Andrea Grillo

Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) consumption is associated with reduced cardiovascular disease risk. Increasing evidence demonstrating a beneficial effect of n-3 PUFA on arterial wall properties is progressively emerging. We reviewed the recent available evidence for the cardiovascular effects of n-3 PUFA focusing on structural and functional properties of the vascular wall. In experimental studies and clinical trials n-3 PUFA have shown the ability to improve arterial hemodynamics by reducing arterial stiffness, thus explaining some of its cardioprotective properties. Recent studies suggest beneficial effects of n-3 PUFA on endothelial activation, which are likely to improve vascular function. Several molecular, cellular, and physiological pathways influenced by n-3 PUFA can affect arterial wall properties and therefore interfere with the atherosclerotic process. Although the relative weight of different physiological and molecular mechanisms and the dose-response on arterial wall properties have yet to be determined, n-3 PUFA have the potential to beneficially impact arterial wall remodeling and cardiovascular outcomes by targeting arterial wall stiffening and endothelial dysfunction.

Ambulatory arterial stiffness indices and non-alcoholic fatty liver disease in essential hypertension

BACKGROUND AND AIM Non-alcoholic fatty liver disease (NAFLD) has been found to be strongly related to an increased arterial stiffness in patients with essential hypertension, suggesting a pathophysiologic link between major cardiovascular and metabolic abnormalities associated with liver steatosis and the functional and structural alterations of the arterial wall. The aim of our study was to investigate, in a group of essential hypertensive patients without additional cardiovascular risk factors, the relationship between NAFLD and arterial stiffness. METHODS AND RESULTS Sixty-eight consecutive patients with essential hypertension underwent 24-h ambulatory blood pressure monitoring (ABPM) and were separated according to the presence (n = 40) or absence (n = 28) of NAFLD at liver ultrasonography. The Ambulatory Arterial Stiffness Index (AASI) and Symmetric AASI (Sym-AASI) were derived from ABPM tracings. Patients with diabetes, obesity, hyperlipidaemia or other risk factors for cardiovascular or liver disease were excluded. Hypertensive patients were compared with a normotensive control group.The two hypertensive groups had comparable age, sex distribution and clinic/ABPM blood pressure levels. In hypertensive patients with NAFLD, body mass index, fasting glucose, insulin, homeostasis model of assessment of insulin resistance index and triglyceride levels were higher, whereas plasma adiponectin was lower than in patients without NAFLD. In hypertensive patients, AASI and Sym-AASI were higher (P < 0.001) than in normotensive subjects, but both indices of vascular stiffness were comparable in patients with and without NAFLD. CONCLUSIONS In essential hypertensive patients without additional cardiovascular risk factors, NAFLD is associated with insulin resistance but not with increased arterial stiffness.

Ambulatory Arterial Stiffness Indexes in Acromegaly

OBJECTIVE Acromegaly is associated with increased cardiovascular morbidity and mortality and with specific heart and vascular abnormalities. The aim of our study was to investigate arterial stiffness using the ambulatory arterial stiffness index (AASI) and symmetric AASI (Sym-AASI), two indexes derived from 24-h ambulatory blood pressure monitoring (ABPM), in a group of normotensive and hypertensive patients with active acromegaly, compared with normotensive controls (NOR-CTR) or hypertensive controls (HYP-CTR). SUBJECTS AND METHODS Ninety-six consecutive patients with active acromegaly (46 males, mean age 49±14 years) underwent 24-h ABPM and evaluation of cardiovascular risk factors. Based on ABPM measurement, acromegalic patients were divided into 64 normotensive (normotensive acromegalic patients (NOR-ACRO)) and 32 hypertensive (hypertensive acromegalic patients (HYP-ACRO)) patients, and were compared with 35 normotensive (NOR-CTR) and 34 hypertensive (HYP-CTR) age-, sex,- and ABPM-matched control subjects. RESULTS The AASI and Sym-AASI indexes were significantly higher in acromegalic patients than in controls, either in the normotensive (NOR-ACRO vs NOR-CTR, P<0.0001 for AASI and P=0.005 for Sym-AASI) or in the hypertensive (HYP-ACRO vs HYP-CTR, P=0.01 for AASI and P=0.01 for Sym-AASI) group. Multiple logistic regression analysis showed a significant association of the highest AASI tertile with serum IGF1 (P=0.034) in the whole acromegalic group. CONCLUSION AASIs are increased in acromegaly, independent of blood pressure (BP) elevation, and may have an important role in predicting cardiovascular risk in this disease.

