Among patients with ischemic cardiomyopathy, coronary-artery bypass grafting added to medical therapy led to significantly lower rates of death from any cause and of cardiovascular death over 10 ...years than did medical therapy alone.
Advances in the management of cardiovascular risk factors and acute coronary syndromes have increased survival among patients with coronary artery disease, transforming it into a chronic disease that affects 15.5 million U.S. patients; however, coronary artery disease still accounts for more than 538,000 deaths yearly in the United States alone.
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The major long-term manifestations of coronary artery disease, left ventricular dysfunction, and heart failure are projected to affect 8 million patients by 2030, which has enormous societal implications.
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Landmark clinical trials have established coronary-artery bypass grafting (CABG) as an effective treatment for patients with disabling angina symptoms.
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BACKGROUND—Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However limited data exist as to how ...CAC compares to functional testing (FT) in estimating prognosis in symptomatic patients.
METHODS—In the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, patients with stable chest pain (or dyspnea) and intermediate pre-test probability for obstructive coronary artery disease (CAD) were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4,209) and compared to results of FT (n=4,602). We stratified CAC and FT results as normal or mildly, moderately or severely abnormal (for CAC0, 1-99 Agatston Score AS, 100-400 AS and >400 AS, respectively; for FTnormal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia and severe=large ischemic region abnormality). The primary endpoint was all-cause death, myocardial infarction or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios and C-statistic to determine predictive and discriminatory value.
RESULTS—Overall, the distribution of normal or mildly, moderately or severely abnormal test results was significantly different between FT and CAC (FT = normal 3588 78.0%, mild 432 9.4%, moderate 217 4.7%, severe 365 7.9%; CAC = normal 1,457 34.6%, mild 1340 31.8%, moderate 772 18.3%, severe 640 15.2%, p <0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderateCAC HR 3.14, 95% CI 1.81-5.44 and FT HR 2.65, 95% CI 1.46-4.83; severeCAC HR 3.56, 95% CI 1.99-6.36 and FT HR 3.88, 95% CI 2.58-5.85. In the CAC arm, the majority of events (n=112/133; 84%) occurred in patients with any positive CAC test (score >0) whereas less than half of events occurred in patients with mild, moderate or severely abnormal FT (n=57/132; 43%) (p<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT vs 35.2% for CAC, p<0.001). Overall discriminatory ability in predicting the primary endpoint of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (c-statistic, 0.67 vs. 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared to FT and CAC testing (C-index0.72).
CONCLUSION—Among stable outpatients presenting with suspected CAD, most patients experiencing clinical events have measurable CAC at baseline while less than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests.
CLINICAL TRIAL REGISTRATION—URLhttps://clinicaltrials.gov; Unique IdentifierNCT01174550
Visceral obesity is intimately associated with metabolic disease and adverse health outcomes. However, a direct association between increasing amounts of visceral fat and end‐organ inflammation and ...scarring has not been demonstrated. We examined the association between visceral fat and liver inflammation in patients with nonalcoholic fatty liver disease (NAFLD) to delineate the importance of visceral fat to progressive steatohepatitis and hence the inflammatory pathogenesis of the metabolic syndrome. We undertook a cross‐sectional, proof of concept study in 38 consecutive adults with NAFLD at a tertiary liver clinic. All subjects had a complete physical examination, anthropometric assessment, and fasting blood tests on the day of liver biopsy. Abdominal fat volumes were assessed by magnetic resonance imaging within 2 weeks of liver biopsy. The extent of hepatic inflammation and fibrosis augmented incrementally with increases in visceral fat (P < 0.01). For each 1% increase in visceral fat, the odds ratio for increasing liver inflammation and fibrosis was 2.4 (confidence interval CI: 1.3‐4.2) and 3.5 (CI: 1.7‐7.1), respectively. Visceral fat remained an independent predictor of advanced steatohepatitis (odds ratio OR 2.1, CI: 1.1‐4.2, P = 0.05) and fibrosis (OR 2.9, CI: 1.4‐6.3, P = 0.006) even when controlled for insulin resistance and hepatic steatosis. Interleukin‐6 (IL‐6) levels, which correlated with visceral fat, also independently predicted increasing liver inflammation. Visceral fat was associated with all components of the metabolic syndrome. Conclusion: Visceral fat is directly associated with liver inflammation and fibrosis independent of insulin resistance and hepatic steatosis. Visceral fat should therefore be a central target for future interventions in nonalcoholic steatohepatitis and indeed all metabolic disease. (HEPATOLOGY 2008.)
