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Adolescent body mass index predicts future cardiovascular risk

18 Apr, 17 | by flee

One-third of the adolescent population in Western countries is now considered to be overweight or obese.  The implications of this epidemic remain unclear but may well lead to an increased prevalence of cardiovascular disease and an erosion in the mortality and morbidity gains that have been apparent in the last few decades.  To further explore this question, records from an Israeli national database containing the BMIs of adolescents was analyzed.  Data for a total of 2.3 million individuals (mean age 17 yrs.) was available between 1967 and 2010 compromising a total of over 42,000,000 years of person follow-up.  Body mass index (BMI) was assessed by centiles and linked to mortality data for the population.  9.1% of deaths in this young cohort were attributable to cardiovascular causes with 1497 from coronary disease, 528 from stroke and 893 from sudden death.  Using a multivariable model adjusting for factors including birth year, sex and socioeconomic class there was a clear and graded increase in the risk of death from cardiovascular causes starting in the group between the 50th and 74th centiles and increasing rapidly as BMI increased such that in the 95th centile, the relative risk of death from coronary disease was 4.9 and from stroke was 2.6.

 

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Heart’s Twitter Journal Club

1 Feb, 17 | by James Rudd

TwitterLogo_#55aceeJoin in our Journal Club on Twitter and engage with readers from across the world!

Each month we will discuss a paper from Heart.

We will select a recent paper ahead of time and then discuss four different aspects of it for about 15 minutes each.

The paper under discussion will be free to access for a week prior to the Journal Club.

Feel free to join the next journal club – they happen monthly, on the first Thursday of each month at 7PM GMT (8PM BST). All Welcome!


To join in you will need to have a Twitter account. To sign up to Twitter, click here (it doesn’t take long and make sure you follow us –@Heart_BMJ).

When it comes to the tweet chat itself, we suggest you use tchat.io. This is a specific site used for tweetchats as it cuts out all the other distractions on Twitter. Log into tchat.io using your Twitter details, then type #HeartJC into the search bar. This pulls up all the tweets using the hashtag. You can tweet from here and it will automatically add the correct hashtag at the end of each tweet for those overexcited tweeps!

You can otherwise tweet using Twitter, but you need to make sure you add the hashtag to each tweet otherwise we won’t see it.

Follow Heart (@Heart_BMJ) for all the latest updates on Twitter. The Journal Club tweets can be identified by the hashtag #HeartJC


The following links take you to transcripts of the discussions and related Analytics, for those interested.

2017

February 2nd – Transcript: All about Cardiac MRI and Analytics: Symplur

March 2nd – Transcript: Pregnancy and heart disease and Analytics: Symplur

April 6th – Transcript: POCUS and Analytics: Symplur

May 4th – Transcript: Saturated fat and CV disease and Analytics: Symplur

June 1st – Transcript: DAPT and Analytics: Symplur

July 6th – Transcript: Twitter at conferences and Analytics: Symplur

2016

May 5th – Transcript: Chocolate and MI risk and Analytics: Symplur

June 2nd – Transcript: Exercise and Heart Disease and Analytics: Symplur

July 7th – Transcript: Gender differences in CAD and Analytics: Symplur

August 4th – Transcript:Loneliness and social isolation as risk factors for CHD and stroke and Analytics: Symplur

September 1st – Transcript: Troponins for MI diagnosis and Analytics: Symplur

October 6th – Transcript: Beta-blockers, COPD and Heart Failure and Analytics: Symplur

November 3rd – Transcript: Cardiac CT and Analytics: Symplur

December 1st – Transcript: Athletes and cardiac screening and Analytics: Symplur

Contemporary Coronary Stents

6 Jan, 17 | by flee

Percutaneous treatment for obstructive coronary artery disease has evolved in conjunction with technological advances from the initial era of balloon angioplasty to the first bare metal stents (BMS) and then through various iterations of drug eluting stent (DES) technology.  Current generation DES data suggest progressively improved re-stenosis and thrombosis rates and on-going trials are examining shorter duration dual antiplatelet therapy regimens, all of which raises questions about the utility of BMS. However, BMS technology has also improved and these stents generally remain less costly. Thus, in this large scale multi-center Norwegian study, over 9000 patients were randomized to receive latest generation BMS or DES technology when undergoing PCI. The primary composite outcome was all cause death and myocardial infarction over 5 years of follow-up.  The primary outcome was neutral between the two groups with rates of 17.1% (BMS) vs 16.6% (DES) (P=0.66), but rates of further revascularization were significantly lower in the DES group (16.5% vs 19.8%; P<0.001) suggesting lower rates of restenosis.  Definite stent thrombosis was also marginally lower in the DES group (0.8% vs 1.2%; P=0.0498) allaying concerns of very late stent thrombosis associated with early generation DES.

