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**Chapter 4**

**Provisional chapter**

**Flow Velocity in Common Carotid Artery**

**Flow Velocity in Common Carotid Artery**

DOI: 10.5772/intechopen.80712

A significant blood flow disruption as seen in cardiovascular diseases and disorders is related to hemodynamic dysfunction. Gender influences the arterial hemodynamic functions. Understanding of gender-related differences in blood flow and pressure is crucial in the prevalence and burden of cardiovascular disease. This chapter presents about characteristic profile of carotid flow velocities to extend the fundamental understanding of arterial hemodynamic functions in gender differences. Comparison of both synchronized carotid blood flow velocity and blood pressures at normodynamics state are introduced to contribute to targeted therapeutic goal based on gender. Gender-related differences in body size has influenced on arterial hemodynamics in carotid artery. Body height has influenced on systolic blood pressure, pulse pressure, wave reflection, pulse wave velocity in carotid artery. Carotid blood flow velocities are largely accounted for not only body height but also body weight. The predictors for modulating blood flow velocities were not only limited to age, but also influenced by several body compositions that largely accounted for the gender-related differences including visceral fat, muscle mass and total body fat. These data may useful to effective prevention and management of cardiovascu-

**Keywords:** flow velocity, common carotid artery, health, gender, body composition

Hemodynamic is dealing with blood flow and forces concerned therein to circulate blood through the cardiovascular system. A significant blood flow disruption as seen in cardiovascular diseases and disorders is related to hemodynamic dysfunction. Doppler ultrasound has potential to serve as a non-invasive method for detecting and quantifying blood flow functions in cardiovascular diseases. However, the use of blood flow in clinical application is

limited and development of blood flow is prevailing rather than blood flow [1].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

A. Rahman Rasyada and Azran Azhim

A. Rahman Rasyada and Azran Azhim

http://dx.doi.org/10.5772/intechopen.80712

**Abstract**

**1. Introduction**

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

lar disease by considering the gender-difference.

#### **Flow Velocity in Common Carotid Artery Flow Velocity in Common Carotid Artery**

DOI: 10.5772/intechopen.80712

#### A. Rahman Rasyada and Azran Azhim A. Rahman Rasyada and Azran Azhim

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.80712

#### **Abstract**

[45] Josephson SA, Bryant SO, Mak HK, et al. Evaluation of carotid stenosis using CT angiography in the initial evaluation of stroke and TIA. Neurology. 2004;**63**(3):457-460

[46] Berg M, Zhang Z, Ikonen A, et al. Multi-detector row CT angiography in the assessment of carotid artery disease in symptomatic patients: Comparison with subtraction angiog-

[47] Shrier DA, Tanaka H, Numaguchi Y, et al. CT-angiography in the evaluation of acute

[48] Alvarez-Linera J, Benito-Leon J, Escribano J, et al. Prospective evaluation of carotid artery stenosis: Elliptic centric contrast-enhanced MR angiography and spiral CT angiography compared with digital subtraction angiography. American Journal of Neuroradiology.

[49] Biffl WL, Ray CE, Moore EE, et al. Noninvasive diagnosis of blunt cerebrovascular injuries. A preliminary report. Journal of Trauma-Injury Infectional Critical Care. 2002;

[50] Hirai T, Korogi Y, Ono K, et al. Prospective evaluation of suspected stenooclusive disease of the intracranial artery: Combined MR angiography and CT angiography compared with digital subtraction angiography. American Journal of Neuroradiology.

[51] Cumming MJ, Morrow IM. Carotid artery stenosis: A prospective comparison of CT angiography and conventional angiography. American Journal of Roentgenology. 1994;

[52] Villablanca JP, Martin N, Jahan R, et al. Volume-rendering helical computed tomography angiography in the detection and characterization of intracranial aneurysms.

[53] Merwick A, Albers GW, Amarenko P, et al. Addition of brain and carotid imaging to the ABCD score to identify patients at early risk of stroke after transient ischaemic attack: A

[54] Rae V, Ford G, Price C. Prehospital assessment of stroke: Time is brain. Journal of Para-

[55] National Stroke Audit Acute Services. Clinical Audit Report, Melbourne, Australia; 2011.

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50 Carotid Artery - Gender and Health

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2002;**23**:93-101

**163**:517-523

pp. 21-27

Journal of Neurosurgery. 2000;**93**:254-264

medic Practice. 2011;**3**(9):483-488

A significant blood flow disruption as seen in cardiovascular diseases and disorders is related to hemodynamic dysfunction. Gender influences the arterial hemodynamic functions. Understanding of gender-related differences in blood flow and pressure is crucial in the prevalence and burden of cardiovascular disease. This chapter presents about characteristic profile of carotid flow velocities to extend the fundamental understanding of arterial hemodynamic functions in gender differences. Comparison of both synchronized carotid blood flow velocity and blood pressures at normodynamics state are introduced to contribute to targeted therapeutic goal based on gender. Gender-related differences in body size has influenced on arterial hemodynamics in carotid artery. Body height has influenced on systolic blood pressure, pulse pressure, wave reflection, pulse wave velocity in carotid artery. Carotid blood flow velocities are largely accounted for not only body height but also body weight. The predictors for modulating blood flow velocities were not only limited to age, but also influenced by several body compositions that largely accounted for the gender-related differences including visceral fat, muscle mass and total body fat. These data may useful to effective prevention and management of cardiovascular disease by considering the gender-difference.

**Keywords:** flow velocity, common carotid artery, health, gender, body composition

#### **1. Introduction**

Hemodynamic is dealing with blood flow and forces concerned therein to circulate blood through the cardiovascular system. A significant blood flow disruption as seen in cardiovascular diseases and disorders is related to hemodynamic dysfunction. Doppler ultrasound has potential to serve as a non-invasive method for detecting and quantifying blood flow functions in cardiovascular diseases. However, the use of blood flow in clinical application is limited and development of blood flow is prevailing rather than blood flow [1].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gender influences the arterial hemodynamic functions. Cardiovascular disease is a leading cause of death for both women and men, but there are crucial gender-related differences in the prevalence and burden of cardiovascular disease. An approach to understand this disparity is to evaluate the underlying changes in hemodynamic functions and discover the relationship between the gender differences and cardiovascular disease risk. Gender-related differences in systolic blood pressure (SBP) are reported in previous studies [2, 3]. It is widely reported that gender differences in blood pressures (i.e. SBP and pulse pressure) and arterial wave reflections are associated to smaller body height of women [4–6].

Azhim et al. have developed a Doppler measurement system to evaluate flow velocity functions in common carotid artery with synchronized monitoring of blood pressure (BP) and electrocardiogram (ECG) [6, 7]. Firstly, this chapter presents about characteristic profile of carotid flow velocities in an attempt to extend the fundamental understanding of arterial hemodynamic functions in gender differences. Secondly, comparison of carotid flow velocity and other parameters at resting posture in gender are introduced. The extent to which body size including body height and weight have influenced on blood velocities in carotid artery is described in Section 3. Furthermore, the blood flow velocity also useful for comparing the effect of fat compositions in gender differences as presented in Section 4.

#### **2. Normohemodynamics in gender**

In hemodynamics studies, abnormality of blood flow can be detected from Doppler waveforms, vascular structure and function may be identified through various quantitative measurements made [1, 8]. This section does not focus on hemodynamic disorders, aging, and response to exercise or during exercise. But, the findings do fill important literature gap in correlation between gender-related differences with hemodynamic variables. The normohemodynamics of carotid artery and other parameters are determined in healthy sedentary subjects to rule out the effects that exercise may have on the dependent variables. From a total of 85 sedentary subjects, 49 of them are men.

second systolic velocity S2. Augmentation of S2 was related to both reflection of pulse wave velocity at branching site and reflection of pressure wave [1, 9]. The peak diastolic velocity, D velocity was the maximum velocity which rises due vascular elastic recoil during cardiac diastole, insicura between systole and diastole (I) [9] and the end-diastolic velocity, d repre-

**Figure 1.** Doppler indices derived from peak systolic velocity (S1), second systolic (S2), insicura between systole and

Flow Velocity in Common Carotid Artery http://dx.doi.org/10.5772/intechopen.80712 53

Usually blood velocity indices or ratios were derived from various combinations of the peak systolic velocity, end-diastolic velocity, and temporal mean values of the maximum Doppler frequency shift envelope [11, 12]. Of various indices, resistance index (RI) has been used extensively to measure the pulsatility that reflects the resistance to blood flow [12]. RI has defined range limit which is between value of 0–1.0. It was suggested to be used for analyzing waveforms with continuous forward flow throughout the diastole such as in carotid artery [8]. Unlike S1/d ratio as developed by Stuart and Drumm [13], RI shows Gaussian distribution and therefore can be analyzed through parametric statistical analyses. The RI data also reported to have better discriminatory performance compared to pulsatility index (PI) data [11]. Velocity reflection index (VRI) and velocity elastic index (VEI) were first proposed by [9] to evaluate aging and exercise effects. The VRI was a relation with S1 and S2 which calculated from (S2 − S1)/S1. The validation of VRI was analyzed using linear regression analysis. It increased with pressure reflection wave of augmentation index (r2 = 0.836). The latter index was calculated from (D − I)/D. It corresponds to vascular elasticity properties during cardiac diastole [9] as shown in **Figure 1**. Because of the velocity features are obtained from same

Rough reference of gender-related differences in hemodynamic characteristics is summarized in **Table 1**. As previously we have reported that carotid flow velocities have influenced by multiple effects including regular exercise, aging and visceral fat accumulation [7, 14–16], the

sents the minimum velocity during diastole [9, 11].

diastole (I), peak diastolic (D) and end-diastolic (d) velocities.

cardiac cycle, the indices are independent of insonation angle [11].

The Doppler frequency shift represents temporal changes in peak velocities of blood cells movement during particular cardiac cycle. Several analytic techniques have been proposed for analyzing the velocity waveform. Most of these techniques involve analysis of maximum velocity at particular points on Doppler waveforms described as peak velocity envelope. By using the developed measurement system by Azhim et al., carotid blood flow velocity was measured simultaneously with commercialized ECG by three-leads and brachial BP [6, 7]. Measurements of ECG and BP were used as reference data. To extract peak velocity values from its velocity spectra, a threshold method and computation using ensemble averaging technique was implemented in this study. As shown in **Figure 1**, 30 consecutive cardiac cycles were selected from 2 minutes spectral to characterize the feature points of peak velocity envelope and calculate its indices. In this study, flow velocities in carotid artery were characterized into five feature points [9, 10]. The first peak systolic velocity wave was peak velocity S1. It represents the maximum velocity during systole. Consequently it is usually used as an ejection parameter in cardiac systole [11]. An augmented velocity in late systole wave was the

Gender influences the arterial hemodynamic functions. Cardiovascular disease is a leading cause of death for both women and men, but there are crucial gender-related differences in the prevalence and burden of cardiovascular disease. An approach to understand this disparity is to evaluate the underlying changes in hemodynamic functions and discover the relationship between the gender differences and cardiovascular disease risk. Gender-related differences in systolic blood pressure (SBP) are reported in previous studies [2, 3]. It is widely reported that gender differences in blood pressures (i.e. SBP and pulse pressure) and arterial

Azhim et al. have developed a Doppler measurement system to evaluate flow velocity functions in common carotid artery with synchronized monitoring of blood pressure (BP) and electrocardiogram (ECG) [6, 7]. Firstly, this chapter presents about characteristic profile of carotid flow velocities in an attempt to extend the fundamental understanding of arterial hemodynamic functions in gender differences. Secondly, comparison of carotid flow velocity and other parameters at resting posture in gender are introduced. The extent to which body size including body height and weight have influenced on blood velocities in carotid artery is described in Section 3. Furthermore, the blood flow velocity also useful for comparing the

In hemodynamics studies, abnormality of blood flow can be detected from Doppler waveforms, vascular structure and function may be identified through various quantitative measurements made [1, 8]. This section does not focus on hemodynamic disorders, aging, and response to exercise or during exercise. But, the findings do fill important literature gap in correlation between gender-related differences with hemodynamic variables. The normohemodynamics of carotid artery and other parameters are determined in healthy sedentary subjects to rule out the effects that exercise may have on the dependent variables. From a total

The Doppler frequency shift represents temporal changes in peak velocities of blood cells movement during particular cardiac cycle. Several analytic techniques have been proposed for analyzing the velocity waveform. Most of these techniques involve analysis of maximum velocity at particular points on Doppler waveforms described as peak velocity envelope. By using the developed measurement system by Azhim et al., carotid blood flow velocity was measured simultaneously with commercialized ECG by three-leads and brachial BP [6, 7]. Measurements of ECG and BP were used as reference data. To extract peak velocity values from its velocity spectra, a threshold method and computation using ensemble averaging technique was implemented in this study. As shown in **Figure 1**, 30 consecutive cardiac cycles were selected from 2 minutes spectral to characterize the feature points of peak velocity envelope and calculate its indices. In this study, flow velocities in carotid artery were characterized into five feature points [9, 10]. The first peak systolic velocity wave was peak velocity S1. It represents the maximum velocity during systole. Consequently it is usually used as an ejection parameter in cardiac systole [11]. An augmented velocity in late systole wave was the

wave reflections are associated to smaller body height of women [4–6].

effect of fat compositions in gender differences as presented in Section 4.

