Changes in extracellular matrix in subcutaneous small resistance arteries of patients with primary aldosteronism

It has been previously demonstrated that aldosterone may possess a strong profibrotic action in vitro and in animal models of genetic or experimental hypertension. Our aim was to evaluate whether such a profibrotic action is present also in the human microcirculation. DESIGN AND PATIENTS: We investigated 13 patients with primary aldosteronism, seven patients with essential hypertension, and 10 normotensive controls. All subjects were submitted to a biopsy of gluteal sc fat tissue. Small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media to internal lumen ratio was measured. MAIN OUTCOME MEASURES: The total collagen content within the tunica media was detected (Sirius red staining and image analysis), and collagen subtypes were evaluated using polarized light microscopy; under this condition thicker type I collagen fibers appear orange or red, whereas thinner type III collagen fibers are yellow or green. RESULTS: Tunica media to internal lumen ratio was significantly increased in primary aldosteronism and in essential hypertension compared with normotensive controls. Clinic blood pressure values were similar in primary aldosteronism and in essential hypertension, and greater than in normotensive controls. Normotensive controls had less total and type III collagen (3.23 +/- 0.58 and 1.60 +/- 0.22%, respectively) in respect to the two hypertensive groups (P < 0.001). Total collagen and type III vascular collagen were significantly greater in primary aldosteronism (total collagen, 8.17 +/- 1.38%; type III collagen, 6.06 +/- 0.74%; P < 0.05) than in essential hypertension (total collagen, 6.84 +/- 1.15%; type III collagen, 5.25 +/- 0.80%). CONCLUSIONS: Our results indicate that, in small resistance arteries of patients with primary aldosteronism, a pronounced fibrosis may be detected, even more evident than in blood-pressure-matched patients with essential hypertension

Vascular alterations in apolipoprotein A-I amyloidosis (Leu75Pro) : a case-control study

Background: Among hereditary amyloidoses, apolipoprotein A-I (APO A-I) amyloidosis (Leu75Pro) is a rare, autosomal dominant condition in which renal, hepatic, and testicular involvement has been demonstrated. Objective: To investigate vascular structural as well as functional alterations. Methods: In 131 carriers of the amyloidogenic Leu75Pro APO A-I mutation (mean age 52 + 16 years, 56 women) and in 131 subjects matched for age, sex, body mass index and clinic blood pressure (BP), arterial stiffness (pulse wave velocity, PWV) and carotid intima-media thickness (IMT) were measured. Results: By definition no differences for age, sex, body mass index, and BP were observed. Meanmax IMT (Mmax-IMT) in the common (CC), bifurcation (BIF) and internal (ICA) carotid artery were comparable in the two groups. After adjustment for high-density lipoprotein cholesterol and renal function differences between the two groups, a lower meanmax-IMT was observed in APO A-I Leu75Pro mutation carriers than in controls (CC Mmax-IMT 0.87 \ub1 0.21 versus 0.93 \ub1 0.2 mm, p = 0.07; BIF Mmax-IMT 1.19 \ub1 0.48 versus 1.36 \ub1 0.46 mm, p = 0.025; ICA Mmax-IMT 0.9 \ub1 0.37 versus 1.02 \ub1 0.35 mm, p = 0.028). On the other hand, aortic stiffness was significantly greater in patients with APO A-I amyloidosis than controls (PWV 11.5 \ub1 2.9 and 10.7 \ub1 2.3 m/s, p < 0.05), even after adjusting for confounders. Conclusions: In carriers of the amyloidogenic Leu75Pro APO A-I mutation, a significant increase in arterial stiffness is observed; on the contrary, carotid artery IMT is comparable to that of control subjects. These results may add significant information to the clinical features of this rare genetic disorder

Angiotensin receptor blockers: therapeutic targets and cardiovascular protection.

