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Objective: The gold standard technique of evaluation microvascular morphology in human is generally considered the measure of media to lumen ratio (M/L) of subcutaneous small vessels obtained by local biopsies and evaluated by wire or pressure micromyography. However, non-invasive techniques for the evaluation of retinal arterioles were recently proposed, in particular two approaches seem to provide interesting information: Scanning Laser Doppler Flowmetry (SLDF) and adaptive optics (AO); both of them provide an estimation of the wall to lumen ratio (WLR) of retinal arterioles. A non-invasive measurement of basal and total capillary density may be obtained by videomicroscopy/capillaroscopy. No direct comparison of the non-invasive techniques in the same population was previously performed, in particular AO was never validated against micromyography. Methods: In the present study, we enrolled 12 normotensive subjects and 8 hypertensive patients undergoing an election surgical intervention; (11/20 were severely obese). All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance artery structure was assessed by wire myography and the M/L was calculated. WLR of retinal arterioles was obtained by SLDF and AO (SLDF, Heidelberg Engineering, Heidelberg, Germany and RTX-1, Imagine Eyes, Orsay, France). Functional (basal) and structural (total) microvascular density were evaluated by capillaroscopy before and after venous congestion. Results: The results are summarized in the Table (slope of the relation: p < 0.01 RTX-1 vs. SLDF). Basal capillary density in the nailfold/M/L Total capillary density in the forearm / ML Basal capillary density in the dorsum of the finger / M/L Total capillary density in the dorsum of the finger /ML Correlation coefficients (n = 20) 0.53, r2 = 0.28, p < 0.05 0.50, r2 = 0.25, p < 0.05 0.17, r2 = 0.29, p = NS 0.34, r2 = 0.12, p = NS W/L retinal arterioles (SLDF)/ M/L W/L retinal arterioles (RTX- 1)/M/L W/L retinal arterioles (SLDF)/ W/L retinal arterioles (RTX-1) Correlation coefficients (n = 20) 0.54, r2 = 0.29, p < 0.01 0.90, r2 = 0.81, p < 0.001 0.71, r2 = 0.50, p < 0.001 Conclusions: Our data suggest that AO has a substantial advantage over SLDF in terms of evaluation of microvascular morphology, since it is more closely correlated with the M/L of subcutaneous small arteries, considered a gold-standard approach.

Objective: It has been previously demonstrated that T lymphocytes may be involved in the development of hypertension and microvascular remodeling, and that circulating T effector lymphocytes may be increased in hypertension. In particular, Th1 and Th17 lymphocytes may contribute to the progression of hypertension and microvascular damage while TREG lymphocytes seem to be protective. However, no data is available about patients with severe obesity, in which pronounced microvascular alterations were observed. Methods: We have investigated 32 severely obese patients undergoing bariatric surgery, 24 normotensive lean subjects and 11 hypertensive lean subjects undergoing an election surgical intervention. No sign of local or systemic inflammation was present in any subject or patient. A peripheral blood sample was obtained before surgery for assessment of CD4+ T lymphocyte subpopulations. Lymphocyte phenotype was evaluated by flow cytometry after 5 hour in vitro activation in order to assess T-effector and T-regulatory (TREG) lymphocytes. Subsets of TREGS were defined as follows: −TREGS recent thymic emigrants (RTE), directly derived from thymus: CD31+; −TREGS naïve: CCR7+CD45RA+; −TREGS central memory (CM): CCR7+CD45RA−; −TREGS effector memory (EM): CCR7−CD45RA−; −TREGS terminal differentiated effector memory (TDEM): CCR7−CD45RA+. Results: The results are summarized in the Table (*p < 0.05, **p < 0.01, ***p < 0.001 vs. lean normotensives; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. lean hypertensives). A marked reduction of several TREG subpopulations was observed in obese patients compared with controls, together with an increased in some T-effector cells. Lean normotensives Lean hypertensives Obese patients TREGs (%) 4.11 ± 1.60 4.64 ± 1.66 2.69 ± 1.81**## TREGs (abs number) 45.4 ± 24.3 45.4 ± 23.8 27.3 ± 21.1**# TREGs naíve (%) 22.1 ± 10.1 18.1 ± 13.1 13.34 ± 12.9** TREGs naíve (abs number) 10.6 ± 7.75 9.71 ± 8.87 3.87 ± 5.28***## TREG CM (%) 32.3 ± 13.8 32.8 ± 17.8 22.7 ± 15.2*# TREGs CM (abs number) 14.7 ± 10.2 14.2 ± 9.08 6.10 ± 8.08***## CD4+ EM (%) 24.4 ± 9.96 26.8 ± 12.5 34.1 ± 13.3** CD161+CD28+ (%) 86.2 ± 28.5 94.9 ± 5.63 97.2 ± 5.39* Conclusion: TREG lymphocytes are clearly reduced in severely obese patients, possibly contributing to the development of marked microvascular alterations previously observed in such a population.

