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Ruptured Superior Mesenteric Artery Aneurysm due to Fibromuscular Dysplasia: A Rare Vascular Presentation in a Patient with Schizophrenia
Ruptured Superior Mesenteric Artery Aneurysm due to Fibromuscular Dysplasia: A Rare Vascular Presentation in a Patient with Schizophrenia Valeria Silvestri, Paolo Sapienza, Paolo Ossola, Raffaele Grande, Gioia Brachini, Antonio V. Sterpetti, and Andrea Mingoli, Rome, Italy
Visceral aneurysms are rare entities, with a reported incidence of 0.01e2%. Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory artery disease, which may predispose to aneurysmal degeneration. Schizophrenia has been linked to an increased cardiovascular risk because of the influence of traditional and disease-specific risk factors. We report the case of a 44-year-old male schizophrenic patient presenting with a ruptured giant aneurysm of superior mesenteric artery, managed by mesenteric ligation. The histologic diagnosis was fibromuscular dysplasia. Another case of visceral aneurysm in schizophrenic patient with similar histologic features has been previously reported in literature.
Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease; its etiology is still unknown.1 FMD may predispose to aneurysmal degeneration, and it has been linked to the occurrence of visceral artery aneurysms along with other conditions such as atherosclerosis, abdominal trauma, hyperflow conditions (pregnancy, portal hypertension), vasculitis, neurofibromatosis, antiphospholipid syndrome, genetic syndromes, and other connective tissue disorders,2e4 which may also involve the visceral arteries. Schizophrenia is a severe mental illness, affecting around 1% of the population. An increased Framingham 10-year risk for cardiovascular disease has been reported in schizophrenia,5 and cardiovascular disease is the principal cause of death in affected patients, accounting for up to 50% cases of early mortality.6
Department of Surgery ‘‘Pietro Valdoni’’, ‘‘Sapienza’’ University of Rome, Rome, Italy. Correspondence to: Paolo Sapienza, MD, PhD, Associate Professor of Surgery, Department of Surgery ‘‘Pietro Valdoni’’, ‘‘Sapienza’’ University of Rome, Policlinico Umberto I Viale del Policlinico, 151 00161 Rome, Italy; E-mail: [email protected] Ann Vasc Surg 2019; 58: 384.e5–384.e8 https://doi.org/10.1016/j.avsg.2018.11.030 Ó 2019 Elsevier Inc. All rights reserved. Manuscript received: September 5, 2018; manuscript accepted: November 9, 2018; published online: 13 February 2019
We present a case of male schizophrenic patient presenting with a ruptured giant aneurysm of superior mesenteric artery due to FMD. A systematic review of literature to identify the incidence, demographic occurrence, racial differences, clinical characteristics, pathology, and diagnostic and treatment options of this rare association was performed.
CASE REPORT A 44-year-old male patient came to the attention of the emergency vascular unit of our hospital because of abdominal pain, localized in lower quadrants of the abdomen, associated with a pulsatile mass in mesohypogastric region, irradiated to the iliac region. Patient’s anamnesis was positive for schizophrenia, diagnosed 30 years previously and on haloperidol treatment since then. No other comorbidity was reported. He was transferred from another hospital, where he had been submitted few hours earlier to an endovascular procedure with coil embolization for a giant ruptured aneurysm of the superior mesenteric artery (Fig. 1A), which failed because of an uncompleted embolization, thus determining a free abdominal blood loss. Failure of the endovascular procedure was due to the dimension of the aneurysmal dilatation. A vascular plug positioning was felt at risk for determining ischemia of the entire small bowel. 384.e5
384.e6 Case reports
Annals of Vascular Surgery
Fig. 1. (A) Preoperative CTA showing the giant superior mesenteric artery aneurysm. (B) CTA showing the failure of endovascular coil positioning.
