Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis

Background: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results: In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions: Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS

Timing of multivessel revascularization in stable patients with STEMI: a systematic review and network meta-analysis

INTRODUCTION AND OBJECTIVES Multivessel percutaneous coronary intervention (MV-PCI) is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD) without cardiogenic shock. The present network meta-analysis investigated the optimal timing of MV-PCI in this context. METHODS We pooled the aggregated data from randomized trials investigating stable STEMI patients with multivessel CAD treated with a strategy of either MV-PCI or culprit vessel-only PCI. The primary outcome was all-cause death. The main secondary outcomes were cardiovascular death, myocardial infarction, and unplanned ischemia-driven revascularization. RESULTS Among 11 trials, a total of 10 507 patients were randomly assigned to MV-PCI (same sitting, n=1683; staged during the index hospitalization, n=3460; staged during a subsequent hospitalization within 45 days, n=3275) or to culprit vessel-only PCI (n=2089). The median follow-up was 18.6 months. In comparison with culprit vessel-only PCI, MV-PCI staged during the index hospitalization significantly reduced all-cause death (risk ratio, 0.73; 95%CI, 0.56-0.92; P=.008) and ranked as possibly the best treatment option for this outcome compared with all other strategies. In comparison with culprit vessel-only PCI, a MV-PCI reduced cardiovascular mortality without differences dependent on the timing of revascularization. MV-PCI within the index hospitalization, either in a single procedure or staged, significantly reduced myocardial infarction and unplanned ischemia-driven revascularization, with no significant difference between each other. CONCLUSIONS In patients with STEMI and multivessel CAD without cardiogenic shock, multivessel PCI within the index hospitalization, either in a single procedure or staged, represents the safest and most efficacious approach. The different timings of multivessel PCI did not result in any significant differences in all-cause death. This study is registered at PROSPERO (CRD42023457794)

Records needed for orthodontic diagnosis and treatment planning: a systematic review

Contains fulltext : 125812.pdf (publisher's version ) (Open Access)BACKGROUND: Traditionally, dental models, facial and intra-oral photographs and a set of two-dimensional radiographs are used for orthodontic diagnosis and treatment planning. As evidence is lacking, the discussion is ongoing which specific records are needed for the process of making an orthodontic treatment plan. OBJECTIVE: To estimate the contribution and importance of different diagnostic records for making an orthodontic diagnosis and treatment plan. DATA SOURCES: An electronic search in PubMed (1948-July 2012), EMBASE Excerpta Medica (1980-July 2012), CINAHL (1982-July 2012), Web of Science (1945-July 2012), Scopus (1996-July 2012), and Cochrane Library (1993-July 2012) was performed. Additionally, a hand search of the reference lists of included studies was performed to identify potentially eligible studies. There was no language restriction. STUDY SELECTION: THE PATIENT, INTERVENTION, COMPARATOR, OUTCOME (PICO) QUESTION FORMULATED FOR THIS STUDY WAS AS FOLLOWS: for patients who need orthodontic treatment (P), will the use of record set X (I) compared with record set Y (C) change the treatment plan (O)? Only primary publications were included. DATA EXTRACTION: Independent extraction of data and quality assessment was performed by two observers. RESULTS: Of the 1041 publications retrieved, 17 met the inclusion criteria. Of these, 4 studies were of high quality. Because of the limited number of high quality studies and the differences in study designs, patient characteristics, and reference standard or index test, a meta-analysis was not possible. CONCLUSION: Cephalograms are not routinely needed for orthodontic treatment planning in Class II malocclusions, digital models can be used to replace plaster casts, and cone-beam computed tomography radiographs can be indicated for impacted canines. Based on the findings of this review, the minimum record set required for orthodontic diagnosis and treatment planning could not be defined. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42012002365

Modified balloons to prepare severely calcified coronary lesions before stent implantation: a systematic review and meta-analysis of randomized trials

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>The performance of modified balloons (namely cutting or scoring balloons) to prepare severely calcified lesions in patients undergoing percutaneous coronary intervention (PCI) remains controversial. We investigated the clinical and imaging outcomes of patients undergoing PCI assigned to modified balloon therapy to prepare severely calcified coronary lesions before stent implantation.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>In this meta-analysis, we aggregated the study-level data from trials enrolling invasively treated patients who were randomly assigned to modified balloon or control therapy to prepare severely calcified lesions before stenting. The primary outcome was major adverse cardiac events (MACE), including death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included the individual components of the primary outcome, coronary perforation and final minimal stent area (MSA) as measured by intracoronary imaging.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>A total of 648 participants in six trials were allocated to modified balloon therapy (<jats:italic>n</jats:italic> = 335) or control therapy (semi-compliant, non-compliant, or super high-pressure balloon, <jats:italic>n</jats:italic> = 313). The median follow-up was 11 months. Overall, MACE occurred in 8.96% of patients assigned to a modified balloon and 12.78% of patients assigned to control therapy [risk ratio = 0.70, 95% confidence interval (CI) 0.35–1.39; <jats:italic>P</jats:italic> = 0.24]. There was a significant treatment effect-by-modified balloon type interaction for the outcome MACE in patients assigned to cutting balloon compared with control therapy [RR = 0.40 (0.28–0.56), P for interaction (<jats:italic>P</jats:italic><jats:sub>int</jats:sub>) < 0.001]. Patients treated with a modified balloon compared with control therapy showed neither a significant difference for the other clinical outcomes nor for final MSA [standardized mean difference = 0.67 (− 0.71, 2.06); <jats:italic>P</jats:italic> = 0.26].</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>In patients treated with PCI for severely calcific coronary artery disease a strategy of lesion preparation with a modified balloon before stenting does not improve clinical or imaging outcomes compared with control therapy. The different performance of cutting and scoring balloons warrants further investigation.</jats:p> </jats:sec><jats:sec> <jats:title>Graphical Abstract</jats:title> </jats:sec&gt