**2. Normohemodynamics in gender**

52 Carotid Artery - Gender and Health

of 85 sedentary subjects, 49 of them are men.

**Figure 1.** Doppler indices derived from peak systolic velocity (S1), second systolic (S2), insicura between systole and diastole (I), peak diastolic (D) and end-diastolic (d) velocities.

second systolic velocity S2. Augmentation of S2 was related to both reflection of pulse wave velocity at branching site and reflection of pressure wave [1, 9]. The peak diastolic velocity, D velocity was the maximum velocity which rises due vascular elastic recoil during cardiac diastole, insicura between systole and diastole (I) [9] and the end-diastolic velocity, d represents the minimum velocity during diastole [9, 11].

Usually blood velocity indices or ratios were derived from various combinations of the peak systolic velocity, end-diastolic velocity, and temporal mean values of the maximum Doppler frequency shift envelope [11, 12]. Of various indices, resistance index (RI) has been used extensively to measure the pulsatility that reflects the resistance to blood flow [12]. RI has defined range limit which is between value of 0–1.0. It was suggested to be used for analyzing waveforms with continuous forward flow throughout the diastole such as in carotid artery [8]. Unlike S1/d ratio as developed by Stuart and Drumm [13], RI shows Gaussian distribution and therefore can be analyzed through parametric statistical analyses. The RI data also reported to have better discriminatory performance compared to pulsatility index (PI) data [11]. Velocity reflection index (VRI) and velocity elastic index (VEI) were first proposed by [9] to evaluate aging and exercise effects. The VRI was a relation with S1 and S2 which calculated from (S2 − S1)/S1. The validation of VRI was analyzed using linear regression analysis. It increased with pressure reflection wave of augmentation index (r2 = 0.836). The latter index was calculated from (D − I)/D. It corresponds to vascular elasticity properties during cardiac diastole [9] as shown in **Figure 1**. Because of the velocity features are obtained from same cardiac cycle, the indices are independent of insonation angle [11].

Rough reference of gender-related differences in hemodynamic characteristics is summarized in **Table 1**. As previously we have reported that carotid flow velocities have influenced by multiple effects including regular exercise, aging and visceral fat accumulation [7, 14–16], the

Data are presented as mean ± standard error of mean. The *p-*value indicates significance difference versus women. NS indicates not significant. d: end-diastolic velocity; S1: peak systolic velocity; S2: second systolic velocity; I: insicura between systole and diastole; D: peak diastolic velocity; RI: resistive index; VRI: velocity reflection index; VEI: vascular elasticity index.

d, S2, I and D velocities. Therefore, women have lower RI and VEI, and had higher VRI than men. Consistent with previous studies, pressure wave reflection and propagation are known to be correlated with body height [2, 3, 18], Azhim et al. also suggests that the reflected wave in flow components was higher in women and is significantly correlated with body height [7].

**Figure 2.** Comparison of typical envelope velocity waveforms in carotid artery for age-matched man (dashed line) and woman (solid line). d: end-diastolic velocity; S1: peak systolic velocity; S2: second systolic velocity; I: insicura between

Flow Velocity in Common Carotid Artery http://dx.doi.org/10.5772/intechopen.80712 55

Effective regulation of blood flow and blood pressure in order to maintain homeostasis is a primary aspect of cardiovascular health. In general young women have lower resting blood pressure [19–21] and in response to physiological changing [22]. The systolic and diastolic BP increased in response to the graded, incremental tilt and the difference observed between men and women is reflective of differences in body size (i.e. in particular height) as shown in **Figure 3** [22]. Epidemiological studies based on brachial artery pressure indicate that blood pressures were lower in young women than in age-matched men [2, 6]. Generally, SBP and pulse pressure increased as a pulse travels from aorta towards the peripheral, the increase

Changes in velocity envelope waveforms at peak systolic velocity, augmented velocity in late systole wave (i.e. S2) and end-diastolic velocity are focused on their relationship with aging and carotid diseases [23]. Addition to S1, d velocities and its index (i.e., RI) decreasing with age, S2, D velocities and its indices (i.e., VRI and VEI) decrease continuously with age that may increase the complication in cardiovascular disease risk [7]. Only few studies have considered the latter velocities and indices in association with gender or disease [22, 24]. To the best of our knowledge, no other studies have characterized the correlations of these velocities with

Men have been reported to have more elastic arterial trees than women [2, 7].

**3. Arterial hemodynamic changes: role of body size**

systole and diastole; D: peak diastolic velocity. Adapted from Azhim et al*.* [7].

being all the more pronounced as the distance of pulse propagation [2].

**Table 1.** Differences in hemodynamic characteristics in women and men.

presented data of hemodynamics differences in gender are also considering the influenced effects of that. The age differences is taken into account by matching the age variable with keeping not significant mean and low standard error. The range subjects' age for men and women are 20–58 years (38.4 ± 2.2) and 20–64 years (35.2 ± 1.9) respectively. Generally men are taller than women.

Study of blood pressure to explain gender-related differences in arterial hemodynamic functions is prevailing than blood flow velocity. It has been reported that hemodynamic dysfunction increases with SBP [17]. Women have a lower SBP when measured in both brachial and ankle-arm and pressure index than age-matched men [2]. Gender-related differences in body height has influenced to arterial hemodynamics such as SBP, pulse pressure, wave reflection and pulse wave velocity in carotid artery [4, 5]. We found that the gender differences in arterial hemodynamics in carotid flow velocities are largely accounted for body height and weight [6, 7].

With increases of blood pressure in men, all velocity waveforms were homeostatically lower. Men and women have different envelope velocity waveforms in carotid artery shown in **Figure 2**. In this study, we found that women have a lower brachial SBP than men, but higher

**Figure 2.** Comparison of typical envelope velocity waveforms in carotid artery for age-matched man (dashed line) and woman (solid line). d: end-diastolic velocity; S1: peak systolic velocity; S2: second systolic velocity; I: insicura between systole and diastole; D: peak diastolic velocity. Adapted from Azhim et al*.* [7].

d, S2, I and D velocities. Therefore, women have lower RI and VEI, and had higher VRI than men. Consistent with previous studies, pressure wave reflection and propagation are known to be correlated with body height [2, 3, 18], Azhim et al. also suggests that the reflected wave in flow components was higher in women and is significantly correlated with body height [7]. Men have been reported to have more elastic arterial trees than women [2, 7].

#### **3. Arterial hemodynamic changes: role of body size**

presented data of hemodynamics differences in gender are also considering the influenced effects of that. The age differences is taken into account by matching the age variable with keeping not significant mean and low standard error. The range subjects' age for men and women are 20–58 years (38.4 ± 2.2) and 20–64 years (35.2 ± 1.9) respectively. Generally men

**Table 1.** Differences in hemodynamic characteristics in women and men.

Data are presented as mean ± standard error of mean. The *p-*value indicates significance difference versus women. NS indicates not significant. d: end-diastolic velocity; S1: peak systolic velocity; S2: second systolic velocity; I: insicura between systole and diastole; D: peak diastolic velocity; RI: resistive index; VRI: velocity reflection index; VEI: vascular

**Variable Women (n = 36) Men (n = 49)** *p***-value** Age (years) 35.2 ± 1.9 38.4 ± 2.2 NS Height (cm) 157.9 ± 0.9 168.8 ± 0.9 <0.01

SBP (mmHg) 118.5 ± 2.4 129.2 ± 2.1 <0.01 DBP (mmHg) 73.7 ± 1.8 80.5 ± 1.8 <0.05 MBP (mmHg) 89.0 ± 2.0 96.7 ± 1.9 <0.01 HR (bpm) 73.8 ± 2.1 73.6 ± 1.6 NS

d (cm/s) 23.7 ± 0.8 18.9 ± 0.7 <0.01 S1 (cm/s) 96.9 ± 3.2 91.2 ± 3.1 NS S2 (cm/s) 64.3 ± 2.0 50.0 ± 1.8 <0.01 I (cm/s) 35.6 ± 1.3 27.5 ± 0.9 <0.01 D (cm/s) 45.6 ± 1.2 39.1 ± 1.0 <0.01 RI 0.750 ± 0.010 0.785 ± 0.009 <0.05 VRI −0.318 ± 0.026 −0.423 ± 0.028 <0.05 VEI 0.223 ± 0.016 0.298 ± 0.017 <0.01

Study of blood pressure to explain gender-related differences in arterial hemodynamic functions is prevailing than blood flow velocity. It has been reported that hemodynamic dysfunction increases with SBP [17]. Women have a lower SBP when measured in both brachial and ankle-arm and pressure index than age-matched men [2]. Gender-related differences in body height has influenced to arterial hemodynamics such as SBP, pulse pressure, wave reflection and pulse wave velocity in carotid artery [4, 5]. We found that the gender differences in arterial hemodynamics in carotid flow velocities are largely accounted for body height and

With increases of blood pressure in men, all velocity waveforms were homeostatically lower. Men and women have different envelope velocity waveforms in carotid artery shown in **Figure 2**. In this study, we found that women have a lower brachial SBP than men, but higher

are taller than women.

**Blood pressure data**

54 Carotid Artery - Gender and Health

**Flow velocity data**

elasticity index.

weight [6, 7].

Effective regulation of blood flow and blood pressure in order to maintain homeostasis is a primary aspect of cardiovascular health. In general young women have lower resting blood pressure [19–21] and in response to physiological changing [22]. The systolic and diastolic BP increased in response to the graded, incremental tilt and the difference observed between men and women is reflective of differences in body size (i.e. in particular height) as shown in **Figure 3** [22]. Epidemiological studies based on brachial artery pressure indicate that blood pressures were lower in young women than in age-matched men [2, 6]. Generally, SBP and pulse pressure increased as a pulse travels from aorta towards the peripheral, the increase being all the more pronounced as the distance of pulse propagation [2].

Changes in velocity envelope waveforms at peak systolic velocity, augmented velocity in late systole wave (i.e. S2) and end-diastolic velocity are focused on their relationship with aging and carotid diseases [23]. Addition to S1, d velocities and its index (i.e., RI) decreasing with age, S2, D velocities and its indices (i.e., VRI and VEI) decrease continuously with age that may increase the complication in cardiovascular disease risk [7]. Only few studies have considered the latter velocities and indices in association with gender or disease [22, 24]. To the best of our knowledge, no other studies have characterized the correlations of these velocities with

**Figure 3.** Blood pressure variability in response to graded, incremental tilt in healthy young men (n = 13) and women (n = 10). (A) Systolic blood pressure and (B) diastolic blood pressure. Tilt angle is indicated in the bar above each panel (i.e., 0° (resting posture), 20°, 40°, 60°, and back to 40°).  In this study, we found significant differences in the carotid velocity waveforms of age-matched men and women to contribute to clinical evaluations and healthcare monitoring [6].

weight and increased heart rate level [6]. It had been reported that women had lower carotid artery distensibility compared with men [25]. From the proposed velocity indices (i.e. VEI), we agreed that women had lower arterial elasticity [6, 7]. The difference in the velocities and its indices were related to smaller body size in women that largely accounted for the gender differences. The difference in velocity indices may also contributed by concentrations of estro-

**Figure 5.** The velocity indices correlated with weight. (A) RI: resistive index (1 − d/S1); (B) VRI: velocity reflection index (S2/S1 − 1); (C) VEI: vascular elasticity index (1 − I/D). Men (n = 30) are represented by open circles and women (n = 20)

Flow Velocity in Common Carotid Artery http://dx.doi.org/10.5772/intechopen.80712 57

Although the risk for cardiovascular disease increases with age, occurrence and burden of cardiovascular disease may possibly higher in men as described by differences in blood flow velocities and blood pressures [2, 7]. Furthermore body fat composition in the specific body region could explain underlying relationship between the gender-related differences and cardiovascular disease risk such as hypertension [15, 27].  In the Framingham Heart Study indicated that small differences in VF among three different body mass index classifications; normal-weight, overweight or obese groups can significantly change health risk profile including hypertension [30]. It also widely known that VF increase with aging and associated with clinical features of metabolic variables including elevated triglyceride, glucose and reduced high density lipoprotein [31, 32]. The presented data in **Table 2** is to demonstrate a rough reference of gender-related differences in body compositions in sedentary healthy subjects. Men showed a greater body mass index, weight and muscle mass. An alternative to general indication of abdominal VF is waist circumference measurement. The prevalence of having higher VF and waist circumference in men was dominant. But, women showed higher

**4. Arterial hemodynamic changes: role of body compositions**

gen in women hormone status of women [26].

represented by closed circles. Adapted from Azhim et al. [6].

total body fat.