On arrival patient was hemodynamically unstable (blood pressure 70/50 mm Hg, heart rate 140 b/min after 4 blood units of concentrate erythrocyte. Laboratory investigations showed marked anemia (7.4 g/dL hemoglobin; 28% hematocrit). An increase in white blood cell count (11 109/L) and lactate (6.25 mmol/L) concentration was observed. A computed tomography angiography in emergency setting showed, apart from a great number of artifacts due to a previous attempt of aneurysm embolization with metallic coils, a 7 8 cm ruptured superior mesenteric artery aneurysm with proximal neck departing immediately after the origin of pancreatic-duodenal arteries (Fig. 1B). Superior mesenteric artery was surgically interrupted just below the emergency of inferior pancreatico-duodenal arteries, after total medial visceral rotation (Mattox extended maneuver). A vein revascularization of the distal superior mesenteric artery was impossible because of an inadequate runoff. Small bowel was viable with no signs of ischemia, thus not needing intraoperative resection. Therefore, the abdomen was closed at the end of the procedure. Cultural samples were sent for histologic and bacteriologic assessment. No evidence of infection was found on microbiologic testing, although histology reported a marked fibrous degeneration of medial and adventitial layers, including vasa vasorum and nervous fibers. Only focal spots of residual external elastic lamina were visible in sample. Fibrin covered arterial lumen. Given the result of histology findings, and the negative result of autoantibody testing performed to exclude vasculitis, the etiology of aneurysm lesion was attributed to FMD. Apart from a mild increase in white blood cell (23 109/L), erythrocyte sedimentation rate (39 mm/hr), and C-reactive protein (520 mg/L), due to mild ischemic intestinal sufferance, not requiring a second-look procedure,
and successfully managed in the intensive care unit with fluids and broad-spectrum antibiotics (Fig. 2), patient’s recovery was uneventful and he is doing well on 1 month’s follow-up.
DISCUSSION To our knowledge, another case of visceral aneurysm7 in schizophrenia could be found reviewing literature. Scopus (www.scopus.com), Embase (www.embase. com), and Medline (www.ncbi.nlm.nih.gov/ pubmed) databases were used for the International literature review. No language restrictions were applied. Manual searching of reference lists for relevant studies and previous reviews was also performed. The primary search term was conducted for any combination of the words ‘‘superior mesenteric artery aneurysm’’ and ‘‘fibromuscular dysplasia’’ and ‘‘schizophrenia.’’ We found the case of a splenic artery aneurysm in a 46-year-old male patient. Histology showed in this case segmental mediolytic arteritis. Interestingly, segmental mediolytic arteritis has been suggested to be a precursor lesion of FMD.8,9 FMD is more common in women than in men by a ratio of 9:1,4 and it is a well-known predisposing factor in the development of aneurysms in many districts.4 Precise data on prevalence are not available; esteems from previous studies suggest a 4% in general population.3 According to the U.S. registry for FMD, celiac and mesenteric arteries were involved in 37.5% of all cases, in the form of stenosis, dissection, or visceral artery aneurysm. Flank or abdominal pain is the major complaint on presentation, reported in 15.7% of cases, complicated by
Volume 58, July 2019
Fig. 2. Control CTA after surgical superior mesenteric artery ligation at postoperative day 7.
