scholarly journals Genetic association analyses highlight IL6, ALPL, and NAV1 as three new susceptibility genes underlying calcific aortic valve stenosis

2019 ◽  
Author(s):  
Sébastien Thériault ◽  
Christian Dina ◽  
David Messika-Zeitoun ◽  
Solena Le Scouarnec ◽  
Romain Capoulade ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Meta Analysis ◽  
Susceptibility Genes ◽  
Association Analyses ◽  
Risk Alleles ◽  
Genome Wide ◽  
Causal Genes ◽  
Artery Disease ◽  
Vessel Integrity

AbstractTo date, only two replicated loci, LPA and PALMD, have been identified as causal genes for calcific aortic valve stenosis (CAVS) using genome-wide and transcriptome-wide association study (TWAS). To identify additional susceptibility genes for CAVS, we performed a GWAS meta-analysis totaling 5,115 cases and 354,072 controls of European descent. Four loci achieved genome-wide significance, including two new loci: IL6 (interleukin 6) on 7p15.3 and ALPL (alkaline phosphatase) on 1p36.12. A TWAS integrating an eQTL study of 233 human aortic valves identified NAV1 (neuron navigator 1) on 1q32.1 as a new candidate causal gene. The CAVS risk alleles were associated with higher mRNA expression of NAV1 in valve tissues. Association results at the genome-wide scale showed genetic correlation with coronary artery disease and cardiovascular risk factors. Our study highlights three new loci implicating inflammation, mineralization and blood vessel integrity in CAVS pathogenesis and supports shared genetic etiology with cardiovascular traits.

scholarly journals Genome-Wide Association Analyses of Equine Metabolic Syndrome Phenotypes in Welsh Ponies and Morgan Horses

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 893 ◽  
Author(s):  
Elaine Norton ◽  
Nichol Schultz ◽  
Ray Geor ◽  
Dianne McFarlane ◽  
James Mickelson ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Candidate Genes ◽  
Meta Analysis ◽  
Complex Trait ◽  
Genome Wide Association ◽  
Protein Coding ◽  
Association Analyses ◽  
Risk Alleles ◽  
Equine Metabolic Syndrome ◽  
Genome Wide

Equine metabolic syndrome (EMS) is a complex trait for which few genetic studies have been published. Our study objectives were to perform within breed genome-wide association analyses (GWA) to identify associated loci in two high-risk breeds, coupled with meta-analysis to identify shared and unique loci between breeds. GWA for 12 EMS traits identified 303 and 142 associated genomic regions in 264 Welsh ponies and 286 Morgan horses, respectively. Meta-analysis demonstrated that 65 GWA regions were shared across breeds. Region boundaries were defined based on a fixed-size or the breakdown of linkage disequilibrium, and prioritized if they were: shared between breeds or across traits (high priority), identified in a single GWA cohort (medium priority), or shared across traits with no SNPs reaching genome-wide significance (low priority), resulting in 56 high, 26 medium, and seven low priority regions including 1853 candidate genes in the Welsh ponies; and 39 high, eight medium, and nine low priority regions including 1167 candidate genes in the Morgans. The prioritized regions contained protein-coding genes which were functionally enriched for pathways associated with inflammation, glucose metabolism, or lipid metabolism. These data demonstrate that EMS is a polygenic trait with breed-specific risk alleles as well as those shared across breeds.

scholarly journals Genetic Association Analyses Highlight IL6 , ALPL , and NAV1 As 3 New Susceptibility Genes Underlying Calcific Aortic Valve Stenosis

2019 ◽  
Vol 12 (10) ◽  
Author(s):  
Sébastien Thériault ◽  
Christian Dina ◽  
David Messika-Zeitoun ◽  
Solena Le Scouarnec ◽  
Romain Capoulade ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Genetic Association ◽  
Aortic Valve Stenosis ◽  
Susceptibility Genes ◽  
Association Analyses

