 (>475/937) Nohria et al (ESCAPE),12 2008PHCSee abovePer 10 mL/min decrement…74.8 (…)<60 (renal insufficiency)∥31.4… Heywood et al (ADHERE),14 2007RO280 centers, United States…118 465 (48)Discharge diagnosis72 (…)≥90∥9.055.2 (29.9)60–8927.430–5943.515–2913.1 85∥10.3‡Median (IQR): 50 (35–66)D2: >71–8510.0D3: >62–719.6D4: >56–6211.0D5: >50–5610.1D6: >44–508.7D7: >38–449.7D8: >32–3811.5D9: >24–328.9D10: ≤2410.3 Smith et al (National Heart Care Project),60 2006ROSee aboveD1: >100¶9.2Median (IQR): 60 (37–85)D2: >90–10010.6D3: >80–909.6D4: >70–8010.0D5: >60–7010.3D6: >50–6010.3D7: >41–5010.0D8: >32–419.9D9: >22–3210.2D10: ≤229.9 Ismailov et al (Worcester HF Study),44 2007RO11 centers, United States12 and 604350 (43)Discharge diagnosis and Framingham criteria98,9976 (…)≥60∥52.7…45–5917.530–4416.7 13.1<30CrCl, mL/min Gustafsson et al (DIAMOND-CHF),58 2004PO34 centers, Denmark60–965491 (60.1)Prespecified criteria and clinical opinionMen: 72 (64–77) 6037.3 Rudiger et al,34 2005PO2 centers, Europe12312 (56)Prespecified criteria73 (12) 84**……Q2: 61–84Q3: 39–60Q4: <38BUN or SUN, mg/dL Tavazzi et al,36 2005POSee above 10023.5 Rohde et al,33 2006POSee above>37 (∼mean value)…36 (22) Klein et al (OPTIME-CHF),13 2008PHCSee aboveQ1: 2–1725.4 (238/936)Median (IQR):Q2: 18–2524.825 (17–41)Q3: 26–4024.5Q4: 41–13625.3 Aronson et al (PRECEDENT),40 2004PHCSee aboveQ1: 45 Filippatos et al (ACTIV in CHF),41 2007PHCSee aboveQ1: ≤1826.830.9 (17.4)Q2: 19–2625.2Q3: 27–3924.8Q4: ≥4023.2 Smith et al (National Heart Care Project),60 2006ROSee aboveD1: ≤1310.4Median (IQR): 25 (18–37)D2: >13–169.4D3: >16–1910.7D4: >19–229.8D5: >22–2410.8D6: >24–289.9D7: >28–337.3D8: >33–4111.3D9: >41–5410.1D10: >5410.3 Rosenthal et al,61 2000ROSee above<2030.3…20–2931.930–3916.140–498.0≥5013.7 Lee et al (EFFECT),67 2003ROSee abovePer 10-mg/dL increment…29.4 (19.3) Goldberg et al,63 2005ROSee above<2027.8 (715/2570)35.2 (…)20–2415.025–4432.6≥4524.6 Goldberg et al,64 2007ROSee abovePer 1-mg/dL increment…Patients died:37.1 (24.1)Patients survived:25.3 (18.9) Kerzner et al,66 2003RO1 center, United StatesMean: 25373 (44)Discharge diagnosis69.1 (…)Per 10-mg/dL increment…Age <75 yPreserved LVEF: 27.8 (19.1)Reduced LVEF:28.6 (18.4)Age ≥75 yPreserved LVEF: 33 (24)Reduced LVEF:29 (17)BUN (mg/dL)/SCr (mg/dL)§ Aronson et al (PRECEDENT),40 2004PHCSee aboveQ1: 27 Rosenthal et al,61 2000ROSee above 0.12 and/or CrCl ∼0.3 (26 μmol/L)All patients:…248 without MC33Without MC: 29 Komukai et al,30 2008PO1 center, Japan∼12 (0–122)109 (67)Framingham criteria98,9972 (1)≥0.222.9… Akhter et al (VMAC),39 2004PHC55 centers, United States6481 (70)Prespecified criteria95∼62 (…)>0.524.8… Nohria et al (ESCAPE),12 2008PHC26 centers, United States6373 (…)Prespecified criteria9656 (14)≥0.329.50.07 (…) Owan et al,15 2006ROMayo Clinic hospitals, United States3, Median: 586440 (56.2)Discharge diagnosis and Framingham criteria98,99∼73 (…)Per 1 mg/dL increase……>0.323.1≥25%25.6 Krumholz et al,43 2000RO18 centers, United States1 and 61681 (42)Discharge diagnosis79 (8)>0.327.9… Forman et al,42 2004RO11 centers, United States…1004 (51)Discharge diagnosis67 (15)>0.327.2…eGFR decrease, mL/min per 1.73 m2 Nohria et al (ESCAPE),12 2008PHCSee above≥25%§…Median discharge: 73.9 (…)Median baseline: 71.4 (…)BUN increase, mg/dL Klein et al (OPTIME-CHF),13 2008PHC80 centers, United States…949 (66)Prespecified criteria100∼67 (…)≥25%394.8 (…)ESC indicates European Society of Cardiology; IQR, interquartile range; PHC, post hoc analysis of clinical trial; PO, prospective observational study; RO, retrospective observational study; and MC, major complications.