mesenteric ischemia in 1.8% of patients. Celiacmesenteric artery involvement requires treatment in 6.0% of cases; 18.1% of total number of procedures on mesenteric arteries were reported for aneurysm/dissection, but no data could be retrieved from registries regarding incidence of rupture in mesenteric aneurysms in FMD.3 Endovascular repair options include embolization, possible if there is sufficient collateral circulation, or the use of stent grafts (covered or multilayer).10 Endovascular methods offer an effective alternative therapy for poor surgical candidates with technical success and visceral preservation rates up to 90%, and major complication rate of 3.7% according to a recently published meta-analysis.2 Schizophrenic patients have a relative risk from 1.3 to 4.9 of morbidity and mortality, resulting from coronary heart disease.11 Traditional cardiovascular risk factors (such as diabetes, hypertension, and dyslipidemia) may in part be responsible of the cardiovascular increased morbidity in these patients due to atherosclerotic conditions.11 A greater prevalence of individual and multiple cardiovascular disease risk factors and an increase in their incidence during follow-up when compared with nonschizophrenic patients has been recently reported.12 Furthermore, antipsychotics increase the incidence of traditional risk factors while modulating immune function and may have an ambivalent role in
Case reports 384.e7
cardiovascular risk definition in these patients.6 Overlapping genetic contributions to cardiovascular disease and psychosis have been suggested because of an increased prevalence of cardiovascular conditions between first-degree relatives of psychotic patients.11 Although the increase cardiovascular risk in patients with schizophrenia may be linked to traditional risk factors that cause atherosclerotic damage of vessels, other pathologic mechanisms may be involved, and this may explain why traditional cardiovascular risk charts may underestimate risk in schizophrenic patients.13 Studies focusing on pathophysiologic pathways that may lead to the observed increase in cardiovascular risk have reported early-onset abnormalities in microvascular endothelial function markers in patients with schizophrenia, which may precede macrovascular impairment. These abnormalities may be explained only partially by influence of traditional risk factors or by activation of nitric oxygen pathway,14 suggesting specific physiopathology cardiovascular pathways in these conditions that have to be further studied. Systemic inflammation is among these additional disease-specific factors. Inflammation may have a role in the physiopathology of schizophrenia,15 and, at the same time, it may be strongly associated with an early vascular-related mortality in these patients.11 Interestingly, an impairment of pathways involved in inflammatory signaling has been reported also in patients with FMD.16 Specifically, among these inflammatory pathways, transforming growth factor (TGF) was previously described as impaired in both psychiatric condition15 and in patients with FMD.16 It is interesting to notice that TGF signaling machinery acts in the central nervous system, where it has a role in controlling neural stem cell maintenance and differentiation,15 but it may also regulate a variety of cellular functions in the arterial wall, as cellular proliferation, differentiation, modulation of extracellular matrix production, and arterial remodeling,16 suggesting possible shared physiopathologic pathways for the 2 conditions. FMD is a nonatherosclerotic condition that may share common inflammatory patterns with schizophrenia. The cooccurrence of the 2 conditions suggests the need for further inquiries on the role of nontraditional risk factors, such as inflammatory conditions, in the definition of cardiovascular risk and specific pathologic features in patients with schizophrenia. In conclusion, the search of aneurysmal dilatations or other acute vascular conditions in patients
384.e8 Case reports
with schizophrenia presenting with abdominal pain should be recommended. We also discourage the use of endovascular procedures in the treatment of giant ruptured visceral aneurysms as a first choice in technically challenging lesions, because of the high risk of unsuccess and of the challenges added by endovascular attempt to the following surgical conversion. The continuity of the superior mesenteric artery should be always reestablished if an adequate runoff is present with the use of a vein. Further studies are needed to inquire on specific nontraditional feature of vascular risk and arterial lesions of surgical interest in patients with schizophrenia. REFERENCES 1. Olin JW, Gornik HL, Bacharach M, et al. Fibromuscular dysplasia: state of the science and critical unanswered questions. A scientific statement from the American Heart Association. Circulation 2004;129:1048e78. 2. van Rijn MJ, Ten Raa S, Hendriks JM, et al. Visceral aneurysms: old paradigms, new insights? Best Pract Res Clin Gastroenterol 2017;31:97e104. 3. Kok HK, Asadi H, Sheehan M, et al. Systematic review and single-center experience for endovascular management of visceral and renal artery aneurysms. J Vasc Interv Radiol 2016;27:1630e41. 4. Kadian-Dodov D, Gornik HL, Gu X, et al. Dissection and aneurysm in patients with fibromuscular dysplasia: findings from the U.S. registry for FMD. J Am Coll Cardiol 2016;68:176e85. 5. Zhao S, Xia H, Mu J, et al. 10-year CVD risk in Han Chinese mainland patients with schizophrenia. Psychiatry Res 2018;264:322e6.