Use and outcomes of emergency treatment strategies in patients with aortic valve stenosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S.M Piepenburg ◽  
K Kaier ◽  
C Olivier ◽  
M Zehender ◽  
C Bode ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Hospital Mortality ◽  
Valve Replacement ◽  
Aortic Valve Stenosis ◽  
Emergency Treatment ◽  
Funding Source ◽  
Artery Disease

Abstract Introduction and aim Current emergency treatment options for severe aortic valve stenosis include surgical aortic valve replacement (SAVR), transcatheter aortic valve replacement (TAVR) and balloon valvuloplasty (BV). So far no larger patient population has been evaluated regarding clinical characteristics and outcomes. Therefore we aimed to describe the use and outcome of the three therapy options in a broad registry study. Method and results Using German nationwide electronic health records, we evaluated emergency admissions of symptomatic patients with severe aortic valve stenosis between 2014 and 2017. Patients were grouped according to SAVR, TAVR or BV only treatments. Primary outcome was in-hospital mortality. Secondary outcomes were stroke, acute kidney injury, periprocedural pacemaker implantation, delirium and prolonged mechanical ventilation >48 hours. Stepwise multivariable logistic regression analyses including baseline characteristics were performed to assess outcome risks. 8,651 patients with emergency admission for severe aortic valve stenosis were identified. The median age was 79 years and comorbidities included NYHA classes III-IV (52%), coronary artery disease (50%), atrial fibrillation (41%) and diabetes mellitus (33%). Overall in-hospital mortality was 6.2% during a mean length of stay of 22±15 days. TAVR was the most common treatment (6,357 [73.5%]), followed by SAVR (1,557 [18%]) and BV (737 8.5%]). Patients who were treated with TAVR or BV were significantly older than patients with SAVR (mean age 81.3±6.5 and 81.2±6.9 versus 67.2±11.0 years, p<0.001), had more relevant comorbidities (coronary artery disease 52–91% vs. 21.8%; p<0.001), worse NYHA classes III-IV (55–65% vs. 34.5%; p<0.001) and higher EuroSCORES (24.6±14.3 and 23.4±13.9 vs. 9.5±7.6; p<0.001) than SAVR patients. Patients treated with BV only had the highest in-hospital mortality compared with TAVR or SAVR (20.9% vs. 5.1 and 3.5%; p<0.001). Compared with BV only, SAVR patients (adjusted odds ratio [aOR] 0.25; 95% confidence interval [CI] 0.14–0.46; p<0.001) and TAVR patients (aOR 0.37; 95% CI 0.28–0.50; p<0.001) had a lower risk for in-hospital mortality. Conclusion In-hospital mortality for emergency patients with symptomatic severe aortic valve stenosis is high. Our results showed that BV only therapy was associated with highest mortality, which is in line with current research. Yet, there is a trend towards more TAVR interventions and this study might imply that balloon valvuloplasty alone is insufficient. The role of BV as a bridging strategy to TAVR or SAVR needs to be further investigated. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Abstract 19440: Reintervention Rates Following Balloon Aortic Valvuloplasty versus Surgical Valve Repair in Isolated Congenital Aortic Valve Stenosis - A Meta-analysis

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
May T Saung ◽  
Courtney McCracken ◽  
Ritu Sachdeva ◽  
Christopher J Petit
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Valve Stenosis ◽  
Meta Analysis ◽  
Valve Repair ◽  
Balloon Aortic Valvuloplasty ◽  
Congenital Aortic Stenosis ◽  
Primary Indication ◽  
Aortic Valvuloplasty