Women had larger reflected waves than men, in part due to shorter body height and closer physical proximity between heart and reflecting sites. However, body height was not sufficient to fully explain higher reflected wave flow and pressure in women. In the study we indicated that the reflected wave had higher in women and was significantly correlated to body height and weight as described in **Figures 4** and **5** [6]. In addition to knowledge that pressure wave reflection and propagation are known to correlate with body height [2, 3], we also found that increased reflected flow wave was partially influenced by decreased body

**Figure 4.** The velocity indices correlated with height. (A) RI: resistive index (1 − d/S1); (B) VRI: velocity reflection index (S2/S1 – 1); (C) VEI: vascular elasticity index (1 − I/D). Men (n = 30) are represented by open circles and women (n = 20) represented by closed circles. Adapted from Azhim et al. [6].

**Figure 5.** The velocity indices correlated with weight. (A) RI: resistive index (1 − d/S1); (B) VRI: velocity reflection index (S2/S1 − 1); (C) VEI: vascular elasticity index (1 − I/D). Men (n = 30) are represented by open circles and women (n = 20) represented by closed circles. Adapted from Azhim et al. [6].

weight and increased heart rate level [6]. It had been reported that women had lower carotid artery distensibility compared with men [25]. From the proposed velocity indices (i.e. VEI), we agreed that women had lower arterial elasticity [6, 7]. The difference in the velocities and its indices were related to smaller body size in women that largely accounted for the gender differences. The difference in velocity indices may also contributed by concentrations of estrogen in women hormone status of women [26].

#### **4. Arterial hemodynamic changes: role of body compositions**

gender, age, visceral fat accumulation and exercise [7, 16]. In this study, we found significant differences in the carotid velocity waveforms of age-matched men and women to contribute

**Figure 3.** Blood pressure variability in response to graded, incremental tilt in healthy young men (n = 13) and women (n = 10). (A) Systolic blood pressure and (B) diastolic blood pressure. Tilt angle is indicated in the bar above each panel

(i.e., 0° (resting posture), 20°, 40°, 60°, and back to 40°). Adapted from Sarafian and Miles-Chan [22].

Women had larger reflected waves than men, in part due to shorter body height and closer physical proximity between heart and reflecting sites. However, body height was not sufficient to fully explain higher reflected wave flow and pressure in women. In the study we indicated that the reflected wave had higher in women and was significantly correlated to body height and weight as described in **Figures 4** and **5** [6]. In addition to knowledge that pressure wave reflection and propagation are known to correlate with body height [2, 3], we also found that increased reflected flow wave was partially influenced by decreased body

**Figure 4.** The velocity indices correlated with height. (A) RI: resistive index (1 − d/S1); (B) VRI: velocity reflection index (S2/S1 – 1); (C) VEI: vascular elasticity index (1 − I/D). Men (n = 30) are represented by open circles and women (n = 20)

to clinical evaluations and healthcare monitoring [6].

56 Carotid Artery - Gender and Health

represented by closed circles. Adapted from Azhim et al. [6].

Although the risk for cardiovascular disease increases with age, occurrence and burden of cardiovascular disease may possibly higher in men as described by differences in blood flow velocities and blood pressures [2, 7]. Furthermore body fat composition in the specific body region could explain underlying relationship between the gender-related differences and cardiovascular disease risk such as hypertension [15, 27].  In the Framingham Heart Study indicated that small differences in VF among three different body mass index classifications; normal-weight, overweight or obese groups can significantly change health risk profile including hypertension [30]. It also widely known that VF increase with aging and associated with clinical features of metabolic variables including elevated triglyceride, glucose and reduced high density lipoprotein [31, 32]. The presented data in **Table 2** is to demonstrate a rough reference of gender-related differences in body compositions in sedentary healthy subjects. Men showed a greater body mass index, weight and muscle mass. An alternative to general indication of abdominal VF is waist circumference measurement. The prevalence of having higher VF and waist circumference in men was dominant. But, women showed higher total body fat.

Similar to this study, association between VF and blood pressures is found consistently in some studies [16, 27]. Using multiple regression analysis, VF becomes superior predictor to hypertension compared to lower body fat and subcutaneous fat in other study [27]. Aging is associated with a significant increase in the prevalence of hypertension and especially of systolic hypertension in elderly [36]. Elevation of blood pressure with aging is mostly associated with structural and functional changes in the arteries like large artery stiffness [9, 37]. However, the predictors for modulating blood flow velocities were not only limited on age, but also influenced by several body compositions that largely accounted for the gender differ-

Flow Velocity in Common Carotid Artery http://dx.doi.org/10.5772/intechopen.80712 59

To evaluate the predisposing factors for flow velocity in common carotid artery, stepwise regression analysis was performed with the following parameters: age, muscle mass, VF and

Muscle mass (kg) −0.22 <0.001

Age (years) −0.87 <0.001

Muscle mass (kg) −0.79 <0.001

Muscle mass (kg) −0.36 <0.001

VF (level) −0.86 <0.001

Age (years) −0.002 <0.001 Muscle mass (kg) 0.002 <0.001

Age (years) 0.01 <0.001 Muscle mass (kg) −0.01 <0.001 Total body fat (kg) 0.004 0.045 **VEI** Constant 0.24 <0.001 0.344

Age (years) −0.004 <0.001 Muscle mass (kg) 0.004 <0.001 Beta (β) value indicates regression coefficient. The *p-*value less than 0.05 indicates predictor variable has significant association with hemodynamic variable. d: end-diastolic velocity; S1: peak systolic velocity; S2: second systolic velocity; I: insicura between systole and diastole; D: peak diastolic velocity; RI: resistive index; VRI: velocity reflection index; VEI:

**Table 4.** Stepwise linear regression analysis of blood flow velocity measurements.

**Variable Predictor β** *p* **r2 d (cm/s)** Constant 30.45 <0.001 0.168

**S1 (cm/s)** Constant 125.93 <0.001 0.355

**S2 (cm/s)** Constant 95.36 <0.001 0.308

**I (cm/s)** Constant 46.55 <0.001 0.193

**D (cm/s)** Constant 46.98 <0.001 0.251

**RI** Constant 0.76 <0.001 0.341

**VRI** Constant −0.58 <0.001 0.667

ences as presented in **Table 4**.

vascular elasticity index.

Data are presented as mean ± standard error of mean. The *p-*value indicates significance difference versus women. NS indicates not significant. VF: visceral fat; BMI: body mass index; WC: waist circumference; TCho: total cholesterol; LDL: low-density lipoprotein cholesterol.

**Table 2.** Differences in body compositions in women and men.

 Chandra et al. demonstrated that hypertension is mainly influenced by VF accumulation compared to lower body fat and subcutaneous fat [27]. The VF is also associated to coronary heart disease and systemic arteriosclerosis [33, 34]. Consequently, VF accumulation contributed to greater aortic stiffness in older adult as measured by pulse wave velocity [35]. Comparison data of gender difference is essential to provide rough indication risk of developing health problems related to fat composition.

It is widely known from literature that rising blood pressure is associated with increased cardiovascular disease risk. Women has lower blood pressures, homeostatically higher velocity waveforms with the heart rate did not comparable different than men. The VF and age were two important determinants for increase in blood pressures in our study as shown in **Table 3**.

Beta (β) value indicates regression coefficient. The *p-*value less than 0.05 indicates predictor variable has significant association with hemodynamic variable. SBP: systolic blood pressure; DBP: diastolic blood pressure; MBP: mean blood pressure.

**Table 3.** Stepwise linear regression analysis of blood pressure measurements.

Similar to this study, association between VF and blood pressures is found consistently in some studies [16, 27]. Using multiple regression analysis, VF becomes superior predictor to hypertension compared to lower body fat and subcutaneous fat in other study [27]. Aging is associated with a significant increase in the prevalence of hypertension and especially of systolic hypertension in elderly [36]. Elevation of blood pressure with aging is mostly associated with structural and functional changes in the arteries like large artery stiffness [9, 37]. However, the predictors for modulating blood flow velocities were not only limited on age, but also influenced by several body compositions that largely accounted for the gender differences as presented in **Table 4**.

To evaluate the predisposing factors for flow velocity in common carotid artery, stepwise regression analysis was performed with the following parameters: age, muscle mass, VF and

Beta (β) value indicates regression coefficient. The *p-*value less than 0.05 indicates predictor variable has significant association with hemodynamic variable. d: end-diastolic velocity; S1: peak systolic velocity; S2: second systolic velocity; I: insicura between systole and diastole; D: peak diastolic velocity; RI: resistive index; VRI: velocity reflection index; VEI: vascular elasticity index.

**Table 4.** Stepwise linear regression analysis of blood flow velocity measurements.

 Chandra et al. demonstrated that hypertension is mainly influenced by VF accumulation compared to lower body fat and subcutaneous fat [27]. The VF is also associated to coronary heart disease and systemic arteriosclerosis [33, 34]. Consequently, VF accumulation contributed to greater aortic stiffness in older adult as measured by pulse wave velocity [35]. Comparison data of gender difference is essential to provide rough indication risk of developing health problems related to fat composition.

Data are presented as mean ± standard error of mean. The *p-*value indicates significance difference versus women. NS indicates not significant. VF: visceral fat; BMI: body mass index; WC: waist circumference; TCho: total cholesterol; LDL:

**Variable Women (n = 36) Men (n = 49)** *p***-Value** VF (level) 3.1 ± 0.3 8.0 ± 0.7 <0.01 Weight (kg) 52.0 ± 1.1 65.2 ± 1.5 <0.01

WC (cm) 72.5 ± 1.2 81.0 ± 1.3 <0.01 Total body fat (kg) 28.2 ± 0.7 19.2 ± 0.8 <0.01 Muscle mass (kg) 34.0 ± 1.1 49.7 ± 0.8 <0.01 TCho (mmol/L) 191.4 ± 6.8 194.3 ± 5.6 NS LDL (mmol/L) 97.2 ± 7.6 109.8 ± 5.3 <0.01

) 20.8 ± 0.4 22.8 ± 3.2 <0.01

It is widely known from literature that rising blood pressure is associated with increased cardiovascular disease risk. Women has lower blood pressures, homeostatically higher velocity waveforms with the heart rate did not comparable different than men. The VF and age were two important determinants for increase in blood pressures in our study as shown in **Table 3**.

> VF (level) 1.30 0.002 Age (years) 0.26 0.045

> Age (years) 0.34 0.002 VF (level) 0.78 0.017

> Age (years) 0.31 0.005 VF (level) 0.95 0.005

Beta (β) value indicates regression coefficient. The *p-*value less than 0.05 indicates predictor variable has significant association with hemodynamic variable. SBP: systolic blood pressure; DBP: diastolic blood pressure; MBP: mean blood

**Variable Predictor β** *p* **r2 SBP (mmHg)** Constant 107.35 <0.001 0.304

**DBP (mmHg)** Constant 60.64 <0.001 0.354

**MBP (mmHg)** Constant 76.21 <0.001 0.359

**Table 3.** Stepwise linear regression analysis of blood pressure measurements.

pressure.

BMI (kg/m2

58 Carotid Artery - Gender and Health

low-density lipoprotein cholesterol.

**Table 2.** Differences in body compositions in women and men.

total body fat. This study found that VF is an important predictor that inversely related to carotid peak diastolic velocity waveform. Using the proposed index by Azhim et al., peak diastolic velocity, D is an important feature waveform to determine arterial elasticity [7]. Consequently poor arterial elasticity is attributed by accumulation of VF [16, 32] and lower arterial elasticity through its index, VEI is observed in women compared to men. Vaidya et al. also reported the same results where postmenopausal women had lower carotid elasticity compared to matched-age men based on its carotid distensibility [38]. This study can only speculate that the difference in this index could also be influenced by the sex hormone stimulation [38].

**Acknowledgements**

**Conflict of interest**

**Author details**

**References**

A. Rahman Rasyada1

Malaysia, Kuantan, Malaysia

0000128420.01881.aa

00004872-199208001-00024

MyBrain15 Postgraduate Scholarship Programme.

The authors do not have any conflict of interest.

and Azran Azhim2

\*Address all correspondence to<EMAIL_ADDRESS>
Islamic University Malaysia, Kuantan, Malaysia

514-519. DOI: 10.1161/01.HYP.26.3.514

1993;**22**:876-883. DOI: 10.1161/01.HYP.22.6.876

\*

1 Department of Biotechnology, Kulliyyah of Sciences, International Islamic University

2 Department of Biomedical Sciences, Kulliyyah of Allied Health Sciences, International

[1] Nichols WW, O'Rourke MF. McDonald's Blood Flow in Arteries: Theoretic, Experimental

[2] London GM, Guerin AP, Pannier B, Marchais SJ, Stimpel M. Influence of sex on arterial haemodynamics and blood pressure: Role of body height. Hypertension. 1995;**26**:

[3] Mitchell GF, Parise H, Benjamin EJ, Larson MG, Keyes MJ, Vita JA, et al. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: The Framingham Heart Study. Hypertension. 2004;**43**:1239-1245. DOI: 10.1161/01.HYP.

