Alessandro Maloberti

Metabolic syndrome in human immunodeficiency virus-positive subjects: prevalence, phenotype, and related alterations in arterial structure and function.

BACKGROUND Human immunodeficiency virus (HIV) infection itself and highly active antiretroviral treatment (HAART) have been proposed to be associated with a higher prevalence of metabolic syndrome, but, to date, prevalence and phenotype of metabolic syndrome among HIV subjects and the related structural and functional vascular alterations are not conclusively defined. METHODS We analyzed the data of 108 HIV-infected subjects without known cardiovascular risk factors: 72 were on HAART (group A, age 46.5±7.5 years, clinical blood pressure 125.7/74.9±11.6/7.8 mmHg) and there 36 in a naïve group (group B, age 40.7±7.9 years, blood pressure 126/75.8±9.8/7.7 mmHg). A total of 224 healthy subjects served as controls (group C, age 44.9±6.9 years, blood pressure 123.7/75.7±9.8/7.1 mmHg). Arterial stiffness was measured by aorto-femoral pulse wave velocity (PWV, sfigmocor), and carotid intima media thickness (IMT) was measured by a semiautomatic echotracking system (Esaote-WTS). RESULTS Metabolic syndrome was more frequent in HIV-positive subjects than in controls (19.4%, 13.8%, 4.5% for groups A, B, and C; P<0.001), with no significant difference between HAART and naïve. In metabolic syndrome subjects, group A displayed lipid profile alterations more frequently (91%, 50%, 57% for groups A, B, and C; P<0.05), whereas others metabolic syndrome components were equally represented in the three groups. In metabolic syndrome subjects, IMT was similar [556±108, 542±164, and 564±110.4 μm for groups A, B, and C; P=not significant (NS)], whereas PWV was significantly greater in HAART subjects when compared with controls (10.8±1.8, 9.±1.1, 9.3±1 cm/sec for groups A, B, and C; P=0.02 for A vs. C). Moreover, in this group (metabolic syndrome+HAART), PWV was higher than in subjects on HAART but without metabolic syndrome. CONCLUSIONS HIV subjects showed a higher prevalence and a different pattern of metabolic syndrome components. HAART, more than HIV infection per se, appeared to be responsible for the increased prevalence of metabolic syndrome and arterial function derangement.

Iron Stores, Hepcidin, and Aortic Stiffness in Individuals with Hypertension.

Background & Aims Iron accumulation within the arterial wall has been hypothesized to promote atherosclerosis progression. Aim of this study was to evaluate whether the hormone hepcidin and iron stores are associated with arterial stiffness in subjects with essential hypertension. Methods Circulating hepcidin, ferritin, and mutations in the hemochromatosis gene were compared between subjects included in the first vs. third tertile (n=284 each) of carotid-femoral pulse wave velocity (PWV) in an unselected cohort of patients with arterial hypertension. Results At univariate logistic regression analysis, high PWV was associated with higher ferritin levels (p=0.010), but lower hepcidin (p=0.045), and hepcidin ferritin/ratio (p<0.001). Hemochromatosis mutations predisposing to iron overload were associated with high PWV (p=0.025). At multivariate logistic regression analysis, high aortic stiffness was associated with older age, male sex, lower BMI, higher systolic blood pressure and heart rate, hyperferritinemia (OR 2.05, 95% c.i. 1.11-3.17 per log ng/ml; p=0.022), and lower circulating hepcidin concentration (OR 0.29, 95% c.i. 0.16-0.51 per log ng/ml; p<0.001). In subgroup analyses, high PWV was associated with indices of target organ damage, including micro-albuminuria (n=125, p=0.038), lower ejection fraction (n=175, p=0.031), cardiac diastolic dysfunction (p=0.004), and lower S wave peak systolic velocity (p<0.001). Ferritin was associated with cardiac diastolic dysfunction, independently of confounders (p=0.006). Conclusions In conclusion, hyperferritinemia is associated with high aortic stiffness and cardiac diastolic dysfunction, while low circulating hepcidin with high aortic stiffness.

