- Email: [email protected]
Gender Differences in Blood Flow Velocities after Carotid Angioplasty and Stenting
Gender Differences in Blood Flow Velocities after Carotid Angioplasty and Stenting Carlos H. Timaran,1 George L. Berdejo,2 Takao Ohki,2 David E. Timaran,3 Frank J. Veith,2 Eric B. Rosero,1 and J. Gregory Modrall,1 Dallas, Texas, Bronx, New York, and Bogota, Colombia
Gender differences have been demonstrated in blood flow velocities by duplex ultrasonography (DU) in patients with carotid stenosis. Currently, DU is the most widely used method of follow-up monitoring after carotid angioplasty and stenting (CAS). To identify possible gender differences in carotid flow velocities, we analyzed our experience with DU obtained before and immediately after CAS. In a series of 47 CAS procedures over a 2.5-year period performed in 31 men and 15 women, carotid angiograms and duplex flow velocities were obtained preoperatively and within 24 hr after CAS. Carotid velocity profiles were compared with the angiographic degree of carotid stenosis. Gender differences in blood velocities were assessed using parametric and nonparametric statistical tests. Overall, women had median blood velocities 5-10% higher than men, although the differences were not statistically significant. DU obtained immediately after CAS revealed that median blood flow velocities were very similar among men and women (P > 0.4). In conclusion, although women have higher carotid blood flow velocities than men do, gender differences are notably absent on follow-up DU after carotid stenting. Our data indicate that similar criteria should be used after CAS for interpreting carotid velocity profiles in both women and men.
INTRODUCTION Anatomic, physiologic, and pathologic differences in the distribution of atherosclerotic carotid lesions among men and women have been demonstrated by several observational studies.1-4 Gender differences have therefore also been observed in blood flow velocities by duplex ultrasonography (DU) in patients with carotid stenosis.5 Consequently, Presented at the Twenty-eighth Annual Conference of the Society for Vascular Ultrasound, Chicago, IL, June 16-18, 2005. 1 University of Texas Southwestern Medical Center, Dallas Veterans Affairs Medical Center, Dallas, TX. 2 Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New york. 3
San Martin University Medical School, Bogota, Colombia.
Correspondence to: Carlos H. Timaran, MD, Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9157, E-mail addresses: Carlos.Timaran@ utsouthwestern.edu; [email protected] Ann Vasc Surg 2007; 21: 576-579 DOI: 10.1016/j.avsg.2007.04.003 Ó Annals of Vascular Surgery Inc. Published online: May 29, 2007
576
different gender criteria for defining carotid velocity thresholds for intervention have been suggested as women with carotid lesions have lower risk of stroke for a given degree of carotid stenosis and a higher risk of perioperative neurologic complications compared with men.6-8 Carotid angioplasty and stenting (CAS) with cerebral protection is an effective alternative for the treatment of carotid stenosis, particularly in highrisk surgical patients, i.e., those with significant comorbidities or a hostile neck from previous surgical procedures or radiation.9-11 In fact, a recent randomized clinical trial revealed superior event-free survival at 1 year in patients at high surgical risk undergoing CAS compared to those undergoing carotid endarterectomy (CEA).12 Because the long-term outcome of patients undergoing CAS is unknown, strict follow-up is recommended. Currently, DU is the most widely used method of follow-up monitoring after CAS.13 This study was designed to assess possible gender differences in carotid flow velocities after CAS and to determine if the same criteria can be used for
Vol. 21, No. 5, 2007
men and women during follow-up. For this purpose, we analyzed our experience and compared carotid angiograms and duplex flow velocities obtained immediately after CAS.
