Abstract: Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease that involves primarily the renal and internal carotid arteries and less often the vertebral, iliac, subclavian, and visceral arteries. Although its pathogenesis is not completely understood, humoral, mechanical, and genetic factors as well as mural ischemia may play a role. The natural history is relatively benign, with progression occurring in only a minority of the patients. Typical clinical manifestations are renovascular hypertension, stroke, subarachnoid hemorrhage, abdominal angina, or claudication of the legs or arms. In patients with symptoms, percutaneous transluminal angioplasty has emerged as the treatment of choice in most involved vascular beds. Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease that involves primarily the renal and internal carotid arteries and less often the vertebral, iliac, subclavian, and visceral arteries. Although its pathogenesis is not completely understood, humoral, mechanical, and genetic factors as well as mural ischemia may play a role. The natural history is relatively benign, with progression occurring in only a minority of the patients. Typical clinical manifestations are renovascular hypertension, stroke, subarachnoid hemorrhage, abdominal angina, or claudication of the legs or arms. In patients with symptoms, percutaneous transluminal angioplasty has emerged as the treatment of choice in most involved vascular beds. Fibromuscular dysplasia (FMD), or fibromuscular hyperplasia, is a nonatherosclerotic and noninflammatory vascular disease that primarily involves the medium-sized and small arteries, most commonly the renal and carotid arteries1Lüscher TF Keller HM Imhof HG Greminger P Kuhlmann U Largiadèr F Schneider E Schneider J Vetter W Fibromuscular hyperplasia: extension of the disease and therapeutic outcome; results of the University Hospital Zurich Cooperative Study on Fibromuscular Hyperplasia.Nephron. 1986; 44: 109-114PubMed Google Scholar (Fig. 1). Young Caucasian women are predominantly affected. The patients may be asymptomatic or may have the initial manifestations of hypertension, stroke, abdominal angina, or other symptoms of vascular insufficiency, depending on the vascular bed involved and the severity of the stenosis. The first description of FMD, long before the term was introduced into the medical literature, has often been attributed to Leadbetter and Burkland.2Leadbetter WF Burkland CE Hypertension in unilateral renal disease.J Urol. 1938; 39: 611-626Abstract Full Text PDF Google Scholar In 1938, they reported on a 5 1/2-year-old boy with hypertension and an ectopic right kidney. His blood pressure was normal after nephrectomy. Histologically, the main renal artery appeared to be partially obstructed by "an intraluminal mass of smooth muscle"; more distally, the arterial wall was thinned. The lesion shown in Figure 6 of their article, however, is likely a histologic artifact rather than the first genuine case of FMD. In 1958, McCormack and associates3McCormack LJ Hazard JB Poutasse EF Obstructive lesions of the renal artery associated with remediable hypertension (abstract).Am J Pathol. 1958; 34: 582Google Scholar introduced the term "fibromuscular hyperplasia" when describing three young patients with renovascular hypertension and an unusual type of renal artery stenosis. Initially, the lesion was thought to be confined to the renal artery. Later, however, it became obvious that other arteries, such as the carotid and vertebral,4Connett MC Lansche JM Fibromuscular hyperplasia of the internal carotid artery: report of a case.Ann Surg. 1965; 162: 59-62Crossref PubMed Google Scholar, 5Mettinger KL Ericson K Fibromuscular dysplasia and the brain: observations on angiographic, clinical and genetic characteristics.Stroke. 