Risks and benefits of renal artery stenting in fibromuscular dysplasia: Lessons from the ARCADIA-POL study.

INTRODUCTION: Although renal stenting is the standard revascularization method for atherosclerotic renal artery stenosis (RAS) (FMD-RAS), stenting in fibromuscular dysplasia (FMD) RAS is usually limited to periprocedural complications of angioplasty and primary arterial dissection. The main aim of the study was to retrospectively analyze the immediate and long-term results of renal stenting versus angioplasty in patients with FMD. METHODS: Of 343 patients in the ARCADIA-POL registry, 58 patients underwent percutaneous treatment due to FMD-RAS (in 70 arteries). Percutaneous transluminal renal angioplasty (PTRA) was performed as an initial treatment in 61 arteries (PTRA-group), whereas primary stenting was undertaken in nine arteries (stent-group). Stent-related complications were defined as: in-stent restenosis > 50% (ISR); stent fracture; under-expansion; or migration. RESULTS: In the PTRA-group, the initial restenosis rate was 50.8%. A second procedure was then performed in 22 arteries: re-PTRA (12 arteries) or stenting (10 arteries). The incidence of recurrent restenosis after re-PTRA was 41.7%. Complications occurred in seven of 10 (70%) arteries secondarily treated by stenting: two with under-expansion and five with ISR. In the stent-group, stent under-expansion occurred in one case (11.1%) and ISR in three of nine stents (33.3%). In combined analysis of stented arteries, either primarily or secondarily, stent-related complications occurred in 11/19 stenting procedures (57.9%): three due to under-expansion and eight due to ISRs. Finally, despite several revascularization attempts, four of 19 (21%) stented arteries were totally occluded and one was significantly stenosed at follow-up imaging. CONCLUSION: Our study indicates that renal stenting in FMD-RAS may carry a high risk of late complications, including stent occlusion. Further observational data from large-scale registries are required.

Psychological determinants of drug adherence and severity of hypertension in patients with apparently treatment-resistant vs. controlled hypertension.

PURPOSE: In a pilot study including 35 patients with apparently treatment-resistant hypertension (ATRH), we documented associations between psychological profile, drug adherence and severity of hypertension. The current study aims to confirm and expand our findings in a larger and more representative sample of patients with ATRH, using controlled hypertensive patients as the comparator. MATERIALS AND METHODS: Patients with ATRH were enrolled in hypertension centres from Brussels and Torino. The psychological profile was assessed using five validated questionnaires. Drug adherence was assessed by high-performance liquid chromatography-tandem mass spectrometry analysis of urine samples, and drug resistance by 24-hour ambulatory blood pressure was adjusted for drug adherence. RESULTS: The study sample totalised 144 patients, including 81 ATRH and 63 controlled hypertensive patients. The mean adherence level was significantly lower in the "resistant" group (78.9% versus 92.7% in controlled patients, p-value = .022). In patients with ATRH, independent predictors of poor drug adherence were somatisation, smoking and low acceptance level of difficult situations, accounting for 41% of the variability in drug adherence. Independent predictors of severity of hypertension were somatisation, smoking, more frequent admissions to the emergency department and low acceptation, accounting for 63% of the variability in the severity of hypertension. In contrast, in patients with controlled hypertension, the single predictors of either drug adherence or severity of hypertension were the number of years of hypertension and, for the severity of hypertension, alcohol consumption, accounting for only 15-20% of the variability. CONCLUSION: Psychological factors, mostly related to somatisation and expression of emotions are strong, independent predictors of both drug adherence and severity of hypertension in ATRH but not in controlled hypertensive patients.

