Paola Vallerio

Endothelial progenitor cells in patients with essential hypertension.

Objective(s) The eventual role of blood pressure on the endothelial progenitor cell (EPC) has rarely been evaluated and data collected so far relate to patients with co-existing coronary heart disease. Methods We have studied the number and functional activity of EPC as well as the number of EPC endothelial colony-forming units (CFU) in a carefully selected group of 36 patients with essential hypertension and 24 normotensive control subjects. Results In patients with essential hypertension, the EPC number was not statistically different from that found in control subjects (mean ± SD, essential hypertension 58 ± 29, controls 53 ± 20; EPC/high power field). CFU per well were not statistically different in patients with essential hypertension compared with normotensive controls (mean ± SD, patients with essential hypertension 2.4 ± 2.6, normotensive controls 3 ± 3.3 CFU/well). In essential hypertension patients, the EPC number was inversely correlated with both total (R = 0.635, P < 0.0001) and low-density lipoprotein (LDL)-cholesterol (R = 0.486, P < 0.05). Neither the EPC number nor the EPC CFU were correlated with age, systolic blood pressure, diastolic blood pressure, body mass index, lipoprotein(a), high-sensitivity C-reactive protein or homocysteine. Conclusions The present study shows that essential hypertension is not characterized by the altered number or functional activity of EPC. Plasma total and LDL-cholesterol are independent predictors of reduced numbers of circulating EPC in essential hypertension patients. The absence of any correlation between the characteristics of EPC and several markers predictive of cardiovascular damage merits further investigation.

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.

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.

Annexin A5 in treated hypertensive patients and its association with target organ damage

Objective: Annexin A5 (AnxA5) has been previously linked to the presence of carotid and cardiac target organ damage (TOD) in the context of heart failure and rheumatologic patients. However, information is scant in the context of hypertension. Aim of our study was to evaluate AnxA5 in treated hypertension patients compared with normotensive controls and to determine whether it is associated with vascular and heart TOD evaluated as arterial stiffness, carotid plaque and left ventricular hypertrophy. Methods: We enrolled 123 consecutive treated hypertension and 124 normotensive controls. TOD was evaluated as pulse wave velocity (PWV, complior), left ventricular hypertrophy (echocardiography) and intima–media thickness and carotid plaque presence (ecographic methods). AnxA5 levels was dosed and compared in patients with and without hypertension and with and without TOD. Results: With similar age hypertension patients showed higher SBP, DBP and AnxA5 levels (13.9 ± 11.1 vs 10.1 ± 8.4 ng/ml, P < 0.001) compared with controls. Regarding TOD hypertension showed higher PWV (8.5 ± 1.8 vs 7.6 ± 1.5 m/s, P < 0.001) and LVMI (121.7 ± 29.3 vs 113.5 ± 21.1 g/m2, P < 0.05), whereas carotid intima–media thickness was superimposable. AnxA5 correlates with PWV (r = 0.13, P < 0.05) and DBP (r = 0.15, P < 0.01), whereas it has never been found as a significant independent predictor of TOD in linear regression analysis. Conclusion: Our data have shown that AnxA5 levels are increased in treated hypertension patients. In this condition, it is probably released in the plasma as a defensive mechanism through its anti-inflammatory and anticoagulants effects. We found a significant association with arterial stiffness, but AnxA5 was not found to be a significant predictor of TOD.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

Determinants of carotid-femoral pulse wave velocity progression in hypertensive patients over a 3.7 years follow-up

Abstract Objective: The role of risk factors on the progression of arterial stiffness has not yet been extensively evaluated. The aim of the current longitudinal study was to evaluate the determinants of the PWV progression over a 4 years follow-up period in hypertensive subjects. Materials and Methods: We enrolled 333 consecutive hypertensive outpatients 18–80 aged, followed by the Hypertension Unit of St. Gerardo Hospital (Monza, Italy). At baseline anamnestic, clinical, BP, laboratory data and cfPWV were assessed. We performed a PWV follow-up examination with a median time amounting to 3.75 ± 0.53 years. Results: At baseline the mean age was 54.5 ± 12.6 years, SBP and DBP were 141.3 ± 18.6 and 86.4 ± 10.4 mmHg and PWV was 8.56 ± 1.92 m/s. Despite an improvement in BP control (from 37 to 60%), at follow-up the population showed a PWV increase (ΔPWV 0.87 ± 3.05 m/s). PWV and ΔPWV gradually increased in age decades. In patients with uncontrolled BP values at follow-up ΔPWV showed a greater increase as compared to patients with controlled BP (1.46 ± 3.67 vs 0.62 ± 2.61 m/s, p < .05). The independent predictors of ΔPWV were age, baseline PWV, baseline SBP/MBP and ΔSBP/MBP. Conclusions: the accelerated arterial aging in treated hypertensive subjects is in large measure explained by age and BP values. PWV changes over time would probably give important information that need further future research studies.