1982; 13: 46-52Crossref PubMed Google Scholar, 6Lüscher T Vetter H Studer A Kuhlmann U Pouliadis G Schmidt I Siegenthaler W Vetter W Extrarenaler Gefässbefall bei fibromuskulär bedingter renovaskulärer Hypertonie.Klin Wochenschr. 1980; 58: 493-500Crossref PubMed Scopus (1) Google Scholar the subclavian and axillary,6Lüscher T Vetter H Studer A Kuhlmann U Pouliadis G Schmidt I Siegenthaler W Vetter W Extrarenaler Gefässbefall bei fibromuskulär bedingter renovaskulärer Hypertonie.Klin Wochenschr. 1980; 58: 493-500Crossref PubMed Scopus (1) Google Scholar, 7Garrett HE Hodosh S DeBakey ME Fibromuscular hyperplasia of the left axillary artery.Arch Surg. 1967; 94: 737-738Crossref PubMed Google Scholar the mesenteric, hepatic, and splenic,6Lüscher T Vetter H Studer A Kuhlmann U Pouliadis G Schmidt I Siegenthaler W Vetter W Extrarenaler Gefässbefall bei fibromuskulär bedingter renovaskulärer Hypertonie.Klin Wochenschr. 1980; 58: 493-500Crossref PubMed Scopus (1) Google Scholar, 8Wylie EJ Binkley FM Palubinskas AJ Extrarenal fibromuscular hyperplasia.Am J Surg. 1966; 112: 149-154Abstract Full Text PDF PubMed Google Scholar, 9Patchefsky AS Paplanus SH Fibromuscular hyperplasia and dissecting aneurysm of the hepatic artery.Arch Pathol. 1967; 83: 141-144PubMed Google Scholar and the iliac,6Lüscher T Vetter H Studer A Kuhlmann U Pouliadis G Schmidt I Siegenthaler W Vetter W Extrarenaler Gefässbefall bei fibromuskulär bedingter renovaskulärer Hypertonie.Klin Wochenschr. 1980; 58: 493-500Crossref PubMed Scopus (1) Google Scholar could be involved as well. An association between FMD and coarctation of the abdominal aorta has also been described in a few cases.6Lüscher T Vetter H Studer A Kuhlmann U Pouliadis G Schmidt I Siegenthaler W Vetter W Extrarenaler Gefässbefall bei fibromuskulär bedingter renovaskulärer Hypertonie.Klin Wochenschr. 1980; 58: 493-500Crossref PubMed Scopus (1) Google Scholar, 10Connolly JE Fibromuscular hyperplasia of the abdominal aorta.J Cardiovasc Surg (Torino). 1978; 19: 563-566PubMed Google Scholar Coronary FMD seems to be extremely rare.11Hill LD Antonius JI Arterial dysplasia: an important surgical lesion.Arch Surg. 1965; 90: 585-595Crossref PubMed Google Scholar Although FMD is thought to be strictly an arterial disease, involvement of the renal veins was confirmed in one patient with FMD of the renal artery.12Rosenberger A Adler O Lichtig H Angiographic appearance of the renal vein in a case of fibromuscular hyperplasia of the artery.Radiology. 1976; 118: 579-580PubMed Google Scholar Information about the prevalence of FMD in patients with vascular disease is incomplete. In the hypertensive population, high blood pressure may be attributable to renovascular FMD in fewer than 2% of the patients.13Youngberg SP Sheps SG Strong CG Fibromuscular disease of the renal arteries.Med Clin North Am. May 1977; 61: 623-641PubMed Google Scholar In patients with renovascular hypertension, FMD is the underlying cause in 20 to 50%.14Simon N Franklin SS Bleifer KH Maxwell MH Clinical characteristics of renovascular hypertension.JAMA. 1972; 220: 1209-1218Crossref PubMed Google Scholar, 15Lüscher TF Vetter H Studer A Pouliadis G Kuhlmann U Glänzer K Largiadèr F Hauri D Greminger P Siegenthaler W Vetter W Renal venous renin activity in various forms of curable renal hypertension.Clin Nephrol. 