[4] London GM, Guerin AP, Pannier B, Marchais SJ, Metivier F. Body height as a determinant of carotid pulse contour in humans. Hypertension. 1992;**10**:93-95. DOI: 10.1097/

[5] Marchais SJ, Guerin AP, Pannier B, Levy BI, Safar ME, London GM. Wave reflections and cardiac hypertrophy in chronic uremia: Influence of body size. Hypertension.

and Clinical Principles. 5th ed. London: Hodder Arnold; 2005

This study was partly supported by Mediprotech Co. LTD., Korea under International Sponsored Research Grant (C18-058-0231) and Ministry of Higher Education Malaysia under

Flow Velocity in Common Carotid Artery http://dx.doi.org/10.5772/intechopen.80712 61

Women had greater vascular reflection wave using the proposed index (i.e. VRI) and second systolic velocity compared with men (see **Table 1**). The augmentation of second systolic flow velocity in carotid artery was related to wave reflection arriving from the lower body or thoracic aorta [39]. The wave reflection in women was related to shorter body height that reflects shorter distance to reflecting site [2, 3]. However, body height was not fully explaining the higher VRI. Significant correlations were observed between body composition variables and VRI, with age, muscle mass and total body fat also contributing to stepwise model for VRI.

Muscle mass found to be correlated with all blood flow velocities and blood pressures, but not with S1 velocity, likely due to a greater range of muscle mass among men. Interestingly, muscle mass was a stronger predictor for the most correlated blood flow velocities and indices, except for D velocity and all blood pressures. In agreement with the findings, study of healthy adults was shown an inversely correlation between thigh muscle mass and aortic pressure from wave reflections when characterized by augmentation pressure and its index [40]. By physiology and anatomy studies, left ventricular hypertrophy was observed in women via ventricular remodeling [41, 42] and had higher systolic left ventricular chamber function compared to men [43]. These factors might contribute consistent increase in the first velocity wave during systole in women. Furthermore RI was significantly lower due to increase of S1 velocity in women (RI = 1 − d/S1).

#### **5. Conclusion**

In conclusion, monitoring of blood flow velocity and blood pressure synchronized measurements may be potential to support the assessment of some main hemodynamic functions in gender difference. A fundamental understanding of gender-related differences in arterial hemodynamics is required for effective prevention and detection of cardiovascular disease at the early stage. Women have lower brachial blood pressure components than men, but higher d, S2, I and D velocities. Therefore, women have lower resistive and vascular elastic indices and had higher velocity reflection than men. Gender difference in arterial hemodynamics in carotid velocity waveforms is largely accounted for body size in particular height and weight. Furthermore unlike blood pressures, the predictors for modulating blood flow velocity not limited on age and VF factors, but also influenced by muscle mass and total body fat. Improvable screening of health problem can be achieved by monitoring the blood flow velocity together with blood pressure measurements and considering its gender-difference to fully assessing hemodynamics function in circulatory system.

### **Acknowledgements**

total body fat. This study found that VF is an important predictor that inversely related to carotid peak diastolic velocity waveform. Using the proposed index by Azhim et al., peak diastolic velocity, D is an important feature waveform to determine arterial elasticity [7]. Consequently poor arterial elasticity is attributed by accumulation of VF [16, 32] and lower arterial elasticity through its index, VEI is observed in women compared to men. Vaidya et al. also reported the same results where postmenopausal women had lower carotid elasticity compared to matched-age men based on its carotid distensibility [38]. This study can only speculate that the difference in this index could also be influenced by the sex hormone stimulation [38]. Women had greater vascular reflection wave using the proposed index (i.e. VRI) and second systolic velocity compared with men (see **Table 1**). The augmentation of second systolic flow velocity in carotid artery was related to wave reflection arriving from the lower body or thoracic aorta [39]. The wave reflection in women was related to shorter body height that reflects shorter distance to reflecting site [2, 3]. However, body height was not fully explaining the higher VRI. Significant correlations were observed between body composition variables and VRI, with age, muscle mass and total body fat also contributing to stepwise model for VRI. Muscle mass found to be correlated with all blood flow velocities and blood pressures, but not with S1 velocity, likely due to a greater range of muscle mass among men. Interestingly, muscle mass was a stronger predictor for the most correlated blood flow velocities and indices, except for D velocity and all blood pressures. In agreement with the findings, study of healthy adults was shown an inversely correlation between thigh muscle mass and aortic pressure from wave reflections when characterized by augmentation pressure and its index [40]. By physiology and anatomy studies, left ventricular hypertrophy was observed in women via ventricular remodeling [41, 42] and had higher systolic left ventricular chamber function compared to men [43]. These factors might contribute consistent increase in the first velocity wave during systole in women. Furthermore RI was significantly lower due to increase of S1

In conclusion, monitoring of blood flow velocity and blood pressure synchronized measurements may be potential to support the assessment of some main hemodynamic functions in gender difference. A fundamental understanding of gender-related differences in arterial hemodynamics is required for effective prevention and detection of cardiovascular disease at the early stage. Women have lower brachial blood pressure components than men, but higher d, S2, I and D velocities. Therefore, women have lower resistive and vascular elastic indices and had higher velocity reflection than men. Gender difference in arterial hemodynamics in carotid velocity waveforms is largely accounted for body size in particular height and weight. Furthermore unlike blood pressures, the predictors for modulating blood flow velocity not limited on age and VF factors, but also influenced by muscle mass and total body fat. Improvable screening of health problem can be achieved by monitoring the blood flow velocity together with blood pressure measurements and considering its gender-difference to

fully assessing hemodynamics function in circulatory system.

velocity in women (RI = 1 − d/S1).

**5. Conclusion**

60 Carotid Artery - Gender and Health

This study was partly supported by Mediprotech Co. LTD., Korea under International Sponsored Research Grant (C18-058-0231) and Ministry of Higher Education Malaysia under MyBrain15 Postgraduate Scholarship Programme.

#### **Conflict of interest**

The authors do not have any conflict of interest.

#### **Author details**

A. Rahman Rasyada1 and Azran Azhim2 \*

\*Address all correspondence to<EMAIL_ADDRESS>
1 Department of Biotechnology, Kulliyyah of Sciences, International Islamic University Malaysia, Kuantan, Malaysia

2 Department of Biomedical Sciences, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan, Malaysia

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**Chapter 5**

Provisional chapter

**Do Women Have a Higher Risk of Adverse Events after**

DOI: 10.5772/intechopen.79527

Carotid artery stenosis is thought to cause up to 10% of ischemic strokes. Till now, the optimal treatment between carotid endarterectomy (CEA) and carotid artery stenting (CAS) remains debated, in particular for specific subgroups of patients. Available data suggest that female have higher risk of perioperative adverse events, but conflicting results comparing CEA and CAS regarding the benefit for male or female are present in the literature. A systematic review of recent publications on gender-related differences in operative risks is reported. Moreover, a consecutive cohort of 912 symptomatic and asymptomatic patients undergoing CEA (407, 44.6%) or CAS (505, 55.4%) in a single institution has been evaluated to determine the influence of gender (59.7% male vs. 40.3% female) on the outcomes after both revascularization procedures at 30 days and during 3 years of followup. Our experience seems to confirm literature data as regarding female higher risk of restenosis. Female patients had higher periprocedural (2.7% female vs. 0.9% male; p < 0.05) and long-term (11.4% female vs. 4.6% male; p < 0.05) restenosis rate. In conclusion, female anatomic and pathologic parameters should be taken into account for an accurate diagnosis

Keywords: carotid endarterectomy, complications, gender, mortality, restenosis, stenting

Carotid artery stenting (CAS) might be a potentially safe and effective therapeutic alternative to carotid endarterectomy (CEA) for carotid artery disease, especially in high-risk

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

of carotid stenosis and guidelines should be adjusted consequently.

Do Women Have a Higher Risk of Adverse Events after

**Carotid Revascularization?**

Carotid Revascularization?

Renato Casana, Chiara Malloggi,

Renato Casana, Chiara Malloggi,

Richard Bulbulia, Alison Halliday,

Richard Bulbulia, Alison Halliday, Vincenzo Silani and Gianfranco Parati

http://dx.doi.org/10.5772/intechopen.79527

Abstract

1. Introduction

Valerio Stefano Tolva, Andrea Odero Jr,

Valerio Stefano Tolva, Andrea Odero Jr,

Vincenzo Silani and Gianfranco Parati

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

#### **Do Women Have a Higher Risk of Adverse Events after Carotid Revascularization?** Do Women Have a Higher Risk of Adverse Events after Carotid Revascularization?

DOI: 10.5772/intechopen.79527

Renato Casana, Chiara Malloggi, Valerio Stefano Tolva, Andrea Odero Jr, Richard Bulbulia, Alison Halliday, Vincenzo Silani and Gianfranco Parati Renato Casana, Chiara Malloggi, Valerio Stefano Tolva, Andrea Odero Jr, Richard Bulbulia, Alison Halliday, Vincenzo Silani and Gianfranco Parati

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.79527

#### Abstract

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[34] Matsuzawa Y, Funahashi T, Nakamura T.  Journal of Athero-

[35] Sutton-Tyrrell K, Newman A, Simonsick EM, Havlik R, Pahor M, Lakatta E, et al. Aortic stiffness is associated with visceral adiposity in older adults enrolled in the study of health, aging and body composition. Hypertension. 2001;**38**:429-433. DOI: 10.1161/01.

[36] Anderson GH. Effect of age on hypertension: Analysis of over 4,800 referred hypertensive patients. Saudi Journal of Kidney Diseases and Transplantation. 1999;**10**(3):286-297.

[37] Pinto E. Blood pressure and ageing. Postgraduate Medical Journal. 2007;**83**:109-114.

[38] Vaidya D, Golden SH, Haq N, Heckbert SR, Liu K, Ouyang P. The association of sex hormones with carotid artery distensibility in men and postmenopausal women: Multi-ethnic study of atherosclerosis. Hypertension. 2015;**65**(5):1020-1025. DOI: 10.1161/

[39] Heffernan KS, Lefferts WK, Augustine JA. Hemodynamic correlates of late systolic flow velocity augmentation in the carotid artery. International Journal of Hypertension. 2013;

[40] Loenneke JP, Christopher A, Fahs CA, Heffernan KS, Rossow LM, Thiebaud RS, et al. Relationship between thigh muscle mass and augmented pressure from wave reflections in healthy adults. European Journal of Applied Physiology. 2013;**113**:395-401. DOI:

[41] Carroll JD, Carroll EP, Feldman T, Ward DM, Lang RM, McGaughey D, et al. Sexassociated differences in left ventricular function in aortic stenosis of the elderly.

[42] Krumholz HM, Larson M, Levy D. Sex differences in cardiac adaptation to isolated systolic hypertension. American Journal of Cardiology. 1993;**72**(3):310-313. DOI: 10.1016/

[43] Hayward CS, Kalnins WV, Kelly RP. Gender-related differences in left ventricular chamber function. Cardiovascular Research. 2001;**49**:3-350. DOI: 10.1016/S0008-6363

Circulation. 1992;**86**:1099-1107. DOI: 10.1161/01.CIR.86.4.1099

sclerosis and Thrombosis. 2011;**18**(8):629-639. DOI: 10.5551/jat.7922

gfg261

64 Carotid Artery - Gender and Health

HYP.38.3.429

PMID: 18212439

DOI: 10.1136/pgmj.2006.048371

HYPERTENSIONAHA.114.04826

**2013**:1-7. DOI: 10.1155/2013/920605

10.1007/s00421-012-2449-y

0002-9149(93)90678-6

(00)00280-7

Carotid artery stenosis is thought to cause up to 10% of ischemic strokes. Till now, the optimal treatment between carotid endarterectomy (CEA) and carotid artery stenting (CAS) remains debated, in particular for specific subgroups of patients. Available data suggest that female have higher risk of perioperative adverse events, but conflicting results comparing CEA and CAS regarding the benefit for male or female are present in the literature. A systematic review of recent publications on gender-related differences in operative risks is reported. Moreover, a consecutive cohort of 912 symptomatic and asymptomatic patients undergoing CEA (407, 44.6%) or CAS (505, 55.4%) in a single institution has been evaluated to determine the influence of gender (59.7% male vs. 40.3% female) on the outcomes after both revascularization procedures at 30 days and during 3 years of followup. Our experience seems to confirm literature data as regarding female higher risk of restenosis. Female patients had higher periprocedural (2.7% female vs. 0.9% male; p < 0.05) and long-term (11.4% female vs. 4.6% male; p < 0.05) restenosis rate. In conclusion, female anatomic and pathologic parameters should be taken into account for an accurate diagnosis of carotid stenosis and guidelines should be adjusted consequently.