This study included 144 patients with Apparently-Treatment Resistant (ATRH) or controlled Hypertension: Patients with ATRH were more often poorly adherent to antihypertensive treatment than controlled hypertensive patients.In patients with ARTH but not patients with controlled hypertension, psychological traits were strong, independent predictors of drug adherence and severity of hypertension, over and above demographic and health-related factors.In patients with ATRH, the tendency to somatize, i.e. expressing somatic symptoms that cannot be adequately explained by organic findings was the most potent predictor of both poor drug adherence and severity of hypertension.These patients also often presented alterations in the expression of emotions. It may be hypothesised that subjects who have difficulties identifying and expressing emotions with words will express them by physical complaints, and, in the mid-long term, might develop overt diseases.In addition to more classical lifestyle and drug management and irrespective of their drug adherence level, patients with ATRH may benefit in priority from psychological evaluation and interventions. However, this needs to be studied in an interventional trial in the future.

Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease's clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.

A structured physical activity program in an adolescent population with overweight or obesity: a prospective interventional study.

Obesity is a significant health problem, with increasing involvement of young population worldwide. The aim of this study was to evaluate the effects of 2 different types of physical exercise (resistance vs. combined aerobic-resistance) on cardiovascular and anthropometric profile of a sample of sedentary adolescents with overweight and obesity. After undergoing clinical, cardiovascular and anthropometric-metabolic evaluation (T0), subjects with overweight and obesity were randomized to a 6-month resistance or combined aerobic-resistance training program. Clinical, cardiovascular and anthropometric-metabolic evaluations were repeated after 6 months of training (T1) and after 3 months of detraining (T2). Thirty adolescents with overweight/obesity were enrolled and 20 subjects completed training program. A significant improvement in body composition was detected after 6 months, with a reduction of body mass index (32.1 [30.5 to 34.4] vs. 31.1 [29.6 to 33.4] kg/m2, p = 0.02) and adipose tissue (45.5 [41.1 to 49.7] vs. 41.6 [37.0 to 49.2] kg, p < 0.01). A reduction in diastolic blood pressure (75.5 ± 8.9 vs. 68.2 ± 6.4 mm Hg, p = 0.02) and pulse wave velocity (5.7 [5.1 to 5.9] vs. 5.2 [4.7 to 5.7] m/s, p = 0.04) was also observed. Persistence of the effect on the most important parameters was observed also after detraining period. In conclusion, regular physical exercise induces positive metabolic and cardiovascular effects, persisting even after brief discontinuation. Novelty: Physical exercise induces positive effect on cardiovascular risk profile. Positive effects persist also after brief discontinuation. Physical exercise reduces early signs of autonomic disfunction.

Increased Collagen Turnover Is a Feature of Fibromuscular Dysplasia and Associated With Hypertrophic Radial Remodeling: A Pilot, Urine Proteomic Study.

Fibromuscular dysplasia (FMD), a nonatherosclerotic, noninflammatory disease of medium-sized arteries, is an underdiagnosed disease. We investigated the urinary proteome and developed a classifier for discrimination of FMD from healthy controls and other diseases. We further hypothesized that urinary proteomics biomarkers may be associated with alterations in medium-sized, but not large artery geometry and mechanics. The study included 33 patients with mostly multifocal, renal FMD who underwent in depth arterial exploration using ultra-high frequency ultrasound. The cohort was separated in a training set of 23 patients with FMD from Belgium and an independent test set of 10 patients with FMD from Italy. For each set, controls matched 2:1 were selected from the Human Urinary Proteome Database. The specificity of the classifier was tested in 700 additional controls from general population studies, patients with chronic kidney disease (n=66) and coronary artery disease (n=31). Three hundred thirty-five urinary peptides, mostly related to collagen turnover, were identified in the training cohort and combined into a classifier. When applying in the test cohort, the area under the receiver operating characteristic curve was 1.00, 100% specificity at 100% sensitivity. The classifier maintained a high specificity in additional controls (98.3%), patients with chronic kidney (90.9%) and coronary artery (96.8%) diseases. Furthermore, in patients with FMD, the proteomic score was positively associated with radial wall thickness and wall cross-sectional area. In conclusion, a proteomic score has the potential to discriminate between patients with FMD and controls. If confirmed in a wider and more diverse cohort, these findings may pave the way for a noninvasive diagnostic test of FMD.

Prevalence and Disease Spectrum of Extracoronary Arterial Abnormalities in Spontaneous Coronary Artery Dissection.

