Abstract:
AIMS:Genome-wide association studies have previously identified INSIG2 as a candidate gene for plasma low-density lipoprotein cholesterol (LDL-c). However, we suspect a role for CCDC93 in the same locus because of its involvement in the recycling of the LDL-receptor (LDLR). METHODS AND RESULTS:Characterization of the INSIG2 locus was followed by studies in over 107 000 individuals from the general population, the Copenhagen General Population Study and the Copenhagen City Heart Study, for associations of genetic variants with plasma lipids levels, with risk of myocardial infarction (MI) and with cardiovascular mortality. CCDC93 was furthermore studied in cells and mice. The lead variant of the INSIG2 locus (rs10490626) is not associated with changes in the expression of nearby genes but is a part of a genetic block, which excludes INSIG2. This block includes a coding variant in CCDC93 p.Pro228Leu, which is in strong linkage disequilibrium with rs10490626 (r2 > 0.96). In the general population, separately and combined, CCDC93 p.Pro228Leu is dose-dependently associated with lower LDL-c (P-trend 2.5 × 10-6 to 8.0 × 10-9), with lower risk of MI (P-trend 0.04-0.002) and lower risk of cardiovascular mortality (P-trend 0.005-0.004). These results were validated for LDL-c, risk of both coronary artery disease and MI in meta-analyses including from 194 000 to >700 000 participants. The variant is shown to increase CCDC93 protein stability, while overexpression of human CCDC93 decreases plasma LDL-c in mice. Conversely, CCDC93 ablation reduces LDL uptake as a result of reduced LDLR levels at the cell membrane. CONCLUSION:This study provides evidence that a common variant in CCDC93, encoding a protein involved in recycling of the LDLR, is associated with lower LDL-c levels, lower risk of MI and cardiovascular mortality.
journal_name
Eur Heart Jjournal_title
European heart journalauthors
Rimbert A,Dalila N,Wolters JC,Huijkman N,Smit M,Kloosterhuis N,Riemsma M,van der Veen Y,Singla A,van Dijk F,Biobank-Based Integrative Omics Studies Consortium.,Frikke-Schmidt R,Burstein E,Tybjærg-Hansen A,van de Sluis B,Kuidoi
10.1093/eurheartj/ehz727subject
Has Abstractpub_date
2020-03-01 00:00:00pages
1040-1053issue
9eissn
0195-668Xissn
1522-9645pii
5599853journal_volume
41pub_type
杂志文章abstract::Clinical management of refractory heart failure remains challenging, with a high rate of rehospitalizations despite advances in medical and device therapy. Care can be provided in person, via telehomecare (by telephone), or telemonitoring, which involves wireless technology for remote follow-up. Telemonitoring wireles...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehr005
更新日期:2011-06-01 00:00:00
abstract::There has been considerable controversy over whether elevated levels of triglycerides, or hypertriglyceridaemia, is an independent risk factor in coronary heart disease (CHD). Discrepancies between findings of univariate and multivariate statistical analyses are likely to be due to the strong inverse correlation betwe...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:
更新日期:1998-07-01 00:00:00
abstract::Late potentials detected by the signal-averaged ECG (SAECG) identify post-infarction patients at risk from sustained ventricular tachycardia (VT) and sudden death. Hypertrophic cardiomyopathy (HCM) is also associated with increased risk of sudden death. In adults, episodes of non-sustained VT on ambulatory ECG monitor...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/14.7.941
更新日期:1993-07-01 00:00:00
abstract:AIMS:To assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS:We performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (m...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehv372
更新日期:2016-04-01 00:00:00
abstract:AIMS:Although cerebral blood flow (CBF) is known to be low in patients with advanced systolic heart failure (HF), little is known of the prognostic significance of this observation. We investigated whether CBF might be associated with the development of adverse outcomes in systolic HF, and whether it might provide prog...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehr345
更新日期:2012-02-01 00:00:00
