Tubular Damage and Worsening Renal Function in Chronic Heart Failure

Objectives This study sought to investigate the relationship between tubular damage and worsening renal function (WRF) in chronic heart failure (HF) Background WRF is associated with poor outcome in chronic HF. It is unclear whether urinary tubular markers may identify patients at risk for WRF. Methods In 2,011 patients with chronic HF, we evaluated the ability of urinary tubular markers (N-acetyl-beta-D-glucosaminidase (NAG), kidney injury molecule (KIM)-1, and neutrophil gelatinase-associated lipocalin (NGAL) to predict WRF. Finally, we assessed the prognostic importance of WRF. Results A total of 290 patients (14.4%) experienced WRF during follow-up, and WRF was a strong and independent predictor of all-cause mortality and HF hospitalizations (hazard ratio [HR]: 2.87; 95% CI: 2.40 to 3.43; p <0.001). Patients with WRF had lower baseline glomerular filtration rate and higher KIM-1, NAG, and NGAL levels. In a multivariableadjusted model, KIM-1 was the strongest independent predictor of WRF (HR: 1.23; 95% CI: 1.09 to 1.39 per log increase; p = 0.001). Conclusions WRF was associated with strongly impaired outcome in patients with chronic HF. Increased level of urinary KIM-1 was the strongest independent predictor of WRF and could therefore be used to identify patients at risk for WRF and poor clinical outcome. (GISSI-HF-Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic CHF; NCT00336336) (J Am Coll Cardiol HF 2013; 1: 417-24) (C) 2013 by the American College of Cardiology Foundatio

Impact of metabolic syndrome traits on cardiovascular function: Should the Adult Treatment Panel III definition be further stratified?

AIMS: The aims of the study were to evaluate whether a further classification of metabolic syndrome according to the number of traits (based on the Adult Treatment Panel III definition) could better explain the impact on cardiovascular remodeling and function, and to assess the role of single metabolic syndrome components in this regard. METHODS: We studied by echocardiography and carotid ultrasound 435 asymptomatic patients with metabolic syndrome. Patients with coronary artery disease or more than mild valvular heart disease were excluded. Carotid stiffness index (β) was measured using a high-resolution echo-tracking system. Patients with metabolic syndrome were divided into two groups: metabolic syndrome with three traits (Gr.1) and metabolic syndrome with four or five traits (Gr. 2). RESULTS: Patients in Gr. 2 had higher left ventricular mass index (P<0.001), left ventricular end-diastolic volume index (P=0.029), left atrial volume index (P=0.002), E/e' ratio (P=0.002), intima-media thickness (P=0.031), and prevalence of plaques (P=0.01) than patients in Gr. 1. Left ventricular ejection fraction was similar in both groups. The mean carotid β index tended to be higher in Gr. 2. Considering metabolic syndrome traits separately, in an age-corrected multivariate analysis, abdominal obesity was found to have the strongest association with cardiac structure and carotid artery atherosclerosis and stiffness. CONCLUSION: An increasing number of metabolic syndrome traits had a significantly worse impact on cardiac remodeling and function and carotid artery atherosclerosis. Abdominal obesity showed the strongest association with cardiac structure, carotid artery stiffness, and intima-media thickness. Prospective studies are needed to evaluate whether a new classification of metabolic syndrome using the number of traits could add prognostic information. © 2014 Italian Federation of Cardiology

Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial

Background: Several epidemiological and experimental studies suggest that n-3 polyunsaturated fatty acids (PUFA) can exert favourable effects on atherothrombotic cardiovascular disease, including arrhythmias. We investigated whether n-3 PUFA could improve morbidity and mortality in a large population of patients with symptomatic heart failure of any cause. Methods: We undertook a randomised, double-blind, placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy. We enrolled patients with chronic heart failure of New York Heart Association class II-IV, irrespective of cause and left ventricular ejection fraction, and randomly assigned them to n-3 PUFA 1 g daily (n=3494) or placebo (n=3481) by a concealed, computerised telephone randomisation system. Patients were followed up for a median of 3\ub79 years (IQR 3\ub70-4\ub75). Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00336336. Findings: We analysed all randomised patients. 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (adjusted hazard ratio [HR] 0\ub791 [95\ub75% CI 0\ub7833-0\ub7998], p=0\ub7041). 1981 (57%) patients in the n-3 PUFA group and 2053 (59%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 0\ub792 [99% CI 0\ub7849-0\ub7999], p=0\ub7009). In absolute terms, 56 patients needed to be treated for a median duration of 3\ub79 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons. In both groups, gastrointestinal disorders were the most frequent adverse reaction (96 [3%] n-3 PUFA group vs 92 [3%] placebo group). Interpretation: A simple and safe treatment with n-3 PUFA can provide a small beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with heart failure in a context of usual care. Funding: Societ\ue0 Prodotti Antibiotici (SPA; Italy), Pfizer, Sigma Tau, and AstraZeneca. \ua9 2008 Elsevier Ltd. All rights reserved

Medical therapy for rheumatic heart disease: is it time to be proactive rather than reactive?

Rheumatic Heart Disease (RHD) is well known to be an active inflammatory process which develops progressive calcification and leaflet thickening over time. The potential for statin therapy in slowing the progression of valvular heart disease is still controversial. Retrospective studies have shown that medical therapy is beneficial for patients with calcific aortic stenosis and recently for rheumatic valve disease. However, the prospective randomized clinical trials have been negative to date. This article discusses the epidemiologic risk factors, basic science, retrospective and prospective studies in valvular heart disease and a future clinical trial to target RHD with statin therapy to slow the progression of this disease. Recent epidemiological studies have revealed the risk factors associated with valvular disease include male gender, smoking, hypertension and elevated serum cholesterol and are similar to the risk factors for vascular atherosclerosis. An increasing number of models of experimental hypercholesterolemia demonstrate features of atherosclerosis in the aortic valve (AV), which are similar to the early stages of vascular atherosclerotic lesions. Calcification, the end stage process of the disease, must be understood as a prognostic indicator in the modification of this cellular process before it is too late. This is important in calcific aortic stenosis as well as in rheumatic valve disease. There are a growing number of studies that describe similar pathophysiologic molecular markers in the development of rheumatic valve disease as in calcific aortic stenosis. In summary, these findings suggest that medical therapies may have a potential role in patients in the early stages of this disease process to slow the progression of RHD affecting the valves. This review will summarize the potential for statin therapy for this patient population