N-3 fatty acids and cardiovascular outcomes in patients with dysglycemia

Publisher Copyright: Copyright © 2012 Massachusetts Medical Society.Background: The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown. Methods: In this double-blind study with a 2-by-2 factorial design, we randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1-g capsule containing at least 900 mg (90% or more) of ethyl esters of n-3 fatty acids or placebo daily and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n-3 fatty acids and placebo are reported here. Results: During a median follow up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n-3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P = 0.72). The use of n-3 fatty acids also had no significant effect on the rates of major vascular events (1034 patients [16.5%] vs. 1017 patients [16.3%]; hazard ratio, 1.01; 95% CI, 0.93 to 1.10; P = 0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; hazard ratio, 0.98; 95% CI, 0.89 to 1.07; P = 0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; hazard ratio, 1.10; 95% CI, 0.93 to 1.30; P = 0.26). Triglyceride levels were reduced by 14.5 mg per deciliter (0.16 mmol per liter) more among patients receiving n-3 fatty acids than among those receiving placebo (P<0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups. Conclusions: Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).Peer reviewe

Echocardiographic chamber quantification in a healthy Dutch population

Aim For accurate interpretation of echocardiographic measurements normative data are required, which are provided by guidelines. For this article, the hypothesis was that these cannot be extrapolated to the Dutch population, since in Dutch clinical practice often higher values are found, which may not be pathological but physiological. Therefore this study aimed to 1) obtain and propose normative values for cardiac chamber quantification in a healthy Dutch population and 2) determine influences of baseline characteristics on these measurements. Methods Prospectively recruited healthy subjects, aged 20–72 years (at least 28 subjects per age decade, equally distributed for gender) underwent physical examination and 2D and 3D echocardiography. Both ventricles and atria were assessed and volumes were calculated. Results 147 subjects were included (age 44 ± 14 years, 50% female). Overall, feasibility was good for both linear and volumetric measurements. Linear and volumetric parameters were consistently higher than current guidelines recommend, while functional parameters were in line with the guidelines. This was more so in the older population. 3D volumes were higher than 2D volumes. Gender dependency was seen in all body surface area (BSA) corrected volumes and with increasing age, ejection fractions decreased. Conclusion This study provides 2D and 3D echocardiographic reference ranges for both ventricles and atria de-rived from a healthy Dutch population. BSA indexed volumes are gender-dependent, age did not influence ventricular volumes and a rise in blood pressure was independently associated with increased right ventricular volumes. The higher volumes found may be indicative for the Dutch population being the tallest in the world

Visit-to-visit variability in multiple biological measurements and cognitive performance and risk of cardiovascular disease:A cohort study

BACKGROUND: Visit-to-visit variability in single biological measurements has been associated with cognitive decline and an elevated risk of cardiovascular diseases (CVD). However, the effect of visit-to-visit variability in multiple biological measures is underexplored. We investigated the effect of visit-to-visit variability in blood pressure (BP), heart rate (HR), weight, fasting plasma glucose, cholesterol, and triglycerides on cognitive performance and CVD.METHODS: Data on BP, HR, weight, glucose, cholesterol, and triglycerides from study visits in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial were used to estimate the association between visit-to-visit variability, cognitive performance (Mini Mental State Examination (MMSE) score) and CVD (non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death). Visit-to-visit variation for each measurement was estimated by calculating each individuals visit-to-visit standard deviation for that measurement. Participants whose standard deviation was in the highest quarter were classified as having high variation. Participants were grouped into those having 0, 1, 2, 3, or ≥ 4 high variation measurements. Regression and survival models were used to estimate the association between biological measures with MMSE and CVD with adjustment for confounders and mean measurement value.RESULTS: After adjustment for covariates, higher visit-to-visit variability in BP, HR, weight, and FPG were associated with poorer MMSE and a higher risk of CVD. Effect sizes did not vary greatly by measurement. The effects of high visit-to-visit variability were additive; compared to participants who had no measurements with high visit-to-visit variability, those who had high visit-to-visit variability in ≥4 measurements had poorer MMSE scores (-0.63 (95 % CI -0.96 to -0·31). Participants with ≥4 measurements with high visit-to-visit variability compared to participants with none had higher risk of CVD (hazard ratio 2.46 (95 % CI 1.63 to 3.70).CONCLUSION: Visit-to-visit variability in several measurements were associated with cumulatively poorer cognitive performance and a greater risk of CVD.</p

Improving analysis of cognitive outcomes in cardiovascular trials using different statistical approaches

Background: The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) questionnaires are commonly used to measure global cognition in clinical trials. Because these scales are discrete and bounded with ceiling and floor effects and highly skewed, their analysis as continuous outcomes presents challenges. Normality assumptions of linear regression models are usually violated, which may result in failure to detect associations with variables of interest. Methods: Alternative approaches to analyzing the results of these cognitive batteries include transformations (standardization, square root, or log transformation) of the scores in the multivariate linear regression (MLR) model, the use of nonlinear beta-binomial regression (which is not dependent on the assumption of normality), or Tobit regression, which adds a latent variable to account for bounded data. We aim to empirically compare the model performance of all proposed approaches using four large randomized controlled trials (ORIGIN, TRANSCEND, COMPASS, and NAVIGATE-ESUS), and using as metrics the Akaike information criterion (AIC). We also compared the treatment effects for the methods that have the same unit of measure (i.e., untransformed MLR, beta-binomial, and Tobit). Results: The beta-binomial consistently demonstrated superior model performance, with the lowest AIC values among nearly all the approaches considered, followed by the MLR with square root and log transformations across all four studies. Notably, in ORIGIN, a substantial AIC reduction was observed when comparing the untransformed MLR to the beta-binomial, whereas other studies had relatively small AIC reductions. The beta-binomial model also resulted in a significant treatment effect in ORIGIN, while the untransformed MLR and Tobit regression showed no significance. The other three studies had similar and insignificant treatment effects among the three approaches. Conclusion: When analyzing discrete and bounded outcomes, such as cognitive scores, as continuous variables, a beta-binomial regression model improves model performance, avoids spurious significance, and allows for a direct interpretation of the actual cognitive measure. Trials registration: ORIGIN (NCT00069784). Registered on October 1, 2003; TRANSCEND (NCT00153101). Registered on September 9, 2005; COMPASS (NCT01776424). Registered on January 24, 2013; NAVIGATE-ESUS (NCT02313909). Registered on December 8, 2014

