Blood pressure, brain lesions and cognitive decline in patients with atrial fibrillation

Désirée Carmine^{1

2}, Stefanie Aeschbacher^{1

2}, Michael Coslovsky^{1

3}, Elisa Hennings^{1

2}, Rebecca E Paladini^{1

2}, Raffaele Peter^{1

2}, Melanie Burger^{1

2}, Tobias Reichlin⁴, Nicolas Rodondi^{5

6}, Andreas S Müller⁷, Peter Ammann⁸, Giulio Conte⁹, Angelo Auricchio⁹, Giorgio Moschovitis⁹, Julia B Bardoczi^{5

6}, Annina Stauber⁷, Maria Luisa De Perna⁹, Christine S Zuern^{1

2}, Tim Sinnecker^{10

11}, Patrick Badertscher^{1

2}, Christian Sticherling^{1

2}, Leo H Bonati¹², David Conen¹³, Philipp Krisai^{1

2}, Stefan Osswald^{1

2}, Michael Kühne^{1

2}

Affiliations

¹ Cardiovascular Research Institute Basel, University Hospital Basel, Basel, Switzerland.
² Department of Cardiology/Electrophysiology, Department of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
³ Clinical Trial Unit Basel, Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
⁴ Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁵ Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
⁶ Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷ Department of Cardiology, Triemli Hospital Zürich, Zürich, Switzerland.
⁸ Department of Cardiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
⁹ Division of Cardiology, Ente Ospedaliero Cantonale (EOC), Cardiocentro Ticino Institute, Regional Hospital of Lugano, Lugano, Switzerland.
¹⁰ Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland.
¹¹ Medical Image Analysis Center (MIAC) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
¹² Research Department, Reha Rheinfelden, Rheinfelden, Switzerland.
¹³ Population Health Research Institute, McMaster University, Hamilton, ON, Canada.

PMID: 39314770
PMCID: PMC11417621
DOI: 10.3389/fcvm.2024.1449506

Blood pressure, brain lesions and cognitive decline in patients with atrial fibrillation

Désirée Carmine et al. Front Cardiovasc Med. 2024.

. 2024 Sep 3:11:1449506.

doi: 10.3389/fcvm.2024.1449506. eCollection 2024.

Authors

Affiliations

¹ Cardiovascular Research Institute Basel, University Hospital Basel, Basel, Switzerland.
² Department of Cardiology/Electrophysiology, Department of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
³ Clinical Trial Unit Basel, Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
⁴ Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁵ Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
⁶ Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷ Department of Cardiology, Triemli Hospital Zürich, Zürich, Switzerland.
⁸ Department of Cardiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
⁹ Division of Cardiology, Ente Ospedaliero Cantonale (EOC), Cardiocentro Ticino Institute, Regional Hospital of Lugano, Lugano, Switzerland.
¹⁰ Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland.
¹¹ Medical Image Analysis Center (MIAC) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
¹² Research Department, Reha Rheinfelden, Rheinfelden, Switzerland.
¹³ Population Health Research Institute, McMaster University, Hamilton, ON, Canada.

PMID: 39314770
PMCID: PMC11417621
DOI: 10.3389/fcvm.2024.1449506

Abstract

Background: The influence of atrial fibrillation (AF) and blood pressure (BP) on brain lesions and cognitive function is unclear. We aimed to investigate the association of BP with different types of brain lesions and cognitive decline in patients with AF.

Methods: Overall, 1,213 AF patients underwent standardized brain magnetic resonance imaging at baseline and after 2 years, as well as yearly neurocognitive testing. BP was measured at baseline and categorized according to guidelines. New lesions were defined as new or enlarged brain lesions after 2 years. We defined cognitive decline using three different neurocognitive tests. Logistic and Cox regression analyses were performed to examine the associations of BP with new brain lesions and cognitive decline.

Results: The mean age was 71 ± 8.4 years, 74% were male and mean BP was 135 ± 18/79 ± 12 mmHg. New ischemic lesions and white matter lesions were found in 5.4% and 18.4%, respectively. After multivariable adjustment, BP was not associated with the presence of new brain lesions after 2 years. There was no association between BP and cognitive decline over a median follow-up of 6 years when using the Montreal Cognitive Assessment or Digit Symbol Substitution Test. However, BP categories were inversely associated with cognitive decline using the Semantic Fluency Test, with the strongest association in patients with hypertension grade 1 [Hazard Ratio (95% Confidence Interval) 0.57(0.42 to 0.77)], compared to patients with optimal BP (p for linear trend: 0.025).

Conclusions: In a large cohort of AF patients, there was no association between BP and incidence of brain lesions after 2 years. Also, there was no consistent association between BP and cognitive decline over a follow-up of 6 years.

Clinical trial registration: https://clinicaltrials.gov/study/NCT02105844, Identifier (NCT02105844).

Keywords: atrial fibrillation; blood pressure; brain lesions; cognitive decline; hypertension.

© 2024 Carmine, Aeschbacher, Coslovsky, Hennings, Paladini, Peter, Burger, Reichlin, Rodondi, Müller, Ammann, Conte, Auricchio, Moschovitis, Bardoczi, Stauber, De Perna, Zuern, Sinnecker, Badertscher, Sticherling, Bonati, Conen, Krisai, Osswald and Kühne.