Radiotherapy: Clinical Aspects and Cardiotoxicity

Radiation therapy (RT) causes inflammation, activation of pro-fibrotic cytokines, and endothelial and microvascular damage. Radiation increases oxidative stress through free radical production and results in recruitment of matrix metalloproteinases and pro-inflammatory mediators. These changes may lead to acute toxicity (evident during or shortly after radiotherapy) and start a chronic process leading to delayed dysfunction that is evident several years later. Acute changes largely result from direct radiation damage and the immediate inflammatory response, while long-term changes are due to stem cell loss and late and persistent tissue fibrosis. Thus, chronic radiation-induced damage is irreversible and can affect multiple cardiac structures including the coronary arteries, myocardium, pericardium, cardiac valves, and the conduction system. The incidence of acute pericarditis has decreased over time from 20 % to 2.5 % with modern radiation techniques; therapy is the same as for acute viral or idiopathic pericarditis. Ventricular dysfunction is a rare event. It is more frequent when an anthracycline or high-dose chemotherapy is administered concurrently, or shortly before RT, since radiation interacts synergistically to induce myocardial damage.Delayed radiation-induced heart disease (RIHD) is a significant problem, especially in long-term survivors of lymphoma and breast cancer. The median time from RT to appearance of clinically significant RIHD is 15 years, with the incidence increasing progressively over time. All the patients treated with mediastinal or chest radiotherapy more than 10 years ago should be object of an active program of prevention and follow-up. The follow-up should last lifelong. Many cancer patients who achieved complete remission are dismissed by the oncological follow-up after 5–10 years. Few patients have the opportunity to be included in a cancer survivor clinic for long-term follow-up of treatment-related disease. The general practitioners and the cardiologists should take care of this problem. The group at highest risk is represented by childhood cancer survivors, and this problem has been addressed in Chap. 16. Coronary Artery Disease (CAD) is the most frequent and relevant form of RIHD. The risk of death due to acute myocardial infarction (AMI) is two- to fourfold higher in patients treated for Hodgkin lymphoma compared with age-matched controls, but can be increased sevenfold or higher in some subgroups. The mechanism involved in plaque formation is thought to mirror spontaneous atherosclerosis; however, plaques in irradiated patients have been found to be more fibrous with decreased lipid content, and the lesions are consistently more proximal, smoother, concentric, tubular, and longer. Left ventricular (LV) dysfunction is a frequent complication of chest RT, and may be due to: macroscopic CAD leading to chronic ischemia; decrease in capillary density resulting in myocyte hypoxia; direct myocyte damage and necrosis, more evident in synergy with anthracycline cardiotoxicity, with progressive fibrosis replacing viable myocardial tissue; increase in type I collagen rather than type III collagen, leading to reduced myocardial distensibility. Valvular heart disease (VHD) ranges from sclerosis to severe, often calcific, valvular stenosis and/or regurgitation. It is more common after mediastinal RT in comparison to chest wall RT for breast cancer. Among breast cancer patients, it is more common after left-sided RT in comparison to right-sided RT. Chronic pericarditis may develop as a consequence of acute pericarditis seen during or shortly after RT and as a delayed complication. Most patients have a combination of restrictive and constrictive disease and pericardial stripping does not afford similar benefits in RT patients compared to those with constriction due to other causes. Arrhythmias can be seen as a consequence of RT, and may be both hyperkinetic and hypokinetic. Inappropriate sinus tachycardia, both at rest and during effort, is common after thoracic RT and is felt to be a consequence of autonomic dysfunction. Bundle branch and atrio-ventricular blocks may also be observed. Radiation-induced carotid disease produces carotid lesions that are more extensive than the traditional bifurcation stenosis and often involves atypical areas such as long segments of the carotid artery. The global risk of cerebrovascular events is increased and the common atherosclerosis risk factors and preexisting atherosclerotic lesions are exacerbating factors In patients presenting with symptoms of dyspnea, fatigue, and reduced exercise tolerance, it is important to consider other organs that may be affected by RT or chemotherapy in the differential diagnosis: acute, chronic and recall radiation pneumonitis should be ruled out; chemotherapyinduced lung disease may be observed with several agents, mostly with bleomycin; radiation fields including the neck (such as mantle field used for HL) may cause thyroid dysfunction, most frequently hypothyroidism..