Real-time study of the transport and biocompatibility of nanomaterials in early embryonic development at single-nanoparticle resolution can offer new knowledge about the delivery and effects of ...nanomaterials in vivo and provide new insights into molecular transport mechanisms in developing embryos. In this study, we directly characterized the transport of single silver nanoparticles into an in vivo model system (zebrafish embryos) and investigated their effects on early embryonic development at single-nanoparticle resolution in real time. We designed highly purified and stable (not aggregated and no photodecomposition) nanoparticles and developed single-nanoparticle optics and in vivo assays to enable the study. We found that single Ag nanoparticles (5–46 nm) are transported into and out of embryos through chorion pore canals (CPCs) and exhibit Brownian diffusion (not active transport), with the diffusion coefficient inside the chorionic space (3 × 10−9 cm2/s) ∼26 times lower than that in egg water (7.7 × 10−8 cm2/s). In contrast, nanoparticles were trapped inside CPCs and the inner mass of the embryos, showing restricted diffusion. Individual Ag nanoparticles were observed inside embryos at each developmental stage and in normally developed, deformed, and dead zebrafish, showing that the biocompatibility and toxicity of Ag nanoparticles and types of abnormalities observed in zebrafish are highly dependent on the dose of Ag nanoparticles, with a critical concentration of 0.19 nM. Rates of passive diffusion and accumulation of nanoparticles in embryos are likely responsible for the dose-dependent abnormalities. Unlike other chemicals, single nanoparticles can be directly imaged inside developing embryos at nanometer spatial resolution, offering new opportunities to unravel the related pathways that lead to the abnormalities.
Human adiposity has long been associated with insulin resistance and increased cardiovascular risk, and abdominal adiposity is considered particularly adverse. Intra-abdominal fat is associated with ...insulin resistance, possibly mediated by greater lipolytic activity, lower adiponectin levels, resistance to leptin, and increased inflammatory cytokines, although the latter contribution is less clear. Liver lipid is also closely associated with, and likely to be an important contributor to, insulin resistance, but it may also be in part the consequence of the lipogenic pathway of insulin action being up-regulated by hyperinsulinemia and unimpaired signaling. Again, intramyocellular triglyceride is associated with muscle insulin resistance, but anomalies include higher intramyocellular triglyceride in insulin-sensitive athletes and women (vs men). Such issues could be explained if the “culprits” were active lipid moieties such as diacylglycerol and ceramide species, dependent more on lipid metabolism and partitioning than triglyceride amount.
Subcutaneous fat, especially gluteofemoral, appears metabolically protective, illustrated by insulin resistance and dyslipidemia in patients with lipodystrophy. However, some studies suggest that deep sc abdominal fat may have adverse properties.
Pericardial and perivascular fat relate to atheromatous disease, but not clearly to insulin resistance.
There has been recent interest in recognizable brown adipose tissue in adult humans and its possible augmentation by a hormone, irisin, from exercising muscle. Brown adipose tissue is metabolically active, oxidizes fatty acids, and generates heat but, because of its small and variable quantities, its metabolic importance in humans under usual living conditions is still unclear.
Further understanding of specific roles of different lipid depots may help new approaches to control obesity and its metabolic sequelae.
Abstract Background Classification of chronic heart failure (HF) is on the basis of criteria that may not adequately capture disease heterogeneity. Improved phenotyping may help inform research and ...therapeutic strategies. Objectives This study used cluster analysis to explore clinical phenotypes in chronic HF patients. Methods A cluster analysis was performed on 45 baseline clinical variables from 1,619 participants in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) study, which evaluated exercise training versus usual care in chronic systolic HF. An association between identified clusters and clinical outcomes was assessed using Cox proportional hazards modeling. Differential associations between clinical outcomes and exercise testing were examined using interaction testing. Results Four clusters were identified (ranging from 248 to 773 patients in each), in which patients varied considerably among measures of age, sex, race, symptoms, comorbidities, HF etiology, socioeconomic status, quality of life, cardiopulmonary exercise testing parameters, and biomarker levels. Differential associations were observed for hospitalization and mortality risks between and within clusters. Compared with cluster 1, risk of all-cause mortality and/or all-cause hospitalization ranged from 0.65 (95% confidence interval 95% CI: 0.54 to 0.78) for cluster 4 to 1.02 (95% CI: 0.87 to 1.19) for cluster 3. However, for all-cause mortality, cluster 3 had a disproportionately lower risk of 0.61 (95% CI: 0.44 to 0.86). Evidence suggested differential effects of exercise treatment on changes in peak oxygen consumption and clinical outcomes between clusters (p for interaction <0.04). Conclusions Cluster analysis of clinical variables identified 4 distinct phenotypes of chronic HF. Our findings underscore the high degree of disease heterogeneity that exists within chronic HF patients and the need for improved phenotyping of the syndrome. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437 )
In a trial involving 10,003 patients with suspected coronary artery disease, clinical outcomes at 2 years were not improved with an initial strategy of CT angiography, as compared with functional ...testing (exercise ECG, nuclear stress testing, or stress echocardiography).