In the prevention and treatment of cardiovascular disease, pharmacological treatment strategies should have several aims: (i) in individuals without overt cardiovascular disease, but with risk factors such as hypertension and/or diabetes, pharmacotherapy should prevent or delay disease development; (ii) in patients who have already progressed to cardiovascular disease, pharmacotherapy should help either to prevent or regress target organ damage (TOD); and (iii) in patients with TOD, pharmacotherapy should prevent events. Any medication intended for long-term therapy also should be well tolerated. Inhibiting the renin-angiotensin system has proven a successful therapeutic strategy in cardiovascular and renal medicine. Angiotensin-converting enzyme (ACE) inhibitors have demonstrated important advantages over conventional agents such as beta-blockers and thiazide diuretics, and have become a relevant part of treatment for heart failure post-myocardial infarction, left ventricular dysfunction and renal disease. Tolerability concerns may prevent their use in some patients, however. Angiotensin AT1 receptor blockers (ARBs) provide a different form of blockade of the renin-angiotensin system and a growing body of evidence suggests that this alternative approach may confer additional cardiovascular protection for some patient subgroups. In addition, ARBs generally are better tolerated than ACE inhibitors, enhancing patient compliance and persistence with long-term therapy. Furthermore, evidence in favour of combining an ACE inhibitor and an ARB in certain circumstances is continuously growing

Relationship between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles evaluated noninvasively by scanning laser Doppler flowmetry

BACKGROUND:: Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media-to-lumen ratio, are frequently present in hypertensive and/or diabetic patients, and may represent the earliest alteration observed. Furthermore, media-to-lumen ratio of small arteries evaluated by micromyography has a strong prognostic significance; however, its extensive evaluation is limited by the invasivity of the assessment, since a biopsy of subcutaneous fat is needed. Noninvasive measurement of wall-to-lumen of retinal arterioles using scanning laser Doppler flowmetry (SLDF) has recently been introduced. However, this new technique has not yet been compared to micromyographic measurement, generally considered the gold standard approach. METHODS AND RESULTS:: We investigated 40 individuals and patients, 24 of them were hypertensive patients and 16 normotensive individuals. All patients underwent a biopsy of subcutaneous fat during an elective surgical intervention. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and media-to-lumen ratio was measured. In addition, an evaluation of wall-to-lumen ratio of retinal arterioles by SLDF was performed (Heidelberg Retina Flowmeter, Heidelberg Engineering). A close correlation was observed between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles (r = 0.76, P < 0.001; P < 0.001, r = 0.57). CONCLUSION:: A noninvasive and easily repeatable procedure (intraobserver and interobserver variation coefficient <13%) such as an evaluation of the arterioles in the fundus oculi by SLDF may provide similar information regarding microvascular morphology compared with an invasive, accurate and prognostically relevant micromyographic measurement of media-to-lumen ratio of subcutaneous small arteries

Blood pressure control in Italy: analysis of clinical data from 2005-2011 surveys on hypertension.

INTRODUCTION: Blood pressure (BP) control is poorly achieved in hypertensive patients, worldwide. AIM: We evaluated clinic BP levels and the rate of BP control in hypertensive patients included in observational studies and clinical surveys published between 2005 and 2011 in Italy. METHODS: We reviewed the medical literature to identify observational studies and clinical surveys on hypertension between January 2005 and June 2011, which clearly reported information on clinic BP levels, rates of BP control, proportions of treated and untreated patients, who were followed in different clinical settings (mostly in general practice, and also in outpatient clinics and hypertension centres). RESULTS: The overall sample included 158\u200a876 hypertensive patients (94\u200a907 women, mean age 56.6\u200a\ub1\u200a9.6 years, BMI 27.2\u200a\ub1\u200a4.2\u200akg/m(2), known duration of hypertension 90.2\u200a\ub1\u200a12.4 months). In the selected studies, average SBP and DBP levels were 145.7\u200a\ub1\u200a15.9 and 87.5\u200a\ub1\u200a9.7\u200ammHg, respectively; BP levels were higher in patients followed in hypertension centres (n\u200a=\u200a10\u200a724, 6.7%; 146.5\u200a\ub1\u200a17.3/88.5\u200a\ub1\u200a10.3\u200ammHg) than in those followed by general practitioners (n\u200a=\u200a148\u200a152, 93.3%; 143.5\u200a\ub1\u200a13.9/84.8\u200a\ub1\u200a8.9\u200ammHg; P\u200

Metabolic syndrome and chronic kidney disease in high-risk Italian hypertensive patients: the I-DEMAND study.

none11noneG. Leoncini; F. Viazzi; E. Agabiti Rosei; E. Ambrosioni; FV. Costa; G. Leonetti; AC. Pessina; B. Trimarco; M. Volpe; G. Deferrari; R. PontremoliLeoncini, Giovanna; Viazzi, FRANCESCA CHIARA; E., Agabiti Rosei; E., Ambrosioni; Costa, F. V.; G., Leonetti; Pessina, A. C.; B., Trimarco; M., Volpe; Deferrari, Giacomo; Pontremoli, Robert