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CPAP fails to improve cardiovascular outcomes in OSA

6 Jan, 17 | by flee

Obstructive sleep apnea (OSA) is associated with increased cardiovascular events in observational studies. Randomized trials have demonstrated continuous positive airway pressure (CPAP) therapy reduces blood pressure, markers of oxidative stress and insulin insensitivity.  Yet, it remains unclear whether treatment with CPAP reduces cardiovascular events.  In the largest study of its kind, 2717 patients aged 45 to 75 years with moderate-to-severe OSA and coronary or cerebrovascular disease were randomized in open-label fashion to receive CPAP treatment or usual care alone. The primary composite end point included cardiovascular death, myocardial infarction, stroke and heart failure with secondary end-points including day-time sleepiness, mood and quality of life indices. At a mean follow-up of 3.7 years, the trial was neutral with no difference in the primary end-point between the CPAP (17.0%) and the usual-care groups (15.4%) (P=0.34), and no difference in the individual components of the primary end-point.  CPAP however significantly improved snoring, daytime sleepiness, mood and health-related quality of life.

 

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Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement

20 Sep, 16 | by flee

Patients with stenotic or regurgitant aortic valve disease appear to cleave multimers of Von Willebrand factor (HMW-multimer), presumably due to high-shear stresses and non-laminar flow. Van Belle and colleagues hypothesized that transcatheter aortic valve replacement (TAVR) would correct this process, but that significant residual paravalvular leak (PVL) following TAVR would abrogate this corrective effect. Moderate to severe PVL has been associated with increased rates of hospitalization, and death compared to mild PVL. Thus, immediate characterization of the degree of PVL post TAVR using echocardiographic, hemodynamic and/or angiographic data is important, though occasionally challenging, particularly if discrepant. In this study, ratios of HMW-multimers and platelet reactivity (CT-ADP) were assessed pre- and post-TAVR in 183 patients receiving the Sapien XT valve at a single center. Among the 137 patients with no regurgitation following TAVR, HMW-multimer ratios and CT-ADP values changed significantly within 15 minutes of the TAVR using point of care testing. Among those with significant PVL, these assays only changed following effective correction of the PVL. These results were unaffected by concomitant use of clopidogrel or pre-existing mitral regurgitation. Using TEE as a reference standard, ROC curves identified a CT-ADP result of ≥180 seconds (AUC = 0.93) and HMW-multimer ratio of ≤ 0.8 (AUC = 0.94) as providing optimal discrimination for significant PVL. In multivariate models, an HMW-ratio < 0.8 or CT-ADP value > 180 seconds at the end of the procedure were both significantly associated with ≥3-fold higher one-year mortality rates.

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Genetic analysis of sudden cardiac death in the young

20 Sep, 16 | by flee

Sudden cardiac death (SCD) is a rare but devastating event among children and young adults. SCD in which no obvious cause is apparent despite comprehensive toxicological and histological autopsy analysis is particularly vexing.  The role of genetic testing in unexplained SCD is studied in this prospective analysis of  Australians and New Zealanders 1 to 35 years old.  Between 2010 and 2012 a total of 490 SCDs were identified across the population of 26.7 million (1.3 per 100,000). Seventy-two percent were boys or men. The highest overall incidence was in persons aged 31-35, in whom coronary artery disease was the commonest cause, and the lowest incidence was in children aged 6-10.  Inherited cardiomyopathies were found in 16% of all cases.  Most deaths (65%) occurred either at rest or during sleep, whereas sudden death during or after exercise was relatively uncommon (15%). Following post-mortem, 40% of cases were classified as unexplained. Female sex, younger age and death at night particularly common in this sub-group.  Subsequent genetic analysis was performed in these individuals using commercial panels of 59 cardiac genes including genes for long QT and catecholamine polymorphic ventricular tachycardia. As an alternative, 72 epilepsy genes were also investigated. Among analyzed individuals, 27% were found to have a clinically relevant cardiac gene disorder considered the probable cause of death (only 6% were found to carry an epilepsy gene).

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Long-term survival benefit for coronary artery bypass grafting surgery in ischemic cardiomyopathy

20 Sep, 16 | by flee

The Surgical Treatment for Ischemic Heart Failure (STICH) trial asked the important question whether coronary artery bypass grafting surgery (CABG) in patients with severe ischemic cardiomyopathy would provide a survival advantage over contemporary medical therapy alone. Reporting 5-year data in 2011, the study reported no significant difference but did demonstrate a tantalizing divergence in survival graphs between 2 and 5 years, which appeared to be increasing with time.  In an extension to the study, 10 year follow-up data is reported.  Out of the original 1212 patients in the study, data was available on 98% of the cohort at long-term follow-up.  Over this long time period the primary outcome of death from any cause occurred in 58.9% in the CABG group and in 66.1% in the medical-therapy group (HR with CABG vs. medical therapy, 0.84; 95% CI, 0.73 to 0.97; P=0.02).  Significant reductions were also seen in cardiovascular death (P=0.006) and hospitalizations for cardiovascular causes (P<0.001) in the CABG group. The overall number needed to treat to prevent 1 death was 14, equating to an overall 16% lower chance of cardiovascular death during the study period and an increase in longevity of approximately 18 months. The effect was consistent across all important sub-group analyses.