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Conflict of interest statement

AA has received consulting fees from Boston Scientific, Cairdac, EP Solutions, Medtronic, Philips, Radcliffe Publishers, and XSpline and payment or honoraria from Boston Scientific, Medtronic, Microport CRM, and Philips and has patents with Boston Scientific, Biosense Webster, and Microport CRM. ASM reports fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St. Jude Medical, and Biosense Webster. Speaker honoraria from Biosense Webster, Medtronic, Abbott/St. Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort, Novartis. Consultant for Biosense Webster, Medtronic, Abbott/St. Jude Medical, and Biotronik (all outside of the current work). CS has received speaker honoraria from Biosense Webster and Medtronic and research grants from Biosense Webster, Daiichi Sankyo and Medtronic. CSZ reports a research grant from Medtronic and speaker fees from Vifor Pharma and Novartis. DC received speaker fees from Servier, and consulting fees from Roche Diagnostics and Trimedics, all outside of the current work. GC reports a research grant from the Swiss National Science Foundation, and research grants from Boston Scientific Inc. GM has received advisory board or speaker’s fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Gebro Pharma, Novartis and Vifor, all outside of the submitted work. LHB received grants from the Swiss National Science Foundation (PBBSB-116873, 33CM30-124119, 32003B-156658, 32003B-197524); Berne, Switzerland), The Swiss Heart Foundation (Berne, Switzerland, the University of Basel (Basel, Switzerland), and the “Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung” (Basel, Switzerland). LHB has received an unrestricted research grant from Astra Zeneca, and consultancy or advisory board fees or speaker’s honoraria from Amgen, Bayer, Bristol-Myers Squibb, and Claret Medical, and travel grants from AstraZeneca and Bayer. MK reports grants from the Swiss National Science Foundation (Grant numbers 33CS30_148474, 33CS30_177520, 32473B_176178, 32003B_197524), the Swiss Heart Foundation, the Foundation for Cardiovascular Research Basel and the University of Basel, grants from Bayer, grants from Pfizer, grants from Boston Scientific, grants from BMS, grants from Biotronik, grants and personal fees from Daiichi Sankyo. NR received a grant from the Swiss Heart Foundation. PK reports speaker fees BMS/Pfizer. Grants from the Swiss Heart Foundation, Foundation for Cardiovascular Research Basel, Machaon Foundation. SA received speaker fee from Roche Diagnostics. SO received grants from the Swiss National Science Foundation for Swiss-AF studies, research support from Roche (biomarker measurements), and is president of the Swiss Heart Foundation. TR has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union [Eurostars 9799 – ALVALE), and the Cardiovascular Research Foundation Basel, all for work outside the submitted study. He has received speaker/consulting honoraria or travel support from Abbott/SJM, Astra Zeneca, Brahms, Bayer, Biosense-Webster, Biotronik, Boston-Scientific, Daiichi Sankyo, Medtronic, Pfizer-BMS, and Roche, all for work outside the submitted study. He has received support for his institution’s fellowship program from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific, and Medtronic, for work outside the submitted study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

**Figure 1**
Flow chart patient enrollment. AF, atrial fibrillation; BP, blood pressure; MRI, magnetic resonance imaging.

**Figure 2**
Incidence of new brain lesions by blood pressure categories. Data are %. P-value was calculated using the χ2 tests or Kruskal-Wallis Tests, as appropriate. *Composite endpoint for microvascular damage of white matter lesions, microbleeds and small non-cortical infarcts. BP, blood pressure. Optimal BP indicates systolic BP <120 and diastolic BP <80 mmHg; Normal BP, systolic BP 120–129 mmHg and/or diastolic BP 80–84 mmHg; High normal BP, systolic BP 130-139 mmHg and/or diastolic BP 85-89 mmHg; Hypertension grade 1, systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg; Hypertension grade 2 and 3, systolic BP ≥160 and/or diastolic BP ≥100 mmHg.

**Figure 3**
Results of the multivariable adjusted logistic and linear regression model of the association between blood pressure and the incidence and volume of new ischemic infarcts and new white matter lesions. Models are adjusted for age, sex, education, body mass index, smoking status, previous stroke or transient ischemic attack, history of diabetes, history of heart failure, history of coronary heart disease, atrial fibrillation type, oral anticoagulation, antithrombotic treatment, and antihypertensive treatment. BP, blood pressure; CI, confidence interval; and OR, odds ratio. Optimal BP indicates systolic BP <120 and diastolic BP <80 mmHg; Normal BP, systolic BP 120–129 mmHg and/or diastolic BP 80–84 mmHg; High normal BP, systolic BP 130–139 mmHg and/or diastolic BP 85–89 mmHg; Hypertension grade 1, systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg; Hypertension grade 2 and 3, systolic BP ≥160 and/or diastolic BP ≥100 mmHg. Valid n for incidence for all patients = 1,213. Valid n for volume of new ischemic lesions = 66. Valid n for volume of new white matter lesions = 223.

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Blood pressure, brain lesions and cognitive decline in patients with atrial fibrillation

Affiliations

Blood pressure, brain lesions and cognitive decline in patients with atrial fibrillation

Authors

Affiliations

Abstract

Conflict of interest statement

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References

Associated data

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