Validation of Real-time Transthoracic 3D echocardiography in Children with Congenital Heart Disease

Aims: Assessment of feasibility, accuracy and applicability in clinical practice of real-time three-dimensional echocardiography (RT-3DE) in children with congenital heart defects. Methods and results: From September 2004 to June 2005, 100 consecutive children (57 infants, 43 children &gt; 1 year of age), who were scheduled for corrective intracardiac surgery, were enrolled in this study. RT-3DE was performed with Philips Sonos 7500 echo-system and off-line analysis with TomTec Echoview© software. Quantitative and qualitative assessments of the region of interest were performed on the 3D reconstruction, comparing these results with the anatomic findings and measurements performed during intracardiac surgery. Acquisition of RT-3DE datasets was feasible in 92 of the 100 (92%) patients and acquisition time was 6 ± 3 minutes. The overall quantitative analyses showed an excellent correlation (r &lt; 0.90) between RT-3De and surgery. Also the qualitative analyses were accurate compared with surgical findings, in all patients in which RT-3DE was feasible. Conclusion: This study shows that RT-3DE can be used in the clinical practice for the assessment of intracardiac anatomy in children with congenital heart disease. The information derived from the 3D reconstructions can be taken into consideration in the preoperative planning and management regarding interventional or surgical therapy

Assessment of pulmonary valve and right ventricular outflow tract with real-time three-dimensional echocardiography

Aim: Assessment of pulmonary valve (PV) and right ventricular outflow tract (RVOT) using real-time 3-dimensional echocardiography (RT3DE). Methods: Two-dimensional echocardiography (2DE) and RT3DE were performed in 50 patients with congenital heart disease (mean age 32 ± 9.5 years, 60% female). Measurements were obtained at parasternal views: short axis (PSAX) at aortic valve level and long axis (PLAX) with superior tilting. RT3DE visualization was evaluated by 4-point score (1: not visualized, 2: inadequate, 3: sufficient, and 4: excellent). Diameters of PV annulus (PVAD), and RVOT (RVOTD) were measured by both 2DE and RT3DE, while areas (PVAA) and (RVOTA) by RT3DE only. Results: By RT3DE, PV was visualized sufficiently in 68% and RVOTexcellently in 40%. PVAD and PVAA were measured in 88%. RVOTD and PVAD by 2DE at PLAX were significantly higher than PSAX (P < 0.0001) and lower than that by RT3DE (P < 0.001). Conclusion: RT3DE helps inRVOT and PV assessment adding more details supplemental to 2DE

Comparison of advanced echocardiographic right ventricular functional parameters with cardiovascular magnetic resonance in adult congenital heart disease

AimsAdvanced transthoracic echocardiography (TTE) using volumetric and deformational indices provides detailed quantification of right ventricular (RV) function in adults with congenital heart disease (ACHD). Two-dimensional multi-plane echocardiography (2D-MPE) has demonstrated regional wall differences in RV longitudinal strain (LS). This study aims to evaluate the association of these parameters with cardiovascular magnetic resonance (CMR).Methods and resultsOne hundred stable ACHD patients with primarily affected RVs were included (age 50±5 years; 53% male). Conventional and advanced echocardiographic RV functional parameters were compared to CMR-derived RV function.Advanced echocardiographic RV functional parameters were measurable in approximately one-half of the study co-hort, whilst multi-wall LS assessment feasibility was lower. CMR RV ejection fraction (CMR-RVEF) was moderately correlated with deformational, area and volumetric parameters (RV global LS [lateral wall and septum], n=55: r=-0.62, p&lt;0.001; RV wall average LS, n=34: r=-0.49, p=0.002; RV lateral wall LS, n=56: r=-0.45, p&lt;0.001; fractional area change [FAC], n=67: r=0.48, p&lt;0.001; 3D-RVEF, n=48: r=0.40, p=0.005). Conventional measurements such as TAPSE and RV S’ correlated poorly. RV global LS best identified CMR-RVEF &lt;45% (AUC: 0.84, p&lt;0.001: cut-off value -19%: sensitivity 100%, specificity 57%). RVEF and LS values were significantly higher when measured by CMR compared to TTE (mean difference RVEF: 5[-9 to 18]%; lateral (free) wall LS: -7[7 to -21]%; RV global LS: -6 [5 to -16]%) whilst there was no association between respective LS values.ConclusionIn ACHD patients, advanced echocardiographic RV functional parameters are moderately correlated with CMR-RVEF, although significant differences exist between indices measurable by both modalities

Louis C. Wyman to John D. Feerick

Letter from Representative Louis C. Wyman to Dean John D. Feerick, regarding his scholarly article on presidential inability.https://ir.lawnet.fordham.edu/twentyfifth_amendment_correspondence/1017/thumbnail.jp