Importance: Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (FMD) and other extracoronary arterial abnormalities. However, the prevalence, severity, and clinical relevance of these abnormalities remain unclear. Objective: To assess the prevalence and spectrum of FMD and other extracoronary arterial abnormalities in patients with SCAD vs controls. Design, Setting, and Participants: This case series included 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31, 2019. Imaging of extracoronary arterial beds was performed by magnetic resonance angiography (MRA). Forty-one healthy individuals were recruited to serve as controls for blinded interpretation of MRA findings. Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referral from the primary care physician or patient self-referral through an online portal. Participants attended the national SCAD referral center for assessment and MRA. Exposures: Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year). Main Outcome and Measures: The diagnosis of FMD, arterial dissections, and aneurysms was established according to the International FMD Consensus. Arterial tortuosity was assessed both qualitatively (presence or absence of an S curve) and quantitatively (number of curves ≥45%; tortuosity index). Results: Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis was 44.5 (7.9) years. The prevalence of FMD was 31.8% (55 patients); 16 patients (29.1% of patients with FMD) had involvement of multiple vascular beds. Thirteen patients (7.5%) had extracoronary aneurysms and 3 patients (1.7%) had dissections. The prevalence and degree of arterial tortuosity were similar in patients and controls. In 43 patients imaged with both computed tomographic angiography and MRA, the identification of clinically significant remote arteriopathies was similar. Over a median 5-year follow-up, there were 2 noncardiovascular-associated deaths and 35 recurrent myocardial infarctions, but there were no primary extracoronary vascular events. Conclusions and Relevance: In this case series with blinded analysis of patients with SCAD, severe multivessel FMD, aneurysms, and dissections were infrequent. The findings of this study suggest that, although brain-to-pelvis imaging allows detection of remote arteriopathies that may require follow-up, extracoronary vascular events appear to be rare.

Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases.

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.

Intrarenal hemodynamics and kidney function in pheochromocytoma and paraganglioma before and after surgical treatment.

PURPOSE: Current evidence regarding renal involvement in pheochromocytoma and paraganglioma (PPGL) is scant. More accurate diagnostic methods, such as renal Doppler ultrasound for intrarenal hemodynamic studies, may provide more detailed information on renal function. It might be postulated that renal function in PPGL patients might be altered by high blood pressure and excess secretion of catecholamines. The aim of this prospective study was to assess intrarenal blood flow parameters in PPGL patients included in the prospective monoamine-producing tumour (PMT) study and to evaluate the effects of normalisation of catecholamine production after surgical treatment on long-term renal function. MATERIALS AND METHODS: Seventy consecutive patients (aged 46.5 ± 14.0 years) with PPGL were included. Forty-eight patients from the PMT study cohort, matched for age, gender, blood pressure level and presence of hypertension, served as a control group. Renal artery doppler ultrasound spectral analysis included mean resistance index (RRI) and pulsatility index (PI). Forty-seven patients completed 12 months follow-up. RESULTS: There were no differences in renal parameters such as RRI, PI and kidney function between PPGL and non-PPGL patients as assessed by renal ultrasound, serum creatinine, eGFR and albumin excretion rate. No correlations between kidney function parameters, intrarenal doppler flow parameters and plasma catecholamines were observed in PPGL patients. At 12 months after surgery, no differences in creatinine level, eGFR, albumin excretion rate, RI and PI were found as compared to baseline results. CONCLUSIONS: In contrast to patients with other forms of secondary hypertension, our study did not show differences in intrarenal blood flow parameters and renal function between PPGL and non-PPGL subjects. Intrarenal hemodynamics and renal function did not change after normalisation of catecholamine levels by surgical treatment.

Lifestyle, psychological, socioeconomic and environmental factors and their impact on hypertension during the coronavirus disease 2019 pandemic.

SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic considerably affects health, wellbeing, social, economic and other aspects of daily life. The impact of COVID-19 on blood pressure (BP) control and hypertension remains insufficiently explored. We therefore provide a comprehensive review of the potential changes in lifestyle factors and behaviours as well as environmental changes likely to influence BP control and cardiovascular risk during the pandemic. This includes the impact on physical activity, dietary patterns, alcohol consumption and the resulting consequences, for example increases in body weight. Other risk factors for increases in BP and cardiovascular risk such as smoking, emotional/psychologic stress, changes in sleep patterns and diurnal rhythms may also exhibit significant changes in addition to novel factors such as air pollution and environmental noise. We also highlight potential preventive measures to improve BP control because hypertension is the leading preventable risk factor for worldwide health during and beyond the COVID-19 pandemic.

The European/International Fibromuscular Dysplasia Registry and Initiative (FEIRI)-clinical phenotypes and their predictors based on a cohort of 1000 patients.

AIMS: Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections. METHODS AND RESULTS: All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on computed tomography angiography, magnetic resonance angiography, and/or catheter-based angiography were eligible. Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46 ± 16 years (12% ≥65 years old), 86% were hypertensive, 72% had multifocal, and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65 years old had more often multifocal FMD, lower estimated glomerular filtration rate and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection, and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke, and multivessel FMD. CONCLUSIONS: The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management, and follow-up of FMD.

Pregnancy-Related Complications in Patients With Fibromuscular Dysplasia: A Report From the European/International Fibromuscular Dysplasia Registry.

Current literature suggests a higher risk of pregnancy-related complications in patients with renal fibromuscular dysplasia (FMD). The aim of our study was to assess the nature and prevalence of pregnancy-related complications in patients subsequently diagnosed with FMD. A call for participation was sent to centers contributing to the European/International FMD Registry. Patients with at least 1 pregnancy were included. Data on pregnancy were collected through medical files and FMD characteristics through the European/International FMD Registry. Data from 534 pregnancies were obtained in 237 patients. Despite the fact that, in 96% of cases, FMD was not diagnosed before pregnancy, 40% of women (n=93) experienced pregnancy-related complications, mostly gestational hypertension (25%) and preterm birth (20%), while preeclampsia was reported in only 7.5%. Only 1 patient experienced arterial dissection and another patient an aneurysm rupture. When compared with patients without pregnancy-related complications, patients with complicated pregnancies were younger at FMD diagnosis (43 versus 51 years old; P<0.001) and had a lower prevalence of cerebrovascular FMD (30% versus 52%; P=0.003) but underwent more often renal revascularization (63% versus 40%, P<0.001). In conclusion, the prevalence of pregnancy-related complications such as gestational hypertension and preterm birth was high in patients with FMD, probably related to the severity of renal FMD. However, the prevalence of preeclampsia and arterial complications was low/moderate. These findings emphasize the need to screen hypertensive women for FMD to ensure revascularization before pregnancy if indicated and appropriate follow-up during pregnancy, without discouraging patients with FMD from considering pregnancy.

Dissecting visceral fibromuscular dysplasia reveals a new vascular phenotype of the disease: a report from the ARCADIA-POL study.

OBJECTIVE: Visceral artery fibromuscular dysplasia (VA FMD) manifestations range from asymptomatic to life-threatening. The aim of the study is to evaluate the prevalence and clinical characteristics of VA FMD. METHODS: A total of 232 FMD patients enrolled into ongoing ARCADIA-POL study were included in this analysis. All patients underwent detailed clinical evaluation including ambulatory blood pressure monitoring, biobanking, duplex Doppler of carotid and abdominal arteries and whole body angio-computed tomography. Three control groups (patients with renal FMD without visceral involvement, healthy normotensive patients and resistant hypertensive patients) matched for age and sex were included. RESULTS: VA FMD was present in 32 patients (13.8%). Among these patients (women: 84.4%), FMD lesions were more frequent in celiac trunk (83.1%), 62.5% of patients showed at least one visceral aneurysm, and five patients presented with severe complications related to VA FMD. No demographic differences were found between patients with VA FMD and individuals from the three control groups, with the exception of lower weight (P < 0.001) and BMI (P < 0.001) in VA FMD patients. Patients with FMD (with or without visceral artery involvement) showed significantly smaller visceral arterial diameters compared with controls without FMD. CONCLUSION: Patients with FMD showed smaller visceral arterial diameters when compared with patients without FMD. This may reflect a new phenotype of FMD, as a generalized arteriopathy, what needs further investigation. Lower BMI in patients with VA FMD might be explained by chronic mesenteric ischemia resulting from FMD lesions. FMD visceral involvement and visceral arterial aneurysms in patients with renal FMD are far to be rare. This strengthens the need for a systematic evaluation of all vascular beds, including visceral arteries, regardless of initial FMD involvement.

