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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.

Abnormalities in orthostatic blood pressure changes upon active standing are associated with morbidity, mortality, and reduced quality of life. However, over the last decade, several population-based cohort studies have reported a remarkably high prevalence (between 25 and 70%) of initial orthostatic hypotension (IOH) among elderly individuals. This has raised the question as to whether the orthostatic blood pressure patterns in these community-dwelling elderly should truly be considered as pathological. If not, redefining of the systolic cutoff values for IOH (i.e., a value ≥ 40 mmHg in systolic blood pressure in the first 15 s after standing up) might be necessary to differ between normal aging and true pathology. Therefore, in this narrative review, we provide a critical analysis of the current reference values for the changes in systolic BP in the first 60 s after standing up and discuss how these values should be applied to large population studies. We will address factors that influence the magnitude of the systolic blood pressure changes following active standing and the importance of standardization of the stand-up test, which is a prerequisite for quantitative, between-subject comparisons of the postural hemodynamic response.

International audience; Renovascular hypertension is one of the most common forms of secondary hypertension. Over 95% of cases of renovascular hypertension are due either to atherosclerosis of the main renal artery trunks or to fibromuscular dysplasia. These two causes of renal artery stenosis have been extensively discussed in recent reviews and consensus. The aim of the current article is to provide comprehensive and up-to-date information on the remaining causes. While these causes are rare or extremely rare, etiologic and differential diagnosis matters both for prognosis and management. Therefore, the clinician cannot ignore them. For didactic reasons, we have grouped these different entities into stenotic lesions (neurofibromatosis type 1 and other rare syndromes, dissection, arteritis, and segmental arterial mediolysis) often associated with aortic coarctation and other arterial abnormalities, and nonstenotic lesions, where hypertension is secondary to compression of adjacent arteries and changes in arterial pulsatility (aneurysm) or to the formation of a shunt, leading to kidney ischemia (arteriovenous fistula). Finally, thrombotic disorders of the renal artery may also be responsible for renovascular hypertension. Although thrombotic/embolic lesions do not represent primary vessel wall disease, they are characterized by frequent macrovascular involvement. In this review, we illustrate the most characteristic aspects of these different entities responsible for renovascular hypertension and discuss their prevalence, pathophysiology, clinical presentation, management, and prognosis.

In summary, long-term exposure to a large, iatrogenic highflow fistula caused very severe systolic hypertension to develop, which was resistant to standard treatment. Closure of the fistula with percutaneous embolization resulted into a marked improvement of the hypertension, which became responsive to drug treatment.

We report a 74-year-old patient who developed an acute aortic syndrome (AAS) with intramural haematoma (IMH) during treatment with nintedanib, a tyrosine kinase inhibitor. As we suspected a role for nintedanib, this was immediately interrupted. Four months later, a computed tomographic angiography (CTA) showed significant regression of the IMH. Therefore, we state that, when patients use nintedanib and develop acute chest or back pain, diagnostic work-up for AAS should be considered. Furthermore, other risk factors for AAS, such as hypertension, genetic diseases and comedication should be taken into account when prescription of medication of this class is considered.

Objectives COVID-19 is an ongoing global pandemic. There is an urgent need for identification and understanding of clinical and laboratory parameters related to progression towards a severe and fatal form of this illness, often preceded by a so-called cytokine-storm syndrome (CSS). Therefore, we explored the hemocytometric characteristics of COVID-19 patients in relation to the deteriorating clinical condition CSS, using the Sysmex XN-10 hematology analyzer. Methods From March 1st till May 16th, 2020, all patients admitted to our hospital with respiratory complaints and suspected for COVID-19 were included (n=1,140 of whom n=533 COVID-19 positive). The hemocytometric parameters of immunocompetent cells in peripheral blood (neutrophils [NE], lymphocytes [LY] and monocytes [MO]) obtained upon admission to the emergency department (ED) of COVID-19 positive patients were compared with those of the COVID-19 negative ones. Moreover, patients with CSS (n=169) were compared with COVID-19 positive patients without CSS, as well as with COVID-19 negative ones. Results In addition to a significant reduction in leukocytes, thrombocytes and absolute neutrophils, it appeared that lymphocytes-forward scatter (LY-FSC), and reactive lymphocytes (RE-LYMPHO)/leukocytes were higher in COVID-19-positive than negative patients. At the moment of presentation, COVID-19 positive patients with CSS had different neutrophils-side fluorescence (NE-SFL), neutrophils-forward scatter (NE-FSC), LY-FSC, RE-LYMPHO/lymphocytes, antibody-synthesizing (AS)-LYMPHOs, high fluorescence lymphocytes (HFLC), MO-SSC, MO-SFL, and Reactive (RE)-MONOs. Finally, absolute eosinophils, basophils, lymphocytes, monocytes and MO-FSC were lower in patients with CSS. Conclusions Hemocytometric parameters indicative of changes in immunocompetent peripheral blood cells and measured at admission to the ED were associated with COVID-19 with and without CSS.