Keywords: carotid endarterectomy, complications, gender, mortality, restenosis, stenting

#### 1. Introduction

Carotid artery stenting (CAS) might be a potentially safe and effective therapeutic alternative to carotid endarterectomy (CEA) for carotid artery disease, especially in high-risk

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

patients, because CAS may avoid anesthetic and surgical risk. In this regard, the merit of using CAS has been questioned in specific subgroups of patients [1, 2]. The role of gender in the selection of the most effective carotid intervention remains a matter of debate. Historically, large randomized controlled studies looking at CEA had indicated an increased perioperative risk for women when gender subgroup analysis was performed. Additionally, all of the large CEA trials showed decreased or no benefit in women when compared to men mostly because these trials were underpowered to show any utility in the relatively small female population studied and, secondly, because the long-term benefit was undermined by the high perioperative morbidity seen in women [3, 4]. The SAPPHIRE trial was the first stenting trial to show noninferiority of CAS to CEA in high-risk patients, but the study did not compare outcomes for gender subgroups and women were underrepresented within the recruited population [5]. More recent trials reported conflicting results regarding risk of peri- and postprocedural adverse events for women and men [1, 6]. Then, reports comparing CEA and CAS failed either to analyze the influence of gender or to show a clear benefit for men or women [7].

circulation [11–13], even if randomized trials currently recommend that postmenopausal hor-

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Other possible factors might be genetic factors, but no evidence for this expectation was found in the literature. Conversely, a recent systematic review showed that women with stroke have

Numerous studies have shown that blood pressure value was higher in men than women of same age [16, 17]. Moreover, peripheral artery disease [18, 19], ischemic heart disease [18, 20–22], and cigarette consumption [18–20, 23, 24] are more frequent among male stroke patients. Women have been shown to be at higher risk than men for atrial fibrillation-related cardioembolic stroke [22, 25–28]. The Swedish Stroke Register has shown that women with atrial fibrillation receive oral anticoagulant therapy less often than men [24]. The higher prevalence of embolic strokes among women could justify their higher stroke severity.

The North American Symptomatic Carotid Endarterectomy Trial (NASCET) investigators standardized the method of quantifying the degree of carotid stenosis, and they considered

Carotid duplex ultrasound scan (DUS) compares favorably with arteriography, and many physicians are using carotid DUS as the definitive diagnostic procedure before CEA even if it is mandatory to submit the patient to computer tomography angiography (CTA) or magnetic resonance angiography (MRA) for CAS to explore arch anatomy [30, 31]. Diagnostic criteria for carotid DUS have been accepted as predictable from laboratories accredited by the Intersocietal Commission for the Accreditation of Vascular Laboratories with ongoing quality programs.

Nevertheless, carotid DUS frequently resulted in overestimation of disease severity in women. This underlined the issue that women may have higher velocities in their carotid arteries than men for similar carotid stenosis. The question is: Are we overdiagnosing disease in women according to gender differences in carotid stenosis? The purpose of Comerota's study was to examine whether there were velocity differences based on gender in patients with carotid artery disease and whether different velocity criteria should be used in women, especially at

Patients who underwent carotid arteriography and carotid DUS were the basis for this study. Data from 1019 carotid bifurcations were available. Comparison was performed on the basis of 938 carotid arteries. Analyses were made in 536 male and 402 female carotid arteries. Arteriography was performed on average 23 days after the ultrasound examination, with 74% of arteriographic examinations performed within 30 days and 95% performed within 82 days of carotid DUS. Additionally, the single most diseased artery per patient was analyzed by gender. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were averaged for data subsets according to 10% intervals of internal carotid artery (ICA) stenoses. For all intervals, PSV and EDV averaged 9 and 6% higher in women than in men. Significant gender differences existed between PSV and EDV for 60 and 70% stenoses. For 70% stenosis, PSV averaged 285 16 cm/s in women and

arteriography the most predictable method for evaluating carotid stenosis [29].

mone therapy should not be used in the primary prevention of stroke [14].

a higher familiarity of stroke than men [15].

2.2. Diagnostic criteria for carotid stenosis by gender

clinically relevant thresholds of disease [32].

Thus, to further inform the debate, we sought to conduct a systematic review of recent publications to assess epidemiologic and diagnostic hypotheses, which could underpin gender-related differences. Moreover, we report a retrospective observational study to determine the impact of gender on the outcomes of both carotid interventions in our institution.

### 2. Gender: stroke epidemiology and carotid disease

#### 2.1. Gender differences in stroke epidemiology

An extensive review on gender differences in stroke epidemiology has shown that stroke is more common in men than in women and male patients are on average younger than female when they are affected by their first stroke [8]. Western European studies demonstrated that stroke incidence was about 30% higher in men than in women, but the strokes that did occur in women tended to be more severe [9]. During the last decade, an extensive number of papers have been published on epidemiological differences between genders.

A systematic review around gender differences in stroke epidemiology, presented by Appelros et al., including 59 incidence studies from 19 countries and 5 continents, showed that the mean age at first-ever stroke was 68.6 years among men and 72.9 years among women [10]. Stroke incidence and prevalence rates were 33 and 41% higher in male than in female, respectively, with large variations between age bands and between populations. The incidence rates of brain infarction and intracerebral hemorrhage were higher among men, whereas the rate of subarachnoid hemorrhage was higher among women, although this difference was not statistically significant. Stroke tended to be more severe in women with a 1-month case fatality of 24.7% compared with 19.7% for men.

The lower stroke incidence in women has been analyzed in systematic reviews in the last decades. A plausible reason might be the protective role of ovarian estrogen on the cerebral circulation [11–13], even if randomized trials currently recommend that postmenopausal hormone therapy should not be used in the primary prevention of stroke [14].

Other possible factors might be genetic factors, but no evidence for this expectation was found in the literature. Conversely, a recent systematic review showed that women with stroke have a higher familiarity of stroke than men [15].

Numerous studies have shown that blood pressure value was higher in men than women of same age [16, 17]. Moreover, peripheral artery disease [18, 19], ischemic heart disease [18, 20–22], and cigarette consumption [18–20, 23, 24] are more frequent among male stroke patients. Women have been shown to be at higher risk than men for atrial fibrillation-related cardioembolic stroke [22, 25–28]. The Swedish Stroke Register has shown that women with atrial fibrillation receive oral anticoagulant therapy less often than men [24]. The higher prevalence of embolic strokes among women could justify their higher stroke severity.

#### 2.2. Diagnostic criteria for carotid stenosis by gender

patients, because CAS may avoid anesthetic and surgical risk. In this regard, the merit of using CAS has been questioned in specific subgroups of patients [1, 2]. The role of gender in the selection of the most effective carotid intervention remains a matter of debate. Historically, large randomized controlled studies looking at CEA had indicated an increased perioperative risk for women when gender subgroup analysis was performed. Additionally, all of the large CEA trials showed decreased or no benefit in women when compared to men mostly because these trials were underpowered to show any utility in the relatively small female population studied and, secondly, because the long-term benefit was undermined by the high perioperative morbidity seen in women [3, 4]. The SAPPHIRE trial was the first stenting trial to show noninferiority of CAS to CEA in high-risk patients, but the study did not compare outcomes for gender subgroups and women were underrepresented within the recruited population [5]. More recent trials reported conflicting results regarding risk of peri- and postprocedural adverse events for women and men [1, 6]. Then, reports comparing CEA and CAS failed either to analyze the influence of gender or to show

Thus, to further inform the debate, we sought to conduct a systematic review of recent publications to assess epidemiologic and diagnostic hypotheses, which could underpin gender-related differences. Moreover, we report a retrospective observational study to determine the impact of

An extensive review on gender differences in stroke epidemiology has shown that stroke is more common in men than in women and male patients are on average younger than female when they are affected by their first stroke [8]. Western European studies demonstrated that stroke incidence was about 30% higher in men than in women, but the strokes that did occur in women tended to be more severe [9]. During the last decade, an extensive number of papers

A systematic review around gender differences in stroke epidemiology, presented by Appelros et al., including 59 incidence studies from 19 countries and 5 continents, showed that the mean age at first-ever stroke was 68.6 years among men and 72.9 years among women [10]. Stroke incidence and prevalence rates were 33 and 41% higher in male than in female, respectively, with large variations between age bands and between populations. The incidence rates of brain infarction and intracerebral hemorrhage were higher among men, whereas the rate of subarachnoid hemorrhage was higher among women, although this difference was not statistically significant. Stroke tended to be more severe in women with a 1-month case fatality of

The lower stroke incidence in women has been analyzed in systematic reviews in the last decades. A plausible reason might be the protective role of ovarian estrogen on the cerebral

gender on the outcomes of both carotid interventions in our institution.

have been published on epidemiological differences between genders.

2. Gender: stroke epidemiology and carotid disease

2.1. Gender differences in stroke epidemiology

24.7% compared with 19.7% for men.

a clear benefit for men or women [7].

66 Carotid Artery - Gender and Health

The North American Symptomatic Carotid Endarterectomy Trial (NASCET) investigators standardized the method of quantifying the degree of carotid stenosis, and they considered arteriography the most predictable method for evaluating carotid stenosis [29].

Carotid duplex ultrasound scan (DUS) compares favorably with arteriography, and many physicians are using carotid DUS as the definitive diagnostic procedure before CEA even if it is mandatory to submit the patient to computer tomography angiography (CTA) or magnetic resonance angiography (MRA) for CAS to explore arch anatomy [30, 31]. Diagnostic criteria for carotid DUS have been accepted as predictable from laboratories accredited by the Intersocietal Commission for the Accreditation of Vascular Laboratories with ongoing quality programs.

Nevertheless, carotid DUS frequently resulted in overestimation of disease severity in women. This underlined the issue that women may have higher velocities in their carotid arteries than men for similar carotid stenosis. The question is: Are we overdiagnosing disease in women according to gender differences in carotid stenosis? The purpose of Comerota's study was to examine whether there were velocity differences based on gender in patients with carotid artery disease and whether different velocity criteria should be used in women, especially at clinically relevant thresholds of disease [32].

Patients who underwent carotid arteriography and carotid DUS were the basis for this study. Data from 1019 carotid bifurcations were available. Comparison was performed on the basis of 938 carotid arteries. Analyses were made in 536 male and 402 female carotid arteries. Arteriography was performed on average 23 days after the ultrasound examination, with 74% of arteriographic examinations performed within 30 days and 95% performed within 82 days of carotid DUS. Additionally, the single most diseased artery per patient was analyzed by gender. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were averaged for data subsets according to 10% intervals of internal carotid artery (ICA) stenoses. For all intervals, PSV and EDV averaged 9 and 6% higher in women than in men. Significant gender differences existed between PSV and EDV for 60 and 70% stenoses. For 70% stenosis, PSV averaged 285 16 cm/s in women and 236 11 cm/s in men (p = 0.01) and EDV averaged 79 7 cm/s in women and 77 6 cm/s in men (p = 0.03). For 60% stenosis, PSV averaged 228 14 cm/s in women and 189 11 cm/s in men (p = 0.03) and EDV averaged 68 6 cm/s in women and 51 4 cm/s in men (p = 0.01).

3. Carotid revascularization: gender differences

with male (66%).

p = 0.064).

ized controlled trials [6].