METHODS Over a 2.5-year period (July 2002-December 2004), 47 CAS procedures were performed in 31 men and 15 women at high risk or with contraindications for CEA. The majority of these procedures were performed as part of U.S. Food and Drug Administration-approved investigational device exemption clinical trials and with the recently approved Guidant Accunet/Acculink system (Guidant, Santa Clara, CA) or, less frequently, as an off-label use of the same devices. Eligibility criteria included 50% or greater symptomatic carotid stenosis or 80% or greater asymptomatic carotid stenosis. Completion carotid angiograms and postoperative DU scans were obtained in all patients after CAS, and data derived from these tests were used for the analyses in this study. Baseline and postoperative angiograms were performed in the operating room with an OEC/GE Model 9800 mobile C-arm (OEC, Salt Lake City, UT). Two angiographic projections that demonstrated the most severe degree of stenosis were selected and used to assess the degree of residual carotid in-stent stenosis according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.7 The smallest diameter at the narrowest portion of the stent was compared with the distal internal carotid artery (ICA) reference diameter in a segment with parallel wall to determine the degree of residual stenosis. Procedural details and CAS protocols at our institution have been described in detail before.11 Briefly, several types and models of cerebral protection devices were used to prevent distal embolization: PercuSurge GuardWire (Medtronic, Minneapolis, MN), Angioguard Filter (Cordis, Warren, NJ), Parodi Anti-Embolization System (PAES; ArteriA, San Francisco, CA), EPI Filter Wire (Boston Scientific, Natick, MA), and the Guidant Accunet/ Acculink system. Three self-expanding stents were used: Carotid Wallstent (Boston Scientific, Natick, MA), PRECISE carotid stent (Cordis), and Guidant Acculink carotid stent. DU scanning was performed in two laboratories accredited by the Intersocietal Commission for the Accreditation of Vascular Laboratories (ICAVL). All studies were performed with the patients lying supine on the examining table with their necks extended 45 degrees toward the head of the table and
Gender differences in blood flow velocity after CAS
577
rotated 45 degrees away from the examiner. The Doppler angle of insonation was usually 60 degrees except for a few instances. The degree of carotid stenosis was measured using B-mode as well as the location of the carotid bifurcation, the distal extent of plaque, the diameter, and presence of redundancy or kinking of the ICA. Carotid bifurcations were imaged in transverse and longitudinal views. Linear transducers in the 5-10 MHz range were used to measure blood flow velocities at the proximal, middle, and distal common carotid arteries (CCAs) and the proximal external carotid artery (ECA). Velocities in the distal CCA and ICA at proximal, middle, and distal portions of the stent were carefully assessed and recorded. Sector probes were used as needed to evaluate the distal ICA or deep vessels. ICA velocity was measured at the site of maximum residual in-stent stenosis. Results obtained with DU were interpreted using two previously validated criteria in our vascular laboratory during ICAVL accreditation that considers ICA stenosis as moderate (peak systolic velocity [PSV] >160 cm/sec) or severe (peak end-diastolic velocity [EDV] >140 cm/sec or ICA-to-CCA PSV ratio >4.0). PSV, EDV, and ICA-CCA PSV ratios were expressed as medians and ranges; these were analyzed with the Mann-Whitney U-test for independent samples. Fisher’s exact test was used for proportions. Correlation coefficients (r) with logarithmic transformation of the velocity data versus arteriographic stenosis in men and women were calculated and compared. Findings were considered statistically significant if the resulting P value was less than 0.05. For statistical analyses, SPSS for Windows, version 11.0 (SPSS, Chicago, IL), and MedCalc statistical software, version 7.2.0.2 (MedCalc Software, Mariakerke, Belgium), were used.
RESULTS Overall, preoperative median PSV values were slightly higher among women, although the differences were not statistically significant. Median PSV in patients with moderate (50-69%) stenosis was 224 cm/sec for women and 194 cm/sec for men (P ¼ 0.1), whereas for patients with severe stenosis (>70%), median PSV was 422 cm/sec for women and 400 cm/sec for men (P ¼ 0.22). Conversely, median EDV and ICA-CCA PSV ratios were not significantly different between men and women with moderate or severe angiographic ICA stenosis (P > 0.2). Scatter plots of PSV, EDV, and ICA-CCA ratios and the percent of ICA stenosis as determined at preoperative arteriography revealed significant