abstract:AIMS:In animal models of obesity and diabetes mellitus, myocardial TG accumulation is associated with decreased myocardial function. In the physiologically ageing heart, myocardial triglyceride (TG) accumulation may also occur due to reduced myocardial fatty acid oxidation. The role of myocardial TG in the ageing human...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehn207
更新日期:2008-06-01 00:00:00
abstract:AIMS:To evaluate clinical disease expression, non-invasive diagnosis, and prognosis in families with dominant vs. recessive arrhythmogenic right ventricular cardiomyopathy (ARVC) due to mutations in related desmosomal proteins plakophilin-2 (PKP2) and plakoglobin (JUP), respectively. METHODS AND RESULTS:One hundred an...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehl184
更新日期:2006-09-01 00:00:00
abstract::The study of 'atrial vulnerability' is often clinically indicated but it requires the use of invasive intracardiac stimulation. The purpose of the study was to assess the use of oesophageal pacing in the evaluation of atrial tachyarrhythmias (ATA). Fifty-five patients with documented ATA (group I) and 60 without (grou...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060632
更新日期:1994-08-01 00:00:00
abstract:AIMS:The vast majority of acute heart failure (AHF) trials to date have targeted dyspnoea. However, they enrolled patients relatively late and did not standardize their methods of dyspnoea measurement. URGENT Dyspnoea was designed to determine changes in dyspnoea in response to initial, standard therapy in patients pre...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究
doi:10.1093/eurheartj/ehp458
更新日期:2010-04-01 00:00:00
abstract::The alterations of the beta-adrenoceptor adenylyl cyclase are reviewed. In failing myocardium, the down-regulation of beta 1-adrenoceptors is accompanied by a decrease in steady state mRNA levels, as studied with quantitative polymerase chain reactions in dilated and ischaemic cardiomyopathy. The density of beta 2-adr...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/15.suppl_d.30
更新日期:1994-12-01 00:00:00
abstract::ACE inhibitors may influence the actual concentrations of the peptides angiotensin I, angiotensin II and bradykinin. Since all three peptides are able to modulate catecholamine release, a change in noradrenaline and adrenaline release should be expected when angiotensin I converting enzyme (kininase II) is inhibited. ...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:
更新日期:1993-11-01 00:00:00
abstract:AIMS:Patients with chronic kidney disease (CKD) pose a worldwide growing burden to health care systems due to accelerated atherosclerosis and subsequent high cardiovascular (CV) morbidity. Atherogenesis is prominently driven by monocytes and monocyte-derived macrophages. The expression of CD14 and CD16 characterizes th...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehq371
更新日期:2011-01-01 00:00:00
abstract::The purpose of this study was to evaluate various methods of diagnosis of left atrial thrombi (LAT) in patients (pts) with mitral stenosis (MS). From 1980 to 1990, 581 pts with MS have undergone open mitral commissurotomy (n = 169) or valve replacement (n = 412). All pts had transthoracic 2D echocardiography (TTE), 10...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/12.suppl_b.70
更新日期:1991-07-01 00:00:00
abstract::We investigated whether left ventricular hypertrophy in elite cyclists is associated with functional changes or abnormal energy metabolism. Left ventricular hypertrophy is a powerful risk factor for sudden cardiac death with different prognostic significance among the various geometric forms. Cyclists may have a combi...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a015046
更新日期:1996-08-01 00:00:00
abstract::In this double-blind placebo-controlled study with enalapril, 74 patients with acute myocardial infarction were followed at 0, 7, 30, 60 and 180 days after the event. Platelets and leukocytes were activated during the first 7 days. During the 6-month period fibrinogen, leukocytes, elastase, and B beta 30-43 remained e...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/oxfordjournals.eurheartj.a060831
更新日期:1995-12-01 00:00:00
abstract:AIMS:The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events. METHODS AND RESULTS:We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials...
