| 1. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 2. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 3. |
- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 4. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Heo, Rachel Haeeun, et al.
(författare)
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Associations of Inflammatory Biomarkers With the Risk of Morbidity and Mortality After Cardiac Surgery : A Systematic Review and Meta-analysis
- 2023
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Ingår i: Canadian Journal of Cardiology. - : Elsevier. - 0828-282X .- 1916-7075. ; 39:11, s. 1686-1694
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Forskningsöversikt (refereegranskat)abstract
- Background: Although inflammatory biomarkers have been associated with cardiovascular events in nonsurgical settings, these associations have not been systematically addressed in patients undergoing cardiac surgery. This review aimed to evaluate the relationships of inflammatory markers with mortality and adverse cardiovascular events in patients undergoing cardiac surgery. Methods: Medline, Embase, and Central databases were systematically searched for studies reporting pre-or postoperative levels of inflammatory biomarkers in patients undergoing cardiac surgery. Outcomes of interest were postoperative mortality, nonfatal myocardial infarction, stroke, congestive heart failure, and major adverse cardiovascular events (MACE). Studies reporting multivariable adjusted risk estimates were included. Risk estimates were pooled with the use of random-effects models and reported as summary odds ratios (ORs).Results: Among 14,465 citations identified, 29 studies including 29,401 participants met the eligibility criteria. The average follow-up time after surgery was 31 months. Preoperative C-reactive protein (CRP) levels were associated with an increased risk of all-cause mortality (OR 1.88, 95% CI 1.60-2.20; I2 = 19%; 11 studies) and MACE (OR 1.73, 95% CI 1.34-2.24; I2 = 0%; 3 studies). CRP levels measured on postoperative day 6 (OR 7.4, 95% CI 2.90-18.88, 1 study) and day 10 (OR 11.8, 95% CI 3.50-39.78, 1 study) were associated with a higher risk of all-cause mortality. Less, but overall similar, information was available for other inflammatory biomarkers. Conclusions: In this large meta-analysis, inflammatory biomarkers measured before or after cardiac surgery were associated with mortality and adverse cardiovascular outcomes in patients undergoing cardiac surgery.
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| 6. |
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| 7. |
- Johnson, Linda S.B., et al.
(författare)
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LVS-HARMED Risk Score for Incident Heart Failure in Patients With Atrial Fibrillation Who Present to the Emergency Department : Data from a World-Wide Registry
- 2021
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Ingår i: Journal of the American Heart Association. - : Wolters Kluwer. - 2047-9980 .- 2047-9980. ; 10:18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) is a common complication to atrial fibrillation (AF), leading to rehospitalization and death. Early identification of patients with AF at risk for HF might improve outcomes. We aimed to derive a score to predict 1-year risk of new-onset HF after an emergency department (ED) visit with AF.Methods and Results: The RE-LY AF (Randomized Evaluation of Long-Term Anticoagulant Therapy) registry enrolled patients with AF presenting to an ED in 47 countries, and followed them for a year. The end point was HF hospitalization and/or HF death. Among 15 400 ED patients, 9765 had no prior HF (mean age, 64.9 +/- 14.9 years). Within 1 year, new-onset HF developed in 6.8% of patients, of whom 21% died of HF. Independent predictors of HF included left ventricular hypertrophy (odds ratio [OR], 1.47; 95% CI, 1.19-1.82), valvular heart disease (OR, 1.55; 95% CI, 1.18-2.04), smoking (OR, 1.42; 95% CI, 1.12-1.78), height (OR, 0.93; 95% CI, 0.90-0.95 per 3 cm), age (OR, 1.11; 95% CI, 1.07-1.15 per 5 years), rheumatic heart disease (OR, 1.77, 95% CI, 1.24-2.51), prior myocardial infarction (OR, 1.85; 95% CI, 1.45-2.36), remaining in AF at ED discharge (OR, 1.86; 95% CI, 1.46-2.36), and diabetes (OR, 1.33; 95% CI, 1.09-1.64). A continuous risk prediction score (LVS-HARMED [left ventricular, valvular heart disease, smoking or other tobacco use, height, age, rheumatic heart disease, myocardial infarction, emergency department discharge rhythm, and diabetes]) had good discrimination (C statistic, 0.735; 95% CI, 0.716-0.755). Validation was conducted internally using bootstrapping (optimism-corrected C statistic, 0.705) and externally (C statistic, 0.699). The 1-year incidence of HF hospitalization and/or HF death across quartile groups of the score was 1.1%, 4.5%, 6.9%, and 14.4%, respectively. LVS-HARMED also predicted incident stroke (C statistic, 0.753; 95% CI, 0.728-0.778).Conclusions: The LVS-HARMED score predicts new-onset HF after an ED visit for AF. Preventative strategies should be considered in patients with high LVS-HARMED HF risk.
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| 8. |
- Johnson, Linda S, et al.