578 Timaran et al.
DISCUSSION The results of our study indicate that though some differences in carotid blood flow velocities are evident preoperatively, DU after CAS amazingly reveals very similar carotid stent velocity profiles in both genders. These postoperative DU findings suggest that similar criteria should probably be used to assess in-stent restenosis in both men and women, although further studies with long-term follow-up are necessary to define appropriate diagnostic velocity thresholds. DU data from a recent observational study revealed that women have higher carotid blood flow velocities than men for similar degrees of ICA stenosis confirmed angiographically.5 This study included exclusively data from DU scans obtained prior to any carotid intervention. Carotid angiography was obtained in all patients, and the NASCET criteria were used to measure the degree of stenosis.7 Based on their findings, the authors suggest that different carotid velocity thresholds for intervention should be used in women. Although similar trends were evident in our study, the differences in carotid blood flow velocities were not statistically significant, which may reflect the small numbers available for comparison in our series. Interestingly, the differences in carotid flow velocities completely disappear after CAS. Because the postprocedural degree of residual stenosis was negligible and similar in both men and women and always <50%, the carotid blood flow velocities obtained after CAS were comparable between genders. These observations
700 MALE 600
PSV (cm / sec)
correlation between the genders (r > 0.4, P < 0.05). The spread between regression fitted lines of PSV as a function of preoperative angiographic stenosis was wider with higher degrees of ICA stenosis (Fig. 1). The frequency of severe contralateral ICA stenosis or occlusion was not significantly different between the two genders (12% in men and 10% in women). Completion angiogram after CAS revealed successful revascularization in each case, and none had >30% residual in-stent stenosis. Interestingly, immediate postoperative duplex scans revealed very similar median PSV among men and women (122 vs. 120 cm/sec, respectively), whereas median EDV (35 cm/sec) and median ICA-CCA ratios (2) were the same for both genders (P > 0.4). Among men and women, a similar proportion of patients had abnormally elevated PSV (>160 cm/sec) consistent with moderate to severe status (12% vs. 10%, respectively; P ¼ 0.6), which did not correlate with the findings of completion angiograms.
Annals of Vascular Surgery
FEMALE
500 400 300 200 100 0 50
60
70
80
90
100
Angiographic Stenosis (%)
Fig. 1. Scatter plots of preoperative PSV and the percent of arteriographic carotid stenosis using NASCET criteria revealed significant correlation among the genders (r > 0.4, P < 0.05). The spread between regression fitted lines of PSV as a function of preoperative angiographic stenosis was wider with higher degrees of carotid stenosis.
indicate that, at least initially, similar criteria should be used for all patients for postoperative surveillance after CAS, particularly if larger studies reveal similar findings. In this regard, our results need to be interpreted with caution as the small sample size of this series is the major limitation of this study, which cannot be overemphasized. Moreover, it is still undetermined if such similarities in carotid velocity profiles persist over time, particularly when in-stent restenosis occurs. Recent observational studies have revealed that carotid blood flow velocities are abnormally elevated after CAS; therefore, different criteria should be used to assess in-stent restenosis.13-15 In fact, similar findings have been observed in our experience. In a recent study, we investigated if DU could detect significant restenosis after CAS. Data derived from DU scans obtained immediately after CAS and during a median follow-up period of 18 months (range 2-36) in an earlier cohort of patients revealed that DU could detect significant restenosis after CAS with acceptable sensitivity and specificity.11 Our previous study also revealed that the initial DU after CAS determines if traditional criteria for carotid artery stenosis can be utilized for future follow-up monitoring. For those patients with abnormally elevated blood flow velocities in the initial DU, significant changes in flow velocities were better criteria for in-stent restenosis. Because only four instances of severe in-stent restenosis occurred during the follow-up, not enough data were available to detect differences in carotid velocity profiles among men
Vol. 21, No. 5, 2007