A previously healthy 51-year-old woman reported recurrent episodes of blue discoloration of one or more fingers associated with pain and swelling and mainly affecting the intermediate phalanges of the fourth finger of each hand. During some episodes, the second and third fingers were also involved.

Fibromuscular dysplasia is a heterogeneous group of systemic, noninflammatory, and nonatherosclerotic diseases of the vascular wall. It is the second-most common abnormality of the renal artery. Although hypertension is the most common presenting symptom, other symptoms, such as pulsatile tinnitus, stroke, chest pain, or abdominal discomfort, may result from other affected vascular beds. Revascularization of the renal artery appears to be effective at lowering blood pressure in many patients with renal artery fibromuscular dysplasia. For a long time, the intrarenal pathophysiological changes and mechanisms leading to hypertension had hardly been studied in patients with renal artery fibromuscular dysplasia. Recent data, however, has provided more insight into the effects of renal artery fibromuscular dysplasia on the intrarenal microvasculature and the intra-renal renin-angiotensin system in these patients. Moreover, these data have changed our view of the pathophysiological mechanisms leading to hypertension in patients with renal artery fibromuscular dysplasia. In this review, we will discuss recent clinical and scientific developments regarding renal artery fibromuscular dysplasia with an emphasis on its effects on the kidney.

Objective: Fibromuscular dysplasia (FMD) can be classified in a multifocal and a unifocal subtype. As unifocal FMD generally leads to more severe hypertension at younger age, we hypothesized that renal hemodynamics are more disturbed in unifocal renal artery FMD as compared with multifocal FMD, leading to increased renin secretion. Methods: We measured renal blood flow ((133)Xenon washout method), renin secretion, and glomerular filtration rate per kidney in 101 patients with FMD (26 unifocal and 75 multifocal), all off medication and prior to balloon angioplasty. Results: We found that renal blood flow and glomerular filtration were substantially lower in kidneys with unifocal FMD as compared with multifocal FMD. In the affected kidney from patients with unilateral FMD for example, mean renal blood flow was 173 +/- 77 in unifocal vs. 244 +/- 79 ml/100 g kidney/min in multifocal FMD (P=0.013). Moreover, lateralization in renin secretion was only observed in a subset of patients with unifocal FMD, but not in any of the patients with multifocal FMD. Conclusion: These findings suggest that the impact of unifocal FMD lesions on the kidney is more severe, resulting in a classical pattern of renovascular hypertension. In multifocal FMD, however, renal blood flow is more preserved, local renin secretion is not increased, and the association between renin levels and blood pressure is inverse. These differences may explain the often more severe clinical presentation and higher success rate of revascularization in unifocal FMD, but also suggest that the pathophysiological mechanisms leading to hypertension may differ between these two disease entities.

BACKGROUND: Revascularization does not restore renal function in most patients with atherosclerotic renal artery stenosis (RAS), likely due to inflammation and fibrosis within the stenotic kidney. Low-energy shockwave therapy (LE-SWT) stimulates angiogenesis in the stenotic kidney, but its ability to improve renal function and structure after revascularization remains unexplored. We tested the hypothesis that a LE-SWT regimen before percutaneous transluminal renal angioplasty (PTRA) would enable PTRA to restore renal function in hypercholesterolemic pigs with RAS (HC+RAS), and that this would be associated with attenuation of renal inflammation and fibrosis. METHODS AND RESULTS: Twenty-six pigs were studied after 16 weeks of HC+RAS, HC+RAS treated with PTRA with or without a preceding LE-SWT regimen (bi-weekly for 3 weeks), and controls. Single-kidney renal blood flow (RBF), glomerular filtration rate (GFR), and oxygenation were assessed in vivo using imaging 4 weeks after PTRA, and then inflammation and fibrosis ex vivo. Four weeks after successful PTRA, blood pressure fell similarly in both revascularized groups. Yet, stenotic-kidney GFR remained lower in HC+RAS and HC+RAS+PTRA (p0.05 vs. normal). Furthermore, reduced inflammation, medullary fibrosis, and cortical hypoxia were only shown in swine stenotic kidneys pre-treated with LE-SWT before PTRA 4 weeks later. CONCLUSIONS: LE-SWT delivery before revascularization permitted PTRA to improve function and decrease cortical and medullary damage in the stenotic swine kidney. This study therefore supports the use of an adjunct SW pre-treatment to enhance the success of PTRA in blunting loss of kidney function in experimental HC+RAS.

