Georgios Georgiopoulos1,2, Georgios Ntritsos3,4, Kimon Stamatelopoulos2, Costas Tsioufis5, Alberto Aimo6, Stefano Masi6,7,8, Evangelos Evangelou3. 1. School of Biomedical Engineering and Imaging Sciences, King's College London, Westminster Bridge Road, London SE1 7EH, UK. 2. Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 3. Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece. 4. Department of Informatics and Telecommunications, School of Informatics and Telecommunications, University of Ioannina, Arta, Greece. 5. First Department of Cardiology, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 6. Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy. 7. National Centre for Cardiovascular Prevention and Outcomes, Institute of Cardiovascular Science, University College London, London EC1A 4NP, UK. 8. Department of Twin Research & Genetic Epidemiology, King's College London, London WC2R 2LS, UK.
Abstract
AIMS: Observational studies suggest elevated blood pressure (BP) as the leading risk factor for incident atrial fibrillation (AF), but whether this relationship is causal remains unknown. In this study, we used Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of developing AF. METHODS AND RESULTS: Genetic variants associated with the BP traits were retrieved from the International Consortium of Blood Pressure-Genome Wide Association Studies (N = 299 024). From 901 reported variants, 894 were assessed in a dedicated Genome-Wide Association Study of AF genetics, including >1 000 000 subjects of European ancestry. We used two-sample MR analyses to examine the potential causal association of systolic BP (SBP) and diastolic BP (DBP) as well as of pulse pressure (PP) with AF. MR analysis identified a potentially causal association between AF and SBP [odds ratio (OR): 1.018 per 1 mmHg increase, 95% confidence interval (CI): 1.012-1.024, P < 0.001], DBP (OR: 1.026, 95% CI: 1.016-1.035, P < 0.001), and PP (OR: 1.014, 95% CI: 1.001-1.028, P = 0.033). These findings were robust in sensitivity analyses, including the MR-Egger method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). The causal relationship of BP and AF did not change when single-nucleotide polymorphisms associated with possible confounders (i.e. coronary artery disease and obesity) of the causal relationship were excluded. CONCLUSIONS: The association between increased BP levels and the risk of AF is likely causal and applies for different BP indices. Independently from other risk factors, optimal BP control might represent an important therapeutic target for AF prevention in the general population. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Observational studies suggest elevated blood pressure (BP) as the leading risk factor for incident atrial fibrillation (AF), but whether this relationship is causal remains unknown. In this study, we used Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of developing AF. METHODS AND RESULTS: Genetic variants associated with the BP traits were retrieved from the International Consortium of Blood Pressure-Genome Wide Association Studies (N = 299 024). From 901 reported variants, 894 were assessed in a dedicated Genome-Wide Association Study of AF genetics, including >1 000 000 subjects of European ancestry. We used two-sample MR analyses to examine the potential causal association of systolic BP (SBP) and diastolic BP (DBP) as well as of pulse pressure (PP) with AF. MR analysis identified a potentially causal association between AF and SBP [odds ratio (OR): 1.018 per 1 mmHg increase, 95% confidence interval (CI): 1.012-1.024, P < 0.001], DBP (OR: 1.026, 95% CI: 1.016-1.035, P < 0.001), and PP (OR: 1.014, 95% CI: 1.001-1.028, P = 0.033). These findings were robust in sensitivity analyses, including the MR-Egger method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). The causal relationship of BP and AF did not change when single-nucleotide polymorphisms associated with possible confounders (i.e. coronary artery disease and obesity) of the causal relationship were excluded. CONCLUSIONS: The association between increased BP levels and the risk of AF is likely causal and applies for different BP indices. Independently from other risk factors, optimal BP control might represent an important therapeutic target for AF prevention in the general population. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: João Gabriel Batista Lage; Alexandre Lemos Bortolotto; Mauricio Ibrahim Scanavacca; Luiz Aparecido Bortolotto; Francisco Carlos da Costa Darrieux Journal: Clinics (Sao Paulo) Date: 2022-03-03 Impact factor: 2.365
Authors: Qin Wang; Tom G Richardson; Eleanor Sanderson; Matthew J Tudball; Mika Ala-Korpela; George Davey Smith; Michael V Holmes Journal: Int J Epidemiol Date: 2022-08-10 Impact factor: 9.685