(författare)
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Markers of Atrial Myopathy in the General Population Prevalence, Predictors, and Inter-Relations
- 2023
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Ingår i: JACC. - : Elsevier. - 2405-500X .- 2405-5018. ; 9:11, s. 2240-2249
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Tidskriftsartikel (refereegranskat)abstract
- Background Atrial myopathy refers to structural and functional cardiac abnormalities associated with atrial fibrillation and stroke, but appropriate diagnostic criteria are lacking.Objectives This study aimed to assess prevalence, clinical correlates, and overlap between potential atrial myopathy markers.Methods The population-based SCAPIS (Swedish CArdioPulmonary bioImage Study) prospectively included 6,013 subjects without atrial fibrillation with 24-hour electrocardiograms. Resting electrocardiograms measuring P-wave indices were collected at 1 screening site (n = 1,201), and a random sample (n = 385) had echocardiographic left atrial volume index (LAVi). Atrial myopathy markers were defined as >= 500 premature atrial complexes/24 h, LAVi >= 34 mL/m(2), P-wave duration >120 milliseconds, or P-wave terminal force in V-1 >4,000 mss. Clinical correlates included age, sex, body mass index, height, smoking, physical activity, coronary artery disease, diabetes, systolic blood pressure, antihypertensive medication, and low education.Results Atrial myopathy was common; 42% of the sample with all diagnostic modalities available had >= 1 atrial myopathy marker, but only 9% had 2 and 0.3% had >= 3. Only P-wave duration and LAVi were correlated (rho = 0.10; P = 0.04). Clinical correlates of premature atrial complexes, P-wave indices, and LAVi differed; current smoking (34% increase; P < 0.001), systolic blood pressure (4%/mm Hg increase; P = 0.01), diabetes (35% increase; P = 0.001), and coronary artery disease (71% increase; P = 0.003) were associated with premature atrial complexes, physical activity >= 2 h/wk was associated with increased LAVi (beta-coefficient = 3.1; P < 0.0001) and body mass index was associated with P-wave duration (beta-coefficient = 0.4/kg/m(2); P < 0.0001).Conclusions In the general population, indirect markers of atrial myopathy are common but only weakly correlated, and their risk factor patterns are different. More studies are needed to accurately identify individuals with atrial myopathy with diagnostic methods.
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| 9. |
- Kloosterman, Marielle, et al.
(författare)
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Characteristics and outcomes of atrial fibrillation in patients without traditional risk factors : an RE-LY AF registry analysis
- 2020
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 22:6, s. 870-877
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Data on patient characteristics, prevalence, and outcomes of atrial fibrillation (AF) patients without traditional risk factors, often labelled 'lone AF', are sparse. Methods and results: The RE-LY AF registry included 15 400 individuals who presented to emergency departments with AF in 47 countries. This analysis focused on patients without traditional risk factors, including age >= 60years, hypertension, coronary artery disease, heart failure, left ventricular hypertrophy, congenital heart disease, pulmonary disease, valve heart disease, hyperthyroidism, and prior cardiac surgery. Patients without traditional risk factors were compared with age- and region-matched controls with traditional risk factors (1:3 fashion). In 796 (5%) patients, no traditional risk factors were present. However, 98% (779/796) had less-established or borderline risk factors, including borderline hypertension (130-140/80-90mmHg; 47%), chronic kidney disease (eGFR<60mL/min; 57%), obesity (body mass index>30; 19%), diabetes (5%), excessive alcohol intake (>14 units/week; 4%), and smoking (25%). Compared with patients with traditional risk factors (n=2388), patients without traditional risk factors were more often men (74% vs. 59%, P<0.001) had paroxysmal AF (55% vs. 37%, P<0.001) and less AF persistence after 1 year (21% vs. 49%, P<0.001). Furthermore, 1-year stroke occurrence rate (0.6% vs. 2.0%, P=0.013) and heart failure hospitalizations (0.9% vs. 12.5%, P<0.001) were lower. However, risk of AF-related re-hospitalization was similar (18% vs. 21%, P=0.09). Conclusion: Almost all patients without traditionally defined AF risk factors have less-established or borderline risk factors. These patients have a favourable 1-year prognosis, but risk of AF-related re-hospitalization remains high. Greater emphasis should be placed on recognition and management of less-established or borderline risk factors.
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| 10. |
- Krisai, Philipp, et al.
(författare)
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Incidence and Predictors of Heart Failure in Patients With Atrial Fibrillation
- 2021
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Ingår i: CJC Open. - : Elsevier BV. - 2589-790X. ; 3:12, s. 1482-1489
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) is a frequent cause of hospitalization and death in patients with atrial fibrillation (AF). Identifying AF patients at risk of HF hospitalization could help select individuals for intensive follow-up and treatment. Methods: We pooled data from 3 randomized trials (ACTIVE-A, RE-LY, AVERROES) of AF patients, for derivation and internal validation of a risk score for first HF hospitalization. Secondary endpoints were cardiovascular death and a composite of HF hospitalizations and cardiovascular death. Results: In 23,503 patients, the mean age was 71.3 years, and 62% were male. Over a mean follow-up of 2.0 years, 875 patients (3.7%) experienced their first HF hospitalization, and 1037 patients (4.4%) died from cardiovascular causes. Incidence rates per 100 patient-years were 1.85 for HF hospitalizations, 2.15 for cardiovascular death, and 3.71 for the composite. Independent predictors for HF hospitalizations included the following: increased age, weight, heart rate and serum creatinine level, lower height and systolic blood pressure, diabetes, vascular disease, valvular disease, heart rhythm, left ventricular hypertrophy, and intraventricular conduction delay. The C-statistic (95% confidence intervals by bootstrap simulations) was 0.717 (0.705-0.732). At 2 years of follow-up, the incidence rate of the primary outcome increased across risk-score quintiles: 0.49, 0.87, 1.29, 2.44, and 4.51 per 100 patient-years, respectively. Patients in the highest quintile had an absolute risk of 6.8% for the primary endpoint at 2 years. Conclusions: In a large AF population, new-onset HF was common. A combination of characteristics can identify high-risk patients for whom strategies to prevent HF should be considered.
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