1981; 15: 314-320PubMed Google Scholar, 16Sos TA Pickering TG Sniderman K Saddekni S Case DB Silane MF Vaughan Jr, ED Laragh JH Percutaneous transluminal renal angioplasty in renovascular hypertension due to atheroma or fibromuscular dysplasia.N Engl J Med. 1983; 309: 274-279Crossref PubMed Google Scholar FMD of the renal artery has also been found in healthy renal transplant donors.13Youngberg SP Sheps SG Strong CG Fibromuscular disease of the renal arteries.Med Clin North Am. May 1977; 61: 623-641PubMed Google Scholar In an autopsy study of 819 consecutive examinations, 9 instances of renovascular FMD were found, an incidence of about 1%.17Heffelfinger MJ Holley KE Harrison Jr, EG Hunt JC Arterial fibromuscular dysplasia studied at autopsy (abstract).Am J Clin Pathol. 1970; 54: 274Google Scholar In patients undergoing carotid angiography, FMD was present in 0.25 to 1%.5Mettinger KL Ericson K Fibromuscular dysplasia and the brain: observations on angiographic, clinical and genetic characteristics.Stroke. 1982; 13: 46-52Crossref PubMed Google Scholar, 13Youngberg SP Sheps SG Strong CG Fibromuscular disease of the renal arteries.Med Clin North Am. May 1977; 61: 623-641PubMed Google Scholar, 18Houser OW Baker Jr, HL Sandok BA Holley KE Cephalic arterial fibromuscular dysplasia.Radiology. 1971; 101: 605-611PubMed Google Scholar, 19Corrin LS Sandok BA Houser OW Cerebral ischemic events in patients with carotid artery fibromuscular dysplasia.Arch Neurol. 1981; 38: 616-618Crossref PubMed Google Scholar More than 1,400 patients with FMD in various vascular beds have been described in the literature.5Mettinger KL Ericson K Fibromuscular dysplasia and the brain: observations on angiographic, clinical and genetic characteristics.Stroke. 1982; 13: 46-52Crossref PubMed Google Scholar Most (60 to 75%) of these patients had renovascular disease at the time of initial examination. Cerebrovascular FMD constitutes 25 to 30% of the published cases.5Mettinger KL Ericson K Fibromuscular dysplasia and the brain: observations on angiographic, clinical and genetic characteristics.Stroke. 1982; 13: 46-52Crossref PubMed Google Scholar, 18Houser OW Baker Jr, HL Sandok BA Holley KE Cephalic arterial fibromuscular dysplasia.Radiology. 1971; 101: 605-611PubMed Google Scholar, 19Corrin LS Sandok BA Houser OW Cerebral ischemic events in patients with carotid artery fibromuscular dysplasia.Arch Neurol. 1981; 38: 616-618Crossref PubMed Google Scholar Similarly, in a study done at one institution, renovascular FMD was found in 75% and cerebrovascular FMD in 24% of 92 patients.1Lüscher TF Keller HM Imhof HG Greminger P Kuhlmann U Largiadèr F Schneider E Schneider J Vetter W Fibromuscular hyperplasia: extension of the disease and therapeutic outcome; results of the University Hospital Zurich Cooperative Study on Fibromuscular Hyperplasia.Nephron. 1986; 44: 109-114PubMed Google Scholar In this series, multivessel involvement seemed common (24%). In 9% of the patients, the mesenteric or subclavian arteries were involved as well, and 5% had FMD of the iliac arteries (Fig. 1). Systemic FMD involving the renal, mesenteric, iliac, and carotid arteries has been reported by others.6Lüscher T Vetter H Studer A Kuhlmann U Pouliadis G Schmidt I Siegenthaler W Vetter W Extrarenaler Gefässbefall bei fibromuskulär bedingter renovaskulärer Hypertonie.Klin Wochenschr. 1980; 58: 493-500Crossref PubMed Scopus (1) Google Scholar, 13Youngberg SP Sheps SG Strong CG Fibromuscular disease of the renal arteries.Med Clin North Am. May 1977; 61: 623-641PubMed Google Scholar, 20Claiborne TS Fibromuscular hyperplasia: report of a case with involvement of multiple arteries.Am J Med. 1970; 49: 103-105Abstract Full Text PDF PubMed Google Scholar, 21Chen W-Y Lin J-T Hsieh B-S Yen T-S Su C-T Tang S-S Lien W-P Renal and extrarenal arterial fibromuscular hyperplasia with hypertension.NZ Med J. 1983; 96: 846-848Google Scholar A pathologic classification of FMD was proposed by Harrison and McCormack22Harrison