Annals of Vascular Surgery
6. Chung KH, Chen PH, Kuo CJ, et al. Risk factors for early circulatory mortality in patients with schizophrenia. Psychiatry Res 2018;267:7e11. 7. Takagi C, Ashizawa N, Eishi K, et al. Segmental mediolytic arteriopathy involving celiac to spenic and left renal arteries. Intern Med 2003;42:818e23. 8. Lie JT. Segmental mediolytic arteritis. Not an arteritis but a variant of arterial fibromuscular dysplasia. Arch Pathol Lab Med 1992;116:238e41. 9. Slavin RE, Saeki K, Bhagavan B, et al. Segmental arterial mediolysis: a precursor to fibromuscular dysplasia? Mod Pathol 1995;8:287e94. 10. Hemp JH, Sabri SS. Endovascular management of visceral arterial aneurysms. Tech Vasc Interv Radiol 2015;18: 14e23. 11. Mothi SS, Tandon N, Padmanabhan J, et al. Increased cardiometabolic dysfunction in first-degree relatives of patients with psychotic disorders. Schizophr Res 2015;165: 103e7. 12. Chiu M, Rahman F, Vigod S, et al. Temporal trends in cardiovascular disease risk factor profiles in a populationbased schizophrenia sample: a repeat cross-sectional study. J Epidemiol Community Health 2018;72:71e7. 13. Azad MC, Shoesmith WD, Al Mamun M, et al. Cardiovascular diseases among patients with schizophrenia. Asian J Psychiatr 2016;19:28e36. 14. Vetter MW, Martin BJ, Fung M, et al. Microvascular dysfunction in schizophrenia: a case-control study. NPJ Schizophr 2015;1:15023. 15. Frydecka D, Misiak B, Beszlej JA, et al. Genetic variants in transforming growth factor-b gene (TGFb1) affect susceptibility to schizophrenia. Mol Biol Rep 2013;40: 5607e14. 16. Ganesh SK, Morissette R, Xu Z, et al. Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-b expression and connective tissue features. FASEB J 2014;28:3313e24.
Visceral aneurysms are rare entities, with a reported incidence of 0.01e2%. Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory artery disease, which may predispose to aneurysmal degeneration. Schizophrenia has been linked to an increased cardiovascular risk because of the influence of traditional and disease-specific risk factors. We report the case of a 44-year-old male schizophrenic patient presenting with a ruptured giant aneurysm of superior mesenteric artery, managed by mesenteric ligation. The histologic diagnosis was fibromuscular dysplasia. Another case of visceral aneurysm in schizophrenic patient with similar histologic features has been previously reported in literature.
Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease; its etiology is still unknown.1 FMD may predispose to aneurysmal degeneration, and it has been linked to the occurrence of visceral artery aneurysms along with other conditions such as atherosclerosis, abdominal trauma, hyperflow conditions (pregnancy, portal hypertension), vasculitis, neurofibromatosis, antiphospholipid syndrome, genetic syndromes, and other connective tissue disorders,2e4 which may also involve the visceral arteries. Schizophrenia is a severe mental illness, affecting around 1% of the population. An increased Framingham 10-year risk for cardiovascular disease has been reported in schizophrenia,5 and cardiovascular disease is the principal cause of death in affected patients, accounting for up to 50% cases of early mortality.6
Department of Surgery ‘‘Pietro Valdoni’’, ‘‘Sapienza’’ University of Rome, Rome, Italy. Correspondence to: Paolo Sapienza, MD, PhD, Associate Professor of Surgery, Department of Surgery ‘‘Pietro Valdoni’’, ‘‘Sapienza’’ University of Rome, Policlinico Umberto I Viale del Policlinico, 151 00161 Rome, Italy; E-mail: [email protected] Ann Vasc Surg 2019; 58: 384.e5–384.e8 https://doi.org/10.1016/j.avsg.2018.11.030 Ó 2019 Elsevier Inc. All rights reserved. Manuscript received: September 5, 2018; manuscript accepted: November 9, 2018; published online: 13 February 2019
We present a case of male schizophrenic patient presenting with a ruptured giant aneurysm of superior mesenteric artery due to FMD. A systematic review of literature to identify the incidence, demographic occurrence, racial differences, clinical characteristics, pathology, and diagnostic and treatment options of this rare association was performed.