3.1. Carotid revascularization outcomes in women compared with men

The literature shows that women have a higher risk of perioperative adverse events during carotid revascularization. In the Asymptomatic Carotid Atherosclerosis Study (ACAS), women had a higher rate of perioperative events (3.6% female [F] vs. 1.7% male [M]) during CEA [42] with a lower rate of events for female (8.7% F vs. 12.1% M) treated with best medical therapy. This result shows a lower 5-year risk reduction for female (17%) compared

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The Asymptomatic Carotid Surgery Trial (ACST) suggested a lower long-term benefit of surgery for female, with male collecting a higher 5-year risk reduction than female (8.21% M vs. 4.08% F) [43]. In the International Carotid Stenting Study (ICSS), female had a higher 120 day event rate for CEA (7.6% F vs. 4.2% M) but a lower rate for CAS (8.0% F vs. 8.7% M) [44]. Reverse results was found in the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) [6]. In this study, 2502 patients were randomly assigned to CEA (n = 1240) or CAS (n = 1262), 872 (34.9%) of whom were female. Rates of the primary endpoint for CAS compared with CEA were 6.2% vs. 6.8% in male (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.66–1.46) and 8.9% vs. 6.7% in female (HR 1.35, 95% CI 0.82–2.23). There was no significant interaction in the primary endpoint between genders (interaction p = 0.34). Periprocedural events occurred in 35 (4.3%) of 807 males assigned to CAS compared with 40 (4.9%) of 823 assigned to CEA (HR 0.90, 95% CI 0.57–1.41) and 31 (6.8%) of 455 females assigned to CAS compared with 16 (3.8%) of 417 assigned to CEA (HR 1.84, 95% CI 1.01–3.37; interaction

In 2014, Jim et al. presented data from the Society for Vascular Surgery Vascular Registry to determine the effect of gender on outcomes after carotid revascularization [45]. There were 9865 patients (40.6% female) who underwent CEA (n = 6492) and CAS (n = 3373). The primary end point was a composite of death, stroke, and MI at 30 days. There were no differences in age and ethnicity between genders, but males were more likely to be symptomatic (41.6% M vs. 38.6% F; p < 0.003). There was a higher prevalence of hypertension and chronic obstructive pulmonary disease in female, whereas male had a higher prevalence of coronary artery disease, history of MI, and smoking history. For disease etiology in CAS, restenosis was more common in female (28.7% F vs. 19.7% M; p < 0.0001) and radiation was higher in male (6.2% M vs. 2.6% F; p < 0.0001). Comparing by gender, there were no statistically significant differences in the primary endpoint for CEA (4.07% F vs. 4.06% M) or CAS (6.69% F vs. 6.80% M). There were no differences after stratification by symptomatology and multivariate risk adjustment. These divergent results seem to be associated with different factors. In the last decades, best medical therapy improved significantly with a wide disposability of statins and antiplatelets with beneficial results on patient outcomes [46]. Another factor seems the fact that females were underrepresented in carotid random-

Williams et al. demonstrated that the diameter of the common carotid arteries (CCA), ICA, and external carotid arteries (ECA) were considerably smaller in women compared to those in men [33]. Schultz et al. showed a remarkable gender-specific difference in the distribution of atherosclerotic plaque. They reviewed 5395 arteriograms from the European Carotid Surgery Trial and compared diameter ratios of the ICA, CCA, and ECA with minimal disease to obtain a real relationship between vessels [34]. Among the 2930 arteriograms available for review, the mean ICA/CCA, ICA/ECA, and outflow/inflow area ratios were larger in women than in men (p < 0.0001). In addition, there were differences in the distribution of carotid plaque, with men more likely to have maximal stenosis in the ICA and women having a greater degree of plaque within the carotid bulb. Moreover, women appeared to have more severe disease in the ECA, which would also bias the distribution of existing flow velocity through the patent ICA.

Hansen et al. showed changes in arterial wall compliance in women who display higher agerelated stiffness of their arteries and develop a higher degree of pulsatility with a higher velocity for any given blood pressure [35, 36].

Moreover, the natural history of carotid atherosclerosis emerges to be divergent in women compared with men. Independently from age, the risk for stroke is higher in men than in women [37]. The risk for stroke is greater in men with similar degrees of carotid stenosis [4, 29, 38] due to the fact that men have greater prevalence of high-risk carotid plaques. Joakimsen et al. showed that atherosclerotic lesions in men were more instable and ultrasound characteristics showed soft and lipid-rich plaques, with more common intraplaque hemorrhage. These characteristics are associated with an increased risk for ischemic events, including myocardial infarction (MI) and stroke [39–41].

According to those anatomic and pathologic gender-related differences, the higher velocity profiles observed in women compared with men could be explained. It needs to be adjusted in guidelines for an accurate and proper diagnosis in carotid stenosis in the near future.

#### 2.2.1. Women gender-specific parameters

### 3. Carotid revascularization: gender differences

236 11 cm/s in men (p = 0.01) and EDV averaged 79 7 cm/s in women and 77 6 cm/s in men (p = 0.03). For 60% stenosis, PSV averaged 228 14 cm/s in women and 189 11 cm/s in men

Williams et al. demonstrated that the diameter of the common carotid arteries (CCA), ICA, and external carotid arteries (ECA) were considerably smaller in women compared to those in men [33]. Schultz et al. showed a remarkable gender-specific difference in the distribution of atherosclerotic plaque. They reviewed 5395 arteriograms from the European Carotid Surgery Trial and compared diameter ratios of the ICA, CCA, and ECA with minimal disease to obtain a real relationship between vessels [34]. Among the 2930 arteriograms available for review, the mean ICA/CCA, ICA/ECA, and outflow/inflow area ratios were larger in women than in men (p < 0.0001). In addition, there were differences in the distribution of carotid plaque, with men more likely to have maximal stenosis in the ICA and women having a greater degree of plaque within the carotid bulb. Moreover, women appeared to have more severe disease in the ECA, which would also bias the distribution of existing flow velocity through the patent ICA.

Hansen et al. showed changes in arterial wall compliance in women who display higher agerelated stiffness of their arteries and develop a higher degree of pulsatility with a higher

Moreover, the natural history of carotid atherosclerosis emerges to be divergent in women compared with men. Independently from age, the risk for stroke is higher in men than in women [37]. The risk for stroke is greater in men with similar degrees of carotid stenosis [4, 29, 38] due to the fact that men have greater prevalence of high-risk carotid plaques. Joakimsen et al. showed that atherosclerotic lesions in men were more instable and ultrasound characteristics showed soft and lipid-rich plaques, with more common intraplaque hemorrhage. These characteristics are associated with an increased risk for ischemic events, including myocardial

According to those anatomic and pathologic gender-related differences, the higher velocity profiles observed in women compared with men could be explained. It needs to be adjusted in

• Different distribution of atherosclerotic plaque with greater degree of plaque within the

• Different arterial wall compliance with higher age-related stiffness and higher degree of

guidelines for an accurate and proper diagnosis in carotid stenosis in the near future.

velocity for any given blood pressure [35, 36].

infarction (MI) and stroke [39–41].

68 Carotid Artery - Gender and Health

2.2.1. Women gender-specific parameters

pulsatility.

• Considerably smaller carotid diameter.

• Higher arterial velocity in carotid artery: PSV and EDV.

carotid bulb and more severe disease in the ECA.

• Presence of artifacts increasing arterial velocity (anemia).

(p = 0.03) and EDV averaged 68 6 cm/s in women and 51 4 cm/s in men (p = 0.01).

#### 3.1. Carotid revascularization outcomes in women compared with men

The literature shows that women have a higher risk of perioperative adverse events during carotid revascularization. In the Asymptomatic Carotid Atherosclerosis Study (ACAS), women had a higher rate of perioperative events (3.6% female [F] vs. 1.7% male [M]) during CEA [42] with a lower rate of events for female (8.7% F vs. 12.1% M) treated with best medical therapy. This result shows a lower 5-year risk reduction for female (17%) compared with male (66%).

The Asymptomatic Carotid Surgery Trial (ACST) suggested a lower long-term benefit of surgery for female, with male collecting a higher 5-year risk reduction than female (8.21% M vs. 4.08% F) [43]. In the International Carotid Stenting Study (ICSS), female had a higher 120 day event rate for CEA (7.6% F vs. 4.2% M) but a lower rate for CAS (8.0% F vs. 8.7% M) [44]. Reverse results was found in the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) [6]. In this study, 2502 patients were randomly assigned to CEA (n = 1240) or CAS (n = 1262), 872 (34.9%) of whom were female. Rates of the primary endpoint for CAS compared with CEA were 6.2% vs. 6.8% in male (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.66–1.46) and 8.9% vs. 6.7% in female (HR 1.35, 95% CI 0.82–2.23). There was no significant interaction in the primary endpoint between genders (interaction p = 0.34). Periprocedural events occurred in 35 (4.3%) of 807 males assigned to CAS compared with 40 (4.9%) of 823 assigned to CEA (HR 0.90, 95% CI 0.57–1.41) and 31 (6.8%) of 455 females assigned to CAS compared with 16 (3.8%) of 417 assigned to CEA (HR 1.84, 95% CI 1.01–3.37; interaction p = 0.064).

In 2014, Jim et al. presented data from the Society for Vascular Surgery Vascular Registry to determine the effect of gender on outcomes after carotid revascularization [45]. There were 9865 patients (40.6% female) who underwent CEA (n = 6492) and CAS (n = 3373). The primary end point was a composite of death, stroke, and MI at 30 days. There were no differences in age and ethnicity between genders, but males were more likely to be symptomatic (41.6% M vs. 38.6% F; p < 0.003). There was a higher prevalence of hypertension and chronic obstructive pulmonary disease in female, whereas male had a higher prevalence of coronary artery disease, history of MI, and smoking history. For disease etiology in CAS, restenosis was more common in female (28.7% F vs. 19.7% M; p < 0.0001) and radiation was higher in male (6.2% M vs. 2.6% F; p < 0.0001). Comparing by gender, there were no statistically significant differences in the primary endpoint for CEA (4.07% F vs. 4.06% M) or CAS (6.69% F vs. 6.80% M). There were no differences after stratification by symptomatology and multivariate risk adjustment. These divergent results seem to be associated with different factors. In the last decades, best medical therapy improved significantly with a wide disposability of statins and antiplatelets with beneficial results on patient outcomes [46]. Another factor seems the fact that females were underrepresented in carotid randomized controlled trials [6].

## 4. Do women have a higher risk of adverse events after carotid revascularization in our experience?

#### 4.1. Study design

A database of 912 consecutive patients with symptomatic or asymptomatic carotid artery stenosis undergoing CEA or CAS for carotid revascularization in the Department of Surgery of a single Institution from 2010 to 2017 was analyzed. Carotid stenosis was ≥80% for asymptomatic or ≥50% for symptomatic patients, as detected by DUS and confirmed by CTA or MRA using NASCET criteria [29].

stents) were employed, as a function of lesion characteristics and vessel anatomy. Temporary distal (Emboshield NAV6, Abbott Vascular, Santa Clara, CA, USA) or proximal (Mo.Ma, Medtronic, Minneapolis, MI, USA) cerebral protection devices were used as per internal protocol. Predilation was performed at the operator's discretion, with 2.0–4.0 mm TREK coronary balloons (Abbott Vascular). Postdilation was performed with a 4.5- or 5.5-mm diameter Rx Viatrac 14 Plus balloons (Abbott Vascular). CAS postoperative medical therapy included clopidogrel (75 mg once daily) for 1 month and aspirin (100 mg once daily) for a lifelong period. For CEA, patients were usually maintained on aspirin therapy. CEA was performed under local anesthesia under electroencephalography (EEG) monitoring or transcutaneous oxygen saturation monitoring. Dacron or bovine pericardium graft angioplasty, or eversion endarter-

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Postprocedural patient evaluation was performed at the periprocedural (30 days) and at the postprocedural periods, at 3 months, 6 months, and yearly thereafter within 3 years, by a

Patient data were captured using a paper case report form. Symptoms status and exact information about clinical adverse events were obtained. Carotid DUS of the supra-aortic

Primary endpoints were rates of death; stroke; MI; a composite of the incidence of any stroke, MI, or death; and restenosis within 30 days. Secondary endpoints were rates of death; stroke; MI; a composite of the incidence of any stroke, MI, or death; and restenosis, during the follow-

For the composite of any stroke, MI, or death, patients might have had more than one event. For example, fatal stroke events are included in both death and stroke outcomes, and subjects might have had both an ipsilateral and a subsequent contralateral stroke. The diagnosis and quantification of restenosis was performed using carotid DUS. Carotid restenosis was set at ≥40% [51, 52]. Categorical variables were reported as number and percentages. For numeric variables, minimum, maximum, mean, and standard deviation were calculated. Continuous data are presented as percentages or mean standard deviation (SD). Rates for comorbidities, complications, and 30-day outcomes were compared between male and female patients and between those undergoing CAS and CEA by χ2 test. Survival, stroke, MI, and restenosis rates were calculated using Kaplan-Meier analysis to compensate for patient dropouts and were reported using current Society for Vascular Surgery (SVS) criteria [53]. Standard errors (SE) are reported in Kaplan-Meier analyses. The log-rank test was used to determine differences among patients

A value of p < 0.05 was considered statistically significant for all measurements. All analyses were performed using STATA™ (STATA Corp., version 14.0, College Station, TX, USA).

vessels was obtained to determine the degree of carotid stenosis.

4.4. Endpoints, definitions, and statistical analysis

up period, within 36 months after the procedure.

ectomy were performed.

4.3. Procedural follow-up

submitted to CEA and CAS.

neurologist and a vascular surgeon.

The choice of revascularization technique (CAS/CEA) was based on general guideline recommendations, for example, European Society for Vascular Surgery (ESVS), American College of Cardiology and American Heart Association (ACC/AHA), and the team center experience according to morphologic and clinical data indicating best suitability with the aim of performing CAS and CEA with low procedural risks. Usually, patients with unfavorable aortic arch anatomy, severe peripheral vascular disease precluding femoral access, or extremely tortuous carotid anatomy were excluded from CAS. Similarly, unstable plaque, known allergies to aspirin, clopidogrel, or contrast media, and renal insufficiency (creatinine ≥1.5 mg/dL) were considered exclusion criteria for CAS.

