Genetic study indicates causal link between elevated BP, AF risk

In a Mendelian randomization study, elevated systolic BP, diastolic BP and pulse pressure were each associated with increased risk for atrial fibrillation.

“Hypertension represents one of the most common and strongest risk factor associated with the risk of AF. Despite this evidence, the association between hypertension and AF might be subject to several confounding factors, as they are both diseases of aging and commonly cluster with other cardiovascular risk factors, including obesity, diabetes, inflammation and dyslipidemia,” Georgios Georgiopoulos, MD, MSc, PhD, of the School of Biomedical Engineering & Imaging Sciences at King’s College London, and the department of clinical therapeutics at the National and Kapodistrian University of Athens School of Medicine, and colleagues wrote. “Using Mendelian randomization, we now provide the first evidence that the relationship between elevated BP and the risk of AF is likely to be causal. Importantly, the association between BP values and the risk of AF was not limited to systolic BP but also involved diastolic BP and pulse pressure.”

For the analysis, researchers attained genetic variants associated with BP from the International Consortium for Blood Pressure genome-wide association studies. A total of 894 variants were evaluated in a dedicated genome-wide association study of AF genetics that included more than 1 million participants of European ancestry. Researchers conducted Mendelian randomization analyses to determine the potential association of systolic BP, diastolic BP and pulse pressure with AF.

After Mendelian randomization, researchers found that every 1 mm Hg increase in systolic BP was associated with a 1.8% greater risk for AF (OR = 1.018; 95% CI, 1.012-1.024; P < .001).

Additionally, researchers demonstrated that for every 1 mm Hg increase in diastolic BP, there was a 2.6% greater risk for AF (OR = 1.026; 95% CI, 1.016-1.035; P < .001) and for every 1 mm Hg rise in pulse pressure, there was a 1.4% increased risk for AF (OR = 1.014; 95% CI, 1.001-1.028; P < .033).

According to the study, the relationship between BP and AF did not change when single nucleotide polymorphisms associated with possible confounders such as CAD and obesity were excluded.

“Several different mechanisms may be involved in the pathogenesis of AF in hypertensive patients. Hemodynamic and nonhemodynamic mechanisms are thought to promote complex changes of the atrial structure, architecture, contraction and electrophysiology with the potential to produce clinically relevant manifestations,” the researchers wrote. “Hemodynamic mechanisms involve the development of hypertensive cardiomyopathy characterized by increased left ventricular wall thickness, raised LV stiffness and impaired LV diastolic function. These processes may lead to a rise in left atrial stretch and pressure, with subsequent remodeling and dysfunction that predispose to AF.

“Among the nonhemodynamic mechanisms, there are histological changes in the atria such as the proliferation of fibroblasts, alterations of the extracellular matrix and hypertrophy of myocytes that can alter interconnections between muscle bundles and lead to electrophysiological remodeling,” the researchers wrote.

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