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Ablation superior to drugs in recurrent ventricular tachycardia

20 Sep, 16 | by flee

Nearly 100, 000 implantable cardiac defibrillators (ICDs) are implanted every year in N. America to treat patients at risk of ventricular tachycardia (VT)  following myocardial infarction.  ICD activation for VT is relatively common and associated with recurrent hospitalizations, reductions in quality of life and mortality. It is therefore important to understand the best course of action to suppress recurrent VT, either through intensifying antiarrhythmic therapy or catheter ablation.  In this multicenter trial of patients with ischemic cardiomyopathy and an ICD, subjects who presented with VT despite anti-arrhythmic therapy were randomized 1:1 in an open-label fashion to either catheter ablation or an escalated antiarrhythmic drug regimen. In the medical therapy arm, amiodarone was initiated or the dose was escalated as appropriate; mexiletine was added if they were already on at least 300 mg per day of amiodarone. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock based on an intention-to-treat strategy.  In total, 259 patients were enrolled with a median follow-up of 27.9±17.1 months.  Catheter ablation significantly reduced the primary end-point from 68.5% to 59.1% (HR 0.72; 95% CI, 0.53 to 0.98; P=0.04) primarily driven by a reduction in recurrent VT with no discernable effect on mortality.

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Cholesterol Lowering in Intermediate-risk Persons without Cardiovascular Disease.

11 Jul, 16 | by flee

Implementation of statin therapy in practice for primary prevention of cardiovascular disease is controversial due to concerns over costs and side-effects with broader use and uncertainty regarding LDL goals in the primary prevention population. Previous primary prevention trials suggest a reduction in cardiovascular outcomes in largely white patients with significant risk factors for coronary disease. The HOPE-3 trial randomized a diverse population of 12,000 individuals over 55 years of age (women over 60) with 1-2 relatively modest risk factors for cardiovascular disease (annual risk ~1%) but otherwise no indication for statin therapy to 10 mg of rosuvastatin daily vs placebo. The composite primary outcome was death from cardiovascular causes, non- fatal MI or stroke. Nearly 13% of patients were excluded following roll-in based on side-effects or lab abnormalities. For remaining patients, over median follow of 5.6 years there was a significant reduction in the primary endpoint: 3.7% vs 4.8% favoring treatment (HR 0.76 [CI 0.64-0.91]) with a NNT of 91. An expanded ‘co-primary’ outcome which also included heart failure, revascularization and resuscitated cardiac arrest resulted in a NNT of 73. Of note, there was a significant increase in muscle aches and weakness in the rosuvastatin group (5.8% vs 4.7%) but this did not clearly impact drug discontinuation, which was common at 23.7%. In fact, therapy discontinuation was 2.5% higher in the placebo group. Myopathy or rhabdomyolysis events were very rare, but there was a significant increase in cataracts in the rosuvastin group.

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Genetic variant protects against coronary disease

11 Jul, 16 | by flee

The links between cholesterol and coronary artery disease are well established and incontrovertible, with modification of serum LDL cholesterol levels repeatedly shown to reduce risk of myocardial infarction and cardiovascular death. But total non-HDL cholesterol levels, encompassing multiple other lipid fractions including Lp(a) and chylomicrons, have the strongest overall association with the risk of incipient coronary artery disease. In this large genome-wide association study, the authors identify a novel noncoding 12-base-pair deletion in intron 4 of the ASGR1 gene that appears to be associated with lower levels of non-HDL cholesterol.  In an initial discovery cohort of 2636 Icelanders, the polymorphism was associated with a reduced risk of atherosclerotic coronary disease. Further testing in a cohort of 398,000 Icelanders demonstrated a prevalence of heterozygous carriers of approximately 1 in 120. These carriers had lower levels of non-HDL cholesterol and a significant 34% reduction in rates of coronary artery disease (95% CI, 21 to 45; P=4.0×10(-6)).  To further validate these associations, five other large European cohorts containing a total of 42,524 case patients and 249,414 controls were analyzed with results consistent to those seen in the Icelandic cohort.  Finally, the authors describe a second loss of function polymorphism in the same ASGR1 gene that again leads to significantly reduced levels of non-HDL cholesterol in carriers, validating their initial hypothesis that ASGR1 is directly implicated in non-HDL cholesterol homeostasis.

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