In the past 10 years, large-scale genotyping has led to discoveries of sequence variants that confer the risk of many common and complex diseases. Due to pioneering work done, in large part, at ...deCODE genetics in Reykjavik, discoveries from Iceland have contributed substantially to key advances in population genetics. In cardiovascular medicine, a number of discoveries have been made, uncovering sequence variants that are associated with disorders such as coronary artery disease, atrial fibrillation, sick sinus syndrome, peripheral vascular disease, aortic aneurysm, and ischemic stroke. Thus, a wealth of genetic data has been accumulated in cardiology and has enhanced our understanding of a number of diseases. In many cases, these findings offer new mechanistic clues into the pathophysiology of complex cardiovascular diseases and may point toward novel therapeutic approaches in drug therapy. The next important step is to begin to transform these findings into practical clinical knowledge with the aim of improving the delivery of cardiovascular health care.
Third universal definition of myocardial infarction THYGESEN, Kristian; ALPERT, Joseph S; JAFFE, Allan S ...
European heart journal,
10/2012, Letnik:
33, Številka:
20
Journal Article, Conference Proceeding, Web Resource
Heart failure (HF) affects over 26 million people worldwide. Multidisciplinary management strategies that include symptom monitoring and patient self-care support reduce HF hospitalization and ...mortality rates. Ideally, HF follow-up and self-care support includes lifestyle-change recommendations and remote monitoring of weight and HF symptoms. Providing these via a digital solution may be ideal for improving HF disease outcomes and reducing the burden on providers and healthcare systems. This study's main objective was to assess the feasibility of a digital solution including remote monitoring, lifestyle-change, and self-care support for HF outpatients in Iceland.
Twenty HF patients (mean age 57.5 years, 80% males) participated in an 8-week study. They were provided with a digital solution (SK-141), including lifestyle-change and disease self-care support, a remote symptom monitoring system, and a secure messaging platform between healthcare providers and patients. This feasibility study aimed to assess patient acceptability of this new intervention, retention rate, and to evaluate trends in clinical outcomes. To assess the acceptability of SK-141, participants completed a questionnaire about their experience after the 8-week study. Participants performed daily assigned activities (missions), including self-reporting symptoms. Clinical outcomes were assessed with the Hospital Anxiety and Depression Scale and the Kansas City Cardiomyopathy Questionnaire at the study's beginning and end with an online survey.
Of the 24 patients invited, 20 were elected to participate. The retention rate of participants throughout the 8-week period was high (80%). At the end of the 8 weeks, thirteen participants completed a questionnaire about their experience and acceptability of the SK-141. They rated their experience positively including on questions whether they would recommend the solution to others (6.8 on a scale of 1-7), whether the solution had improved their life and well-being (5.7 on a scale of 1-7), and whether it was user friendly (5.5 on a scale of 1-7). Many of the clinical parameters studied exhibited a promising trend towards improvement over the 8-week period.
The digital solution, SK-141, was very acceptable to patients and also showed promising clinical results in this small feasibility study. These results encourage us to conduct a longer, more extensive, adequately powered, randomized-controlled study to assess whether this digital solution can improve the quality of life and clinical outcomes among HF patients.
Genetic insight into sick sinus syndrome Thorolfsdottir, Rosa B; Sveinbjornsson, Gardar; Aegisdottir, Hildur M ...
European heart journal,
05/2021, Letnik:
42, Številka:
20
Journal Article
Recenzirano
Odprti dostop
The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development.
We performed a genome-wide association ...study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1-1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10-20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05).
We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.
Eur J Clin Invest 2011; 41 (9): 995–1003
Background The anti‐inflammatory or anti‐arrhythmic effects of n‐3 long‐chain polyunsaturated fatty acids (LC‐PUFA) may decrease the risk of postoperative ...atrial fibrillation (POAF), but interventional studies have yielded conflicting results. We examined the association between n‐3 LC‐PUFA and n‐6 LC‐PUFA in plasma phospholipids (PL) and POAF in patients undergoing coronary artery bypass grafting (CABG).
Methods A total of 125 patients undergoing CABG were enrolled in the study. The levels of fatty acids in PL were measured preoperatively and on the third postoperative day. The endpoint was defined as POAF lasting ≥5 min. The incidence of POAF was compared between quartiles of the level of each fatty acid in plasma PL by univariate and multivariable analysis.
Results The incidence of POAF was 49·6%. By univariate analysis, the incidence of POAF increased significantly with each higher quartile of pre‐ and postoperative docosahexaenoic acid (DHA) and diminished significantly with each higher quartile of pre‐ and postoperative arachidonic acid (AA). For postoperative total n‐3 LC‐PUFA, there was a significant U‐curve relationship where the second quartile had the lowest incidence of POAF or 25·8%. In multivariable analysis, this U‐curve relationship between n‐3 LC‐PUFA levels and POAF risk was not significant, whereas the association between POAF and DHA or AA remained statistically significant.
Conclusions This study suggests that n‐3 LC‐PUFA supplements might prevent POAF in CABG patients with low baseline levels of these fatty acids in plasma PL, but may be harmful in those with high levels. AA may play an important role in electrophysiological processes.
The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for ...coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR-Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.
Third Universal Definition of Myocardial Infarction Thygesen, Kristian; Alpert, Joseph S; Jaffe, Allan S ...
Journal of the American College of Cardiology,
10/2012, Letnik:
60, Številka:
16
Journal Article, Conference Proceeding, Web Resource
Recenzirano
Odprti dostop
.1595 Abbreviations and acronyms ACCF = American College of Cardiology Foundation ACS = acute coronary syndrome AHA = American Heart Association CAD = coronary artery disease CABG = coronary artery ...bypass grafting CKMB = creatine kinase MB isoform cTn = cardiac troponin CT = computed tomography CV = coefficient of variation ECG = electrocardiogram ESC = European Society of Cardiology FDG = fluorodeoxyglucose h = hour(s) HF = heart failure LBBB = left bundle branch block LV = left ventricle LVH = left ventricular hypertrophy MI = myocardial infarction mlBG = meta-iodo-benzylguanidine min = minute(s) MONICA = Multinational MONItoring of trends and determinants in CArdiovascular disease MPS = myocardial perfusion scintigraphy MRI = magnetic resonance imaging mV = millivolt(s) ng/L = nanogram(s) per liter Non-Q Ml = non-Q wave myocardial infarction NSTEMI = non-ST-elevation myocardial infarction PCI = percutaneous coronary intervention PET = positron emission tomography pg/mL = pictogram(s) per milliliter Q wave Ml = Q wave myocardial infarction RBBB = right bundle branch block sec = second(s) SPECT = single photon emission computed tomography STEMI = ST elevation myocardial infarction ST-T = ST-segment -T wave URL = upper reference limit WHF = World Heart Federation WHO = World Health Organization Introduction Myocardial infarction (MI) can be recognized by clinical features, including electrocardiographic (ECG) findings, elevated values of biochemical markers (biomarkers) of myocardial necrosis, and by imaging, or may be defined by pathology. Additionally, the management of patients with MI has significantly improved, resulting in less myocardial injury and necrosis, in spite of a similar clinical presentation. ...it appears necessary to distinguish the various conditions which may cause MI, such as 'spontaneous' and 'procedure-related' MI. ...physicians, other healthcare providers and patients require an up-to-date definition of MI.
PDF
