Gender differences of aortic wave reflection and influence of menopause on central blood pressure in patients with arterial hypertension

Evidences suggest that central hemodynamics indexes are independent predictors of future cardiovascular events and all-cause mortality. Central pressures do not exactly correspond to brachial pressures because of pressure pulse amplification from the aorta to the peripheral arteries [1]. Compared to peripheral pressure, central blood pressure has been shown to be a better predictor of cardiovascular disease and holds a prognostic value for both cardiovascular fatal and non fatal events. The augmentation index (AIx) is a variable obtained by analysis of pulse waves acquired by applanation tonometry, and basically reproduces an increase of the pressure waveform resulting from backward reflected wave from periphery to the aorta. It is shown that AIx can predict clinical events independently of peripheral pressures [1]_. Multiple factors have potential influence on large arteries functional properties: height [2, 3], heart rate [3], left ventricular ejection duration [4] and blood pressure level [3, 5]. However, information about the influence of gender and postmenopausal period on these properties is scarce. We aimed to evaluate the influence of gender and menopause status on central aortic pressure, aortic wave reflection and carotid artery properties in hypertensive patients.

In a cross-sectional study we evaluated 122 hypertensive patients. The average duration of hypertension was 9.99 ± 7.9 years and 47.1% had BP levels under control (< 140/90 mmHg). The Fig. 1 shows the flow chart of the study and the main exclusion reasons. Clinical characteristics according the gender are described in Table 1. Height and weight were significantly lower in women than in men at the same age. Conversely, some variables values were significantly higher in women than in men, such as: AIx (32.7 ± 9.8% vs. 20.1 ± 11.7%, p < 0.01), AIx75 (29.6 ± 6.7% vs. 18.3 ± 9.4%, p < 0.01) and central systolic blood pressure (136 ± 30 vs. 125 ± 23 mmHg, p = 0.03), respectively. There was a negative correlation between radial AIx (r = − 0.48, p < 0.01) and AIx75 (r = − 0.55, p < 0.01) with the height of patients.

Differences in AIx (22.2 ± 12.7 vs. 30.9 ± 12.2, p < 0.01) and AIx75 (20.5 ± 9.41 vs. 27.7 ± 8.12, p < 0.01) between women and men were maintained even after adjustment for height, weight and SBP. There were no differences among the groups according to hypertension duration and blood pressure level.

Menopause was registered in 70% of women. Young men (group 1) had lower AIx than both young (group 2) and older women (group 4) (16.5 ± 9.93 vs. 27.3 ± 8.74, 34.9 ± 9.77, p < 0.01) and the lowest AIx75 (14.5 ± 6.98) than all other groups respectively: young women (25.4 ± 7.87), older men (21.8 ± 8.53) and older women (30.9 ± 6.57). Conversely, young women (group 2) had both AIx and AIx75 comparable to older men group (AIx: 27.3 ± 8.74 vs. 23.2 ± 12.4, p = 0.9 and AIx75: 25.4 ± 7.87 vs. 21.8 ± 7.87, p = 0.7, respectively). When all groups were compared, the menopausal women (group 4) had the worst indexes of aortic wave reflection (AIx: 34.9 ± 9.77 (group 4) vs. 16.5 ± 9.93 (group 1), 27.3 ± 8.74 (group 2), 23.2 ± 12.4 (group 3), p = < 0.01 and AIx75: 30.9 ± 6.57 (group 4) vs. 14.5 ± 6.98 (group 1), 25.4 ± 7.87 (group 2), 21.8 ± 8.53 (group 3), p = < 0.01) (Fig. 2). There were no differences among groups according to values of brachial blood pressure (SBP p = 0.3; DBP p = 0.6).

Young women (group 2) had the lowest carotid diameter (6.68 ± 0.74 vs. 7.37 ± 0.69 (group 1), 7.49 ± 0.63 (group 3), 7.38 ± 0.92 (group 4), p < 0.01) (Fig. 3). Younger men and women groups (group 1: 6.12 ± 2.62 and group 2: 5.71 ± 1.91) had higher carotid distention than their older pairs (group 3: 4.01 ± 1.85 and group 4: 4.41 ± 1.13, p < 0.01). (Fig. 3).

Concerning the use of antihypertensive drugs that could possibly interfere in central aortic pressures, including beta-blockers, no significant differences were observed among the four groups.

The main finding of our study is that indexes related to an increase of wave reflection, radial AIx and AIx75, were higher in women than in men with hypertension, even after adjustments for the main recognized variables related to reflected waves as body height, weight and brachial SBP. Furthermore, postmenopausal women showed the highest indexes, compared to men at the same age or younger women.

Arterial wave reflection originates from every branching of arterial vessels. The aortic length matches with body height, thus arterial wave reflection occurs later in taller individuals [14, 15]. The height is one of the possible variables that could explain the elevated values of augmentation index in women compared to men in our population, because on average women are shorter than men. Women were on average 13 cm shorter than men in our sample, but the differences between men and women in AIx and AIx75 persisted even after adjustment for height. Moreover, there was a negative correlation between AIx and height, and there were no differences on blood pressure or on age that could explain the high values of Alx and AIx75 in women compared to men.

Gatzka et al. [16] studied elderly untreated hypertensives including 104 pairs of men and women with identical body height. The authors demonstrated that arterial wave reflection occurred earlier during systole in women than in men with the same height. The study also showed that women had more reduced arterial diameter and an increased arterial stiffness when compared to height-matched men, which cause the reflected wave to travel faster and arrive in central arteries earlier with greater amplitude and duration. In our study, although women had lower height than men at the same age, AIx, AIx75 and central systolic BP were higher, related probably to a faster reflected wave resulting in an increased augmentation index.

It has been demonstrated an increase in left ventricle pulsatile afterload [17] and changes in central (carotid) arterial pressure waveform [18] with aging, due to aorta stiffening. In our study, young women had smaller carotid diameter than other groups, thus resulting in an earlier return of the reflected arterial wave and greater augmentation index than men at the same age. Two studies had shown that women had smaller diameter and stiffer arteries which increased pulse wave velocity, resulting in an earlier return of the reflected arterial wave, an increased pulse pressure, and greater augmentation index [16, 19].

Evidence have shown that menopause has a negative influence on atherosclerotic risk factors [20] and amplifies the age-dependent increase in arterial stiffness [21]. Menopause was present in a high percentage (70%) of women in our sample. Zaydun G et al. [22] have suggested that, in the early postmenopausal phase, estrogen deficiency may increase the age-related arterial stiffness. Although studies have demonstrated an association between age and arterial stiffness, many studies did not investigate the prevalence of the menopause and also did not evaluate arterial stiffness in a narrow range of age (such as postmenopausal period) [23, 24]. Furthermore, there were no difference on BP and age and even after adjusting for height and weight, the menopausal women group still showed the highest values of AIx and AIx75, suggesting a possible influence of menopause on arterial stiffness.

Hypertensive women had an increased reflected aortic pressure waveform and a higher central blood pressure than men at same age. Postmenopausal hypertensive women had the highest values of indexes related to increased wave reflection. These findings highlight the influence of gender and the possible role of menopause on arterial stiffness.