Subclinical Atherosclerosis Is Associated With Incident Atrial Fibrillation

A Systematic Review and Meta-analysis

Kit Engedal Kristensen; Cille Cederholm Knage; Liv Havgaard Nyhegn; Bart A. Mulder; Michiel Rienstra; Isabelle C. Van Gelder; Axel Brandes


Europace. 2020;22(7):991-1000. 

In This Article

Abstract and Introduction


Aims: Coronary artery disease is an established risk factor for incident atrial fibrillation (AF), but it is unclear whether subclinical atherosclerosis also increases the risk of incident AF. Therefore, the aim was to assess the association between subclinical atherosclerosis, defined by increased carotid intima-media thickness (cIMT) or coronary artery calcium score (CACS), and incident AF.

Methods and results: A systematic review of MEDLINE, EMBASE, and Cochrane was done to find all cohort studies investigating the association between subclinical atherosclerosis, defined by increased cIMT or CACS, and incident AF. Eligible articles had to be available in an English full-text version; include adults over the age of 18 years; include ≥100 participants; and have a follow-up period ≥12 months. Data on cIMT were pooled using a fixed-effects model, while data on CACS (I 2 >25) were pooled using a random-effects model. Five studies on cIMT including 36 333 patients and two studies on CACS including 34 603 patients were identified. All studies investigating the association between increased cIMT and incident AF showed a significant association, with an overall hazard ratio (HR) of 1.43 [95% confidence interval (CI) 1.27–1.59]. The two studies investigating the association between increased CACS and AF also showed a significant association with an overall HR of 1.07 (95% CI 1.02–1.12).

Conclusion: Data from seven observational studies suggest that subclinical atherosclerosis defined by increased cIMT or CACS is associated with an increased risk of incident AF. These findings emphasize the need for further research investigating whether treatment of subclinical atherosclerosis should be a part of the initiatives to prevent AF.


Atrial fibrillation (AF) is the most frequent clinical arrhythmia. The prevalence and incidence increase with advancing age, affecting ~4% of the population older than 60 years and more than 10% of the population older than 80 years. In western countries, the demographic dependency ratio is growing, and AF has become a major public health problem. Atrial fibrillation is associated with reduced quality of life, excess risk of stroke, dementia, heart failure, and death.[1]

Atrial fibrillation is commonly considered a progressive disease and perpetuated by ongoing electrical and structural remodelling of the atria.[2] In recent years, an increasing number of risk factors and conditions have been identified that are associated with the development and progression of AF, including advancing age, coronary heart disease, hypertension, diabetes, heart failure, and obesity.[3] Many of them have also been found to contribute to atherosclerosis.[4] While previous myocardial infarction is a well-established risk factor for incident AF,[3] it is less well-established, whether subclinical atherosclerosis promotes structural atrial changes and, thus, creates a substrate for AF already during its long asymptomatic phase of progression. Interestingly, Weijs et al. found a high proportion of subclinical coronary artery disease (CAD) among patients undergoing catheter ablation for AF, which were originally diagnosed with lone AF.[5]

Subclinical atherosclerosis can be assessed using different measures.[4] Carotid intima-media thickness (cIMT), which is measured by carotid ultrasound and coronary artery calcium score (CACS), which is measured using non-contrast computed tomography of the coronary arteries, are non-invasive and widely accepted tools to detect subclinical atherosclerosis.[4,6,7]

We performed a systematic review and meta-analysis to evaluate, whether subclinical atherosclerosis, defined by increased cIMT and CACS, is associated with incident AF.