Isolated systolic hypertension in the young: A position paper endorsed by the European Society of Hypertension

Whether isolated systolic hypertension in the young (ISHY) implies a worse outcome and needs antihypertensive treatment is still a matter for dispute. ISHY is thought to have different mechanisms than systolic hypertension in the elderly. However, findings from previous studies have provided inconsistent results. From the analysis of the literature, two main lines of research and conceptualization have emerged. Simultaneous assessment of peripheral and central blood pressure led to the identification of a condition called pseudo or spurious hypertension, which was considered an innocent condition. However, an increase in pulse wave velocity has been found by some authors in about 20% of the individuals with ISHY. In addition, obesity and metabolic disturbances have often been documented to be associated with ISHY both in children and young adults. The first aspect to consider whenever evaluating a person with ISHY is the possible presence of white-coat hypertension, which has been frequently found in this condition. In addition, assessment of central blood pressure is useful for identifying ISHY patients whose central blood pressure is normal. ISHY is infrequently mentioned in the guidelines on diagnosis and treatment of hypertension. According to the 2013 European Guidelines on the management of hypertension, people with ISHY should be followed carefully, modifying risk factors by lifestyle changes and avoiding antihypertensive drugs. Only future clinical trials will elucidate if a benefit can be achieved with pharmacological treatment in some subgroups of ISHY patients with associated risk factors and/or high central blood pressure. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

Hypertension and atrial fibrillation: Diagnostic approach, prevention and treatment. Position paper of the Working Group &apos;Hypertension Arrhythmias and Thrombosis&apos; of the European Society of Hypertension

Hypertension is the most common cardiovascular disorder and atrial fibrillation is the most common clinically significant arrhythmia. Both these conditions frequently coexist and their prevalence increases rapidly with aging. There are different risk factors and clinical conditions predisposing to the development of atrial fibrillation, but due its high prevalence, hypertension is still the main risk factor for the development of atrial fibrillation. Several pathophysiologic mechanisms (such as structural changes, neurohormonal activation, fibrosis, atherosclerosis, etc.) have been advocated to explain the onset of atrial fibrillation. The presence of atrial fibrillation per se increases the risk of stroke but its coexistence with high blood pressure leads to an abrupt increase of cardiovascular complications. Different risk models are available for the risk stratification and the prevention of thromboembolism in patients with atrial fibrillation. In all of them hypertension is present and is an important risk factor. Antihypertensive treatment may contribute to reduce this risk, and it seems some classes are superior to others in the prevention of new-onset atrial fibrillation and prevention of stroke. Antithrombotic treatment with warfarin is effective in the prevention of thromboembolic events, although quite recently, new classes of anticoagulants that do not require international normalized ratio monitoring have been introduced with promising results. © 2012 Wolters Kluwer Health | Lippincott Williams &amp; Wilkins

Effect of treatment with candesartan or enalapril on subcutaneous small artery structure in hypertensive patients with noninsulin-dependent diabetes mellitus

Structural alterations of subcutaneous small resistance arteries are associated with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes mellitus (NIDDM). However, no data are presently available about the effects of antihypertensive therapy on vascular structure in hypertensive patients with NIDDM. Therefore, we have investigated the effect of an angiotensin-converting enzyme inhibitor, enalapril, and a highly selective angiotensin receptor blocker, candesartan cilexetil, on indices of subcutaneous small resistance artery structure in 15 patients with mild hypertension and NIDDM. Eight patients were treated with candesartan (8 to 16 mg per day) and 7 with enalapril (10 to 20 mg per day) for 1 year. Each patient underwent a biopsy of the subcutaneous fat from the gluteal region at baseline and after 1 year of treatment. Small arteries were dissected and mounted on a micromyograph and the media-to-internal lumen ratio was evaluated; moreover, endothelium-dependent vasodilation to acetylcholine was assessed. A similar blood pressure-lowering effect and a similar reduction of the media-to-lumen ratio of small arteries was observed with the 2 drugs. Vascular collagen content was reduced and metalloproteinase-9 was increased by candesartan, but not by enalapril. Changes of circulating indices of collagen turnover and circulating matrix metalloproteinase paralleled those of vascular collagen. The 2 drugs equally improved endothelial function. In conclusion, antihypertensive treatment with drugs that inhibit the renin-angiotensin-aldosterone system activity is able to correct, at least in part, alterations in small resistance artery structure in hypertensive patients with NIDDM. Candesartan may be more effective than enalapril in reducing collagen content in the vasculature