Background: In patients with Systemic lupus erythematosus (SLE) a greater prevalence of structural and functional cardiovascular (CV) alterations has been described, possibly explaining the higher incidence of CV events, as compared to subjects matched for age and sex. Aim of this study was to analyze the presence of target organ damage in premenopausal women with SLE and in controls matched not only for demographic characteristics but also for other cardiovascular risk factors. Subjects and methods: 4 patients with SLE clinically stable(SLEDAI Score 2.5±1.5)(age 32±7years, range 19-44)and 34 controls matched for sex, age, BMI, clinic blood pressure(BP) and antihypertensive treatment(if present), underwent:24 hours BP monitoring, echocardiography with tissue Doppler analysis(TDI) for the evaluation of left ventricular(LV)structure and of systolic and diastolic function, carotid ultrasound for intima-media thickness(IMT), carotid distensibility measurement, and pulse wave velocity measurement(PWV). Results: By definition no difference was observed for age, sex, BMI and clinic BP values and a similar Framingham risk score was observed between SLE and controls(1.3±2.7 vs 1.5±2.3%, p=ns). No significant differences were observed for all echocardiographic parameters except LV longitudinal systolic function(Sm), an early index of LV systolic dysfunction(see Table). Carotid IMT and distensibility, as well as PWV and the prevalence of an abnormal aortic stiffness were both similar in the two groups. At the logistic analysis, PWV was independently associated with LV mass in controls and with the steroid weekly dose in SLE patients. Conclusions: In patients with SLE and low activity index of the disease we did not observe significant vascular alterations as compare to controls with similar cardiovascular risk. The early LV systolic impairment observed in this group of patients needs confirmation in larger cohorts.

Background: The determinants of aortic stiffness have been elucidated in several studies, while few data are available for carotid stiffness. Aim of the study was to identify the main determinants of carotid arterial stiffness parameters in a general population in Northern-Italy(Vobarno Study). Methods:183subjects(61% female, mean age 55± 4,53% hypertensives,59% treated) underwent laboratory examinations and both clinic and 24 hours BP measurement (Spacelabs 90207). A non-invasive echotracking system was used to measure intima-media thickness, diameter, distension, distensibility (Dist), distensibility coefficient (CDist), compliance coefficient (CC) and elastic modulus (Einc) on 4-cm long common carotid artery segment. Results: correlation coefficient of Dist, CDist and Einc are shown in Table 1. Dist CDist Einc R p r p r p Age (years) −0.240* 0.001 −0.241* 0.001 0.210* 0.005 BMI (Kg/m2) −0.192* 0.01 −0.192* 0.010 0.169* 0.024 Clinic SBP (mmHg) −0.501* 0.001 −0.477* 0.000 0.511* 0.000 Clinic DBP (mmHg) −0.181* 0.015 −0.184* 0.014 0.262* 0.000 Clinic MBP (mmHg) −0.374* 0.001 −0.362* 0.000 0.422* 0.000 24 hours SBP (mmHg) −0.207* 0.006 −0.198* 0.009 0.222* 0.003 24 hours DBP (mmHg) −0.183* 0.016 −0.191* 0.012 0.207* 0.006 24 hours MBP(mmHg) −0.13 0.094 −0.125 0.099 0.166* 0.029 At multivariate analysis the independent predictor of Dist,CDist and Einc were age (β=−0.22, β=−0.22 and β=0.18, respectively, all p

Background. The anticontractile effect of perivascular adipose tissue(PVAT) is lost in obese patients due to adipocyte hypertrophy, leading to hypoxia, inflammation, and oxidative stress(Circulation 2009; 119(12):1661–1670).We recently demonstrated that the property of PVAT, partially maintained in an animal model of genetic obesity, seems to be related to the activity of BKCA channels, since is selectively blocked by iberiotoxin. We aimed to investigate functional responses of small mesenteric arteries in an animal model of genetic obesity after chronic treatment with melatonin, an endogenous hormone with antioxidant and vasculoprotective properties. Methods. Obese mice (n = 9) (B6.V-Lep ob/OlaHsd, Harlan Laboratories S.r.l.) (ob/ob) and control lean mice (n = 8) (CLM) were treated with melatonin (MEL)100 mg/kg per day for 8 weeks (from the5th to the 13th week of age).Data were compared from untreated ob/ob (n = 15) and CLM (n = 10) animals. Mesenteric small resistance arteries were dissected and mounted on a wire myograph. Concentration-response to norepinephrine was evaluated in vessels with intact PVAT (WF) and in vessels in which PVAT was removed (NoF) under normoxic and hypoxic (30’95% N2/5%CO2) conditions. Norepinephrine concentration-response curve was repeated with iberiotoxin(30’preincubation 100 nm/L). Results. MEL significantly reduced the contractile response in NoF ob/ob and CLM vessels (ANOVA P = 0.014 and P = 0.049 respectively).The improvement after MEL was also seen in CLM NoF vessels during hypoxia(ANOVA p < 0.05) and following preincubation with iberiotoxin(P < 0.05), with no significant improvements in ob/ob. Increases in contractility following hypoxia and iberiotoxin treatment were restored byMEL in Ob/Ob WF vessels (P = 0.013 and P = 0.036 respectively),whereas MEL only rescued the effects of hypoxia(P = 0.045) in CLM WF arteries. In conclusion, MEL exerts a protective effect in small vessels with and without PVAT from both ob/ob and CLM, counteracting the adverse effect of hypoxia and iberiotoxin in vessels with PVAT and in CLM vessels whitout PVAT. However, in Ob/Ob animals MEL rescues the effects only in the presence of PVAT indicating the importance of PVAT oxidative stress in vascular dysfunction observed in Ob/Ob animals.