Supplementation of Omega-3 Polyunsaturated Fatty Acids Prevents Increase in Arterial Stiffness After Experimental Menopause

Background: Menopause is associated with increased arterial stiffness, an independent marker of cardiovascular risk. Omega-3 polyunsaturated fatty acids (N3-PUFAs) are thought to have multiple cardiovascular benefits, including prevention of arterial stiffness. We investigated whether treatment with N3-PUFA prevents increase in arterial stiffness in ovariectomized rats, an animal model of experimental menopause. Methods: A total of 43 Wistar rats, 2 months old, were divided into 3 groups, control, sham surgery, normal diet (CTRL, n = 15); ovariectomy, normal diet (OVX, n = 14); and ovariectomy with N3-PUFA supplementation (0.8 g/kg/d in daily gavages administration; OVX + O3, n = 14). Two months after surgery, carotid–femoral pulse wave velocity (PWV) and arterial blood pressure (BP) were measured by carotid and femoral cannulation. Aortic morphometric measurements were performed after dissection. Results: Ovariectomy caused a significant increase in BP (P < .05), PWV (P < .0001), and elastic modulus (P = .001) compared to CTRL. After ovariectomy, N3-PUFA supplementation completely prevented increase in arterial stiffness (P < .0001 vs OVX) and BP (P < .05 vs OVX) and resulted in a significant increase in body weight and aortic thickness. Conclusions: In an experimental model of menopause, N3-PUFA supplementation prevents arterial stiffening and other vascular changes induced by ovariectomy. These results represent a therapeutic benefit of N3-PUFAs in prevention of postmenopausal cardiovascular disease.

Baroreflex sensitivity and central hemodynamics after omega-3 polyunsaturated fatty acids supplementation in an animal model of menopause.

OBJECTIVE Baroreflex sensitivity (BRS) and central arterial function are significantly worsened after menopausal transition. This study tested the hypothesis that administration of n-3 polyunsaturated fatty acids (n-3 PUFA) might contribute to prevent these adverse changes in the vascular function of ovariectomized rats, an animal model of experimental menopause. METHODS We randomized 30 female Wistar rats, 2months old, into 3 groups: control (CTRL), sham surgery, normal diet; ovariectomized with normal diet (OVX) and ovariectomized with n-3 PUFA supplementation by daily gavage (0.8g/kg/d) (OVX+O3). Two months after surgery, BRS was calculated as the bradycardic response to phenylephrine-induced blood pressure increase, while large artery function was estimated by the graphical analysis of the aortic pressure wave (diastolic to systolic pressure-time integral ratio, DTI/STI). RESULTS Ovariectomy caused a significant decrease in BRS (CTRL: 6.23±0.68ms/mmHg; OVX: 2.85±0.75; p<0.001). n-3 PUFA supplementation prevented part of the decline of BRS caused by surgical menopause (OVX+O3: 4.75±0.53; p<0.01 vs OVX). In animals treated with n-3 PUFA, the central arterial pressure profile did not show the changes in DTI/STI ratio seen in OVX (OVX: 3.31±1.72; OVX+O3: 3.83±1.52; p<0.01). CONCLUSIONS In an experimental model of menopause, treatment with n-3 PUFA normalized central hemodynamics and prevented the decrease in BRS, associated with the reduction of compliance of the arterial wall. These findings suggest a therapeutic benefit of n-3 PUFA supplementation in the prevention of postmenopausal vascular disease.

Ambulatory Blood Pressure Monitoring-Derived Short-Term Blood Pressure Variability in Primary Aldosteronism

The aim of this study was to investigate the short‐term blood pressure (BP) variability (BPV) derived from ambulatory blood pressure monitoring (ABPM) in patients with primary aldosteronism (PA), either idiopathic hyperaldosteronism (IHA) or aldosterone‐producing adenoma (APA), in comparison with patients with essential hypertension (EH) and normotensive (NT) controls. Thirty patients with PA (16 with IHA and 14 with APA), 30 patients with EH, and 30 NT controls, matched for sex, age, body mass index, and antihypertensive therapy, were studied. The standard deviation (SD) of 24‐hour, daytime, and nighttime BP; 24‐hour weighted SD of BP; and 24‐hour BP average real variability were not different between patients with PA and those with EH (P=not significant). All BPV indices were higher in patients with PA, either IHA or APA subtypes, and patients with EH, compared with NT controls (P<.001 to P<.05). ABPM‐derived short‐term BPV is increased in patients with PA, and it may represent an additional cardiovascular risk factor in this disease. The role of aldosterone excess in BPV has to be clarified.

Noninvasive estimation of central blood pressure and analysis of pulse waves by applanation tonometry

Noninvasive estimation of central blood pressure and analysis of pulse waves by applanation tonometry

Ambulatory Arterial Stiffness Indexes in Cushing’s Syndrome

Long-standing exposure to endogenous cortisol excess is associated with high cardiovascular risk. The aim of our study was to investigate arterial stiffness, which has been recognized as an independent predictor of adverse cardiovascular outcome, in a group of patients with Cushings syndrome. Twenty-four patients with Cushings syndrome (3 males, mean age 49±13 years; 20 pituitary-dependent Cushings disease and 4 adrenal adenoma) underwent 24-h ambulatory blood pressure monitoring (ABPM) and evaluation of cardiovascular risk factors. The Ambulatory Arterial Stiffness Index (AASI) and symmetric AASI (sAASI) were derived from ABPM tracings. Cushing patients were divided into 8 normotensive (NOR-CUSH) and 16 hypertensive (HYP-CUSH) patients, and were compared with 8 normotensive (NOR-CTR) and 16 hypertensive (HYP-CTR) control subjects, matched for demographic characteristics, 24-h ABPM and cardiometabolic risk factors. The AASI and sAASI indexes were significantly higher in Cushing patients than in controls, either in the normotensive (p=0.048 for AASI and p=0.013 for sAASI) or in the hypertensive (p=0.004 for AASI and p=0.046 for sAASI) group. No difference in metabolic parameters was observed between NOR-CUSH and NOR-CTR or between HYP-CUSH and HYP-CTR groups. AASI and sAASI were both correlated with urinary cortisol in patients with endogenous hypercortisolism (Spearmans rho=0.40, p=0.05, and 0.61, p=0.003, respectively), while no correlation was found in controls. Both AASI and sAASI are increased in Cushing syndrome, independent of BP elevation, and may represent an additional cardiovascular risk factor in this disease. The role of excess cortisol in arterial stiffness has to be further clarified.