#### 4.2. CAS and CEA protocols

For CAS, the patient was given dual antiplatelet therapy beginning 1 day before the procedure. All patients received a 300 mg loading dose of clopidogrel 1 hour before the procedure.

Clinical investigation included a baseline assessment of a physical examination, carotid DUS of the supra-aortic vessels, procedural angiography, and neurological assessment measured using the National Institutes of Health Stroke Scale (NIHSS) [47]. All aortic arch types were included.

All procedures were performed following a standardized protocol in the operating room, equipped with a portable imaging fluoroscopic C-arm (OEC 9900 elite; GE Medical Siemens, Waukesha, WI, USA), by a single vascular team. Two skilled operators with high volume experience (>50 CEA/CAS procedures per year as first operator) performed all procedures [48– 50]. Iodinated or gadolinium contrast was used in patients with normal creatinine level or creatinine >1.5 mg/dL (132 mmol/L), respectively. All patients received an intravenous heparin bolus (100 units/kg heparin) to achieve intraoperative anticoagulation (activated clotting time (ACT) ≥ 250 s throughout the procedure). In our center, with increasing experience, the number of CAS increased over time allowing CEA to be used for fewer and more complex cases in recent years. All procedures were carried out via femoral access. The introducer sheath (8 Fr) and guiding catheters (Zuma, Medtronic, MN, USA; Flexor, Cook Medical, IN, USA; Mach 1, Boston Scientific Corporation, MA, USA) ranged from 6 to 8 Fr, using inner catheters (coaxial method) with different shapes according to the anatomy of the arch (Imager II, Boston Scientific Corporation). Variable models of carotid stents (open-cell, closed-cell, hybrid, and micromesh stents) were employed, as a function of lesion characteristics and vessel anatomy. Temporary distal (Emboshield NAV6, Abbott Vascular, Santa Clara, CA, USA) or proximal (Mo.Ma, Medtronic, Minneapolis, MI, USA) cerebral protection devices were used as per internal protocol. Predilation was performed at the operator's discretion, with 2.0–4.0 mm TREK coronary balloons (Abbott Vascular). Postdilation was performed with a 4.5- or 5.5-mm diameter Rx Viatrac 14 Plus balloons (Abbott Vascular). CAS postoperative medical therapy included clopidogrel (75 mg once daily) for 1 month and aspirin (100 mg once daily) for a lifelong period.

For CEA, patients were usually maintained on aspirin therapy. CEA was performed under local anesthesia under electroencephalography (EEG) monitoring or transcutaneous oxygen saturation monitoring. Dacron or bovine pericardium graft angioplasty, or eversion endarterectomy were performed.

#### 4.3. Procedural follow-up

4. Do women have a higher risk of adverse events after carotid

A database of 912 consecutive patients with symptomatic or asymptomatic carotid artery stenosis undergoing CEA or CAS for carotid revascularization in the Department of Surgery of a single Institution from 2010 to 2017 was analyzed. Carotid stenosis was ≥80% for asymptomatic or ≥50% for symptomatic patients, as detected by DUS and confirmed by CTA or MRA

The choice of revascularization technique (CAS/CEA) was based on general guideline recommendations, for example, European Society for Vascular Surgery (ESVS), American College of Cardiology and American Heart Association (ACC/AHA), and the team center experience according to morphologic and clinical data indicating best suitability with the aim of performing CAS and CEA with low procedural risks. Usually, patients with unfavorable aortic arch anatomy, severe peripheral vascular disease precluding femoral access, or extremely tortuous carotid anatomy were excluded from CAS. Similarly, unstable plaque, known allergies to aspirin, clopidogrel, or contrast media, and renal insufficiency (creatinine ≥1.5 mg/dL)

For CAS, the patient was given dual antiplatelet therapy beginning 1 day before the procedure. All patients received a 300 mg loading dose of clopidogrel 1 hour before the procedure.

Clinical investigation included a baseline assessment of a physical examination, carotid DUS of the supra-aortic vessels, procedural angiography, and neurological assessment measured using the National Institutes of Health Stroke Scale (NIHSS) [47]. All aortic arch types were

All procedures were performed following a standardized protocol in the operating room, equipped with a portable imaging fluoroscopic C-arm (OEC 9900 elite; GE Medical Siemens, Waukesha, WI, USA), by a single vascular team. Two skilled operators with high volume experience (>50 CEA/CAS procedures per year as first operator) performed all procedures [48– 50]. Iodinated or gadolinium contrast was used in patients with normal creatinine level or creatinine >1.5 mg/dL (132 mmol/L), respectively. All patients received an intravenous heparin bolus (100 units/kg heparin) to achieve intraoperative anticoagulation (activated clotting time (ACT) ≥ 250 s throughout the procedure). In our center, with increasing experience, the number of CAS increased over time allowing CEA to be used for fewer and more complex cases in recent years. All procedures were carried out via femoral access. The introducer sheath (8 Fr) and guiding catheters (Zuma, Medtronic, MN, USA; Flexor, Cook Medical, IN, USA; Mach 1, Boston Scientific Corporation, MA, USA) ranged from 6 to 8 Fr, using inner catheters (coaxial method) with different shapes according to the anatomy of the arch (Imager II, Boston Scientific Corporation). Variable models of carotid stents (open-cell, closed-cell, hybrid, and micromesh

revascularization in our experience?

were considered exclusion criteria for CAS.

4.1. Study design

70 Carotid Artery - Gender and Health

using NASCET criteria [29].

4.2. CAS and CEA protocols

included.

Postprocedural patient evaluation was performed at the periprocedural (30 days) and at the postprocedural periods, at 3 months, 6 months, and yearly thereafter within 3 years, by a neurologist and a vascular surgeon.

Patient data were captured using a paper case report form. Symptoms status and exact information about clinical adverse events were obtained. Carotid DUS of the supra-aortic vessels was obtained to determine the degree of carotid stenosis.

#### 4.4. Endpoints, definitions, and statistical analysis

Primary endpoints were rates of death; stroke; MI; a composite of the incidence of any stroke, MI, or death; and restenosis within 30 days. Secondary endpoints were rates of death; stroke; MI; a composite of the incidence of any stroke, MI, or death; and restenosis, during the followup period, within 36 months after the procedure.

For the composite of any stroke, MI, or death, patients might have had more than one event. For example, fatal stroke events are included in both death and stroke outcomes, and subjects might have had both an ipsilateral and a subsequent contralateral stroke. The diagnosis and quantification of restenosis was performed using carotid DUS. Carotid restenosis was set at ≥40% [51, 52].

Categorical variables were reported as number and percentages. For numeric variables, minimum, maximum, mean, and standard deviation were calculated. Continuous data are presented as percentages or mean standard deviation (SD). Rates for comorbidities, complications, and 30-day outcomes were compared between male and female patients and between those undergoing CAS and CEA by χ2 test. Survival, stroke, MI, and restenosis rates were calculated using Kaplan-Meier analysis to compensate for patient dropouts and were reported using current Society for Vascular Surgery (SVS) criteria [53]. Standard errors (SE) are reported in Kaplan-Meier analyses. The log-rank test was used to determine differences among patients submitted to CEA and CAS.

A value of p < 0.05 was considered statistically significant for all measurements. All analyses were performed using STATA™ (STATA Corp., version 14.0, College Station, TX, USA).

The study was approved by the local Ethic Committee of Istituto Auxologico Italiano (statement CE 30.05.2006). Written consent was obtained from all patients before both CAS and CEA revascularization.

insufficiency (20.9% M vs. 12.0% F, p < 0.05), whereas women had a higher prevalence of hypertension (82.0% F vs. 68.0% M, p < 0.05), diabetes (39.3% F vs. 24.8% M, p < 0.05), and

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Patients were required to undergo DUS and neurological examination at 1 month and subse-

Periprocedural outcome measures in male patients compared with female patients are reported in Table 2. The death rate in the overall population was 0.3% (3/912), with no significant differences in rates between the two groups (0.4% M vs. 0.3% F) and between the two procedures (0.5% CEA vs. 0.2% CAS). Periprocedural outcomes were similar for male and female patients for 30-day death, stroke, MI, and a composite of any stroke, MI, or death rates. Female patients had higher periprocedural restenosis rate (2.7% F vs. 0.9% M; p < 0.05). Periprocedural outcomes were similar for CEA and CAS for 30-day death, stroke, and MI rates. Female patients undergoing CEA had a higher 30-day rate of any stroke, MI, or death (5.5% F vs. 3.1% M, p < 0.05). Female patients undergoing CAS had a higher 30-day rate of any stroke, MI, or death (7.6% F vs. 5.4% M, p < 0.05) and restenosis (4.8% F vs. 1.2% M, p < 0.05). For long-term follow-up, 95, 91, 78, 75, and 62% of patients attended their 3-, 6-, 12-, 24-, and 36 month follow-up appointments, respectively. Patients were not able to attend follow-up mainly because they moved to remote locations or because they declined further visits for personal

reasons. Most recent patients could not attend their 24- and 36-month appointments yet.

Long-term outcomes were similar for male and female patients for 36-month death and stroke. Male patients experienced a slightly higher rate of MI. Female patients had higher long-term restenosis rate (11.4% F vs. 4.6% M; p < 0.05). Female patients undergoing CEA had a higher 36-month rate of stroke (14.0% F vs. 6.7% M; p < 0.05) and restenosis (11.5% F vs. 2.5% M,

M (n = 544) F (n = 368) CEA (n = 407) CAS (n = 505)

Death 2 (0.4%) 1 (0.3%) 1 (0.3%) 1 (0.5%) 1 (0.4%) 0 (0.0%) Stroke 7 (1.3%) 5 (1.4%) 2 (0.6%) 3 (1.5%) 5 (2.1%) 2 (1.4%) MI 13 (2.4%) 10 (2.7%) 6 (1.8%) 5 (2.5%) 7 (2.9%) 5 (3.5%) Stroke, MI, or death 9 (1.7%) 6 (1.6%) 10 (3.1%) 11 (5.5%) 13 (5.4%) 11 (7.6%) Restenosis 5 (0.9%) 10 (2.7%) 2 (0.6%) 3 (1.5%) 3 (1.2%) 7 (4.8%)

Death 37 (6.8%) 35 (9.5%) 17 (5.2%) 12 (6.0%) 20 (8.3%) 23 (15.9%) Stroke 52 (9.6%) 59 (16.0%) 22 (6.7%) 28 (14.0%) 30 (12.4%) 31 (21.4%) MI 38 (7.0%) 22 (6.0%) 20 (5.1%) 11 (4.1%) 18 (6.4%) 11 (5.2%) Stroke, MI, or death 101 (18.6%) 87 (23.7%) 45 (13.8%) 46 (23.1%) 56 (23.2%) 41 (28.4%) Restenosis 25 (4.6%) 42 (11.4%) 8 (2.5%) 23 (11.5%) 17 (7.0%) 19 (13.1%)

Table 2. Periprocedural (30 days) outcomes after carotid revascularization in male and female patients receiving CEA or CAS.

M: male; F: female; CEA: carotid endarterectomy; CAS: carotid angioplasty and stenting; and MI: myocardial infarction.

M (n = 326) F (n = 200) M (n = 241) F (n = 145)

hyperlipidemia (77.1% F vs. 62.0% M, p < 0.05).

Short-term (≤30 days) outcomes, n (%)

Long-term (>30 days) outcomes, n (%)

quently at 3, 6, 12, 24, and 36 months after the procedure.

#### 4.5. Results

From 2010 to 2017, a total of 912 patients underwent interventions for carotid stenosis. There were 544 (59.7%) males and 368 (40.3%) females. Mean age was 71.1 8.6 and 69.4 9.0 for male and female patients, respectively. About 193 (35.4%) male and 128 (34.7%) female patients were symptomatic. Of the 912 carotid revascularizations, 407 (44.6%) were by CEA and 505 (55.4%) were by CAS. Demographic and baseline characteristics of study participants after separation by gender and procedure are presented in Table 1. Female patients were older (72.1 9.0 F vs. 68.4 8.6 M, p < 0.05) and more likely to have a history of hypertension (79.7% F vs. 72.5% M, p < 0.05) and hyperlipidemia (74.4% F vs. 69.2% M, p < 0.05) with respect to male patients. Male patients were more likely to be smokers (35.0% M vs. 33.3% F, p < 0.05) and to have history of MI (19.7% M vs. 17.5% F, p < 0.05), chronic renal insufficiency (20.5% M vs. 11.9% F, p < 0.05), and CAD (28.0% M vs. 26.1% F, p < 0.05). The distribution of comorbidities within the two procedural groups was similar. For CAS patients, men were more likely to have diabetes (37.9% M vs. 33.5% F, p < 0.05) and chronic renal insufficiency (18.0% M vs. 13.8% F, p < 0.05) and women had a higher prevalence of hypertension (89.5% F vs. 71.5% M, p < 0.05) and hyperlipidemia (82.9% F vs. 72.0% M, p < 0.05). For CEA patients, men tended to have a higher prevalence of history of MI (20.3% M vs. 16.0% F, p < 0.05) and chronic renal

M: male; F: female; CEA: carotid endarterectomy; CAS: carotid artery stenting; SD: standard deviation; CAD: coronary artery disease; MI: myocardial infarction; CHF: congestive heart failure; and COPD: chronic obstructive pulmonary disease.