Fibromuscular dysplasia (FMD) is a heterogeneous group of nonatherosclerotic, noninflammatory vascular diseases that can be classified into 2 subtypes based on their angiographic appearance: the multifocal type, with its typical string-of-beads pattern, and the unifocal type, presenting as a single focal stenosis.1,2 Because these 2 FMD entities differ substantially with regard to clinical and histopathologic characteristics, it has been suggested that unifocal and multifocal FMDs in fact represent 2 different vascular diseases.3 Recently, however, we observed a patient in whom imaging studies suggest the coexistence of unifocal and multifocal FMD in a single patient. [...]

Background: Initial orthostatic hypotension (IOH) is a clinical syndrome of transient orthostatic hypotension that is defined as a drop in blood pressure of >40 mmHg systolic and/or >20 mmHg diastolic within 15 s after standing, accompanied by symptoms of cerebral hypoperfusion, but without sustained orthostatic hypotension (blood pressure decrease >20/10 mm Hg after 1-3 min of standing). As the etiology of syncope remains unknown in a large proportion of patients, we hypothesized that IOH is highly prevalent among patients with unexplained syncope. Methods: We studied 250 consecutive outpatients with unexplained syncope that were evaluated in the syncope-unit of our tertiary referral hospital. We measured hemodynamic changes in response to active standing using a beat-to-beat blood pressure measurement device, first after lying supine for >5 min and then after squatting for 30 s. Results: 11.2% of the patients were diagnosed with syncope due to IOH, with a mean fall in blood pressure of 47.4 +/- 12.5/29.0 +/- 10.7 mmHg within 15 s after standing up. Therefore, IOH was the second commonest cause of syncope in our cohort. 46.2% of the patients diagnosed with syncope due to IOH used antihypertensive drugs, mostly betablockers (41.6%) and/or tamsulosin (24.9%). The squatting-to-standing-test in addition to the lying-to-standing-test resulted in only 3 additional patients diagnosed with syncope due to IOH. Conclusions: IOH is highly prevalent among patients with previously unexplained syncope. Therefore, beat-to-beat blood pressure measurement should be considered in patients with unexplained syncope. (c) 2018 Elsevier B.V. All rights reserved.

Background: Angiotensin-(1-7) modulates renal blood flow in humans with essential hypertension by inducing vasodilation and counterbalancing angiotensin II-induced vasoconstriction. Little is, however, known about the effects of angiotensin-(1-7) in kidneys with atherosclerotic renal artery stenosis. We previously demonstrated that the effect of angiotensin-(1-7) is reduced in patients with increased activity of the renin-angiotensin system. As the renin-angiotensin system is also activated in kidneys with renal artery stenosis, we hypothesized that the vasodilatory effect of angiotensin-(1-7) is also reduced in such kidneys. Method: Therefore, we selectively measured mean renal blood flow (133 Xenon washout method) before and during local infusion of angiotensin-(1-7) (0.27, 0.9, and 2.7 ng/kg per min) in hypertensive patients who were angiographically evaluated for the presence of renovascular abnormalities. Data were analyzed in three groups: stenotic kidneys, nonstenotic kidneys with renal artery stenosis of the contralateral kidney (contralateral stenotic kidneys), or essentially hypertensive controls without renovascular abnormalities (matched for urinary sodium excretion). Results: Angiotensin-(1-7) infusion resulted in an increase in renal blood flow in matched controls. In stenotic kidneys however, the effect of angiotensin-(1-7) was significantly reduced as compared to controls. The angiotensin-(1-7) effect in contralateral stenotic kidneys was comparable to controls. Conclusion: Angiotensin-(1-7)-induced vasodilation is reduced in stenotic kidneys, but not in contralateral stenotic kidneys. This suggests that the altered blood flow regulation in kidneys with atherosclerotic renal artery stenosis is a local phenomenon and not related to generalized atherosclerotic burden. Probably, the renin-angiotensin system activation, bioavailability of nitric oxide, and structural changes in the stenotic kidney play a role in this phenomenon.