Jr, EG McCormack LJ Pathologic classification of renal arterial disease in renovascular hypertension.Mayo Clin Proc. 1971; 46: 161-167PubMed Google Scholar in 1971 and was revised by Stanley and colleagues23Stanley JC Gewertz BL Bove EL Sottiurai V Fry WJ Arterial fibrodysplasia: histopathologic character and current etiologic concepts.Arch Surg. 1975; 110: 561-566Crossref PubMed Google Scholar in 1975. The histologic classification is based on the predominant site of dysplasia in the arterial wall: the intima, media, or adventitia (Fig. 2). Hence, three main types of FMD have been identified—intimal fibroplasia, medial FMD, and periarterial or periadventitial fibroplasia. Lesions involving the medial layer of the artery may be further subdivided into medial fibroplasia, perimedial fibroplasia, and medial hyperplasia.22Harrison Jr, EG McCormack LJ Pathologic classification of renal arterial disease in renovascular hypertension.Mayo Clin Proc. 1971; 46: 161-167PubMed Google Scholar Originally, medial dissection had been considered a fourth subtype of medial FMD. Medial dissections, aneurysms, and arteriovenous fistulas, however, are complications of FMD and should not be classified as separate or distinct pathologic entities. Although this classification has been introduced for renovascular FMD, most types of the disorder have also been noted in other vascular beds23Stanley JC Gewertz BL Bove EL Sottiurai V Fry WJ Arterial fibrodysplasia: histopathologic character and current etiologic concepts.Arch Surg. 1975; 110: 561-566Crossref PubMed Google Scholar (Fig. 3). This classification has the advantage of showing an excellent correlation between the angiographic appearance and the pathologic findings.24McCormack LJ Poutasse EF Meaney TF Noto Jr, TJ Dustan HP A pathologic-arteriographic correlation of renal arterial disease.Am Heart J. 1966; 72: 188-198Abstract Full Text PDF PubMed Google Scholar, 25Osborn AG Anderson RE Angiographic spectrum of cervical and intracranial fibromuscular dysplasia.Stroke. 1977; 8: 617-626Crossref PubMed Google ScholarFig. 3Angiograms of medial fibroplasia in renal (A), internal carotid (B), and external iliac (C) arteries. Note typical string-of-beads stenoses.View Large Image Figure ViewerDownload (PPT) Among the three main fibromuscular vascular lesions, medial FMD is the most frequent type. The most common subtype, accounting for 70 to 95% of all fibromuscular vascular lesions, is medial fibroplasia. The angiographic appearance of this lesion is the classic string-of-beads stenoses (Fig. 3). Typically, the "beads" exceed the diameter of the proximal unaffected part of the artery. Multifocal thickened fibromuscular ridges alternating with areas of pronounced thinning of the vascular wall give rise to this phenomenon (Fig. 4). In the renal artery, the distal two-thirds is typically involved (Fig. 3 A). Often, the lesion extends into the branch arteries. In the cerebrovascular circulation, this type of FMD characteristically affects the internal carotid artery at the level of the C-1 and C-2 vertebrae, sparing the origins and proximal segments of the major extracranial arteries5Mettinger KL Ericson K Fibromuscular dysplasia and the brain: observations on angiographic, clinical and genetic characteristics.Stroke. 1982; 13: 46-52Crossref PubMed Google Scholar, 18Houser OW Baker Jr, HL Sandok BA Holley KE Cephalic arterial fibromuscular dysplasia.Radiology. 1971; 101: 605-611PubMed Google Scholar, 25Osborn AG Anderson RE Angiographic spectrum of cervical and intracranial fibromuscular dysplasia.Stroke. 