and women. In our current series, although few men and women revealed abnormally elevated blood flow velocities on initial DU, despite completion angiograms with no significant residual in-stent restenosis, the carotid velocity profiles were almost the same in all patients. Moreover, the same proportion of men and women had PSV >160 cm/sec, our validated criterion for moderate to severe stenosis. Differences in carotid flow velocities among men and women have been attributed to different factors. For instance, gender differences in the size of the ICA and CCA as well as in the distribution of atherosclerotic carotid plaques have been demonstrated in preoperative angiograms.1,2 To what extent these factors affect the blood flow velocities detected by DU has not been clearly elucidated. In our series, most nitinol stents used were 8 mm in diameter in both men and women, whereas stainless steel stents were 10 mm in diameter. Sizing was based on the diameter of the CCA, although because oversizing was the rule, stent size was similar among patients of both genders. Only recently have tapered stents been used. Data about the diameter of the CCA and ICA in our patients undergoing CAS are unfortunately unavailable. It is possible that the stents were oversized further in women than in men. The similar carotid velocity profiles observed in men and women after CAS may in part be due to the similar stent sizes used in both genders. The presence of a metallic stent alters the arterial wall compliance of the ICA and CCA. Carotid blood flow velocities detected after CAS by DU are thus no longer affected by arterial stiffness or pulsatility, which have been shown to be different among the genders before any intervention.1 Because similar changes in arterial wall compliance occur in all patients once a stent is placed, no gender differences in carotid velocities should be expected. The arterial wall stiffness related to carotid stenting may account for the similar carotid velocities in men and women observed in our series. Finally, the frequency of contralateral severe stenosis or occlusion was similar in men and women and therefore did not affect carotid blood flow velocities after CAS. Other data about other factors that may affect blood flow velocities, such as body mass index and anemia, were not available and could not be analyzed.
Gender differences in blood flow velocity after CAS
579
In conclusion, although women have slightly higher carotid blood flow velocities than men on preoperative DU, gender differences were notably absent after carotid stenting. Our data indicate that similar criteria should be used after CAS for interpreting carotid velocity profiles in women and men. REFERENCES 1. Williams MA, Deacon DFS, Nicolaides AN. Common carotid blood velocity and cerebrovascular symptoms. Br J Surg 1987;6:546. 2. Schulz UG, Rothwell PM. Gender differences in carotid bifurcation anatomy and the distribution of atherosclerotic plaque. Stroke 2001;1:335. 3. Israel BA, Schulz AJ, Parker EA, Becker AB. Communitybased participatory research: policy recommendations for promoting a partnership approach in health research. Educ Health (Abingdon) 2001;2:182-197. 4. Smulyan H, Asmar RG, Rudnicki A, London GM, Safar ME. Comparative effects of aging in men and women on the properties of the arterial tree. J Am Coll Cardiol 2001;5: 1374-1380. 5. Comerota AJ, Salles-Cunha SX, Daoud Y, Jones L, Beebe HG. Gender differences in blood velocities across carotid stenoses. J Vasc Surg 2004;5:939-944. 6. Taylor DW. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;7:445-453. 7. Barnett HJM, Taylor W, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med 1998;20:1415-1425. 8. Carotid endarterectomy for patients with asymptomatic internal carotid-artery stenosis. J Neurol Sci 1995;1:76-77. 9. Veith FJ, Amor M, Ohki T, et al. Current status of carotid bifurcation angioplasty and stenting based on a consensus of opinion leaders. J Vasc Surg 2001;2:S111-S116. 10. Ohki T, Roubin GS, Veith FJ, Iyer SS, Brady E. Efficacy of a filter device in the prevention of embolic events during carotid angioplasty and stenting: an ex vivo analysis. J Vasc Surg 1999;6:1034-1042. 11. Ohki T, Veith FJ, Grenell S, et al. Initial experience with cerebral protection devices to prevent embolization during carotid artery stenting. J Vasc Surg 2002;6:1175-1185. 12. Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotidartery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004;15:1493-1501. 13. Lal BK, Hobson RW, Goldstein J, Chakhtoura EY, Duran WN. Carotid artery stenting: is there a need to revise ultrasound velocity criteria? J Vasc Surg 2004;1:58-66. 14. Robbin ML, Lockhart ME, Weber TM, et al. Carotid artery stents: early and intermediate follow-up with Doppler US. Radiology 1997;3:749-756. 15. Ringer AJ, German JW, Guterman LR, Hopkins LN. Followup of stented carotid arteries by Doppler ultrasound. Neurosurgery 2002;3:639-643.