[BP.07.05] ASSOCIATION BETWEEN URIC ACID AND CARDIAC, VASCULAR AND RENAL TARGET ORGAN DAMAGE IN HYPERTENSIVES SUBJECTS.

Objective: To date no definitive results exist about the relationship of Serum Uric Acid (SUA) and Target Organ Damage (TOD) in hypertensives subjects (HT). We sought to determine if such an association exist between SUA and subclinical cardiac, vascular and renal alterations in HT. Design and method: We enrolled 632 consecutive outpatients, followed by the Hypertension Unit of S. Gerardo Hospital (Monza, Italy) affected by essential HT. We evaluated anamnestic data, clinical Blood Pressure (BP) and laboratory data as well as TOD with cardiac echocardiography (both as Left Ventricular Mass Index – LMVI and diastolic function – E/A), carotid ultrasound (Intima Media Thickness – IMT), arterial stiffness (Pulse Wave Velocity – PWV) and renal function analysis (creatinine and microalbumiuria). Results: Mean age was 53.4 ± 12.7 years, Systolic and Diastolic BP (SBP/DBP) were 140.5 ± 18.8 and 85.1 ± 13.1 mmHg and SUA was 5.2 ± 1.4 mg/dL. Regarding TOD mean LVMI was 109.6 ± 31.4 g/m2, IMT 0.71 ± 0.1 mm, PWV 8.5 ± 2.2 m/s, while creatinine and microalbuminuria were 0.8 ± 0.2 mg/dL and 25.4 ± 126.1 mg/24 h respectively. When subjects were divided into high and low SUA group (depending on the median SUA of 5.2 mg/dL), with similar age and BP values the first group showed significantly higher values of metabolic index (BMI: 27.9 ± 4.1 vs 25.7 ± 4.1 kg/m2; HDL chol: 49.8 ± 13.1 vs 56.8 ± 14.1 mg/dL; triglicerides: 136.1 ± 81.9 vs 104.2 ± 58.1 mg/dL; glucose: 95.4 ± 27.4 vs 86.4 ± 18.2 mg/dL, p < 0.01 for all), LVMI (117.1 ± 32.8 vs 102.1 ± 28.1 g/m2, p < 0.01), IMT (0.73 ± 0.1 vs 0.70 ± 0.1, p = 0.04), PWV (8.8 ± 2.4 vs 8.3 ± 2.1 m/s, p = 0.01) and creatinine (0.9 ± 0.2 vs 0.7 ± 0.1 mg/dL, p < 0.01) and lower E/A (1,0 ± 0.3 vs 1.1 ± 0.3, p < 0.01). SUA showed significant correlation with sex (r = -0.41, p < 0.01), age (r = 0.12, p = 0.01), BMI (r = 0.33, p < 0.01), SBP (r = 0.10, p < 0.01), HDL chol (r = -0.29, p < 0.01), triglicerides (r = 0.34, p < 0.01), glucose (r = 0.21, p < 0.01), creatinine (r = 0.42, p < 0.01), IMT (r = 0.12, p < 0.01), LVMI (r = 0.24, p < 0.01) and E/A (r = -0.15, p < 0.01). Regarding TOD only creatinine presents SUA as as significant determinant in logistic regression analysis with age, sex, BMI, HDL chol, triglicerides and glucose as covariates. Conclusions: In HT, SUA values correlate with metabolic derangements and with cardiac, vascular and renal TOD. The most significant correlation is with renal damage.