New-onset, stable chest pain is a common clinical problem that results in approximately 4 million stress tests annually in the United States in ambulatory patients without diagnosed heart disease.
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Despite advances in cardiac testing, there is scant information on health-related outcomes and little consensus about which noninvasive test is preferable.
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As a result, current patterns of care have been questioned, including the testing of very-low-risk populations
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and the catheterization of patients who do not have obstructive coronary artery disease (CAD).
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The development of coronary computed tomographic angiography (CTA) and its application in this context has the potential to . . .
In patients with heart failure and atrial fibrillation (AF), several clinical trials have reported improved outcomes, including freedom from AF recurrence, quality of life, and survival, with ...catheter ablation. This article describes the treatment-related outcomes of the AF patients with heart failure enrolled in the CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation).
The CABANA trial randomized 2204 patients with AF who were ≥65 years old or <65 years old with ≥1 risk factor for stroke at 126 sites to ablation with pulmonary vein isolation or drug therapy including rate or rhythm control drugs. Of these, 778 (35%) had New York Heart Association class >II at baseline and form the subject of this article. The CABANA trial's primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest.
Of the 778 patients with heart failure enrolled in CABANA, 378 were assigned to ablation and 400 to drug therapy. Ejection fraction at baseline was available for 571 patients (73.0%), and 9.3% of these had an ejection fraction <40%, whereas 11.7% had ejection fractions between 40% and 50%. In the intention-to-treat analysis, the ablation arm had a 36% relative reduction in the primary composite end point (hazard ratio, 0.64 95% CI, 0.41-0.99) and a 43% relative reduction in all-cause mortality (hazard ratio, 0.57 95% CI, 0.33-0.96) compared with drug therapy alone over a median follow-up of 48.5 months. AF recurrence was decreased with ablation (hazard ratio, 0.56 95% CI, 0.42-0.74). The adjusted mean difference for the AFEQT (Atrial Fibrillation Effect on Quality of Life) summary score averaged over the entire 60-month follow-up was 5.0 points, favoring the ablation arm (95% CI, 2.5-7.4 points), and the MAFSI (Mayo Atrial Fibrillation-Specific Symptom Inventory) frequency score difference was -2.0 points, favoring ablation (95% CI, -2.9 to -1.2).
In patients with AF enrolled in the CABANA trial who had clinically diagnosed stable heart failure at trial entry, catheter ablation produced clinically important improvements in survival, freedom from AF recurrence, and quality of life relative to drug therapy. These results, obtained in a cohort most of whom had preserved left ventricular function, require independent trial verification. Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT00911508; Unique identifier: NCT0091150.
Abstract This review summarizes evidence from 2 lines of research previously thought to be unrelated: the unexpectedly positive results of TACT (Trial to Assess Chelation Therapy), and a body of ...epidemiological data showing that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. Considering these 2 areas of work together may lead to the identification of new, modifiable risk factors for atherosclerotic cardiovascular disease. We examine the history of chelation up through the report of TACT. We then describe work connecting higher metal levels in the body with the future risk of cardiovascular disease. We conclude by presenting a brief overview of a newly planned National Institutes of Health trial, TACT2, in which we will attempt to replicate the findings of TACT and to establish that removal of toxic metal stores from the body is a plausible mechanistic explanation for the benefits of edetate disodium treatment.
The Stroop and stop-signal tasks are commonly used to index prepotent response inhibition in studies of cognitive development and individual differences. Inhibitory measures from the two tasks have ...been derived using a variety of methods. Findings of low inter-correlations amongst these measures have been interpreted as evidence for different kinds of inhibitory functions. Our previous study found Stroop and stop-signal accuracy measures to be uncorrelated and they loaded on different inhibitory components in a principal component analysis. The present study examined whether this finding is replicated across different task contexts, derived measures, and methods of derivation. Adolescents (N = 247) were administered a number-quantity Stroop and word and number stop-signal tasks. For each stop-signal task, inhibitory efficiency was estimated using a stop-signal reaction time measure estimated with the central versus the integration methods. For the Stroop interference task, inhibitory efficiency was indexed by reaction time measures (including inverse efficiency scores) generated from difference scores and regression residuals, and delta-plot slopes. The reaction time measures from the two tasks were generally not correlated. The only exception was that Stroop inhibitory ability, indexed by Stroop errors, was related to stop-signal inhibitory efficiency, indexed by stop-signal reaction time. These findings are consistent with previous findings suggesting that measures from the Stroop and stop-signal tasks are influenced by different underlying processes. The impact of variations in dependent measure derivation on the resulting reliabilities of Stroop and stop-signal measures and on observed correlations between them were examined. Variables that may have contributed to the null findings are discussed.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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