Table 1.

The study was approved by the local Ethic Committee of Istituto Auxologico Italiano (statement CE 30.05.2006). Written consent was obtained from all patients before both CAS and CEA

From 2010 to 2017, a total of 912 patients underwent interventions for carotid stenosis. There were 544 (59.7%) males and 368 (40.3%) females. Mean age was 71.1 8.6 and 69.4 9.0 for male and female patients, respectively. About 193 (35.4%) male and 128 (34.7%) female patients were symptomatic. Of the 912 carotid revascularizations, 407 (44.6%) were by CEA and 505 (55.4%) were by CAS. Demographic and baseline characteristics of study participants after separation by gender and procedure are presented in Table 1. Female patients were older (72.1 9.0 F vs. 68.4 8.6 M, p < 0.05) and more likely to have a history of hypertension (79.7% F vs. 72.5% M, p < 0.05) and hyperlipidemia (74.4% F vs. 69.2% M, p < 0.05) with respect to male patients. Male patients were more likely to be smokers (35.0% M vs. 33.3% F, p < 0.05) and to have history of MI (19.7% M vs. 17.5% F, p < 0.05), chronic renal insufficiency (20.5% M vs. 11.9% F, p < 0.05), and CAD (28.0% M vs. 26.1% F, p < 0.05). The distribution of comorbidities within the two procedural groups was similar. For CAS patients, men were more likely to have diabetes (37.9% M vs. 33.5% F, p < 0.05) and chronic renal insufficiency (18.0% M vs. 13.8% F, p < 0.05) and women had a higher prevalence of hypertension (89.5% F vs. 71.5% M, p < 0.05) and hyperlipidemia (82.9% F vs. 72.0% M, p < 0.05). For CEA patients, men tended to have a higher prevalence of history of MI (20.3% M vs. 16.0% F, p < 0.05) and chronic renal

M (n = 544) F (n = 368) CEA (n = 407) CAS (n = 505)

Age, mean SD 68.4 8.6 72.1 9.0 68.9 8.5 71.5 9.3 68.0 8.7 72.8 8.6 Symptomatic, n (%) 193 (35.4%) 128 (34.7%) 108 (33.1%) 70 (34.9%) 85 (35.0%) 58 (40.1%) Smokers, n (%) 191 (35.0%) 123 (33.3%) 109 (33.4%) 77 (38.8%) 82 (33.8%) 45 (31.3%) Hypertension, n (%) 395 (72.5%) 293 (79.7%) 222 (68.0%) 164 (82.0%) 173 (71.5%) 129 (89.5%) Diabetes, n (%) 172 (31.7%) 127 (34.5%) 81 (24.8%) 78 (39.3%) 91 (37.9%) 48 (33.5%) Hyperlipidemia, n (%) 376 (69.2%) 274 (74.4%) 202 (62.0%) 154 (77.1%) 174 (72.0%) 120 (82.9%) CAD, n (%) 152 (28.0%) 96 (26.1%) 86 (26.4%) 55 (27.5%) 66 (27.3%) 41 (28.5%) History of stroke, n (%) 133 (24.5%) 78 (21.3%) 71 (21.9%) 44 (21.8%) 62 (25.6%) 35 (24.0%) History of MI, n (%) 107 (19.7%) 64 (17.5%) 66 (20.3%) 32 (16.0%) 41 (17.0%) 32 (22.4%) Chronic renal insufficiency, n (%) 112 (20.5%) 44 (11.9%) 68 (20.9%) 24 (12.0%) 43 (18.0%) 20 (13.8%) CHF, n (%) 54 (9.8%) 42 (11.5%) 29 (8.8%) 19 (9.5%) 25 (10.3%) 23 (16.1%) COPD, n (%) 105 (19.4%) 54 (14.6%) 61 (18.6%) 30 (15.1%) 45 (18.5%) 24 (16.5%) Cancer history, n (%) 101 (18.6%) 72 (19.5%) 53 (16.3%) 37 (18.5%) 48 (19.7%) 35 (24.1%) M: male; F: female; CEA: carotid endarterectomy; CAS: carotid artery stenting; SD: standard deviation; CAD: coronary artery disease; MI: myocardial infarction; CHF: congestive heart failure; and COPD: chronic obstructive pulmonary

M (n = 326) F (n = 200) M (n = 241) F (n = 145)

revascularization.

72 Carotid Artery - Gender and Health

4.5. Results

disease.

Table 1. Baseline characteristics of study participants (n = 912).

Patients were required to undergo DUS and neurological examination at 1 month and subsequently at 3, 6, 12, 24, and 36 months after the procedure.

Periprocedural outcome measures in male patients compared with female patients are reported in Table 2. The death rate in the overall population was 0.3% (3/912), with no significant differences in rates between the two groups (0.4% M vs. 0.3% F) and between the two procedures (0.5% CEA vs. 0.2% CAS). Periprocedural outcomes were similar for male and female patients for 30-day death, stroke, MI, and a composite of any stroke, MI, or death rates. Female patients had higher periprocedural restenosis rate (2.7% F vs. 0.9% M; p < 0.05). Periprocedural outcomes were similar for CEA and CAS for 30-day death, stroke, and MI rates. Female patients undergoing CEA had a higher 30-day rate of any stroke, MI, or death (5.5% F vs. 3.1% M, p < 0.05). Female patients undergoing CAS had a higher 30-day rate of any stroke, MI, or death (7.6% F vs. 5.4% M, p < 0.05) and restenosis (4.8% F vs. 1.2% M, p < 0.05).

For long-term follow-up, 95, 91, 78, 75, and 62% of patients attended their 3-, 6-, 12-, 24-, and 36 month follow-up appointments, respectively. Patients were not able to attend follow-up mainly because they moved to remote locations or because they declined further visits for personal reasons. Most recent patients could not attend their 24- and 36-month appointments yet.

Long-term outcomes were similar for male and female patients for 36-month death and stroke. Male patients experienced a slightly higher rate of MI. Female patients had higher long-term restenosis rate (11.4% F vs. 4.6% M; p < 0.05). Female patients undergoing CEA had a higher 36-month rate of stroke (14.0% F vs. 6.7% M; p < 0.05) and restenosis (11.5% F vs. 2.5% M,

M: male; F: female; CEA: carotid endarterectomy; CAS: carotid angioplasty and stenting; and MI: myocardial infarction.

Table 2. Periprocedural (30 days) outcomes after carotid revascularization in male and female patients receiving CEA or CAS.

p < 0.05). No significant differences in long-term outcomes were observed between male and female patients undergoing CAS (Table 2).

The 36-month risk of any cause mortality was 5.6 (1.6)% (mean (SD)) for male patients and 15.2 (3.3)% for female patients, with a significant difference in Kaplan-Meier estimates at 36 months between the two groups according to log-rank test. Female patients undergoing CAS experience lower 3-year freedom from death rate, with no significance difference with respect to the other groups (82.5% vs. 94.5, 94.2, and 86.4% for F-CAS, M-CAS, M-CEA, and F-CEA patients, respectively, p > 0.05; Figure 1).

The risk of stroke at 36 months was 10.8 (2.2)% for male and 21.4 (3.7)% for female (p < 0.05). Male patients undergoing CEA had a higher 36-month freedom from stroke rate as compared to the other groups (91.6% vs. 85.8, 82.2, and 73.7% for M-CEA, M-CAS, F-CEA, and F-CAS patients, respectively, p < 0.05) with a significant difference in the comparison between M-CEA and F-CAS (Figure 2).

Male patients had a greater risk of MI than female patients. The 12-, 24-, and 36-month estimates of MI rates were 4.9 (1.4)%, 6.0 (1.6)%, and 7.6 (1.8)% for male and a constant rate equal to 5.8 (2.0)% for female (p > 0.05). There were no differences in the risk of experiencing a MI during follow-up among male and female patients undergoing CEA or CAS (Figure 3).

The overall risk of any stroke, MI, or death was equal to 20.4 (2.8)% for male patients and 30.9 (4.2)% for female patients (p < 0.05). The 3-year freedom from any stroke, MI, or death was 84.4, 72.6, 72.2, and 64.9% for M-CEA, M-CAS, F-CEA, and F-CAS patients, respectively, with significant differences in the comparison between M-CEA and F-CAS (Figure 4).

Figure 2. Stroke. Male and female patients submitted to CEA or CAS who experienced a stroke during follow-up. Error bars are omitted for clarity. Standard errors did not exceed 10% at all-time intervals that were analyzed. The number of

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Figure 3. Myocardial infarction (MI). Male and female patients submitted to CEA or CAS who experienced a MI during follow-up. Error bars are omitted for clarity. Standard errors did not exceed 10% at all-time intervals that were analyzed.

The number of patients at risk at each time interval is shown below the figure.

patients at risk at each time interval is shown below the figure.

Figure 1. Mortality. Male and female patients submitted to CEA or CAS who survived during follow-up. Error bars are omitted for clarity. Standard errors did not exceed 10% at all-time intervals that were analyzed. The number of patients at risk at each time interval is shown below the figure.

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p < 0.05). No significant differences in long-term outcomes were observed between male and

The 36-month risk of any cause mortality was 5.6 (1.6)% (mean (SD)) for male patients and 15.2 (3.3)% for female patients, with a significant difference in Kaplan-Meier estimates at 36 months between the two groups according to log-rank test. Female patients undergoing CAS experience lower 3-year freedom from death rate, with no significance difference with respect to the other groups (82.5% vs. 94.5, 94.2, and 86.4% for F-CAS, M-CAS, M-CEA, and F-CEA patients,

The risk of stroke at 36 months was 10.8 (2.2)% for male and 21.4 (3.7)% for female (p < 0.05). Male patients undergoing CEA had a higher 36-month freedom from stroke rate as compared to the other groups (91.6% vs. 85.8, 82.2, and 73.7% for M-CEA, M-CAS, F-CEA, and F-CAS patients, respectively, p < 0.05) with a significant difference in the comparison between M-CEA

Male patients had a greater risk of MI than female patients. The 12-, 24-, and 36-month estimates of MI rates were 4.9 (1.4)%, 6.0 (1.6)%, and 7.6 (1.8)% for male and a constant rate equal to 5.8 (2.0)% for female (p > 0.05). There were no differences in the risk of experiencing a MI during follow-up among male and female patients undergoing CEA or CAS (Figure 3).

The overall risk of any stroke, MI, or death was equal to 20.4 (2.8)% for male patients and 30.9 (4.2)% for female patients (p < 0.05). The 3-year freedom from any stroke, MI, or death was 84.4, 72.6, 72.2, and 64.9% for M-CEA, M-CAS, F-CEA, and F-CAS patients, respectively, with

Figure 1. Mortality. Male and female patients submitted to CEA or CAS who survived during follow-up. Error bars are omitted for clarity. Standard errors did not exceed 10% at all-time intervals that were analyzed. The number of patients at

significant differences in the comparison between M-CEA and F-CAS (Figure 4).

female patients undergoing CAS (Table 2).

respectively, p > 0.05; Figure 1).

74 Carotid Artery - Gender and Health

risk at each time interval is shown below the figure.

and F-CAS (Figure 2).

Figure 2. Stroke. Male and female patients submitted to CEA or CAS who experienced a stroke during follow-up. Error bars are omitted for clarity. Standard errors did not exceed 10% at all-time intervals that were analyzed. The number of patients at risk at each time interval is shown below the figure.

Figure 3. Myocardial infarction (MI). Male and female patients submitted to CEA or CAS who experienced a MI during follow-up. Error bars are omitted for clarity. Standard errors did not exceed 10% at all-time intervals that were analyzed. The number of patients at risk at each time interval is shown below the figure.

During follow-up, female patients exhibited higher restenosis risk with respect to male [2.5 (1.0)%, 3.0 (1.1)%, and 3.6 (1.3)% vs. 8.2 (2.3)%, 10.8 (2.7)%, and 13.5 (3.0)% for 12-, 24-, and 36 month rates, for male and female patients, respectively (p < 0.05)]. Male patients undergoing CEA experienced higher freedom from restenosis rates at 3 years (98.5% vs. 93.5%, 86.8%, and 86.2%, for M-CEA, M-CAS, F-CEA, and F-CAS patients, respectively) with significant differences in the comparisons between M-CEA and F-CAS and between M-CEA and F-CEA (Figure 5).

Do Women Have a Higher Risk of Adverse Events after Carotid Revascularization?