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Endocrinology and Metabolism Clinics of... Dec 2019Renovascular disease (RVD) is a major cause of secondary hypertension. Atherosclerotic renal artery stenosis is the most common type of RVD followed by fibromuscular... (Review)
Review
Renovascular disease (RVD) is a major cause of secondary hypertension. Atherosclerotic renal artery stenosis is the most common type of RVD followed by fibromuscular dysplasia. It has long been recognized as the prototype of angiotensin-dependent hypertension. However, the mechanisms underlying the physiopathology of hypertensive occlusive vascular renal disease are complex and distinction between the different causes of RVD should be made. Recognition of these distinct types of RVD with different degrees of renal occlusive disease is important for management. The greatest challenge is to individualize and implement the best approach for each patient in the setting of widely different comorbidities.
Topics: Fibromuscular Dysplasia; Humans; Hypertension, Renal; Hypertension, Renovascular; Nephritis; Renal Artery Obstruction
PubMed: 31655775
DOI: 10.1016/j.ecl.2019.08.007 -
Journal of the American College of... Oct 2022Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI) in young to middle-aged women. (Observational Study)
Observational Study
BACKGROUND
Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI) in young to middle-aged women.
OBJECTIVES
We aim to define the long-term natural history of SCAD.
METHODS
We performed a multicenter, prospective, observational study of patients with nonatherosclerotic SCAD presenting acutely from 22 North American centers. We recorded baseline demographics, in-hospital characteristics, precipitating and predisposing conditions, angiographic features (adjudicated), in-hospital and 3-year major adverse cardiovascular events (MACE). Cox regression multivariable analysis was performed.
RESULTS
We prospectively enrolled 750 consecutive patients with SCAD from June 2014 to June 2018. Mean age was 51.7 ± 10.5 years, 88.5% were women (55.0% postmenopausal); 31.3% presented with ST-segment elevation myocardial infarction, and 68.3% with non-ST-segment elevation myocardial infarction. Precipitating emotional stressor was reported in 50.3%, and physical stressor in 28.9%. Predisposing conditions included fibromuscular dysplasia in 42.9% (56.4% in those with complete screening), peripartum state 4.5%, and genetic disorders 1.6%. Most patients were treated conservatively (84.3%); 14.1% underwent percutaneous coronary intervention (PCI), 0.7% coronary artery bypass graft. At 3.0-year median follow-up, mortality was 0.8%, recurrent MI 9.9% (extension of previous SCAD 3.5%, de novo recurrent SCAD 2.4%, iatrogenic dissection 1.9%), with overall MACE 14.0%. Presence of genetic disorders, peripartum SCAD, and extracoronary fibromuscular dysplasia were independent predictors of 3-year MACE. Patients who underwent PCI at index hospitalization had similar postdischarge MACE compared with no PCI. At 3 years, 80.0% remained on aspirin and 73.5% on beta-blockade.
CONCLUSIONS
Long-term mortality and de novo recurrent SCAD was low in our contemporary large SCAD cohort that included low revascularization rate and high use of beta-blockade and aspirin. Genetic disorders, extracoronary fibromuscular dysplasia, and peripartum SCAD were independent predictors of long-term MACE.
Topics: Humans; Middle Aged; Female; Adult; Male; Fibromuscular Dysplasia; Cohort Studies; Coronary Vessels; Prospective Studies; Aftercare; Coronary Angiography; Canada; Patient Discharge; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Aspirin
PubMed: 36265953
DOI: 10.1016/j.jacc.2022.08.759 -
International Journal of Molecular... May 2018Fibromuscular Dysplasia (FMD) is “an idiopathic, segmental, non-atherosclerotic and non-inflammatory disease of the musculature of arterial walls, leading to... (Review)
Review
Fibromuscular Dysplasia (FMD) is “an idiopathic, segmental, non-atherosclerotic and non-inflammatory disease of the musculature of arterial walls, leading to stenosis of small and medium-sized arteries” (Persu, et al; 2014). FMD can lead to hypertension, arterial dissections, subarachnoid haemorrhage, stroke or mesenteric ischemia. The pathophysiology of the disease remains elusive. While familial cases are rare (<5%) in contemporary FMD registries, there is evidence in favour of the existence of multiple genetic factors involved in this vascular disease. Recent collaborative efforts allowed the identification of a first genetic locus associated with FMD. This intronic variant located in the phosphatase and actin regulator 1 gene () may influence the transcription activity of the endothelin-1 gene () located nearby on chromosome 6. Interestingly, the locus has also been involved in vascular hypertrophy in normal subjects, carotid dissection, migraine and coronary artery disease. National and international registries of FMD patients, with deep and harmonised phenotypic and genetic characterisation, are expected to be instrumental to improve our understanding of the genetic basis and pathophysiology of this intriguing vascular disease.
