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The association of chronic kidney disease and microalbuminuria with heart failure with preserved vs. reduced ejection fraction.

ABSTRACT: AIMS:Chronic kidney disease (CKD) and microalbuminuria are associated with incident heart failure (HF), but their relative contributions to HF with preserved vs. reduced EF (HFpEF and HFrEF) are unknown. We sought to evaluate the associations of CKD and microalbuminuria with incident HF subtypes in the community-based Framingham Heart Study (FHS). METHODS AND RESULTS:We defined CKD as glomerular filtration rate <60 mL/min/1.73 m2 , and microalbuminuria as a urine albumin to creatinine ratio (UACR) ?17 mg/g in men and ?25 mg/g in women. We observed 754 HF events (324 HFpEF/326 HFrEF/104 unclassified) among 9889 FHS participants with serum creatinine measured (follow-up 13 ± 4 years). In Cox models adjusted for clinical risk factors, CKD (prevalence = 9%) was associated with overall HF [hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.01-1.51], but was not significantly associated with individual HF subtypes. Among 2912 individuals with available UACR (follow-up 15 ± 4 years), 192 HF events (91 HFpEF/93 HFrEF/8 unclassified) occurred. Microalbuminuria (prevalence = 17%) was associated with a higher risk of overall HF (HR 1.71, 95% CI 1.25-2.34) and HFrEF (HR 2.10, 95% CI 1.35-3.26), but not HFpEF (HR 1.26, 95% CI 0.78-2.03). In cross-sectional analyses, microalbuminuria was associated with LV systolic dysfunction (odds ratio 3.19, 95% CI 1.67-6.09). CONCLUSIONS:Microalbuminuria was associated with incident HFrEF prospectively, and with LV systolic dysfunction cross-sectionally in a community-based sample. In contrast, CKD was modestly associated with overall HF but not differentially associated with HFpEF vs. HFrEF. The mechanisms responsible for the relationship of microalbuminuria to future development of HFrEF warrant further investigation.

SUBMITTER: Nayor M

PROVIDER: S-EPMC5423843 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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The association of chronic kidney disease and microalbuminuria with heart failure with preserved vs. reduced ejection fraction.

Nayor Matthew M Larson Martin G MG Wang Na N Santhanakrishnan Rajalakshmi R Lee Douglas S DS Tsao Connie W CW Cheng Susan S Benjamin Emelia J EJ Vasan Ramachandran S RS Levy Daniel D Fox Caroline S CS Ho Jennifer E JE

European journal of heart failure 20170220 5

<h4>Aims</h4>Chronic kidney disease (CKD) and microalbuminuria are associated with incident heart failure (HF), but their relative contributions to HF with preserved vs. reduced EF (HFpEF and HFrEF) are unknown. We sought to evaluate the associations of CKD and microalbuminuria with incident HF subtypes in the community-based Framingham Heart Study (FHS).<h4>Methods and results</h4>We defined CKD as glomerular filtration rate <60 mL/min/1.73 m<sup>2</sup> , and microalbuminuria as a urine albumi ...[more]

PMID: 28217978

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Project description:AimsThis study aimed to assess short-term outcomes among emergency department (ED) patients with acute heart failure (AHF) by preserved (≥50%) vs. reduced (<50%) ejection fraction (EF).Methods and resultsWe conducted a retrospective, multicentre study of adult ED patients with AHF from 2017 to 2018 in an integrated healthcare system with 21 hospitals. Among patients with known EF, our primary outcome was 30 day all-cause mortality, comparing patients with heart failure with preserved EF (HFpEF) and heart failure with reduced EF (HFrEF), adjusted for known risk factors. We ran separate multivariate regression models to compare 30 day mortality between HFpEF and HFrEF patients stratified by ED disposition (admit, observe, and discharge). Our secondary outcomes were adjusted 30 day all-cause return hospital admission and rates of non-fatal serious adverse events, including new intra-aorta balloon pump, endotracheal intubation, renal failure requiring dialysis, myocardial infarction, or coronary revascularization. We conducted a sensitivity analysis among patients with EF ≤ 40% and compared our primary and secondary outcomes among patients with EF ≤ 40% with those with EF ≥ 50%. Among the 26 050 total ED encounters for AHF, 15 275 (58.6%) had known EF and 62.4% had HFpEF. The mean age was 76, 49.6% were women, and 60.5% were white. We found that 62.4% of patients were admitted, 18.3% were observed, and 19.3% were discharged from the ED. The 30 day all-cause mortality rate was lowest among discharged patients (3.9%), intermediate among observed patients (5.9%), and highest among admitted patients (13.9%). Overall, the adjusted 30 day mortality rate was significantly higher among HFpEF patients compared with HFrEF patients (10.2% vs. 8.4%, P = 0.0004). HFpEF patients had higher mortality regardless of ED disposition, although the difference was only significant among admitted patients. The adjusted 30 day return hospital admission rates were not significantly different between HFpEF and HFrEF patients (17.9% vs. 17.8%, P = 0.89). The adjusted 30 day non-fatal serious adverse event rates were significantly higher among HFrEF patients compared with HFpEF patients (13.7% vs. 11.1%, P < 0.0001), driven by myocardial infarction and coronary revascularization. We found that 3692 patients had EF ≤ 40%. Patients with EF ≥ 50% had significantly higher adjusted 30 day mortality rates compared with those with EF ≤ 40% (10.2% vs. 8.4%, P < 0.05).ConclusionIn a contemporary population, almost three quarters of ED patients with AHF and known EF have HFpEF. These patients have higher 30 day adjusted mortality compared with those with HFrEF. Further studies might evaluate the underlying factors associated with this difference and target interventions to improve outcomes.