1977; 8: 617-626Crossref PubMed Google Scholar (Fig. 3 B). This classic type of FMD also has been noted in the iliac1Lüscher TF Keller HM Imhof HG Greminger P Kuhlmann U Largiadèr F Schneider E Schneider J Vetter W Fibromuscular hyperplasia: extension of the disease and therapeutic outcome; results of the University Hospital Zurich Cooperative Study on Fibromuscular Hyperplasia.Nephron. 1986; 44: 109-114PubMed Google Scholar, 6Lüscher T Vetter H Studer A Kuhlmann U Pouliadis G Schmidt I Siegenthaler W Vetter W Extrarenaler Gefässbefall bei fibromuskulär bedingter renovaskulärer Hypertonie.Klin Wochenschr. 1980; 58: 493-500Crossref PubMed Scopus (1) Google Scholar (Fig. 3 C), axillary,7Garrett HE Hodosh S DeBakey ME Fibromuscular hyperplasia of the left axillary artery.Arch Surg. 1967; 94: 737-738Crossref PubMed Google Scholar and, in one patient, the epicardial coronary26Lie JT Berg KK Isolated fibromuscular dysplasia of the coronary arteries with spontaneous dissection and myocardial infarction.Hum Pathol. 1987; 18: 654-656Abstract Full Text PDF PubMed Google Scholar arteries. In the subtype perimedial fibroplasia, some angiographic characteristics of string-of-beads stenoses may be evident. The "beads," however, are usually less numerous than in medial fibroplasia and are smaller in diameter than the proximal unaffected part of the artery24McCormack LJ Poutasse EF Meaney TF Noto Jr, TJ Dustan HP A pathologic-arteriographic correlation of renal arterial disease.Am Heart J. 1966; 72: 188-198Abstract Full Text PDF PubMed Google Scholar (Fig. 5). Histologically, this type of FMD is characterized by extensive fibroplasia of the outer half of the media, and the external elastic membrane often is effaced22Harrison Jr, EG McCormack LJ Pathologic classification of renal arterial disease in renovascular hypertension.Mayo Clin Proc. 1971; 46: 161-167PubMed Google Scholar (Fig. 6). It is found almost exclusively in women younger than 30 years of age who have right-sided renal artery stenosis, substantial collateral circulation, and hypertension. Clinically significant types of this lesion have been detected almost exclusively in the renal circulation. In the subtype medial hyperplasia, excessive medial smooth muscle without associated fibrosis causes focal concentric stenoses. The stenosis is usually subtotal, sometimes tubular, and smooth. In the renal artery, it typically involves the middle or distal part and does not affect branchings and segmental vessels. In the internal carotid artery, the lesion is characteristically found at the C1-2 interspace. This unusual type of FMD probably accounts for fewer than 5% of fibroplastic stenoses.22Harrison Jr, EG McCormack LJ Pathologic classification of renal arterial disease in renovascular hypertension.Mayo Clin Proc. 1971; 46: 161-167PubMed Google Scholar, 23Stanley JC Gewertz BL Bove EL Sottiurai V Fry WJ Arterial fibrodysplasia: histopathologic character and current etiologic concepts.Arch Surg. 1975; 110: 561-566Crossref PubMed Google Scholar Intimal fibroplasia is angiographically indistinguishable from medial hyperplasia (Fig. 7 A and C). Histologically, it is characterized by a circumferential or eccentric accumulation of fibrous tissue in the intima (Fig. 6). The internal elastic lamina is always identifiable.23Stanley JC Gewertz BL Bove EL Sottiurai V Fry WJ Arterial fibrodysplasia: histopathologic character and current etiologic concepts.Arch Surg. 1975; 110: 561-566Crossref PubMed Google Scholar In contrast to other vascular diseases involving the intima, no inflammatory or lipid component is present, unless superimposed arteriosclerotic changes develop.22Harrison Jr, EG McCormack LJ Pathologic classification of renal arterial disease in renovascular hypertension.Mayo Clin Proc. 1971; 46: 161-167PubMed Google Scholar Both sexes seem to be affected with