Gender differences have been demonstrated in blood flow velocities by duplex ultrasonography (DU) in patients with carotid stenosis. Currently, DU is the most widely used method of follow-up monitoring after carotid angioplasty and stenting (CAS). To identify possible gender differences in carotid flow velocities, we analyzed our experience with DU obtained before and immediately after CAS. In a series of 47 CAS procedures over a 2.5-year period performed in 31 men and 15 women, carotid angiograms and duplex flow velocities were obtained preoperatively and within 24 hr after CAS. Carotid velocity profiles were compared with the angiographic degree of carotid stenosis. Gender differences in blood velocities were assessed using parametric and nonparametric statistical tests. Overall, women had median blood velocities 5-10% higher than men, although the differences were not statistically significant. DU obtained immediately after CAS revealed that median blood flow velocities were very similar among men and women (P > 0.4). In conclusion, although women have higher carotid blood flow velocities than men do, gender differences are notably absent on follow-up DU after carotid stenting. Our data indicate that similar criteria should be used after CAS for interpreting carotid velocity profiles in both women and men.
INTRODUCTION Anatomic, physiologic, and pathologic differences in the distribution of atherosclerotic carotid lesions among men and women have been demonstrated by several observational studies.1-4 Gender differences have therefore also been observed in blood flow velocities by duplex ultrasonography (DU) in patients with carotid stenosis.5 Consequently, Presented at the Twenty-eighth Annual Conference of the Society for Vascular Ultrasound, Chicago, IL, June 16-18, 2005. 1 University of Texas Southwestern Medical Center, Dallas Veterans Affairs Medical Center, Dallas, TX. 2 Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New york. 3
San Martin University Medical School, Bogota, Colombia.
Correspondence to: Carlos H. Timaran, MD, Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9157, E-mail addresses: Carlos.Timaran@ utsouthwestern.edu; [email protected] Ann Vasc Surg 2007; 21: 576-579 DOI: 10.1016/j.avsg.2007.04.003 Ó Annals of Vascular Surgery Inc. Published online: May 29, 2007
576
different gender criteria for defining carotid velocity thresholds for intervention have been suggested as women with carotid lesions have lower risk of stroke for a given degree of carotid stenosis and a higher risk of perioperative neurologic complications compared with men.6-8 Carotid angioplasty and stenting (CAS) with cerebral protection is an effective alternative for the treatment of carotid stenosis, particularly in highrisk surgical patients, i.e., those with significant comorbidities or a hostile neck from previous surgical procedures or radiation.9-11 In fact, a recent randomized clinical trial revealed superior event-free survival at 1 year in patients at high surgical risk undergoing CAS compared to those undergoing carotid endarterectomy (CEA).12 Because the long-term outcome of patients undergoing CAS is unknown, strict follow-up is recommended. Currently, DU is the most widely used method of follow-up monitoring after CAS.13 This study was designed to assess possible gender differences in carotid flow velocities after CAS and to determine if the same criteria can be used for
Vol. 21, No. 5, 2007
men and women during follow-up. For this purpose, we analyzed our experience and compared carotid angiograms and duplex flow velocities obtained immediately after CAS.