[PP.09.08] HEART STRUCTURE AND VASCULAR FUNCTION IN YOUNG PATIENTS AFTER ENDOVASCULAR REPAIR FOR BLUNT THORACIC AORTIC INJURY

Objective: Thoracic Endovascular Aortic Repair (TEVAR) currently represents the gold standard of treatment for blunt thoracic aortic injury (BTAI). Nevertheless there is an ongoing debate surrounding its safety and efficacy and its subsequent cardiovascular effects. The present study is aimed at assessing heart and aortic structure and function after TEVAR in BTAI young patients. Design and method: In 20 patients (18 men, age 41 ± 14 years) treated with TEVAR (11 with Gore CTAG, 9 with Medtronic Valiant) after BTAI, between 2004–2015, after a median follow-up time of 3 years (range 12-1 years; T1) we measured brachial Blood Pressure (BP, sfigmomanometry) and Pulse Wave velocity (cfPWV, sphygmocor) and obtained an echocardiogram with Left Ventricular Mass Index (LVMI) calculation. Results: At baseline all the patients were normotensive; At T1 evaluation patients showed mean normal BP value (131 ± 12/85 ± 10) while 11 of them (55%) were hypertensives. Also LVMI (81,84 ± 28,11 g/m2) and PWV (7,58 ± 1,48 m/s) mean values were within the normal range. When patients were divided accordingly to the used graft patients treated with Medtronic Valiant showed a significantly higher LVMI (97.17 ± 35.78 vs 69.58 ± 11.24 g/m2; p < 0,05) and PWV (7,78 ± 1,74 vs 6,45 ± 1,54 m/s; p < 0,05) compared with those treated with Gore CTAG. Same figures were fouded when patients were divided accordingly to the treating time with those treated more than 3 years before the evaluation that showed higher LVMI (91,16 ± 34,73 vs 70,20 ± 9,44 g/m2; p < 0,01) and PWV (7,50 ± 1,98 vs 6,38 ± 1,04 m/s; p < 0,05). Conclusions: Our study showed for the first time that descending aorta TEVAR for BTAI is associated after some years with the development of hypertension and heart and vascular alterations. The presence of TEVAR modify aortic functional properties and induce in young subject an increase in BP and LVMI probably related to the presence of a rigid aorta .These findings suggest to include a cardiologic follow up of young patients treated with TEVAR.

[PP.27.11] 24 HOUR ARTERIAL DISTENSIBILITY IS RELATED WITH ABPM NON-DIPPING PATTERN IN HIV-POSITIVE PATIENTS

Objective: The use of Anti-Retroviral Therapy (ART) has decreased AIDS–related mortality. However, ART treated HIV-patients have higher cardiovascular (CV) morbidity and mortality than general population. Although hypertension is a frequent risk factor in HIV-patients (both due to HIV inflammatory activation and ART drugs), existing data on Ambulatory Blood Pressure Monitoring (ABPM) phenotypes in this setting are limited, but suggest an increased prevalence of a non-dipping Blood Pressure (BP) pattern. The present study is aimed at determining the prevalence of non-dipping pattern in a population of unselected HIV-patients and its association with arterial stiffness over 24 hour. Design and method: We studied 40 patients (72% man; 53.4 ± 8.8years). We measured office and 24 hour systolic (S) and diastolic (D) BP, the QKd interval during the ABPM evaluation (Dyasis Integra-Novacor, France). QKd represents an index of arterial stiffness and is calculated as the time (measured in ms) between the onset of the depolarization on the electrocardiogram (Q) and the detection of the last Korotkoff sound (K) during cuff deflation. We also obtained information on blood glucose and lipid values. Results: Our HIV positive patients showed normal mean office (127.8/76.5 ± 16.1/7.1 mmHg) and 24 h ABPM (121.1/79.8 ± 13.1/10.7 mmHg) BP values. Regarding CV risk factors 30% of them were smokers, 25% took antihypertensive and 17.5% lipid-lowering drugs. Seventeen patients (42.5%) showed non-dipping pattern at ABPM. Non-dipping patients were superimposable for age, office BP, 24 h and day ABPM, glucose and lipids values and HIV characteristics (infection time, ART time and drugs) to normal dipping patients. On the contrary, they showed a lower QKD (219.9 ± 22.8 vs 203.7 ± 21.3 ms for dippers and non-dippers respectively, p = 0.02). QKd correlates with age (r = −0.57, p < 0.001), 24hDBP (r = 0.32, p = 0.04) and glucose (r = −0.36, p = 0.03) but not with HIV charactheristics and CV risk factors. The independent predictors of QKd at multivariate analysis were age (&bgr; = 0.54, p = 0.001) and 24hDBP (&bgr; = 0.34, p = 0.01). Conclusions: Our results suggest that non-dipping BP is a frequent pattern in HIV-patients and is associated with impairment of arterial distensibility. Nor HIV-infection status parameters nor ART seems to be directly responsible for non-dipping pattern; on the contrary age and 24 hour DBP seem to be strictly related both with dipping and distensibility.