Relationship Between 24-Hour Ambulatory Central Systolic Blood Pressure and Left Ventricular MassNovelty and Significance: A Prospective Multicenter Study

We investigated the relationship between left ventricular mass and brachial office as well as brachial and central ambulatory systolic blood pressure in 7 European centers. Central systolic pressure was measured with a validated oscillometric device, using a transfer function, and mean/diastolic pressure calibration. M-mode images were obtained by echocardiography, and left ventricular mass was determined by one single reader blinded to blood pressure. We studied 289 participants (137 women) free from antihypertensive drugs (mean age: 50.8 years). Mean office blood pressure was 145/88 mm Hg and mean brachial and central ambulatory systolic pressures were 127 and 128 mm Hg, respectively. Mean left ventricular mass was 93.3 kg/m2, and 25.6% had left ventricular hypertrophy. The correlation coefficient between left ventricular mass and brachial office, brachial ambulatory, and central ambulatory systolic pressure was 0.29, 0.41, and 0.47, respectively (P=0.003 for comparison between brachial office and central ambulatory systolic pressure and 0.32 for comparison between brachial and central ambulatory systolic pressure). The results were consistent for men and women, and young and old participants. The areas under the curve for prediction of left ventricular hypertrophy were 0.618, 0.635, and 0.666 for brachial office, brachial, and central ambulatory systolic pressure, respectively (P=0.03 for comparison between brachial and central ambulatory systolic pressure). In younger participants, central ambulatory systolic pressure was superior to both other measurements. Central ambulatory systolic pressure, measured with an oscillometric cuff, shows a strong trend toward a closer association with left ventricular mass and hypertrophy than brachial office/ambulatory systolic pressure. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01278732.

Asymptomatic aortic mural thrombus in a minimally atherosclerotic vessel

Aortic mural thrombi in a normal (non-aneurysmal or minimally atherosclerotic) vessel are an uncommon condition. They are usually located in the descending aorta and, less frequently, in the aortic arch or in the abdominal aorta. The typical clinical presentation is the appearance of symptoms/signs of peripheral arterial embolization, such as lower limb or visceral ischaemia, but these can also be accidentally found in asymptomatic patients. We report the case of a 40-year old man with untreated hypertension and dyslipidaemia admitted to hospital for atypical chest pain associated with an elevation in high-sensitivity troponin T with normal creatine kinase isoenzime MB creatine kinase isoenzyme. Elektrocardiogram (EKG) and transthoracic echocardiography were non-diagnostic; in order to exclude an aortic dissection, a gated chest computed tomography was performed and showed an aortic thrombus on a minimally atherosclerotic wall. Then, a transoesophageal echocardiography confirmed an aortic floating thrombus (7 × 4 mm). Cardiac surgeons advised against surgery and therapy with antiplatelet, low molecular weight heparin, β-blocker, antihypertensive and lipid-lowering drugs was initiated. A complete resolution of the thrombus was observed at the 12-day tomographic control.

Effects of Cancer Therapy Targeting Vascular Endothelial Growth Factor Receptor on Central Blood Pressure and Cardiovascular System.

BACKGROUND In the last 2 decades, new drugs that oppose the effects of vascular endothelial growth factor receptor (VEGFR), and thus angiogenesis, have considerably improved treatment of solid tumors. These anti-VEGFR drugs, however, are burdened by several side effects, particularly relevant on heart and vessels. The aim of this study was to analyze the changes in cardiovascular structure and function associated with use of anti-VEGFR drugs. METHODS Twenty-nine patients (27 affected by renal and 2 by thyroid cancer), received treatment with anti-VEGFR drugs. Brachial blood pressure (BP), central BP, carotid-femoral pulse wave velocity (cfPWV), augmentation index (Aix), and several echocardiographic markers of systolic and diastolic left ventricular functions including global longitudinal strain were measured before starting treatment (T0), after 2 (T1), and 6 weeks (T2) of treatment. RESULTS Anti-VEGFR treatment was accompanied by a significant increase of both peripheral (systolic BP +13±15.5mm Hg, diastolic BP +7.1±9.3mm Hg, P < 0.001) and central BP (systolic BP +14±14.2mm Hg, diastolic BP +7.3±10.4mm Hg, P < 0.001) and a significant raise of cfPWV (+1.3±1.8 m/sec, P = 0.003). There was also a significant alteration of markers of diastolic and subclinical left ventricular systolic function, including global longitudinal strain (-19.9±3.8% at T0, -17.8±2.6% at T2, P < 0.05). All the changes were already evident at T1, worsened at T2 in patients who maintained oncological treatment, but disappeared at T2 in patients in whom treatment was stopped. CONCLUSIONS All the changes regarding BP and cfPWV appear early after treatment initiation and seem to be reversible if treatment is stopped, instead diastolic and systolic left ventricular function are persistently altered by anti-VEGFR drugs.