equal frequency. The lesion accounts for 1 to 5% of all fibromuscular arterial lesions.22Harrison Jr, EG McCormack LJ Pathologic classification of renal arterial disease in renovascular hypertension.Mayo Clin Proc. 1971; 46: 161-167PubMed Google Scholar, 23Stanley JC Gewertz BL Bove EL Sottiurai V Fry WJ Arterial fibrodysplasia: histopathologic character and current etiologic concepts.Arch Surg. 1975; 110: 561-566Crossref PubMed Google Scholar In young patients, long tubular stenoses are more common, whereas smooth focal stenoses predominate in older patients.23Stanley JC Gewertz BL Bove EL Sottiurai V Fry WJ Arterial fibrodysplasia: histopathologic character and current etiologic concepts.Arch Surg. 1975; 110: 561-566Crossref PubMed Google Scholar True idiopathic intimal hyperplasia is rare and morphologically indistinguishable from atherosclerotic intimal fibrosis. The rarest type of FMD is periarterial fibroplasia. In this disease, fibroplasia with collagen encompasses the adventitia and extends into the surrounding tissue (Fig. 6). Slight focal infiltration with lymphocytes and plasma cells may be present.22Harrison Jr, EG McCormack LJ Pathologic classification of renal arterial disease in renovascular hypertension.Mayo Clin Proc. 1971; 46: 161-167PubMed Google Scholar The differential diagnosis of FMD includes arteriosclerosis, inflammatory vascular diseases such as Takayasu's arteritis, and vascular lesions of neurofibromatosis. Certain types of hereditary connective tissue diseases, such as Ehlers-Danlos syndrome, may angiographically mimic the aneurysmal type of FMD.27Lüscher TF Essandoh LK Lie JT Hollier LH Sheps SG Renovascular hypertension: a rare cardiovascular manifestation of the Ehlers-Danlos syndrome.Mayo Clin Proc. 1987; 62: 223-229Abstract Full Text Full Text PDF PubMed Google Scholar FMD is a histologic diagnosis; however, the diagnosis can be made with a high degree of accuracy on the basis of the angiographic appearance. Classic string-of-beads stenoses are consistent with FMD (Fig. 3). Both intimal and medial hyperplasia, however, may sometimes be confused with atherosclerotic plaques on an angiogram. Atherosclerotic stenoses are usually located within 1 cm of the orifice of the main renal or internal carotid artery and are typically eccentric. Furthermore, atherosclerotic renal artery stenoses are often associated with atherosclerotic changes in the abdominal aorta. FMD almost always involves the middle or distal segment of the renal or carotid artery, and the focal stenoses are concentric and typically have a smooth appearance. In their active stage, inflammatory vascular diseases usually are accompanied by laboratory evidence of inflammation.28Sheps SG McDuffie FC Vasculitis.in: Juergens JL Spittell Jr, JA Fairbairn II, JF Allen-Barker-Hines Peripheral Vascular Diseases. Fifth edition. WB Saunders Company, Philadelphia1980: 493-553Google Scholar Takayasu's arteritis has a different pattern of arterial involvement than FMD. In this arteritis, the aorta is almost always involved, and the large arteries are stenotic or, rarely, aneurysmal at and near their origin. Other types of vasculitis involve different and smaller arteries than those affected in FMD.26Lie JT Berg KK Isolated fibromuscular dysplasia of the coronary arteries with spontaneous dissection and myocardial infarction.Hum Pathol. 