METHODS Over a 2.5-year period (July 2002-December 2004), 47 CAS procedures were performed in 31 men and 15 women at high risk or with contraindications for CEA. The majority of these procedures were performed as part of U.S. Food and Drug Administration-approved investigational device exemption clinical trials and with the recently approved Guidant Accunet/Acculink system (Guidant, Santa Clara, CA) or, less frequently, as an off-label use of the same devices. Eligibility criteria included 50% or greater symptomatic carotid stenosis or 80% or greater asymptomatic carotid stenosis. Completion carotid angiograms and postoperative DU scans were obtained in all patients after CAS, and data derived from these tests were used for the analyses in this study. Baseline and postoperative angiograms were performed in the operating room with an OEC/GE Model 9800 mobile C-arm (OEC, Salt Lake City, UT). Two angiographic projections that demonstrated the most severe degree of stenosis were selected and used to assess the degree of residual carotid in-stent stenosis according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.7 The smallest diameter at the narrowest portion of the stent was compared with the distal internal carotid artery (ICA) reference diameter in a segment with parallel wall to determine the degree of residual stenosis. Procedural details and CAS protocols at our institution have been described in detail before.11 Briefly, several types and models of cerebral protection devices were used to prevent distal embolization: PercuSurge GuardWire (Medtronic, Minneapolis, MN), Angioguard Filter (Cordis, Warren, NJ), Parodi Anti-Embolization System (PAES; ArteriA, San Francisco, CA), EPI Filter Wire (Boston Scientific, Natick, MA), and the Guidant Accunet/ Acculink system. Three self-expanding stents were used: Carotid Wallstent (Boston Scientific, Natick, MA), PRECISE carotid stent (Cordis), and Guidant Acculink carotid stent. DU scanning was performed in two laboratories accredited by the Intersocietal Commission for the Accreditation of Vascular Laboratories (ICAVL). All studies were performed with the patients lying supine on the examining table with their necks extended 45 degrees toward the head of the table and
Gender differences in blood flow velocity after CAS
577
rotated 45 degrees away from the examiner. The Doppler angle of insonation was usually 60 degrees except for a few instances. The degree of carotid stenosis was measured using B-mode as well as the location of the carotid bifurcation, the distal extent of plaque, the diameter, and presence of redundancy or kinking of the ICA. Carotid bifurcations were imaged in transverse and longitudinal views. Linear transducers in the 5-10 MHz range were used to measure blood flow velocities at the proximal, middle, and distal common carotid arteries (CCAs) and the proximal external carotid artery (ECA). Velocities in the distal CCA and ICA at proximal, middle, and distal portions of the stent were carefully assessed and recorded. Sector probes were used as needed to evaluate the distal ICA or deep vessels. ICA velocity was measured at the site of maximum residual in-stent stenosis. Results obtained with DU were interpreted using two previously validated criteria in our vascular laboratory during ICAVL accreditation that considers ICA stenosis as moderate (peak systolic velocity [PSV] >160 cm/sec) or severe (peak end-diastolic velocity [EDV] >140 cm/sec or ICA-to-CCA PSV ratio >4.0). PSV, EDV, and ICA-CCA PSV ratios were expressed as medians and ranges; these were analyzed with the Mann-Whitney U-test for independent samples. Fisher’s exact test was used for proportions. Correlation coefficients (r) with logarithmic transformation of the velocity data versus arteriographic stenosis in men and women were calculated and compared. Findings were considered statistically significant if the resulting P value was less than 0.05. For statistical analyses, SPSS for Windows, version 11.0 (SPSS, Chicago, IL), and MedCalc statistical software, version 7.2.0.2 (MedCalc Software, Mariakerke, Belgium), were used.
RESULTS Overall, preoperative median PSV values were slightly higher among women, although the differences were not statistically significant. Median PSV in patients with moderate (50-69%) stenosis was 224 cm/sec for women and 194 cm/sec for men (P ¼ 0.1), whereas for patients with severe stenosis (>70%), median PSV was 422 cm/sec for women and 400 cm/sec for men (P ¼ 0.22). Conversely, median EDV and ICA-CCA PSV ratios were not significantly different between men and women with moderate or severe angiographic ICA stenosis (P > 0.2). Scatter plots of PSV, EDV, and ICA-CCA ratios and the percent of ICA stenosis as determined at preoperative arteriography revealed significant
