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Aims: To examine the associations between antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), β-blockers, diuretics, or calcium-antagonists, and risk of atrial fibrillation. We examined these associations using the entire Danish population from 1995 through 2010., Methods and Results: Excluding medication used in atrial fibrillation, we matched individuals on ACEi monotherapy 1:1 with individuals on β-blocker (n = 48 658), diuretic (n = 69 630), calcium-antagonist (n = 57 646), and ARB monotherapy (n = 20 158). Likewise, individuals on ARB monotherapy were matched 1:1 with individuals on β-blocker (n = 20 566), diuretic (n = 20 832), calcium-antagonist (n = 20 232), and ACEi monotherapy (n = 20 158). All were free of atrial fibrillation and of predisposing diseases like heart failure, ischaemic heart disease, diabetes mellitus, and hyperthyroidism at baseline and none received any other antihypertensive medication. We studied risk of atrial fibrillation, and used risk of stroke, influenced by lowering blood pressure rather than renin-angiotensin system blockade per se, as an indicator of the importance of blood pressure lowering per se. Hazard ratios of atrial fibrillation for ACEi and ARB monotherapy were 0.12 (95% CI: 0.10-0.15) and 0.10 (0.07-0.14) compared with β-blocker, 0.51 (0.44-0.59) and 0.43 (0.32-0.58) compared with diuretic, and 0.97 (0.81-1.16) and 0.78 (0.56-1.08) compared with calcium-antagonist monotherapy. Risk of stroke did not differ among the five antihypertensive medications., Conclusion: Use of ACEis and ARBs compared with β-blockers and diuretics associates with a reduced risk of atrial fibrillation, but not stroke, within the limitations of a retrospective study reporting associations. This suggests that controlling activation of the renin-angiotensin system in addition to controlling blood pressure is associated with a reduced risk of atrial fibrillation.

Background: Atrial fibrillation is associated with inflammation. In contrast to inflammatory markers like C-reactive protein (CRP) and fibrinogen produced in the liver, YKL-40 is produced at the site of inflammation including in the myocardium. We hypothesized that elevated plasma YKL-40 levels associate with increased risk of atrial fibrillation., Method and Results: We measured plasma YKL-40 in 8731 participants from the prospective Copenhagen City Heart Study including 896 individuals who developed atrial fibrillation during up to 18 years of follow-up. Additionally, we measured YKL-40 in 6621 individuals from the cross-sectional Copenhagen General Population Study including 337 cases with atrial fibrillation. A YKL-40 level >95% percentile (>204 μg/L) versus <25% percentile (<36 μg/L) associated prospectively with a 2.10-fold (95%CI:1.43-3.09) increased risk of atrial fibrillation. Hazard ratios attenuated slightly after multifactorial adjustment to 2.01 (1.35-2.98), and further after additional adjustment for heart failure to 1.89 (1.27-2.80), for plasma CRP to 1.79 (1.20-2.67), and for fibrinogen levels to 1.89 (1.27-2.81). Adjusting multifactorially including both heart failure, CRP, and fibrinogen attenuated the risk of atrial fibrillation to 1.79 (1.20-2.67). These findings were supported in the cross-sectional study with an odds ratio of 2.73 (1.46-5.11) for a YKL-40 level >95% percentile versus <25% percentile, attenuating to an odds ratio of 2.13 (1.09-4.18) when adjusting multifactorially including heart failure, CRP, and fibrinogen., Conclusions: Elevated plasma YKL-40 levels robustly associated with increased risk of atrial fibrillation originating from hospital admissions or visits to the emergency department, independent of heart failure, and CRP and fibrinogen levels. These findings need to be confirmed in other independent studies., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Aims: Activation of the angiotensin II type 1 (AT1 ) receptor has been shown to mediate the structural and electrical remodelling of the atrial myocardium associated with atrial fibrillation. We hypothesized that AT1 genotypic variation is associated with atrial fibrillation or diseases predisposing to atrial fibrillation, such as hypertension, heart