1987; 18: 654-656Abstract Full Text PDF PubMed Google Scholar Patients with hereditary connective tissue disorders may have aneurysms of major arteries similar to those of FMD.27Lüscher TF Essandoh LK Lie JT Hollier LH Sheps SG Renovascular hypertension: a rare cardiovascular manifestation of the Ehlers-Danlos syndrome.Mayo Clin Proc. 1987; 62: 223-229Abstract Full Text Full Text PDF PubMed Google Scholar Patients with Ehlers-Danlos syndrome have characteristic clinical signs such as joint laxity and increased skin elasticity. Neurofibromatosis may be associated with stenoses at the orifice of the renal, celiac, and superior mesenteric arteries and, less frequently, with narrowing of the abdominal aorta.29Reubi F Neurofibromatose et lésions vasculaires.Schweiz Med Wochenschr. 1945; 75: 463-465Google Scholar, 30Halpern M Currarino G Vascular lesions causing hypertension in neurofibromatosis.N Engl J Med. 1965; 273: 248-252Crossref Google Scholar, 31Allan TNK Davies ER Neurofibromatosis of the renal artery.Br J Radiol. 1970; 43: 906-908Crossref PubMed Google Scholar The proximal site of the arterial involvement, along with stigmas of neurofibromatosis of the skin and bones, which are almost always present, helps to distinguish this disease from FMD. Congenital abdominal coarctation also may be associated with proximal renal artery stenosis. Progression of FMD has been confirmed on repeated angiograms in a substantial number of patients with renovascular disease. Meaney and co-workers32Meaney TF Dustan HP McCormack LJ Natural history of renal arterial disease.Radiology. 1968; 91: 881-887PubMed Google Scholar reported that during an observation period of 6 months to 10 years, renovascular disease progressed in 36% of patients with atherosclerosis but in only 16% of those with FMD. In a Mayo Clinic series, during a mean observation period of 3 years, FMD of the renal arteries progressed in 35% of the patients.33Sheps SG Kincaid OW Hunt JC Serial renal function and angiographic observations in idiopathic fibrous and fibromuscular stenoses of the renal arteries.Am J Cardiol. 1972; 30: 55-60Abstract Full Text PDF PubMed Google Scholar Progression was more common in older patients with focal or tubular stenoses than in those with medial fibroplasia. Similarly, Kincaid and associates34Kincaid OW Davis GD Hallermann FJ Hunt JC Fibromuscular dysplasia of the renal arteries: arteriographic features, classification, and observations on natural history of the disease.Am J Roentgenol. 1968; 104: 271-282Crossref Google Scholar and Pohl and Novick35Pohl MA Novick AC Natural history of atherosclerotic and fibrous renal artery disease: clinical implications.Am J Kidney Dis. 1985; 5: A120-A130PubMed Google Scholar observed progression of renovascular FMD in 36% and 38% of their patients, respectively; no patient had progression of the disease to occlusion of vessels. Development of hypertension has been noted in previously normotensive patients with fibromuscular changes of the renal artery.36Felts JH Whitley NO Johnston FR Progression of medial fibroplasia of the renal artery and the development of renovascular hypertension.Nephron. 1979; 24: 89-90Crossref PubMed Google Scholar Spontaneous reversal of fibromuscular vascular lesions with reversal of hypertension may occur in very rare instances.37Siegler RL Miller FJ Mineau DE Moatamed F Spontaneous reversal of hypertension caused by fibromuscular dysplasia.J Pediatr. 1982; 100: 83-85Abstract Full Text PDF PubMed Google Scholar In patients with renovascular hypertension, the natural history of FMD may be influenced by the development of superimposed arteriosclerotic vascular lesions. Also, smoking is particularly common in patients with renovascular FMD and may affect the natural history of the disease.38Nicholson JP Teichman SL Alderman MH Sos TA Pickering TG Laragh JH Cigarette smoking and renovascular hypertension.Lancet. 1983; 2: 765-766Abstract PubMed Scopus (0) Google Scholar In patients with cerebrovascular FMD, Corrin and colleagues19Corrin LS Sandok BA Houser OW Cerebral ischemic events in patients with carotid artery fibromuscular dysplasia.Arch Neurol. 