CASE REPORT A 44-year-old male patient came to the attention of the emergency vascular unit of our hospital because of abdominal pain, localized in lower quadrants of the abdomen, associated with a pulsatile mass in mesohypogastric region, irradiated to the iliac region. Patient’s anamnesis was positive for schizophrenia, diagnosed 30 years previously and on haloperidol treatment since then. No other comorbidity was reported. He was transferred from another hospital, where he had been submitted few hours earlier to an endovascular procedure with coil embolization for a giant ruptured aneurysm of the superior mesenteric artery (Fig. 1A), which failed because of an uncompleted embolization, thus determining a free abdominal blood loss. Failure of the endovascular procedure was due to the dimension of the aneurysmal dilatation. A vascular plug positioning was felt at risk for determining ischemia of the entire small bowel. 384.e5
384.e6 Case reports
Annals of Vascular Surgery
Fig. 1. (A) Preoperative CTA showing the giant superior mesenteric artery aneurysm. (B) CTA showing the failure of endovascular coil positioning.
On arrival patient was hemodynamically unstable (blood pressure 70/50 mm Hg, heart rate 140 b/min after 4 blood units of concentrate erythrocyte. Laboratory investigations showed marked anemia (7.4 g/dL hemoglobin; 28% hematocrit). An increase in white blood cell count (11 109/L) and lactate (6.25 mmol/L) concentration was observed. A computed tomography angiography in emergency setting showed, apart from a great number of artifacts due to a previous attempt of aneurysm embolization with metallic coils, a 7 8 cm ruptured superior mesenteric artery aneurysm with proximal neck departing immediately after the origin of pancreatic-duodenal arteries (Fig. 1B). Superior mesenteric artery was surgically interrupted just below the emergency of inferior pancreatico-duodenal arteries, after total medial visceral rotation (Mattox extended maneuver). A vein revascularization of the distal superior mesenteric artery was impossible because of an inadequate runoff. Small bowel was viable with no signs of ischemia, thus not needing intraoperative resection. Therefore, the abdomen was closed at the end of the procedure. Cultural samples were sent for histologic and bacteriologic assessment. No evidence of infection was found on microbiologic testing, although histology reported a marked fibrous degeneration of medial and adventitial layers, including vasa vasorum and nervous fibers. Only focal spots of residual external elastic lamina were visible in sample. Fibrin covered arterial lumen. Given the result of histology findings, and the negative result of autoantibody testing performed to exclude vasculitis, the etiology of aneurysm lesion was attributed to FMD. Apart from a mild increase in white blood cell (23 109/L), erythrocyte sedimentation rate (39 mm/hr), and C-reactive protein (520 mg/L), due to mild ischemic intestinal sufferance, not requiring a second-look procedure,
and successfully managed in the intensive care unit with fluids and broad-spectrum antibiotics (Fig. 2), patient’s recovery was uneventful and he is doing well on 1 month’s follow-up.
