Hypertension plays a significant role in the etiology of various cardiovascular diseases. Pulse pressure (PP), defined as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP), has a strong and independent association with cardiovascular morbidity and mortality.1

Atrial fibrillation (AF) is the most common sustained arrhythmia, for which the classical risk factors are age, diabetes, obesity, hypertension, left ventricular hypertrophy, coronary artery disease, heart failure and valvular disease.2 Previous studies have indicated that both high blood pressure (BP)3 and elevated PP independently predict development of AF.4 Additionally, increased PP is associated with left atrial (LA) enlargement, which is another known risk factor for AF.5 Although pathophysiologically it has been proposed that increased arterial stiffness can lead to increased left ventricular load by elevating PP, it has been determined that PP elevation is a more important risk factor for AF than increased arterial stiffness.6

Delayed atrial conduction is important in the development in AF via initiation of reentry.7 Atrial electromechanical delay (EMD), defined as the time from the onset of the P wave on the electrocardiogram (ECG) to the onset of the late diastolic wave (A) from the ventricular annulus and atrial walls on tissue Doppler imaging (the PA interval), is one of the indicators of an arrhythmogenic substrate in patients with AF.8,9

There are few data on the role of delayed atrial conduction in the development of AF in hypertensive patients with increased PP. In this study, we investigated the relationship between PP and atrial EMD, which are both important precursors of AF, in hypertensive patients with no structural cardiac abnormalities.

Patients’ baseline characteristics are given in Table 1. Of the 157 patients included in the study, 101 had normal PP and 56 had elevated PP. There were 61 women in the normal PP group and 31 women in the elevated PP group (60% and 55%, respectively). Apart from the difference in SBP, there was no difference between the groups with regard to baseline demographic characteristics and laboratory results. Antihypertensive treatments were similar.

Echocardiographic data are shown in Table 2. LVMI (77.3±13.5 g/m2 vs. 80.9±19.6 g/m2, p=0.180) and LAVI (23.6±4.9 ml/m2 vs. 25.2±6.5 ml/m2, p=0.141) were higher in patients with elevated PP, but without statistical significance. The frequency of grade I diastolic dysfunction was similar in both groups (42% vs. 53%, p=0.242).

Inter-atrial EMD was 33.6±9.2 ms in patients with normal PP, and 41.5±11.3 ms in patients with elevated PP (p<0.001). Intra-left atrial EMD (23.0±8.8 ms vs. 28.2±10.6 ms, p=0.001) and intra-right atrial EMD (10.5±5.8 ms vs. 13.2±4.9 ms, p=0.004) were significantly prolonged in patients with elevated PP (Table 3). P-maximum (108±8 ms vs. 114±9 ms, p<0.001) and Pd (30±13 ms vs. 38±13 ms, p<0.001) were also prolonged in patients with elevated PP.

According to the correlation analysis, there was a significant positive correlation between PP and inter-atrial EMD (r=0.425, p<0.001), intra-left atrial EMD (r=0.326, p<0.001) and intra-right atrial EMD (r=0.200, p=0.012) (Figure 1). Multivariate linear regression was used to determine the effect of PP on atrial EMD. PP was independently associated with inter-atrial EMD (β=0.379, t=4.088, p<0.001) and intra-left atrial EMD (β=1.473, t=3.931, p<0.001) after controlling for potential confounders. PP lost its significance for intra-right atrial EMD in multivariate linear regression analysis (p=0.261).

Figure 1.

Pearson's correlation analysis demonstrating the correlation between pulse pressure and atrial electromechanical delay. EMD: electromechanical delay.

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Our results show that atrial EMD and Pd were greater in patients with elevated PP and no significant cardiac structural remodeling. Moreover, PP was found to be independently associated with atrial EMD. This finding suggests that patients with elevated PP may have increased risk of AF before the development of severe structural remodeling.

Atrial EMD can easily be detected by transthoracic echocardiography, and when prolonged is an indicator of arrhythmogenic and diseased atrial tissue.7 Prolonged atrial EMD has been reported in various diseases involving electrical and structural remodeling of the atrium, including atrial septal defect,15 mitral stenosis,16 type 2 diabetes17 and some autoimmune diseases.18 It has been proposed that the conduction blockage and increased atrial conduction delay that occur in these diseases due to atrial fibrosis and remodeling could be a trigger and driving force for AF through the development of reentry loops.