5B.05: MARFAN SYNDROME: ASSESSMENT OF AORTIC DISSECTION RISK BY ANALYSIS OF AORTIC VISCOELASTIC PROPERTIES.

Objective: Marfan syndrome is an autosomal dominant genetic disorder characterized by an abnormal fibrillin-1 synthesis. Aortic root dilation and dissection are the main problems affecting patients prognosis in these patients. Their pharmacological prophylaxis with losartan or with a beta-blocker counteracts the aortic root dilation, but a close follow-up is required to assess therapeutic response rate and to identify non-responders. Unfortunately genotype-phenotype studies do not allow to determine the exact risk profile in these patients and there is no reliable method to accurately predict their risk of aortic dissection. Aim of this study was to evaluate non-invasive markers for identification of Marfan patients at higher risk of aortic complications. Design and method: We studied 187 Marfan patients (identified according to 2010 Revised Ghent Criteria and positive genetic analysis), age 32.3 ± 16.5 yrs (mean ± SD). 52 patients (27.8%) had undergone surgical ascending aorta replacement (David or Bentall procedure). Central pressure curves were recorded by PulsePen tonometer, and the aortic viscoelastic aortic properties were studied by determination of carotid-femoral pulse wave velocity (PWV). Results: With reference to the age related distribution of PWV values in a normal population, defined according to Arterial-Stiffness-Collaboration, PWV mean values in Marfan patients corresponded to 60th percentile in non- operated patients and to the 67th percentile in those operated. Adult Marfan patients (n = 146) generally displayed a low blood pressure, because of the pharmacological prophylaxis, and were compared with a population of 189 adult healthy subjects (81 males), matched by age (38 ± 13 vs 38 ± 16 yrs.), heart rate (64 ± 9 bpm vs 64 ± 11 bpm) and blood pressure (mean BP = 78 ± 9 mmHg vs 79 ± 4 mmHg) values. Average PWV value was higher than in healthy controls (PWV = 7.0 ± 1.7) both in not operated (PWV = 7.6 ± 1.6; p = 0.0003) and in operated (PWV = 9.5 ± 3.2; p < 0.0001) Marfan patients. Among non operated patients, PWV was significantly correlated to aortic root diameters (Aortic annulus: R2 = 0.14; Valsalva sinuses: R2 = 0.22; Sinotubular junction: R2 = 0.28). Conclusions: A significant reduction of the distensibility of the aorta was found in Marfan syndrome. Further analyses are needed to assess the prognostic significance of PWV changes seen in these in these patients.

Systolic time intervals assessed from analysis of the carotid pressure waveform

OBJECTIVE The timing of mechanical cardiac events is usually evaluated by conventional echocardiography as an index of cardiac systolic function and predictor of cardiovascular outcomes. We aimed to measure the systolic time intervals, namely the isovolumetric contraction time (ICT) and pre-ejection period (PEP), by arterial tonometry. APPROACH Sixty-two healthy volunteers (age 47  ±  17 years) and 42 patients with heart failure and reduced ejection fraction were enrolled (age 66  ±  14 years). Pulse waves were recorded at the carotid artery by arterial tonometry together with simultaneous aortic transvalvular flow by Doppler-echocardiography, synchronized by electrocardiographic gating. The ICT was determined from the time delay between the electrical R wave and the carotid pressure waveform, after adjustment for the pulse transit time from the aortic valve to the carotid artery site, estimated by an algorithm based on the carotid-femoral pulse wave velocity. The PEP was evaluated by adding the electrical QR duration to the ICT. MAIN RESULTS The ICT derived from carotid pulse wave analysis was closely related to that measured by echocardiography (r  =  0.90, p  <  0.0001), with homogeneous distribution in Bland-Altman analysis (mean difference and 95% confidence interval  =  0.2 from  -14.2 to 14.5 ms). ICT and PEP were higher in cardiac patients than in healthy volunteers (p  <  0.0001). The ratio between PEP and left ventricular ejection time was related to the ejection fraction measured with echocardiography (r  =  0.555, p  <  0.0001). SIGNIFICANCE The timing of electro-mechanical cardiac events can be reliably obtained from the carotid pulse waveform and carotid-femoral PWV, evaluated using arterial tonometry. Systolic time intervals assessed with this approach showed good agreement with measurements performed with conventional echocardiography and may represent a promising additional application of arterial tonometry.