DISCUSSION To our knowledge, another case of visceral aneurysm7 in schizophrenia could be found reviewing literature. Scopus (www.scopus.com), Embase (www.embase. com), and Medline (www.ncbi.nlm.nih.gov/ pubmed) databases were used for the International literature review. No language restrictions were applied. Manual searching of reference lists for relevant studies and previous reviews was also performed. The primary search term was conducted for any combination of the words ‘‘superior mesenteric artery aneurysm’’ and ‘‘fibromuscular dysplasia’’ and ‘‘schizophrenia.’’ We found the case of a splenic artery aneurysm in a 46-year-old male patient. Histology showed in this case segmental mediolytic arteritis. Interestingly, segmental mediolytic arteritis has been suggested to be a precursor lesion of FMD.8,9 FMD is more common in women than in men by a ratio of 9:1,4 and it is a well-known predisposing factor in the development of aneurysms in many districts.4 Precise data on prevalence are not available; esteems from previous studies suggest a 4% in general population.3 According to the U.S. registry for FMD, celiac and mesenteric arteries were involved in 37.5% of all cases, in the form of stenosis, dissection, or visceral artery aneurysm. Flank or abdominal pain is the major complaint on presentation, reported in 15.7% of cases, complicated by
Volume 58, July 2019
Fig. 2. Control CTA after surgical superior mesenteric artery ligation at postoperative day 7.
mesenteric ischemia in 1.8% of patients. Celiacmesenteric artery involvement requires treatment in 6.0% of cases; 18.1% of total number of procedures on mesenteric arteries were reported for aneurysm/dissection, but no data could be retrieved from registries regarding incidence of rupture in mesenteric aneurysms in FMD.3 Endovascular repair options include embolization, possible if there is sufficient collateral circulation, or the use of stent grafts (covered or multilayer).10 Endovascular methods offer an effective alternative therapy for poor surgical candidates with technical success and visceral preservation rates up to 90%, and major complication rate of 3.7% according to a recently published meta-analysis.2 Schizophrenic patients have a relative risk from 1.3 to 4.9 of morbidity and mortality, resulting from coronary heart disease.11 Traditional cardiovascular risk factors (such as diabetes, hypertension, and dyslipidemia) may in part be responsible of the cardiovascular increased morbidity in these patients due to atherosclerotic conditions.11 A greater prevalence of individual and multiple cardiovascular disease risk factors and an increase in their incidence during follow-up when compared with nonschizophrenic patients has been recently reported.12 Furthermore, antipsychotics increase the incidence of traditional risk factors while modulating immune function and may have an ambivalent role in
Case reports 384.e7
cardiovascular risk definition in these patients.6 Overlapping genetic contributions to cardiovascular disease and psychosis have been suggested because of an increased prevalence of cardiovascular conditions between first-degree relatives of psychotic patients.11 Although the increase cardiovascular risk in patients with schizophrenia may be linked to traditional risk factors that cause atherosclerotic damage of vessels, other pathologic mechanisms may be involved, and this may explain why traditional cardiovascular risk charts may underestimate risk in schizophrenic patients.13 Studies focusing on pathophysiologic pathways that may lead to the observed increase in cardiovascular risk have reported early-onset abnormalities in microvascular endothelial function markers in patients with schizophrenia, which may precede macrovascular impairment. These abnormalities may be explained only partially by influence of traditional risk factors or by activation of nitric oxygen pathway,14 suggesting specific physiopathology cardiovascular pathways in these conditions that have to be further studied. Systemic inflammation is among these additional disease-specific factors. Inflammation may have a role in the physiopathology of schizophrenia,15 and, at the same time, it may be strongly associated with an early vascular-related mortality in these patients.11 Interestingly, an impairment of pathways involved in inflammatory signaling has been reported also in patients