578 Timaran et al.
DISCUSSION The results of our study indicate that though some differences in carotid blood flow velocities are evident preoperatively, DU after CAS amazingly reveals very similar carotid stent velocity profiles in both genders. These postoperative DU findings suggest that similar criteria should probably be used to assess in-stent restenosis in both men and women, although further studies with long-term follow-up are necessary to define appropriate diagnostic velocity thresholds. DU data from a recent observational study revealed that women have higher carotid blood flow velocities than men for similar degrees of ICA stenosis confirmed angiographically.5 This study included exclusively data from DU scans obtained prior to any carotid intervention. Carotid angiography was obtained in all patients, and the NASCET criteria were used to measure the degree of stenosis.7 Based on their findings, the authors suggest that different carotid velocity thresholds for intervention should be used in women. Although similar trends were evident in our study, the differences in carotid blood flow velocities were not statistically significant, which may reflect the small numbers available for comparison in our series. Interestingly, the differences in carotid flow velocities completely disappear after CAS. Because the postprocedural degree of residual stenosis was negligible and similar in both men and women and always <50%, the carotid blood flow velocities obtained after CAS were comparable between genders. These observations
700 MALE 600
PSV (cm / sec)
correlation between the genders (r > 0.4, P < 0.05). The spread between regression fitted lines of PSV as a function of preoperative angiographic stenosis was wider with higher degrees of ICA stenosis (Fig. 1). The frequency of severe contralateral ICA stenosis or occlusion was not significantly different between the two genders (12% in men and 10% in women). Completion angiogram after CAS revealed successful revascularization in each case, and none had >30% residual in-stent stenosis. Interestingly, immediate postoperative duplex scans revealed very similar median PSV among men and women (122 vs. 120 cm/sec, respectively), whereas median EDV (35 cm/sec) and median ICA-CCA ratios (2) were the same for both genders (P > 0.4). Among men and women, a similar proportion of patients had abnormally elevated PSV (>160 cm/sec) consistent with moderate to severe status (12% vs. 10%, respectively; P ¼ 0.6), which did not correlate with the findings of completion angiograms.
Annals of Vascular Surgery
FEMALE
500 400 300 200 100 0 50
60
70
80
90
100
Angiographic Stenosis (%)
Fig. 1. Scatter plots of preoperative PSV and the percent of arteriographic carotid stenosis using NASCET criteria revealed significant correlation among the genders (r > 0.4, P < 0.05). The spread between regression fitted lines of PSV as a function of preoperative angiographic stenosis was wider with higher degrees of carotid stenosis.
indicate that, at least initially, similar criteria should be used for all patients for postoperative surveillance after CAS, particularly if larger studies reveal similar findings. In this regard, our results need to be interpreted with caution as the small sample size of this series is the major limitation of this study, which cannot be overemphasized. Moreover, it is still undetermined if such similarities in carotid velocity profiles persist over time, particularly when in-stent restenosis occurs. Recent observational studies have revealed that carotid blood flow velocities are abnormally elevated after CAS; therefore, different criteria should be used to assess in-stent restenosis.13-15 In fact, similar findings have been observed in our experience. In a recent study, we investigated if DU could detect significant restenosis after CAS. Data derived from DU scans obtained immediately after CAS and during a median follow-up period of 18 months (range 2-36) in an earlier cohort of patients revealed that DU could detect significant restenosis after CAS with acceptable sensitivity and specificity.11 Our previous study also revealed that the initial DU after CAS determines if traditional criteria for carotid artery stenosis can be utilized for future follow-up monitoring. For those patients with abnormally elevated blood flow velocities in the initial DU, significant changes in flow velocities were better criteria for in-stent restenosis. Because only four instances of severe in-stent restenosis occurred during the follow-up, not enough data were available to detect differences in carotid velocity profiles among men
Vol. 21, No. 5, 2007