Within-visit BP variability, cardiovascular risk factors, and BP control in central and eastern Europe: Findings from the BP-CARE study

Introduction and objective: Blood pressure variability (BPV) within 24 h or between visits has been found to represent an independent risk factor for cardiovascular disease. The present study was aimed at determining whether a clinical significance can be given also to the BP variations occurring within a single clinical visit. Methods: BPV was quantified as coefficient of variation and as standard deviation (SD) of the mean of three systolic SBP values within a visit in the context of a large-cross subclinical survey (BP-CARE) of treated hypertensive patients living in Eastern European countries. The study population was divided into coefficient of variation and SD quartiles and for each quartile a relationship was sought with a large number of cardiovascular risk factors based on patients’ history, physical and laboratory examinations. Results: The 6425 hypertensive patients had an age of 59.2 ± 11 years (mean ± SD); they were equally distributed by sex and displayed an average SD and coefficient of variation amounting to 5.1 ± 6.2 mmHg and 3.5 ± 4.0%, respectively. Compared with the lowest coefficient of variation quartile (Q1), patients in the highest quartile (Q4) showed a significantly greater prevalence of several cardiovascular risk factors, such as age (Q1: 58.5 ± 11 vs. Q4: 60.3 ± 11 years, P < 0.001), serum total cholesterol (Q1: 213.0 ± 46 vs. Q4: 216.4 ± 51 mg/dl, P < 0.05), blood glucose (Q1: 106.2 ± 35 vs. Q4: 109.8 ± 39 mg/dl, P < 0.005), previous cardiovascular events (Q1: 57.4 vs. Q4: 63.9%, P < 0.001), and resistant hypertension (Q1: 26.3 vs. Q4: 34.1%, P < 0.001). They also showed higher office (Q1: 143.2 ± 18 vs. Q4: 154.3 ± 19 mmHg, P < 0.001) and 24-h ambulatory SBP values (Q1: 134.8 ± 17 vs. Q4: 141.2 ± 18 mmHg, P < 0.001). Similar results were obtained when BPV was expressed as SD. Conclusion: Our study provides evidence that greater within-visit BP variabilities are associated with a worse cardiovascular risk profile. This suggests that even this type of BPV may have clinical significance.

Brachial and central blood pressure in HIV-infected subjects

HIV infected subjects present an unfavorable cardiovascular (CV) risk profile that is determined by the infection itself, highly active anti-retroviral therapy (HAART) and other factors, such as chronic kidney disease (CKD). Information is scant and contradictory on whether these factors are associated with arterial stiffness and blood pressure (BP) alteration. Our study aimed to evaluate those parameters in HIV-positive subjects both with and without HAART and with and without CKD, which was defined as the presence of microalbuminuria with a normal glomerular filtration rate. We enrolled 94 HIV-infected subjects without known CV risk factors and compared them with 37 control subjects. We recorded brachial and central BP (pulse wave analysis) and pulse wave velocity ( SphygmoCor). HIV-positive subjects of similar ages and with similar BP values showed central pulse pressure values that were significantly greater than those of controls; this was also the case for the Aix value. Central systolic and pulse pressure values and Aix were significantly greater in HIV-positive subjects with HAART and CKD than in the other HIV-positive subgroups and control subjects. PWV was also superimposable between groups when the data were analyzed relative to the presence of HAART and CKD. Our study shows that the unfavorable CV risk profile associated with HIV infection includes an increase in both central BP and Aix. The central BP increase seems to be favored by renal damage, which apparently has a role in the early stages of the disease.

