From an epidemiological standpoint, some clinical studies confirmed the role of LV hypertrophy and left atrial enlargement as predictors of atrial fibrillation. For example, in a study by Ciaroni et al., 97 consecutive patients with hypertension who attended a cardiology outpatients clinic were followed for a mean of 25 months, and 19 patients subsequently developed atrial fibrillation. In the multivariable analysis, age, daytime SBP, echocardiographic LV mass, and left atrial dimension were independent predictors for the onset of atrial fibrillation. More recently, a report from the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale study showed that in a large cohort of hypertensive patients, left atrial enlargement and LV mass were independent predictors of atrial fibrillation .
Interestingly, inflammation acts as a catalyst to the remodeling processes of left ventricle and left atrium and is a stimulus for increased RAAS activity and production of angiotensin II .
Some studies showed that chronic inflammation, estimated by high C reactive protein (CRP) levels, is associated with LV hypertrophy occurrence independent of several other important factors, such as adipose tissue distribution, hemodynamic factors, presence of diabetes and CAD, serum lipids, renal function, age, and sex [35,36].
Moreover, results of atrial biopsies taken from patients in atrial fibrillation compared with controls have demonstrated evidence of inflammatory infiltrates and oxidative damage within the atrial tissue [37,38]. In particular, one of these studies documented abnormal atrial histology in 12 patients with lone atrial fibrillation, compared with normal histology in all of the controls, with 66% of the atrial fibrillation group showing evidence of occult myocarditis .
Finally, there is histological evidence to support a potential link between inflammation, the RAAS, and atrial fibrillation. Both inflammation and atrial fibrillation have been shown to upregulate angiotensin receptors [39,40], and an experimental canine model linked increased atrial expression of angiotensin II receptors with increased atrial cell death and leukocyte infiltration .
At this regard, the new posthoc analysis of the Losartan Intervention For Endpoint reduction in hypertension study , published in this issue of the Journal, adds further evidence linking atrial fibrillation with inflammatory conditions in hypertension.
Historically, the clinical association between atrial fibrillation and inflammation is supported by the frequent association of atrial fibrillation with inflammatory diseases of the heart, such as myocarditis and pericarditis [43,44] and by the evidence that the peak incidence of atrial fibrillation occurs on the second and third postoperative days, which coincide with the peak elevation of CRP levels . With their analysis, Bang et al.  extended these evidence among hypertensive patients noting that atrial fibrillation is linked with systemic inflammatory disease such as psoriasis. Specifically, they observed that psoriasis was associated with an increased risk of new-onset atrial fibrillation (hazard ratio: 1.74; 95% confidence interval: 1.06–2.86, P = 0.029). Such association was independent of other risk factors for the development of atrial fibrillation, including age, sex, diabetes, BP, incident CHF, left atrial size, and LV hypertrophy . Although intriguing, this analysis is limited by its posthoc nature and by the modest number of atrial fibrillation cases observed during follow-up. In particular, only 17 (11%) patients in the psoriasis group (n = 154) developed new-onset atrial fibrillation. We should also consider other aspects. The study by Bang et al. did not address the value of psoriasis over and behind inflammatory markers, whether assessed by serum or plasma indices. Consequently, the results do not inform us on whether the link between psoriasis and atrial fibrillation is merely association or causal in the complex pathophysiology of this arrhythmia.
Finally, emerging data supporting the association between inflammation and atrial fibrillation created exciting potential opportunities to target inflammatory processes for the prevention of atrial fibrillation. In particular, there is evidence supporting the use of some drug therapies, such as RAAS-blockers and statins, to prevent atrial fibrillation by modulating inflammatory pathways [15,46]. Although Bang et al.  did not find any interaction between randomized treatment (losartan vs. atenolol) and psoriasis in predicting new-onset atrial fibrillation, the number of patients with psoriasis at baseline is not large enough to show what contribution individual antihypertensive agents may have had on the risk of atrial fibrillation.
This study was funded in part by the Fondazione Umbra Cuore e Ipertensione – ONLUS, Perugia, Italy.
None of the authors of this study has financial or other reasons that could lead to a conflict of interest.
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