and women. In our current series, although few men and women revealed abnormally elevated blood flow velocities on initial DU, despite completion angiograms with no significant residual in-stent restenosis, the carotid velocity profiles were almost the same in all patients. Moreover, the same proportion of men and women had PSV >160 cm/sec, our validated criterion for moderate to severe stenosis. Differences in carotid flow velocities among men and women have been attributed to different factors. For instance, gender differences in the size of the ICA and CCA as well as in the distribution of atherosclerotic carotid plaques have been demonstrated in preoperative angiograms.1,2 To what extent these factors affect the blood flow velocities detected by DU has not been clearly elucidated. In our series, most nitinol stents used were 8 mm in diameter in both men and women, whereas stainless steel stents were 10 mm in diameter. Sizing was based on the diameter of the CCA, although because oversizing was the rule, stent size was similar among patients of both genders. Only recently have tapered stents been used. Data about the diameter of the CCA and ICA in our patients undergoing CAS are unfortunately unavailable. It is possible that the stents were oversized further in women than in men. The similar carotid velocity profiles observed in men and women after CAS may in part be due to the similar stent sizes used in both genders. The presence of a metallic stent alters the arterial wall compliance of the ICA and CCA. Carotid blood flow velocities detected after CAS by DU are thus no longer affected by arterial stiffness or pulsatility, which have been shown to be different among the genders before any intervention.1 Because similar changes in arterial wall compliance occur in all patients once a stent is placed, no gender differences in carotid velocities should be expected. The arterial wall stiffness related to carotid stenting may account for the similar carotid velocities in men and women observed in our series. Finally, the frequency of contralateral severe stenosis or occlusion was similar in men and women and therefore did not affect carotid blood flow velocities after CAS. Other data about other factors that may affect blood flow velocities, such as body mass index and anemia, were not available and could not be analyzed.
Gender differences in blood flow velocity after CAS
579
In conclusion, although women have slightly higher carotid blood flow velocities than men on preoperative DU, gender differences were notably absent after carotid stenting. Our data indicate that similar criteria should be used after CAS for interpreting carotid velocity profiles in women and men. REFERENCES 1. Williams MA, Deacon DFS, Nicolaides AN. Common carotid blood velocity and cerebrovascular symptoms. Br J Surg 1987;6:546. 2. Schulz UG, Rothwell PM. Gender differences in carotid bifurcation anatomy and the distribution of atherosclerotic plaque. Stroke 2001;1:335. 3. Israel BA, Schulz AJ, Parker EA, Becker AB. Communitybased participatory research: policy recommendations for promoting a partnership approach in health research. Educ Health (Abingdon) 2001;2:182-197. 4. Smulyan H, Asmar RG, Rudnicki A, London GM, Safar ME. Comparative effects of aging in men and women on the properties of the arterial tree. J Am Coll Cardiol 2001;5: 1374-1380. 5. Comerota AJ, Salles-Cunha SX, Daoud Y, Jones L, Beebe HG. Gender differences in blood velocities across carotid stenoses. J Vasc Surg 2004;5:939-944. 6. Taylor DW. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;7:445-453. 7. Barnett HJM, Taylor W, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med 1998;20:1415-1425. 8. Carotid endarterectomy for patients with asymptomatic internal carotid-artery stenosis. J Neurol Sci 1995;1:76-77. 9. Veith FJ, Amor M, Ohki T, et al. Current status of carotid bifurcation angioplasty and stenting based on a consensus of opinion leaders. J Vasc Surg 2001;2:S111-S116. 10. Ohki T, Roubin GS, Veith FJ, Iyer SS, Brady E. Efficacy of a filter device in the prevention of embolic events during carotid angioplasty and stenting: an ex vivo analysis. J Vasc Surg 1999;6:1034-1042. 11. Ohki T, Veith FJ, Grenell S, et al. Initial experience with cerebral protection devices to prevent embolization during carotid artery stenting. J Vasc Surg 2002;6:1175-1185. 12. Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotidartery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004;15:1493-1501. 13. Lal BK, Hobson RW, Goldstein J, Chakhtoura EY, Duran WN. Carotid artery stenting: is there a need to revise ultrasound velocity criteria? J Vasc Surg 2004;1:58-66. 14. Robbin ML, Lockhart ME, Weber TM, et al. Carotid artery stents: early and intermediate follow-up with Doppler US. Radiology 1997;3:749-756. 15. Ringer AJ, German JW, Guterman LR, Hopkins LN. Followup of stented carotid arteries by Doppler ultrasound. Neurosurgery 2002;3:639-643.