Large-Scale Genetic Analysis Indicates Increased Blood Pressure Causes Atrial Fibrillation

Georgios Georgiopoulos, MD, MSc, PhD

New research from an international team of investigators has provided genetic evidence that high blood pressure was associated with the development of atrial fibrillation.

The study, which included data from more than a million patients and nearly 900 genetic variants, demonstrated each 1 mmHg rises in systolic blood pressure, diastolic blood pressure and pulse pressure were associated with 1.8%, 2.6% and 1.4% relative increases in the risk of atrial fibrillation, respectively, and lead investigators to purport these results prove atrial fibrillation is a preventable condition.

"The results provide strong evidence of a causal relationship between blood pressure and atrial fibrillation. Using genetic information in the analyses minimizes the likelihood of reverse causality or that other traits linked with atrial fibrillation (confounders) were responsible. Our study showed that the relationship was not driven by other conditions including coronary artery disease and obesity,” said Georgios Georgiopoulos, MD, MSc, PhD, of King's College London, UK and National and Kapodistrian University of Athens, in a statement from the European Society of Cardiology.

With atrial fibrillation representing the most common heart rhythm disorder across the world and previous studies suggesting a link between elevated blood pressure and development of atrial fibrillation, investigators designed the current study as a Mendelian randomization study aimed at assessing potential causal relationship between blood pressure levels and incident atrial fibrillation. Using data from the International Consortium of Blood Pressure-Genome Wide Association Studies, investigators identified 894 genetic variants and more than 1 million patients of European ancestry.

Of the 894 genetic variants identified for inclusion in the analyses, 266 were associated with systolic blood pressure, 345 were associated with diastolic blood pressure, and 283 were associated with pulse pressure. Of the 1,030,836 individuals included in the study, 60,620 had atrial fibrillation and 970,216 did not. For the purpose of the study, investigators used two-sample Mendelian randomization analyses to examine the potential causal association blood pressure and atrial fibrillation.

Results of the investigators' Mendelian randomization analyses demonstrated a potentially causal relationship with atrial fibrillation and systolic blood pressure, diastolic blood pressure, and pulse pressure. As previously mentioned, results indicated relative increases in risk of 1.8%, 2.6% and 1.4% for systolic blood pressure (OR, 1.018; 95% CI, 1.012-1.024; P <.001), diastolic blood pressure (OR, 1.026; 95% CI, 1.016-1.035; P <.001), and pulse pressure (OR, 1.014; 95% CI, 1.001-1.028; P=.033), respectively, for each 1 mmHg increase.

Investigators also noted these results were robust in sensitivity analyses, including the Mendelian randomization-Egger method and the MR pleiotropy residual sum and outlier test. Additionally, there were no changes observed in the causal relationship of blood pressure and atrial fibrillation when excluding potential confounders of the relationship, such as ischemic heart disease and obesity.

"Our findings confirm the hypothesis that atrial fibrillation is preventable. This indicates that strict blood pressure control could be an effective strategy to stop atrial fibrillation and its complications, which include stroke, heart failure, dementia, and depression," added Georgiopoulos.

This study, “The relationship between blood pressure and risk of atrial fibrillation: a Mendelian randomization study,” was published in the European Journal of Preventive Cardiology.