failure, ischaemic heart disease and myocardial infarction, in the general population., Methods: We resequenced the AT1 gene in 760 individuals with atrial fibrillation and identified two nonsynonymous variants (I103T and A244S), which were subsequently genotyped in the prospective Copenhagen City Heart Study (n = 10 603) and the prospective Copenhagen General Population Study (n = 60 647)., Results: Risk of atrial fibrillation for heterozygotes for AT1 genetic variants A244S and I103T/A244S vs. noncarriers was increased by 2.7-fold (95% confidence interval 1.5- to 5.1-fold) and 2.6-fold (95% confidence interval 1.6- to 4.2-fold), respectively, for men., Conclusions: Heterozygosity for the nonsynonymous AT1 genetic variants A244S and I103T/A244S was associated with increased risk of atrial fibrillation in men. The AT1 recptor might be a target for the pharmaceutical industry. This finding needs to be validated in independent studies., (© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)

Objectives: The purpose of this study was to test whether the association of C-reactive protein (CRP) with increased risk of atrial fibrillation is a robust and perhaps even causal association., Background: Elevated levels of CRP previously have been associated with increased risk of atrial fibrillation., Methods: We studied 10,276 individuals from the prospective Copenhagen City Heart Study, including 771 individuals who had atrial fibrillation during follow-up, and another 36,600 persons from the cross-sectional Copenhagen General Population Study, including 1,340 cases with atrial fibrillation. Individuals were genotyped for 4 CRP gene polymorphisms and had high-sensitivity CRP levels measured., Results: A CRP level in the upper versus lower quintile associated with a 2.19-fold (95% confidence interval [CI]: 1.54- to 3.10-fold) increased risk of atrial fibrillation. Risk estimates attenuated slightly after multifactorial adjustment to 1.77 (95% CI: 1.22 to 2.55), and after additional adjustment for heart failure and plasma fibrinogen level to 1.47 (95% CI: 1.02 to 2.13) and 1.63 (95% CI: 1.21 to 2.20), respectively. Genotype combinations of the 4 CRP polymorphisms associated with up to a 63% increase in plasma CRP levels (p < 0.001), but not with increased risk of atrial fibrillation. The estimated causal odds ratio for atrial fibrillation by instrumental variable analysis for a doubling in genetically elevated CRP levels was lower than the odds ratio for atrial fibrillation observed for a doubling in plasma CRP on logistic regression (0.94 [95% CI: 0.70 to 1.27] vs. 1.36 [95% CI: 1.30 to 1.44]; p < 0.001)., Conclusions: Elevated plasma CRP robustly associated with increased risk of atrial fibrillation; however, genetically elevated CRP levels did not. This suggests that elevated plasma CRP per se does not increase atrial fibrillation risk., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims Activation of the angiotensin II type 1 (AT1) receptor has been shown to mediate the structural and electrical remodelling of the atrial myocardium associated with atrial fibrillation. We hypothesized that AT1 genotypic variation is associated with atrial fibrillation or diseases predisposing to atrial fibrillation, such as hypertension, heart failure, ischaemic heart disease and myocardial infarction, in the general population. Methods We resequenced the AT1 gene in 760 individuals with atrial fibrillation and identified two nonsynonymous variants ( I103 T and A244 S), which were subsequently genotyped in the prospective Copenhagen City Heart Study ( n = 10 603) and the prospective Copenhagen General Population Study ( n = 60 647). Results Risk of atrial fibrillation for heterozygotes for AT1 genetic variants A244 S and I103 T/ A244 S vs. noncarriers was increased by 2.7-fold (95% confidence interval 1.5- to 5.1-fold) and 2.6-fold (95% confidence interval 1.6- to 4.2-fold), respectively, for men. Conclusions Heterozygosity for the nonsynonymous AT1 genetic variants A244 S and I103 T/ A244 S was associated with increased risk of atrial fibrillation in men. The AT1 recptor might be a target for the pharmaceutical industry. This finding needs to be validated in independent studies. [ABSTRACT FROM AUTHOR]