Assessment of a non-physician screening program for hypertension and cardiovascular risk in community pharmacies.

BACKGROUND AND AIMS: The strategic role of prevention in hypertension setting is well known but, with the only exception of annually events promoted by international scientific societies, no other screening campaigns are available. Aim of this study was to assess the feasibility of a non-physician pharmacy-based screening program and to describe the cardiovascular risk and the BP status of participating subjects. METHODS AND RESULTS: 2731 costumers participated to the screening program, answering to a questionnaire about personal cardiovascular risk and measuring their BP with an Omron HEM 1040-E. Since no threshold for hypertension diagnosis is currently available for community pharmacies BP measurements, we assessed high BP prevalence according to 3 different cut-offs (≥140/90, ≥135/85 and ≥ 130/80 mmHg) and compared normotensives and hypertensives on major cardiovascular risk factors. According to the proposed cut-offs, prevalence of hypertension was respectively of 31%, 45% and 59.5%, and it increased among younger subjects (31-65 y) when the lowest cut-offs were applied. High BP was found in a large percentage of subjects self-declared on-/not on-treatment (uncontrolled hypertensives) or normotensives (presumptive hypertensives) and among those not aware of their own BP values (presumptive hypertensives). Prevalence of CV risk factors was higher in hypertensives than in normotensives. CONCLUSIONS: Our findings demonstrated that a community pharmacy-based screening is feasible and attracts the interests of many subjects, improving awareness on their BP status. The screening was also showed to be useful in order to detect potentially uncontrolled and/or suspected new hypertensives, especially among young adults, to refer to general practitioners for confirmatory diagnosis or further evaluation.

Predictors of blood pressure control in patients with resistant hypertension after intensive management in two expert centres: the Brussels-Torino experience.

Background: Management of resistant hypertension (RHTN) is challenging and often implies the use of complex polypharmacy and interventional therapies. The main objectives of this study were (i) to describe the characteristics of patients with RHTN referred to two expert centres; (ii) to identify predictors of blood pressure (BP) control after intensive management. Methods: We reviewed electronic medical files of all patients referred for RHTN to the Brussels and Torino centres, and extracted detailed clinical data, informations on drug adherence and psychological profile. All patients with confirmed diagnosis of RHTN, according to office and ambulatory BP monitoring (ABPM) measurements, were considered eligible. Results: 313 patients (51% men; age: 56 ± 12 years; office BP 177/98 mmHg; 24-hour ABPM 153/90 mmHg) were included. At the end of follow-up (median: 2 years [1-4]), only 26% of patients (n = 81) reached BP control. When compared to patients remaining resistant, patients eventually controlled had lower pulse pressure (71 vs. 82 mmHg, p < 0.001), less often myocardial infarction (6% vs. 20%, p < 0.005) and showed a higher recourse to cognitive reappraisal as far as emotion regulation is concerned (4.8 ± 1.1 vs. 3.9 ± 1.2, p = 0.009; ERQ Questionnaire). In a multivariate analysis looking for predictors of controlled BP, only the psychological characteristic of cognitive reappraisal (i.e., changing one's thoughts about a potentially emotion-eliciting event) remained significant (OR 2.06 [1.10; 3.84], p = 0.02). Conclusions: Even in expert centres, only a minority of patients with RHTN reached BP control, irrespective of the centre involved or the interventions applied. Patients who eventually responded to therapy had lower arterial stiffness and less cardiac organ damage. Furthermore, besides vascular damage, the single predictor of BP control was the ability to modify the emotional impact of stressful situations.