Structural and Functional Abnormalities of Carotid Artery and Their Relation with EVA Phenomenon

Early vascular aging is a process characterized by a reduction in arterial elastin with an increase in collagen that has been related to cardiovascular risk factor and can determine an increased arterial stiffness and central blood pressure. It can be measured by several non invasive methods and in different arterial segment. The present paper will focus on functional (local stiffness parameter) and structural (intima media thickness) carotid arteries alterations typically evaluated by ultrasound methods. Methodological, research and clinical issue has been reviewed.

Does the 9p region affect arterial stiffness? Results from a cohort of hypertensive individuals

Abstract Objective. Evidence exists that arterial stiffness, i.e. an independent predictor of cardiovascular and all-causes mortality, has a genetic component. The 9p21 region is associated with a greater susceptibility to coronary disease. Whether this can be ascribed to the fact that genes located on chromosome 9p may also regulate arterial stiffness is largely unknown, however. We evaluate the influence of single nucleotide polymorphisms (SNPs) from 9p on carotid–femoral pulse wave velocity (C-F PWV), measured via the Complior method, in a cohort of 821 hypertensive subjects. Design. The selected tagSNPs were screened with a custom-designed 384-plex VeraCode GoldenGate Genotyping assay on Illumina BeadXpress Reader platform. Association analysis was done using PLINK considering C-F PWV as a quantitative trait (linear regression assuming an additive model) adjusting for sex, age, systolic blood pressure and body mass index (BMI). We used false discovery rate (FDR) to account for multiple testing. Results. Although none of the 384 SNPs was significant after adjusting for multiple testing, probably due to the small sample size of the study population, a trend of association with C-F PWV was observed for rs300622 and rs2381640. Conclusions. These data suggest that SNPs located on chromosome 9p may affect arterial stiffness. Further studies are needed to confirm our finding on a larger sample and define the physiopathological link of the present results.

Increased nocturnal heart rate and wave reflection are early markers of cardiovascular disease in Williams-Beuren syndrome children.

Objective: Williams–Beuren syndrome (WBS) is a genetic disorder that involves elastin gene causing cardiovascular abnormalities and increased risk. However, data on arterial function in these patients are only few and conflicting. Aim of this study was to evaluate dynamic behaviour of central and peripheral blood pressure (BP) and arterial stiffness parameters early in the course of WBS. Methods: We enrolled 19 WBS paediatric patients (age 13 ± 4 years) and 23 age, height and BP-matched controls (10 ± 4 years). We evaluated 24-h ambulatory BP values via an ambulatory blood pressure monitoring (ABPM) system (Mobil-O-Graph) also capable to calculate 24-h central BP and 24-h arterial stiffness parameters. Carotid-femoral PWV (cf-PWV) was assessed in all WBS individuals (Complior). Results: BP values were similar in WBS and control, during the daytime and the night-time. The same behaviour applies to 24-h central BP. However, during the night, WBS showed heart rate values (HR; 78 ± 10 vs. 71 ± 9 bpm; P < 0.03), augmentation index (Aix; 24.6 ± 13.5% vs. 16.5 ± 8.9%; P = 0.03) and reflection magnitude (68 5.8 vs. 63.5 8.1; P = 0.02) higher than controls. The HR, Aix and reflection magnitude reduction in the day–night shift was lower in WBS than in controls. Cf-PWV in WBS children did not differ when compared with their normalized expected value. Conclusion: In WBS children, the higher night-time HR, Aix and reflection magnitude and their impaired physiological reduction in the day–night shift suggests an abnormal sympathetic cardiovascular control, an augmented wave reflection and an increase in small arteries resistance. These alterations possibly due to a sympathetic overactivity can be regarded as earlier hallmarks of cardiovascular dysfunction in these patients.