As is known, increased BP is an important risk factor for AF.19 Office PP has been found to be independently associated with cardiovascular morbidity and mortality and correlates strongly with ambulatory blood pressure monitoring (ABPM).20 Previous studies have reported that office SBP and PP are independent risk factors for AF, while mean BP and DBP are not.4 Okin et al. noted the importance of SBP in new-onset AF.21 However, as a pulsatile component of BP, PP elevation resulting from either increased SBP or decreased DBP is a more powerful predictor of AF development than other BP parameters.22 Although PP is regarded as an indirect indicator of aortic stiffness, according to Roetker et al. the association between AF and PP cannot be explained by aortic stiffness, and they proposed PP as an independent predictor of AF.6 It is not clear how increased PP produces an AF substrate in the atrium. It is thought that acute elevations in PP together with chronic remodeling processes occurring in the left ventricle and left atrium may play a role in new-onset AF by increasing LA wall tension.23 Furthermore, AF development may also be triggered by PP elevation leading to neurohumoral activation24 and cardiovascular inflammation.25 Electrophysiologically, hypertension leads to global atrial conduction disturbances and facilitates AF inducibility.26 In our study, higher intra-left atrial and inter-atrial EMD values and prolonged Pd in patients with elevated PP were indicators of slow atrial conduction. These findings suggest that electrophysiological remodeling in hypertensive patients is more prominent in those with elevated PP. Although an independent predictor of AF on its own, elevated PP is often found together with additional conditions that are known to be closely associated with AF. A higher prevalence of complications such as left ventricular hypertrophy, LA enlargement and diastolic dysfunction in patients with elevated PP will tend to favor the development of an AF substrate.5,6,27 In our study population, none of the complications of hypertension in the left heart were observed more frequently in patients with elevated PP. Patients with moderate and severe diastolic dysfunction were excluded from our study, based on the assumption that the effect of PP on atrial EMD may be obscured in these patients.28 The mechanism by which PP was a predictor of atrial EMD independently of LAVI, LVMI, SBP and mild diastolic dysfunction on multivariate analysis is not clear; however this finding may be a reflection of increased LA wall tension. Some studies have found that increased atrial natriuretic peptide levels resulting from increased LA wall tension are associated with AF.29 Furthermore, acute elevation in PP may cause an abrupt increase in LA pressure, and can predict recurrence of AF.30 The pathogenesis of the independent arrhythmogenic effect of PP is not fully understood and it is not clear whether setting control of PP as a clinical target would help to decrease the incidence of newly diagnosed AF. Antihypertensive treatments decrease AF frequency by decreasing atrial dilatation and fibrosis and the atrial refractory period.31 Moreover, regression in LA size achieved by antihypertensive treatment decreases new-onset AF attacks.32 Control of PP optimizes control of left intra-atrial pressure in hypertensive patients, and therefore may reduce the frequency of new-onset AF by decreasing tension-related waves originating from the superior pulmonary veins.30,33 In our study, there was no difference between the two groups with regard to various antihypertensive drugs.

One limitation of our study is the relatively small number of patients. Although the prolate ellipse method used to calculate LAVI has been reported to give relatively low LA volume values, especially in patients with increased anteroposterior diameter, there was no apparent enlargement in this diameter in our patient group.11 Another limitation was the fact that LA wall tension and pressure were not assessed, which could have been relevant to the etiopathogenesis of AF. Assessment of BP by ABPM would also have given additional information and might have helped to diagnose white coat hypertension and masked hypertension. Types of drugs and their dosages might have influenced the results, but this would have been difficult to control for given the large number of antihypertensive agents used and their different dosages.

In conclusion, our study showed that elevated PP is associated with higher atrial EMD and Pd in the early stages of hypertension before the development of significant structural remodeling. Elevated PP is a contributor to increased atrial EMD independently of SBP, LAVI, LVMI and mild diastolic dysfunction. These findings may help to understand the greater tendency of patients with elevated PP to develop AF. Further studies are needed to understand atrial electrical remodeling in patients with elevated PP.

The authors have no conflicts of interest to declare.