Background: Angiotensin II (Ang II) is thought to play an important role in the development of hypertension. Nevertheless, knowledge on the angiotensin II type-1-receptors (AT(1)Rs) in the hypertensive kidney and the influence of sodium intake and renin-angiotensin system activity on intrarenal AT(1)R blockade is scarce. To improve our understanding of renal AT(1)Rs in hypertensive patients, we studied the effects of acute, local administration of AT(1)R-blocker eprosartan in kidneys of patients with essential hypertension (off medication). Method: In 73 hypertensive patients who were scheduled for diagnostic renal angiography, we measured renal blood flow (133 Xenon washout method) before and during intrarenal infusion of two incremental doses of eprosartan (3 and 10 mg/kg/min for 15 min per dose). We hypothesized that the vasodilatory effects of eprosartan would be enhanced by low sodium intake and would be reduced during Ang II co-infusion. Therefore, we allocated the patients to either a high or a low sodium diet and coinfused Ang II (1 ng/kg/min) in a subgroup. Results: Eprosartan infusion resulted in intrarenal vasodilation in all groups. No differences in the magnitude of this effect were found between the groups. No correlation was found between 24-h urinary sodium excretion (a proxy for dietary sodium intake) and the effect of eprosartan. Conclusion: Eprosartan-induced vasodilation is not influenced by sodium intake and/or co-infusion of Ang II. These rather unexpected findings could be explained by differences between circulating and tissue Ang II levels, variations in AT(1)R expression, and/or stimulation of other vasodilatory pathways.

Background: Fibromuscular dysplasia (FMD) is the second most common cause of renovascular hypertension. Nonetheless, knowledge on the renal microvasculature and renin-angiotensin system (RAS) activity in kidneys with FMD is scarce. Given the fairly good results of revascularization, we hypothesized that the renal microvasculature and RAS are relatively spared in kidneys with FMD. Method: In 58 hypertensive patients with multifocal renal artery FMD (off medication) and 116 matched controls with essential hypertension, we measured renal blood flow (133 Xenon washout method) per kidney and drew blood samples from the aorta and both renal veins to determine renin secretion and glomerular filtration rate per kidney. Results: We found that renal blood flow and glomerular filtration rate in FMD were comparable to those in controls. Although systemic renin levels were somewhat higher in FMD, renal renin secretion was not elevated. Moreover, in patients with unilateral FMD, no differences between the affected and unaffected kidney were observed with regard to renal blood flow, glomerular filtration rate, or renin secretion. In men, renin levels and renin secretion were higher as compared with women. The renal blood flow response to RAS modulation (by intrarenal infusion of angiotensin II, angiotensin-(1-7), an angiotensin II type 1 receptor blocker, or a nitric oxide synthase blocker) was also comparable between FMD and controls. Conclusion: Renal blood flow, glomerular filtration, and the response to vasoactive substances in kidneys with multifocal FMD are comparable to patients with essential hypertension, suggesting that microvascular function is relatively spared. Renin secretion was not increased and the response to RAS modulation was not affected in kidneys with FMD.

Current evidence suggests that angiotensin-(1–7) plays an important role in the regulation of tissue blood flow. This evidence, however, is restricted to studies in animals and human forearm. Therefore, we studied the effects of intrarenal angiotensin-(1–7) infusion on renal blood flow in hypertensive humans. To assess the influence of renin–angiotensin system activity, sodium intake was varied and co-infusion with angiotensin II was performed in a subgroup. In 57 hypertensive patients who were scheduled for renal angiography, renal blood flow was measured ( 133 Xenon washout method) before and during intrarenal infusion of angiotensin-(1–7) (3 incremental doses: 0.27, 0.9, and 2.7 ng/kg per minute). Patients were randomized into low or high sodium intake. These 2 groups of patients received angiotensin-(1–7), with or without intrarenal co-infusion of angiotensin II (0.3 ng/kg per minute). Angiotensin-(1–7) infusion resulted in intrarenal vasodilation in patients adhering to a sodium-rich diet. This vasodilatory effect of angiotensin-(1–7) was clearly attenuated by low sodium intake, angiotensin II co-infusion, or both. Regression analyses showed that the prevailing renin concentration was the only independent predictor of angiotensin-(1–7)–induced renal vasodilation. In conclusion, angiotensin-(1–7) induces renal vasodilation in hypertensive humans, but the effect of angiotensin-(1–7) is clearly attenuated by low sodium intake and co-infusion of angiotensin II. This supports the hypothesis that angiotensin-(1–7) induced renal vasodilation depends on the degree of renin-angiotensin-system activation.