Arterial Stiffness Predicts Incident Atrial Fibrillation in the Framingham Heart Study: A Mechanistic Contribution in People With High Blood Pressure or History of Hypertension.

Hypertension is, due to the high prevalence in the general population, by far the most important risk factor for the development of atrial fibrillation (AF). A recent study confirmed that blood pressures even in the upper normal or prehypertensive range are associated with an increased risk of AF. Independently, in people with high cardiovascular risk, left ventricular hypertrophy, serum creatinine, history of hypertension, and history of cerebrovascular disease were highly significant predictors, as were body mass index and history of coronary heart disease. This analysis of populations participating in 2 large outcome trials of similar design (n=30 424) documented the connection between hypertension, or its end-organ damage as well as risk factors, and the risk of incident AF. The relationship between the history of hypertension and risk of AF persists, despite confounding by the extensive vascular disease or complicated diabetes mellitus that the participants had, or maybe these diseases even escalated the relationship. The dominating role of high blood pressure in the pathogenesis, pathophysiology, prediction, diagnosis, and treatment of AF has been extensively reviewed by a working group of the European Society of Hypertension. Perhaps the most remarkable finding was that up to ≈90% of patients with AF who participated in some of the recent large randomized clinical outcome trials of new anticoagulant or antiarrhythmic medications in people with AF had a history of hypertension even without baseline workup using ambulatory 24-hour blood pressure measurements to detect people with masked hypertension. This suggests that AF is in most cases a typical complication of hypertension, and even more so than stroke or heart failure. It is not entirely surprising but confirmatory in a slightly different type of population that left ventricular hypertrophy is a strong predictor of AF. In a large study of patients with left ventricular hypertrophy (n=9193), blood pressures, Cornell voltage-duration product left ventricular hypertrophy on ECG, heart rate, age, and male sex were the predictors. In this study, there was less incident AF with regression of left ventricular hypertrophy during antihypertensive treatment. Because a difference in stroke drove the difference in the primary end point in favor of angiotensin receptor blocker over β-blocker, it is not particularly surprising that less new-onset AF during treatment with angiotensin receptor blocker compared with β-blocker contributed to fewer incident strokes and the difference in the primary composite end point. Furthermore, hypertension is a strong factor in not only remodeling left ventricular structure but also strongly related to left atrial size. Increased left atrial size then implies stretching of the atrial myocardial fibers, which again leads to less cross-talk between atrial myocardial cells provoking AF. In addition, data from the same study suggested that reducing left atrial size during antihypertensive therapy translates into reduced risk of new-onset AF. A recent and detailed analysis shows that, in patients with left ventricular hypertrophy, pulse pressure was equivalent to systolic and diastolic blood pressures combined in predicting new-onset AF, but when forced into the same statistical model, the pulse pressure was by far the strongest predictor of new-onset AF among the various blood pressure components. This strong association with pulse pressure suggests that in advanced hypertensive disease, the stiff arteries with high hemodynamically increased afterload and stretch of atrial walls with atrial chamber dilation and pressure up into the pulmonary veins may be a key mechanism for promoting unstable electric properties that lead to AF. The presence of left ventricular hypertrophy by ECG, increased age, and coronary heart disease were similarly significant confounding covariates in another large population (n=15 245) of hypertensive people participating in a clinical trial also with proper serial ECG detection of incident AF. New-onset AF strongly portended an increased risk of congestive heart failure, which may be explained by the fact that people with the more advanced cardiac disease cannot sustain the impact of losing approximately 20% to 25% of their cardiac output by losing the atrial component of left ventricular filling. However, maybe more important, the unfavorable hemodynamic state of increased vascular stiffness and hypertension may lead to increased left ventricular filling pressures, increased left atrial volumes, and increased left atrial pressure that per se leads The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. From the University of Oslo, Institute for Clinical Medicine, Norway (S.E.K.); Department of Cardiology, Oslo University Hospital, Norway (S.E.K., T.A.A., K.W.); and Department of Medicine, Division of Cardiology, Weill Cornell Medical College, New York (P.M.O.). Correspondence to Sverre E. Kjeldsen, Department of Cardiology, Oslo University Hospital Ullevaal, Kirkeveien 166, N-0407 Oslo, Norway. E-mail [email protected] Arterial Stiffness Predicts Incident Atrial Fibrillation in the Framingham Heart Study A Mechanistic Contribution in People With High Blood Pressure or History of Hypertension