1981; 38: 616-618Crossref PubMed Google Scholar noted subsequent cerebral ischemic events after the initial angiogram in only 3 of 79 patients during a mean observation period of 5 years. Although this assessment of the natural history of the disease is clinical rather than angiographic, progression seems to be less pronounced in cerebrovascular than in renovascular FMD. In part, this outcome might be related to the high incidence of hypertension among patients with renovascular FMD. The cause of FMD remains unknown. Several hypotheses on the pathogenesis have been proposed. The most important concepts are (1) the humoral hypothesis, in which involvement of the female sex hormones has been suggested; (2) the mechanical hypothesis, in which the importance of trauma or repeated microtrauma has been emphasized; (3) the genetic hypothesis; and (4) the hypothesis of ischemia of the blood vessel wall. It is unlikely that all subtypes of FMD have the same underlying cause. In most series of patients with FMD, a preponderance of female over male patients has been noted.1Lüscher TF Keller HM Imhof HG Greminger P Kuhlmann U Largiadèr F Schneider E Schneider J Vetter W Fibromuscular hyperplasia: extension of the disease and therapeutic outcome; results of the University Hospital Zurich Cooperative Study on Fibromuscular Hyperplasia.Nephron. 1986; 44: 109-114PubMed Google Scholar, 4Connett MC Lansche JM Fibromuscular hyperplasia of the internal carotid artery: report of a case.Ann Surg. 1965; 162: 59-62Crossref PubMed Google Scholar, 6Lüscher T Vetter H Studer A Kuhlmann U Pouliadis G Schmidt I Siegenthaler W Vetter W Extrarenaler Gefässbefall bei fibromuskulär bedingter renovaskulärer Hypertonie.Klin Wochenschr. 1980; 58: 493-500Crossref PubMed Scopus (1) Google Scholar, 7Garrett HE Hodosh S DeBakey ME Fibromuscular hyperplasia of the left axillary artery.Arch Surg. 1967; 94: 737-738Crossref PubMed Google Scholar, 14Simon N Franklin SS Bleifer KH Maxwell MH Clinical characteristics of renovascular hypertension.JAMA. 1972; 220: 1209-1218Crossref PubMed Google Scholar, 15Lüscher TF Vetter H Studer A Pouliadis G Kuhlmann U Glänzer K Largiadèr F Hauri D Greminger P Siegenthaler W Vetter W Renal venous renin activity in various forms of curable renal hypertension.Clin Nephrol. 1981; 15: 314-320PubMed Google Scholar Typically, women in the childbearing ages are affected. In one series of cerebrovascular incidents among patients taking oral contraceptives, radiologic features consistent with FMD were found in 18% of the patients.39Hardy-Godon S Fredy D Chodkiewicz JP Perez J Bories J Angiography of cerebrovascular accidents in patients taking contraceptive pills: an analysis of 85 cases.J Neuroradiol. 1979; 6: 239-254PubMed Google Scholar Oral contraceptives may cause intimal hyperplasia.40Irey NS Manion WC Taylor HB Vascular lesions in women taking oral contraceptives.Arch Pathol. 1970; 89: 1-8PubMed Google Scholar During pregnancy, alterations of the vascular media and the elastic tissue may occur.41Manalo-Estrella P Barker AE Histopathologic findings in human aortic media associated with pregnancy: a study of 16 cases.Arch Pathol. 1967; 83: 336-341PubMed Google Scholar Some smooth muscle cells and fibroblasts increase the production of collagen after exposure to estrogen in vitro.42Ross R Klebanoff SJ The smooth muscle cell. I. In vivo synthesis of connective tissue proteins.J Cell Biol. 1971; 50: 159-171Crossref PubMed Google Scholar In patients with FMD, however, gravidity and parity rates do not differ from those in the general population. Also, pregnancy does not seem to worsen the natur