Topics: Animals; Endothelin-1; Fibromuscular Dysplasia; Genetic Loci; Genetic Predisposition to Disease; Genomics; Humans; Microfilament Proteins; Transcriptional Activation
PubMed: 29883369
DOI: 10.3390/ijms19051526 -
CVIR Endovascular Jan 2021Paediatric hypertension, defined as systolic blood pressure > 95th percentile for age, sex and height is often incidentally diagnosed. Renovascular hypertension... (Review)
Review
Paediatric hypertension, defined as systolic blood pressure > 95th percentile for age, sex and height is often incidentally diagnosed. Renovascular hypertension (RVH) is responsible for 5-25% of hypertension in children. Renal artery stenosis and middle aortic syndrome can both can be associated with various conditions such as fibromuscular dysplasia, Williams syndrome & Neurofibromatosis type 1. This paper discusses the approaches to diagnosis and interventional management and outcomes of renovascular hypertension in children. Angiography is considered the gold standard in establishing the diagnosis of renovascular disease in children. Angioplasty is beneficial in the majority of patients and generally repeated angioplasty is considered more appropriate than stenting. Surgical options should first be considered before placing a stent unless there is an emergent requirement. Given the established safety and success of endovascular intervention, at most institutions it remains the preferred treatment option.
PubMed: 33411105
DOI: 10.1186/s42155-020-00176-5 -
Circulation. Genomic and Precision... Dec 2022The risk of arterial diseases may be elevated among family members of individuals having multifocal fibromuscular dysplasia (FMD). We sought to investigate the risk of...
BACKGROUND
The risk of arterial diseases may be elevated among family members of individuals having multifocal fibromuscular dysplasia (FMD). We sought to investigate the risk of arterial diseases in families of individuals with FMD.
METHODS
Family histories for 73 probands with FMD were obtained, which included an analysis of 463 total first-degree relatives focusing on FMD and related arterial disorders. A polygenic risk score for FMD (PRS) was constructed from prior genome-wide association findings of 584 FMD cases and 7139 controls and evaluated for association with an abdominal aortic aneurysm (AAA) in a cohort of 9693 AAA cases and 294 049 controls. A previously published PRS was also assessed among the FMD cases and controls.
RESULTS
Of all first degree relatives of probands, 9.3% were diagnosed with FMD, aneurysms, and dissections. Aneurysmal disease occurred in 60.5% of affected relatives and 5.6% of all relatives. Among 227 female first-degree relatives of probands, 4.8% (11) had FMD, representing a relative risk (RR) of 1.5 ([95% CI, 0.75-2.8]; =0.19) compared with the estimated population prevalence of 3.3%, though not of statistical significance. Of all fathers of FMD probands, 11% had AAAs resulting in a RR of 2.3 ([95% CI, 1.12-4.6]; =0.014) compared with population estimates. The PRS was found to be associated with an AAA (odds ratio, 1.03 [95% CI, 1.01-1.05]; =2.6×10), and the PRS was found to be associated with FMD (odds ratio, 1.53 [95% CI, 1.2-1.9]; =9.0×10) as well.
CONCLUSIONS
FMD and AAAs seem to be sex-dimorphic manifestations of a heritable arterial disease with a partially shared complex genetic architecture. Excess risk of having an AAA according to a family history of FMD may justify screening in family members of individuals having FMD.
Topics: Male; Humans; Female; Fibromuscular Dysplasia; Genome-Wide Association Study; Aortic Aneurysm, Abdominal; Arteries; Risk Factors
PubMed: 36374587
DOI: 10.1161/CIRCGEN.121.003496 -
Nature Communications Oct 2021Fibromuscular dysplasia (FMD) is an arteriopathy associated with hypertension, stroke and myocardial infarction, affecting mostly women. We report results from the first... (Meta-Analysis)
Meta-Analysis
Fibromuscular dysplasia (FMD) is an arteriopathy associated with hypertension, stroke and myocardial infarction, affecting mostly women. We report results from the first genome-wide association meta-analysis of six studies including 1556 FMD cases and 7100 controls. We find an estimate of SNP-based heritability compatible with FMD having a polygenic basis, and report four robustly associated loci (PHACTR1, LRP1, ATP2B1, and LIMA1). Transcriptome-wide association analysis in arteries identifies one additional locus (SLC24A3). We characterize open chromatin in arterial primary cells and find that FMD associated variants are located in arterial-specific regulatory elements. Target genes are broadly involved in mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, central to vascular contraction. We find significant genetic overlap between FMD and more common cardiovascular diseases and traits including blood pressure, migraine, intracranial aneurysm, and coronary artery disease.