Background: Carotid-femoral pulse wave velocity (cfPWV) is an independent predictor of cardiovascular events and its measurement is recommended by current hypertension guidelines. Few data are available on the progression of PWV over time. The aim of the present study was to assess the progression of aortic stiffness over a 5-year period in a general population in Northern Italy (Vobarno Study). Methods: 227 subjects,42% males(age 50±4 years, hypertension in 51% at baseline visit, BL), underwent a BL and a follow up (FU) visit, after 5.1±0.4 years. In all subjects laboratory examinations, measurement of clinic and 24 hours blood pressure(BP) and of cfPWV were performed at BL and at FU. Results: In the overall population cfPWV increased from 8.28±1.27 at BL to 8.51±3.2 m/s at FU(p

Objective: Wall-to-lumen ratio of retinal arterioles might serve as an in-vivo parameter of vascular damage. Previous studies have shown a correlation between retinal arteriolar structure and blood pressure values, measured both in the clinic and during 24 hours ambulatory monitoring. We analyzed the impact of brachial clinic blood pressure (BP), of central BP and of 24 hours BP values on wall-to-lumen ratio of retinal arterioles. Methods: In 267 subjects (129 males, age range 20–72 years; mean 54±7 years) wall-to-lumen ratio of retinal arterioles was assessed in vivo using scanning laser doppler flowmetry (Heidelberg retina flowmeter, Heidelberg Engineering). In addition clinic and 24 hours BP values were measured. Central hemodynamics and augmentation index (Ai) were assessed by pulse wave analysis. Results: In never treated patients with essential hypertension (n=56) a higher wall-to-lumen ratio (0.37±0.19 vs. 0.30±0.13, P=0.05) was observed in comparison with normotensive individuals (n=115); no significant differences were observed between treated (n=96) and untreated hypertensive patients. Wall to lumen ratio and wall cross sectional area of retinal arterioles were significantly related to clinic systolic BP(r=0.23, P=0.005) and PP(r=0.18, P=0.005), to 24 hours systolic BP(r=0.28, P=0.0001) and PP(r=0.19, P=0.003) and to central systolic BP(r=0.20, P=0.01) and central PP(r=0.21, P=0.001). Multiple regression analysis including all BP indices revealed that only mean systolic 24 hours BP is independently associated with an increased wall-to-lumen ratio of retinal arterioles. Conclusion: in this quite large group of hypertensive patients and normotensive individuals 24 hours systolic BP seems to be the strongest determinant of increased WLR of retinal arterioles.

Background: Hereditary amyloidosis are late-onset autosomal dominant disorders characterized by amyloid deposition in various tissues. Among them, Apolipoprotein A-I amyloidosis (Leu75Pro) is a rare autosomal dominant condition in which renal, hepatic, and testicular involvement has been demonstrated.No data are available about vascular alterations in this condition.Aim of the study was to evaluate arterial stiffness,assessed by pulse wave velocity (PWV)and carotid artery intima-media thickness (IMT),evaluated by ultrasound, in patients with Apolipoprotein A-I amyloidosis (APO AI). Patients: In 104 patients with APO AI(mean age 52±16 years,56 F) and in 104 subjects matched for age, sex, body mass index (BMI) and blood pressure (BP), PWV and IMT were measured. Results: By definition no differences for age, sex, BMI, BP, heart rate were observed. PWV was significantly higher in patients with APO AI than controls (11.5±2.9 and 10.7±2.3,p< 0.05), even after adjusting for cholesterol, creatinine, mean BP and heart rate measured during PWV assessment. In patients with APO AI the prevalence of increased arterial stiffness (defined as PWV>12m/sec) was significantly greater than in controls (31% vs 17%, p