journal_title:European heart journal
pub_type: 杂志文章,meta分析,评审
doi:10.1093/eurheartj/ehv072
更新日期:2015-06-21 00:00:00
abstract::Increased sympathetic tone is found in about 30% of patients with hypertension. This abnormality is closely associated with the metabolic syndrome of dyslipidaemia and hyperinsulinaemia. In this short review we discuss the mechanisms by which sympathetic over-activity could cause the metabolic syndrome. Sympathetic st...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:
更新日期:1998-06-01 00:00:00
abstract::The aim of the study was to assess the relationship between paroxysmal atrial fibrillation during acute myocardial infarction and the long-term prognosis of patients after acute myocardial infarction. The incidence of paroxysmal atrial fibrillation among 5803 consecutive hospitalized patients was 9.9% (557/5803). Inci...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060046
更新日期:1992-01-01 00:00:00
abstract:AIMS:Morphological characteristics of non-significant coronary plaques (NSCPs) that develop rapid progression have not been fully elucidated. The aim of this study was to clarify the morphological characteristics of NSCPs in patients with coronary artery disease (CAD) using intravascular optical coherence tomography (O...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehr284
更新日期:2012-01-01 00:00:00
abstract:AIM:It has recently been suggested that exercise testing may be more valuable prognostically than it is diagnostically in apparently healthy subjects. We wanted to compare the accuracy of CHD risk assessment based on classical risk factors with an assessment also based on multiple exercise test parameters. METHODS AND...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1016/j.ehj.2004.04.009
更新日期:2004-06-01 00:00:00
abstract::The present study applies a non-invasive method to the quantitative evaluation of left ventricular stiffness in normal subjects and in patients with ischaemic heart disease (IHD). We have studied 20 patients with IHD and 25 healthy subjects. The third heart sound (S3) was detectable in all patients. We have correlated...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a059876
更新日期:1991-02-01 00:00:00
abstract::Patients who have an accessory pathway (AP) of atrioventricular (AV) conduction may develop circus movement tachycardia otherwise known as atrioventricular re-entrant tachycardia (AVRT). Orthodromic AVRT is the most common form. It occurs as a result of antegrade conduction through the normal AV conduction system and ...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:
更新日期:1998-05-01 00:00:00
abstract:AIMS:Our objectives were (i) to compare the discriminatory performance of the Thrombolysis in Myocardial Infarction risk score (TIMI RS), Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy risk score (PURSUIT RS), and Global Registry of Acute Cardiac Events risk score (GRAC...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究
doi:10.1093/eurheartj/ehm004
更新日期:2007-05-01 00:00:00
abstract::The advent of platelet membrane glycoprotein (GP) IIb/IIIa inhibitors has changed the landscape of interventional cardiology. Given the commercial availability of abciximab and expected regulatory approvals for other receptor blockers, defining appropriate use of these agents in the interventional setting is mandated....
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:
更新日期:1998-04-01 00:00:00
abstract::The aim of our study was to examine if echocardiography can reproducibly be used in a multicentre study to select high risk patients with reduced left ventricular function early after an acute myocardial infarction (MI). In the TRAndolapril Cardiac Evaluation Study (TRACE) patients with reduced left ventricular systol...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/oxfordjournals.eurheartj.a060443
更新日期:1994-12-01 00:00:00
abstract::A 55-year-old woman presented with fever and malaise. Three blood cultures were positive for Streptococcus sanguis. A diagnosis of endocarditis was made and the patient was treated with intravenous penicillin and gentamicin. Endocardiography revealed a large left atrial tumour. At operation a myxoma covered by deposit...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060109
更新日期:1992-11-01 00:00:00
abstract:AIM:To investigate fatalities from myocardial infarction at 28 days and one-year among patients aged 35-64 years in the Nordic and Lithuanian centres participating in the World Health Organization MONICA (Monitoring of Trends and Determinants of Cardiovascular Disease) Project. METHODS AND RESULTS:Altogether 9100 myoc...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a015124
更新日期:1997-01-01 00:00:00
abstract::The effect of sublingually administered nitroglycerin (0.5 mg) on distribution of blood volume in 16 patients with congestive heart failure (NYHA class II and III), randomly assigned to placebo (N = 8) or nitroglycerin (N = 8) was studied 20 minutes after in vivo labelling of red blood cells with 99m-Tc pertechnetate....
journal_title:European heart journal
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/oxfordjournals.eurheartj.a062177
更新日期:1987-10-01 00:00:00
abstract:Aims:Bioresorbable scaffolds (BRS) provide short-term coronary artery scaffolding and drug delivery. Although prior trials showed a higher rate of device failure compared with conventional drug-eluting stents (DES), only a single trial investigated patients undergoing percutaneous coronary intervention (PCI) for acute ...
journal_title:European heart journal
pub_type: 杂志文章,随机对照试验
doi:10.1093/eurheartj/ehy710
更新日期:2019-01-07 00:00:00
abstract:AIMS:Cardioprotective effects of erythropoietin (EPO) have been shown in experimental and smaller clinical studies. We performed a prospective, multicentre, randomized trial to assess the effects of a single high dose of EPO after primary coronary intervention (PCI) for an ST-elevation myocardial infarction (STEMI). Me...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/eurheartj/ehq304
更新日期:2010-11-01 00:00:00