Topics: Adult; Arteries; Cardiovascular Diseases; Cytoskeletal Proteins; Female; Fibroblasts; Fibromuscular Dysplasia; Gene Expression Regulation; Genome-Wide Association Study; Humans; Intracranial Aneurysm; Low Density Lipoprotein Receptor-Related Protein-1; Male; Microfilament Proteins; Middle Aged; Plasma Membrane Calcium-Transporting ATPases; Sodium-Calcium Exchanger; Transcriptome
PubMed: 34654805
DOI: 10.1038/s41467-021-26174-2 -
Vascular Health and Risk Management 2023Fibromuscular dysplasia (FMD) is a rare idiopathic, segmental, noninflammatory and nonatherosclerotic arteriopathy of medium-sized arteries. It is classically considered... (Review)
Review
Fibromuscular dysplasia (FMD) is a rare idiopathic, segmental, noninflammatory and nonatherosclerotic arteriopathy of medium-sized arteries. It is classically considered to be a disease of young and middle adulthood, with females more commonly affected than males. FMD is a systemic disease. Although historically considered to be rare, cerebrovascular FMD (C-FMD) has now been recognized to be as common as the renovascular counterpart. Extracranial carotid and vertebral arteries are the most commonly involved vascular territories in C-FMD with the clinical presentation determined by vessels affected. Common symptoms include headaches and pulsatile tinnitus, with transient ischemic attacks, ischemic stroke and subarachnoid or intracerebral hemorrhage constituting the more severe clinical manifestations. Cervical artery dissection involving carotids more often than vertebral arteries and intracranial aneurysms account for the cerebrovascular pathologies detected in C-FMD. Our understanding regarding C-FMD has been augmented in the recent past on account of dedicated C-FMD data from North American, European and other international FMD cohorts. In this review article, we provide an updated and comprehensive overview on epidemiology, clinical presentation, etiology, diagnosis and management of C-FMD.
Topics: Female; Male; Humans; Adult; Fibromuscular Dysplasia; Arteries; Headache; Ischemic Attack, Transient; Ischemic Stroke
PubMed: 37664168
DOI: 10.2147/VHRM.S388257 -
Orphanet Journal of Rare Diseases Jun 2007Fibromuscular dysplasia (FMD), formerly called fibromuscular fibroplasia, is a group of nonatherosclerotic, noninflammatory arterial diseases that most commonly involve... (Review)
Review
Fibromuscular dysplasia (FMD), formerly called fibromuscular fibroplasia, is a group of nonatherosclerotic, noninflammatory arterial diseases that most commonly involve the renal and carotid arteries. The prevalence of symptomatic renal artery FMD is about 4/1000 and the prevalence of cervicocranial FMD is probably half that. Histological classification discriminates three main subtypes, intimal, medial and perimedial, which may be associated in a single patient. Angiographic classification includes the multifocal type, with multiple stenoses and the 'string-of-beads' appearance that is related to medial FMD, and tubular and focal types, which are not clearly related to specific histological lesions. Renovascular hypertension is the most common manifestation of renal artery FMD. Multifocal stenoses with the 'string-of-beads' appearance are observed at angiography in more than 80% of cases, mostly in women aged between 30 and 50 years; they generally involve the middle and distal two-thirds of the main renal artery and in some case also renal artery branches. Cervicocranial FMD can be complicated by dissection with headache, Horner's syndrome or stroke, or can be associated with intracerebral aneurysms with a risk of subarachnoid or intracerebral hemorrhage. The etiology of FMD is unknown, although various hormonal and mechanical factors have been suggested. Subclinical lesions are found at arterial sites distant from the stenotic arteries, and this suggests that FMD is a systemic arterial disease. It appears to be familial in 10% of cases. Noninvasive diagnostic tests include, in increasing order of accuracy, ultrasonography, magnetic resonance angiography and computed tomography angiography. The gold standard for diagnosing FMD is catheter angiography, but this invasive procedure is only used for patients in whom it is clinically pertinent to proceed with revascularization during the same procedure. Differential diagnosis include atherosclerotic stenoses and stenoses associated with vascular Ehlers-Danlos and Williams' syndromes, and type 1 neurofibromatosis. Management of cases with renovascular hypertension includes antihypertensive therapy, percutaneous angioplasty of severe stenoses, and reconstructive surgery in cases with complex FMD that extends to segmental arteries. The therapeutic options for securing ruptured intracerebral aneurysms are microvascular neurosurgical clipping and endovascular coiling. Stenosis progression in renal artery FMD is slow and rarely leads to ischemic renal failure.
Topics: Adult; Age Distribution; Aortic Dissection; Angiography; Cardiovascular Agents; Carotid Arteries; Causality; Comorbidity; Diagnosis, Differential; Female; Fibromuscular Dysplasia; Humans; Male; Prevalence; Prognosis; Renal Artery; Sex Distribution; Vascular Diseases
PubMed: 17555581
DOI: 10.1186/1750-1172-2-28