with FMD.16 Specifically, among these inflammatory pathways, transforming growth factor (TGF) was previously described as impaired in both psychiatric condition15 and in patients with FMD.16 It is interesting to notice that TGF signaling machinery acts in the central nervous system, where it has a role in controlling neural stem cell maintenance and differentiation,15 but it may also regulate a variety of cellular functions in the arterial wall, as cellular proliferation, differentiation, modulation of extracellular matrix production, and arterial remodeling,16 suggesting possible shared physiopathologic pathways for the 2 conditions. FMD is a nonatherosclerotic condition that may share common inflammatory patterns with schizophrenia. The cooccurrence of the 2 conditions suggests the need for further inquiries on the role of nontraditional risk factors, such as inflammatory conditions, in the definition of cardiovascular risk and specific pathologic features in patients with schizophrenia. In conclusion, the search of aneurysmal dilatations or other acute vascular conditions in patients
384.e8 Case reports
with schizophrenia presenting with abdominal pain should be recommended. We also discourage the use of endovascular procedures in the treatment of giant ruptured visceral aneurysms as a first choice in technically challenging lesions, because of the high risk of unsuccess and of the challenges added by endovascular attempt to the following surgical conversion. The continuity of the superior mesenteric artery should be always reestablished if an adequate runoff is present with the use of a vein. Further studies are needed to inquire on specific nontraditional feature of vascular risk and arterial lesions of surgical interest in patients with schizophrenia. REFERENCES 1. Olin JW, Gornik HL, Bacharach M, et al. Fibromuscular dysplasia: state of the science and critical unanswered questions. A scientific statement from the American Heart Association. Circulation 2004;129:1048e78. 2. van Rijn MJ, Ten Raa S, Hendriks JM, et al. Visceral aneurysms: old paradigms, new insights? Best Pract Res Clin Gastroenterol 2017;31:97e104. 3. Kok HK, Asadi H, Sheehan M, et al. Systematic review and single-center experience for endovascular management of visceral and renal artery aneurysms. J Vasc Interv Radiol 2016;27:1630e41. 4. Kadian-Dodov D, Gornik HL, Gu X, et al. Dissection and aneurysm in patients with fibromuscular dysplasia: findings from the U.S. registry for FMD. J Am Coll Cardiol 2016;68:176e85. 5. Zhao S, Xia H, Mu J, et al. 10-year CVD risk in Han Chinese mainland patients with schizophrenia. Psychiatry Res 2018;264:322e6.
Annals of Vascular Surgery
6. Chung KH, Chen PH, Kuo CJ, et al. Risk factors for early circulatory mortality in patients with schizophrenia. Psychiatry Res 2018;267:7e11. 7. Takagi C, Ashizawa N, Eishi K, et al. Segmental mediolytic arteriopathy involving celiac to spenic and left renal arteries. Intern Med 2003;42:818e23. 8. Lie JT. Segmental mediolytic arteritis. Not an arteritis but a variant of arterial fibromuscular dysplasia. Arch Pathol Lab Med 1992;116:238e41. 9. Slavin RE, Saeki K, Bhagavan B, et al. Segmental arterial mediolysis: a precursor to fibromuscular dysplasia? Mod Pathol 1995;8:287e94. 10. Hemp JH, Sabri SS. Endovascular management of visceral arterial aneurysms. Tech Vasc Interv Radiol 2015;18: 14e23. 11. Mothi SS, Tandon N, Padmanabhan J, et al. Increased cardiometabolic dysfunction in first-degree relatives of patients with psychotic disorders. Schizophr Res 2015;165: 103e7. 12. Chiu M, Rahman F, Vigod S, et al. Temporal trends in cardiovascular disease risk factor profiles in a populationbased schizophrenia sample: a repeat cross-sectional study. J Epidemiol Community Health 2018;72:71e7. 13. Azad MC, Shoesmith WD, Al Mamun M, et al. Cardiovascular diseases among patients with schizophrenia. Asian J Psychiatr 2016;19:28e36. 14. Vetter MW, Martin BJ, Fung M, et al. Microvascular dysfunction in schizophrenia: a case-control study. NPJ Schizophr 2015;1:15023. 15. Frydecka D, Misiak B, Beszlej JA, et al. Genetic variants in transforming growth factor-b gene (TGFb1) affect susceptibility to schizophrenia. Mol Biol Rep 2013;40: 5607e14. 16. Ganesh SK, Morissette R, Xu Z, et al. Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-b expression and connective tissue features. FASEB J 2014;28:3313e24.