Project description:BackgroundMicrovascular dysfunction plays an important role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link between systemic microvasculature and congestion, a central feature of the syndrome, has yet been investigated.ObjectivesThis study aimed to investigate capillary-interstitium fluid exchange in HFpEF, including lymphatic drainage and the potential osmotic forces exerted by any hypertonic tissue Na+ excess.MethodsPatients with HFpEF and healthy control subjects of similar age and sex distributions (n = 16 per group) underwent: 1) a skin biopsy for vascular immunohistochemistry, gene expression, and chemical (water, Na+, and K+) analyses; and 2) venous occlusion plethysmography to assess peripheral microvascular filtration coefficient (measuring capillary fluid extravasation) and isovolumetric pressure (above which lymphatic drainage cannot compensate for fluid extravasation).ResultsSkin biopsies in patients with HFpEF showed rarefaction of small blood and lymphatic vessels (p = 0.003 and p = 0.012, respectively); residual skin lymphatics showed a larger diameter (p = 0.007) and lower expression of lymphatic differentiation and function markers (LYVE-1 [lymphatic vessel endothelial hyaluronan receptor 1]: p < 0.05; PROX-1 [prospero homeobox protein 1]: p < 0.001) compared with control subjects. In patients with HFpEF, microvascular filtration coefficient was lower (calf: 3.30 [interquartile range (IQR): 2.33 to 3.88] l × 100 ml of tissue-1 × min-1 × mm Hg-1 vs. 4.66 [IQR: 3.70 to 6.15] μl × 100 ml of tissue-1 × min-1 × mm Hg-1; p < 0.01; forearm: 5.16 [IQR: 3.86 to 5.43] l × 100 ml of tissue-1 × min-1 × mm Hg-1 vs. 5.66 [IQR: 4.69 to 8.38] μl × 100 ml of tissue-1 × min-1 × mm Hg-1; p > 0.05), in keeping with blood vascular rarefaction and the lack of any observed hypertonic skin Na+ excess, but the lymphatic drainage was impaired (isovolumetric pressure in patients with HFpEF vs. control subjects: calf 16 ± 4 mm Hg vs. 22 ± 4 mm Hg; p < 0.005; forearm 17 ± 4 mm Hg vs. 25 ± 5 mm Hg; p < 0.001).ConclusionsPeripheral lymphatic vessels in patients with HFpEF exhibit structural and molecular alterations and cannot effectively compensate for fluid extravasation and interstitial accumulation by commensurate drainage. Reduced lymphatic reserve may represent a novel therapeutic target.

Project description:AimsThe Kansas City Cardiomyopathy Questionnaire (KCCQ) is a widely used patient-reported outcome measure in heart failure (HF). The KCCQ was validated in patients with HF with reduced ejection fraction (HFrEF), leaving knowledge gaps regarding its applicability in HF with preserved ejection fraction (HFpEF). This study addresses the psychometric properties of internal consistency and reliability, construct, and known-group validity of KCCQ in both HFrEF and HFpEF. We aimed to evaluate the psychometric properties of the KCCQ and their prognostic significance in HFpEF and HFrEF, within a large prospective multinational HF cohort.Methods and resultsWe examined the 23-item KCCQ in the prospective multinational ASIAN-HF study [4470 HFrEF (ejection fraction <40%); 921 HFpEF (ejection fraction ≥50%)]. Internal consistency (using Cronbach's alpha) showed high reliability in HFrEF and HFpeF: functional status score: 0.89 and 0.91 and clinical summary score: 0.89 and 0.90, respectively. Confirmatory factor analysis in HFrEF validated the five original domains of KCCQ (physical function, symptoms, self-efficacy, social limitation, and quality of life); in HFpEF, questions measuring physical function and social limitation had strong correlation (r = 0.66) and different domains emerged. We proposed an additional physical independence summary score, especially in HFpEF (comprising the original physical function and social limitation domains), which showed good internal consistency (α = 0.89) and has comparable receiver operating characteristic curve 0.766 ± 0.037 with the clinical summary score (receiver operating characteristic curve 0.774 ± 0.037), in predicting 1 year death and/or HF hospitalization.ConclusionsOur results confirmed the robustness of the KCCQ clinical summary score in HF regardless of ejection fraction group. In the assessment of physical capacity in HFpEF, our results suggest strong interaction with social limitation, and we propose a summary score comprising both components be used.

Dataset Information

The association of chronic kidney disease and microalbuminuria with heart failure with preserved vs. reduced ejection fraction.

Publications

The association of chronic kidney disease and microalbuminuria with heart failure with preserved vs. reduced ejection fraction.

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