*Percentage of men is based on original study population, not on final population available for analysis.†Median where noted.‡To convert μmol/L of SCr to mg/dL, divide by 88.5.§MDRD prediction equation: eGFR (mL/min per 1.73 m2)=186×(serum creatinine in mg/dL)−1.154×(age in years)−0.203×0.742 (if female)×1.212 (if black).81DefinitionsThe definitions of RI and WRF varied widely across the 42 studies identified in this review (Tables 1 and 2). RI was defined or stratified using 4 different laboratory measures, including SCr, eGFR, CrCl, and BUN or serum urea nitrogen, as well as 2 combined measures, including BUN/SCr, and SCr and/or CrCl (Table 1). Eleven studies provided multiple definitions of RI using several laboratory measures,12,13,33,36,40,41,60,61,63,64,67 all of which were included in this review. The majority of studies that assessed WRF defined the condition as a ≥ 0.3 mg/dL increase in SCr after admission (Table 2). Additional definitions included other absolute and/or relative increases in SCr, a relative decrease in eGFR, and an absolute increase in BUN after admission. Two studies provided multiple definitions of WRF; 1 study defined WRF using 2 different laboratory measures,12 whereas another study provided alternative cut points for an increase in SCr.29Health OutcomesIn-Hospital MortalityThree prospective (n=4000) and 4 retrospective observational studies (n=162 967) evaluated the association between RI and in-hospital mortality14,31,33,36,44,45,63 (Table 3). Of these 7 studies, 2 prospective (n=1193) and 3 retrospective studies (n=160 863) found a significant association for all RI definitions assessed,14,31,33,44,45 whereas 2 studies (n=5411) found a significant association for some definitions.36,63 In addition, 1 prospective (n=299) and 2 retrospective studies (n=2685) evaluated the association between WRF and inpatient mortality,26,42,43 of which 2 studies (n=2685) found a significant association.42,43 The prospective study noted a significant association when all patients were included (n=299); however, the association lost significance when patients with major complications (n=51) were excluded.26Table 3. Renal Impairment, Mortality, and Readmission in Acute Heart FailureStudy (Trial/Registry), YearDesignFollow-Up, moDefinition/Stratification of RI/BRFMortality OR/RR/HR (95% CI), P ValueReadmission OR/RR/HR (95% CI), P ValueReadmission/Mortality OR/RR/HR (95% CI), P ValueIn-HospitalFollow-UpSCr, mg/dL† Tavazzi et al,36 2005PO…Per 1-mg/dL incrementOR=NS*……… Rohde et al,33 2006PO…>1.4 (mean value)OR=2.1 (1.1–4.1), P=0.02……… Siirilä-Waris et al (FINN-AKVA),35 2006PO12>1.36 (120 μmol/L)…HR=1.9 (1.3–2.7), P=0.0009…… Zannad et al (EFICA),59 2006PO12>2.26 (200 μmol/L)…RR=1.8 (1.2–2.8), P=0.005…… Nohria et al,53 2003PO12Per 1-mg/dL increment…HR=1.4 (…), P 2.26 (200 μmol/L)OR=3.4 (1.5–7.7), P=0.003……… Alla et al (EPICAL),54 2000PO12>2.04 (180 μmol/L)…Patients w/dilated cardiomyopathy: RR=2.7 (2.6–3.0), P=0.009 Patients w/ischemic heart disease: RR=2.3 (2.2–2.4), P=0.004…… Cowie et al,55 2002POMean: 19Per 0.11 (10-μmol/L) increment…HR=1.1 (1.04–1.1), P<0.05…… Cowie et al,56 2000POMean: 16 (6–26)Per log 0.01 (1-μmol/L) increment…HR=2.6 (1.9–3.7), P 1.8 vs Q1: <1.0…RR=1.2 (0.7–1.8), P=0.54…… Akhter et al (VMAC),39 2004PHC6≥1.5…RR=2.7 (1.8–4.2), P=0.0001…… Nohria et al (ESCAPE),12 2008PHC6Per 0.3-mg/dL increment…HR=1.2 (1.1–1.3), P<0.0001…HR=1.1 (1.1–1.2), P 2.3 vs D1: ≥0.8…HR=2.2 (2.1–2.4)…… Abraham et al (OPTIMIZE-HF),45 2008RO…Per 0.3-mg/dL increment up to 3.5OR=1.2 (1.16–1.20), P<0.0001……… O'Connor et al (OPTIMIZE-HF),47 2008RO2–3Per 1-mg/dL increment up to 4…HR=1.3 (1.1–1.6), P=0.0069…HR=1.3 (1.2–1.4), P<0.0001 Rosenthal et al,61 2000RO1Per 1-category increment:…OR=1.2 (1.1–1.4), P=0.004……<1.51.5–2.4≥2.5 Velavan et al (Euro Heart Failure Study),62 2008RO≤31 SD (1.16;103 μmol) increment…OR=1.2 (1.2–1.3), P<0.001…… Owan et al,15 2006RO3, Median: 58Per 1-mg/dL increment…3 mo……OR=1.1 (1.05–1.2), P=0.0004Overall follow-upHR=1.1 (1.07–1.13), P 2.0…1 mo……OR=NS* Goldberg et al,63 2005RO12Q4: ≥1.8OR=1.0………vs Q1: 1.0(0.4–2.1)* Goldberg et al,64 2007RO3, 12, 60Per 1-mg/dL increment…3 mo……OR=0.9 (0.7–1.0)*12 moOR=0.9 (0.8–1.0)*60 moOR=1.1 (0.9–1.2)* McClellan et al,11 2002RO12Women: >1.4…RR=1.4 (1.1–1.9), P=0.018……Men: >1.5 (CKD) Parkash et al,65 2005RO60>2.0…HR=2.4 (1.5–3.6), P 1.36 (120 μmol/L)…Probability survival……RR=0.6 (0.4–0.8), P=0.001eGFR, mL/min per 1.73 m2 Tavazzi et al,36 2005PO…Per 1 mL/min per 1.73 m2 increment‡OR=NS*……… van Kimmenade et al,37 2006PO2<60‡…OR=2.0 (1.2–3.5), P<0.001…… O'Connor et al (IMPACT-HF),57 2005PO2<60‡………OR=1.03 (0.72–1.47), P=0.89 Komukai et al,30 2008PO∼12 (0–122)<45‡……HF-related HR=1.9 (1.03–3.4), P=0.041… Klein et al (OPTIME-CHF),13 2008PHC2Q1: median=82 (75–94)‡ vs Q4: median=29 (25–33)…HR=4.7 (2.4–9.4)…OR=2.8 (1.9‒4.2), P<0.01 Nohria et al (ESCAPE),12 2008PHC6Per 10-mL/min decrement‡…HR=1.3 (1.1–1.4), P<0.0001…HR=1.1 (1.05–1.2), P 85…HR=2.0 (1.9–2.2)…… Smith et al (National Heart Care Project),60 2006RO12D10: ≤22§ vs D1: >100…HR=2.6 (2.4–2.8)…… Ismailov et al (Worcester Heart Failure Study),44 2007RO12 and 60Q1: <30‡ vs Q4: ≥60OR=1.9 (1.3–2.7)12 moHR=2.3……(1.9–2.8)60 moHR=1.7(1.5–1.9)CrCl (mL/min) Gustafsson et al (DIAMOND-CHF),58 2004PO60–96Per 20-mL/min increment∥…RR=0.7 (0.69–0.8)…… Rudiger et al,34 2005PO12<50∥…OR=2.5 (1.4–4.3)…… Ochiai et al,32 2005PO12Per 1-mL/min decrement¶…RR=1.03 (1.01–1.04), P<0.001…… Aronson et al (PRECEDENT),40 2004PHCMean: ∼12Q4: 84…RR=1.6 (0.9–2.8), P=0.09……BUN or SUN, mg/dL Tavazzi et al,36 2005PO…Per 1-mg/dL incrementOR=1.007 (1.003–1.012), P=0.0012……… Rohde et al,33 2006PO…>37 (mean value)OR=2.1 (1.1–4.0), P = 0.03……… Klein et al (OPTIME-CHF),13 2008PHC2Q4: 46…68 vs Q1: 2–16…HR=8.3 (3.8–18.3)…OR=3.7 (2.5–5.6), P 45 vs Q1 54 vs D1: ≤13…HR=3.3 (3.1–3.5)…… Rosenthal et al,61 2000RO1Q5: ≥50 vs Q1: <20…OR=2.2 (1.6–3.1), P<0.001…… Lee et al (EFFECT),67 2003RO1 and 12Per 10-mg/dL increment…1 mo……OR=1.6 (1.4–1.7), P<0.00112 moOR=1.5 (1.4–1.6), P<0.001 Goldberg et al,63 2005RO12Q4: ≥45 vs Q1: <20OR=2.1 (1.05–4.3)……… Gol
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