Register-based predictors of adherence among new statin users in Finland.

Background: Although register-based studies on statin adherence are increasing, for administrative data, little is known about the explanatory power of the predictors that explain adherence.

Objective: The aim was to explore the ability of variables in administrative data to predict statin adherence in an unselected, universally insured population and, especially, to explore dispensation delay (time elapsed between prescription and dispensation) and out-of-pocket costs as explanatory factors.

Methods: Statin initiators who were aged 45 to 75 years in 2000-2004 (n = 247, 051) were identified in the Finnish Prescription Register.

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia.

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.

Computed tomographic coronary angiography for patients with heart failure (CTA-HF): a randomized controlled trial (IMAGE HF Project 1-C).

Background: The prevalence of heart failure (HF) is rising in industrialized and developing countries. Though invasive coronary angiography (ICA) remains the gold standard for anatomical assessment of coronary artery disease in HF patients, alternatives are being sought. Computed tomographic coronary angiography (CTA) has emerged as an accurate non-invasive diagnostic tool for coronary artery disease (CAD) and has been demonstrated to have prognostic value.

Heart rate variability associates with asymptomatic coronary atherosclerosis.

Purpose: Heart rate variability (HRV) becomes impaired in symptomatic coronary artery disease (CAD), particularly, after myocardial infarction. The mechanism how CAD results in impairment of cardiac autonomic regulation is not known. Whether it results rather from coronary atherosclerosis itself than myocardial ischemia and myocardial injury has remained elusive.

Fine-scale mapping of the FGFR2 breast cancer risk locus: putative functional variants differentially bind FOXA1 and E2F1.

The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus.

Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions.

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included.

A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46,450 cases and 42,461 controls from the breast cancer association consortium.

Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70,917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46,450 breast cancer cases and 42,461 controls of European origin as part of a multi-consortium project (COGS).

Testing of common electromagnetic environments for risk of interference with cardiac pacemaker function.

Background: Cardiac pacemakers are known to be susceptible to strong electromagnetic fields (EMFs). This in vivo study investigated occurrence of electromagnetic interference with pacemakers caused by common environmental sources of EMFs.

Methods: Eleven volunteers with a pacemaker were exposed to EMFs produced by two mobile phone base stations, an electrically powered commuter train, and an overhead high voltage transmission lines.

Preventive strategies for atrial fibrillation after cardiac surgery in Nordic countries.

Background And Aims: Atrial fibrillation is a common arrhythmia after cardiac surgery. It increases morbidity, length of hospital stay, and costs of operative treatment. Beta-blockers, sotalol, amiodarone, corticosteroids, and biatrial pacing have been shown to be efficient in the prevention of postoperative atrial fibrillation.

Thromboembolic complications after cardioversion of acute atrial fibrillation: the FinCV (Finnish CardioVersion) study.

Objectives: This study sought to explore the incidence and risk factors of thromboembolic complications after cardioversion of acute atrial fibrillation.

Background: Anticoagulation therapy is currently recommended after cardioversion of acute atrial fibrillation in patients with risk factors for stroke, but the implementation of these new consensus-based guidelines has been slow.

Methods: A total of 7,660 cardioversions were performed in 3,143 consecutive patients with atrial fibrillation lasting <48 h in 3 hospitals.

The UGT1A6_19_GG genotype is a breast cancer risk factor.

Validation of an association between the UGT1A6_19_T>G (rs6759892) polymorphism and overall breast cancer risk. A pilot study included two population-based case-control studies from Germany (MARIE-GENICA). An independent validation study comprised four independent breast cancer case-control studies from Finland (KBCP, OBCS), Germany (BBCC), and Sweden (SASBAC).

Arrhythmic complications after electrical cardioversion of acute atrial fibrillation: the FinCV study.

Aims: To determine the incidence and risk factors of arrhythmic complications after electrical cardioversion of acute atrial fibrillation (AF).

Methods And Results: Our retrospective multicentre study collected data from 7660 cardioversions of acute (<48 h) AF in 3143 consecutive patients. Immediate arrhythmic complications were evaluated after 6906 (90.

Matriptase-2 gene (TMPRSS6) variants associate with breast cancer survival, and reduced expression is related to triple-negative breast cancer.

Matriptase-2 (TMPRSS6) has been identified as a breast cancer risk factor. Here, we examined relationships between TMPRSS6 genetic variations and breast cancer risk and survival, and determined the gene and protein expressions in breast tumors and assessed their clinical importance. Thirteen TMPRSS6 polymorphisms were genotyped in 462 invasive breast cancer cases and 458 controls.

Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled.

Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers.

Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element.

Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS).

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants.

Large-scale genotyping identifies 41 new loci associated with breast cancer risk.

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping.

Intravenous metoprolol versus biatrial pacing in the prevention of atrial fibrillation after coronary artery bypass surgery: a prospective randomized open trial.

Background And Aims: Atrial fibrillation (AF) is the most common arrhythmia after coronary artery bypass surgery (CABG). Intravenous metoprolol and biatrial pacing have been reported to be effective in AF prophylaxis after cardiac surgery. The purpose of this trial was to compare the efficacy of intravenous metoprolol versus biatrial pacing combined with oral metoprolol in the prevention of AF after CABG.

Baroreflex sensitivity in asymptomatic coronary atherosclerosis.

Background: Baroreflex sensitivity (BRS) reflects the effectiveness of cardiac parasympathetic regulation. BRS becomes impaired in stable coronary artery disease (CAD) and after myocardial infarction and carries prognostic information in these patients. Whether impaired BRS is found already in asymptomatic subjects, with subclinical coronary atherosclerosis, has remained elusive.

Electromagnetic interference with cardiac pacemakers and implantable cardioverter-defibrillators from low-frequency electromagnetic fields in vivo.

Aims: Electromagnetic interference (EMI) can pose a danger to workers with pacemakers and implantable cardioverter-defibrillators (ICDs). At some workplaces electromagnetic fields are high enough to potentially inflict EMI. The purpose of this in vivo study was to evaluate the susceptibility of pacemakers and ICDs to external electromagnetic fields.

Dotted collar placed around carotid artery induces asymmetric neointimal lesion formation in rabbits without intravascular manipulations.

Background: Neointimal formation in atherosclerosis has been subject for intense research. However, good animal models mimicking asymmetrical lesion formation in human subjects have been difficult to establish. The aim of this study was to develop a model which would lead to the formation of eccentric lesions under macroscopically intact non-denuded endothelium.

Genetic polymorphisms and protein expression of NRF2 and Sulfiredoxin predict survival outcomes in breast cancer.

NRF2 activates several protective genes, such as sulfiredoxin (SRXN1), as a response to oxidative and xenobiotic stress. Defects in NRF2 pathway may increase cancer susceptibility. In tumor cells, activation of NRF2 may lead to chemo- and radioresistance and thus affect patient outcome.

Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670.