Introduction: The optimal treatment for congenital aortic stenosis (AS) is debated despite decades of experience with both balloon aortic valvuloplasty (BAV) and surgical aortic valve repair (SAV). While BAV has been the mainstay of therapy for AS, recent single-center reports suggest optimal results following SAV. Hypothesis: We propose that reintervention rates following SAV and BAV are equivalent. Methods: We queried Medline, EMBASE and Web of Science for eligible studies using the keywords: “congenital aortic stenosis”, “balloon valvotomy”, “aortic valve stenosis surgery” and “treatment outcome or reintervention”. Studies were excluded when cohort size was <20 pts, when follow-up was < 2.5 yrs from primary intervention, and when primary indication was not AS (e.g. SAV in the setting of aortic valve regurgitation (AR)). Outcomes analyzed included death, reintervention and moderate or severe AR. Analysis was performed using Comprehensive Meta Analysis v3 using random effects models. Results: A total of 20 studies were included in our meta-analysis: SAV alone (n=3), BAV alone (n=12), and both (n=5). The mean age at BAV was 3.1 years (range, 4 days - 7 years) with a mean follow-up duration of 6.8 years, while mean age at SAV was 2.8 years (range, 14.2 days - 7.1 years) with a mean follow-up duration of 9.1 years. Mortality rates following BAV and SAV were 12.3% (95% CI: 7.7 - 19.1) and 10.2% (95% CI: 7.0 - 14.5), respectively (p=0.27). Reintervention following initial procedure for treatment of AS was higher following BAV (35.7% [95% CI: 29 - 43.1]) compared to SAV (25.2% [95% CI: 19.9 - 31.3])(p=0.012). Long-term and mid-term follow-up in these studies showed moderate to severe AR was present in 24.1% and 28.1% of BAV and SAV patients, respectively. Conclusions: Notwithstanding publication bias, both survival rates and development of late AR following BAV and SAV are similar. However, reintervention rates are significantly higher following BAV compared to SAV.

Abstract 15209: LPA Variants Are Associated With Aortic Valve Stenosis, Heart Failure and Chronic Kidney Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ozan Dikilitas ◽  
Benjamin A Satterfield ◽  
Maya Safarova ◽  
Shoa L Clarke ◽  
Catherine Tcheandjieu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
European Ancestry ◽  
Atherosclerotic Cardiovascular Disease ◽  
Disease Phenotypes ◽  
Emerge Network ◽  
Artery Disease

Background: The pathophysiology of lipoprotein (a) [Lp(a)] remains obscure. We conducted a phenome wide analysis study (PheWAS) to identify pleiotropic effects of LPA variants. Methods: Among 51,843 European-ancestry participants (age 58±16 years, 54% female) of the electronic MEdical Records and Genomics (eMERGE) network we assessed whether LPA variants exhibited pleiotropic affects through an electronic health record-based PheWAS. We adjusted significant associations by presence of atherosclerotic cardiovascular disease (ASCVD; defined as a composite of coronary heart disease, cerebrovascular disease, and peripheral artery disease) to determine whether those associations were independent of ASCVD. Results: In PheWAS analysis, we tested 864 phecodes with 36 independent LPA variants. We identified 21 significant associations with non-ASCVD phenotypes including heart failure, aortic valve stenosis, and chronic kidney disease of which 14 were replicated across independent cohorts. The strength of associations between the LPA variant rs10455872 and both heart failure and aortic valve stenosis related phecodes were significantly attenuated after adjustment for ASCVD. However, the association with chronic kidney disease phecode remained independent following adjustment for ASCVD without any attenuation in the estimated odds ratio (Table). Conclusions: LPA genetic variants were associated with aortic valve stenosis, heart failure and chronic kidney disease. The observed association of LPA variant rs10455872 with aortic stenosis and heart failure appear to be partially mediated by ASCVD, while the association with chronic kidney disease appears to be independent of ASCVD. Additional studies are needed to elucidate potential mechanisms by which Lp(a) may contribute to the pathogenesis of non-ASCVD disease phenotypes.

PREDICTORS OF CALCIFIC AORTIC VALVE STENOSIS PROGRESSION AS MEASURED BY CHANGE IN PEAK VELOCITY: A META-ANALYSIS AND META-REGRESSION

2020 ◽  
Vol 75 (11) ◽  
pp. 2172
Author(s):  
Navneet Sharma ◽  
Sareena George ◽  
Ramsey Kalil ◽  
Prateek Sharma ◽  
Paul Kim ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Peak Velocity ◽  
Meta Analysis ◽  
Meta Regression
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