Francesca Cesana

Low anthracyclines doses-induced cardiotoxicity in acute lymphoblastic leukemia long-term female survivors†

High dosage anthracyclines in pediatric patients with acute lymphoblastic leukemia (ALL) is associated with cardiotoxicity. However, data on the cardiac effects of lower cumulative doses of these drugs are not conclusive. The aim of this study was to assess the cardiac effects of low cumulative anthracycline doses in long‐term survivors of ALL.

Regional differences in sympathetic activation in lean and obese normotensive individuals with obstructive sleep apnoea.

Objective: Obstructive sleep apnoea (OSA) is characterized by a marked sympathetic overdrive, as documented by the elevated sympathetic nerve firing rate detected in peripheral muscle nerves. No data are available, however, on the behaviour of sympathetic drive in vascular regional districts other than the muscle circulation. Design and methods: In 66 middle-aged normotensive individuals classified according to BMI, waist-to-hip ratio and apnoea–hypopnea index as lean individuals without (n = 20) or with (n = 14) OSA and as obese individuals without (n = 13) or with (n = 19) OSA, we measured blood pressure, heart rate, muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA), respectively, via microneurography. Measurements also included SSNA responses to an emotional stimulus. Results: The four groups were matched for age, sex and blood pressure values. Both in lean and obese individuals, presence of OSA was accompanied by MSNA values significantly greater than those found in non-OSA individuals. In contrast, no significant difference was found in SSNA values between OSA and non-OSA patients both in the lean and in the obese groups. This was the case also for the SSNA responses to an emotional arousal. Conclusion: These data provide the first evidence that in OSA, the adrenergic overdrive seen in the muscle circulation is not detected in cutaneous circulation and thus it cannot be regarded as a generalized phenomenon affecting the whole cardiovascular system. Further studies are needed to clarify whether in OSA, sympathetic drive of other vascular districts, such as the coronary, renal or cerebral circulation, is activated or normal.

Blood Pressure Control in Italian Essential Hypertensives Treated by General Practitioners

BACKGROUND Adequate control of blood pressure (BP) is limited worldwide. This has serious consequences for public health because in hypertensive patients, uncontrolled BP is associated with a higher incidence of cardiovascular events, particularly stroke. The aim of this study was to investigate BP control in a cohort of treated patients with diagnosed hypertension, who were under general practitioner care in Italy. METHODS Data were collected by 2,643 physicians on 8,572 individual Italian patients. Office BP was measured 5 min after seating each patient and then 3-5 min later. For each patient, data such as medical history of patients, physical examination data, antihypertensive drug usage, and self-BP measurement frequency were obtained. RESULTS Male prevalence was 48.4%, and mean age was 64.3 ± 10.5 years. Based on the second measurement, BP control (<140/90 mm Hg) was observed in 33.5% of all patients (34.2% in men and 33.4% in women). BP control was much lower for systolic BP than for diastolic BP (35.9 vs. 61.3%, P < 0.0001); moreover, BP control was much more common in patients who were engaged in self-BP measurement (61.2 vs. 38.8%, P < 0.0001). A stricter BP control recommended by the guidelines of the European Society of Hypertension (ESH) and European Society of Cardiology (ESC) (<130/80 mm Hg) was observed in only 5.5% of diabetic patients. CONCLUSIONS In treated Italian hypertensives effective BP control remains uncommon largely due to the failure to appropriately reduce the systolic BP. The stricter values recommended by the ESH/ESC guidelines for diabetic patients are achieved only by a small fraction of hypertensive diabetic population.

Increased pulse wave velocity and not reduced ejection fraction is associated with impaired baroreflex control of heart rate in congestive heart failure.

Background It is known that baroreflex sensitivity (BRS) is impaired in cardiac patients with myocardial infarction (MI). Nevertheless, it is unknown whether factors other than a reduced ejection fraction play a role in the baroreflex impairment of these patients. Methods and results Heart failure patients [congestive heart failure (CHF), n = 31, age 63 ± 1.2 years, mean ± SEM)], age-matched controls (n = 29) and coronary artery disease (CAD) patients without MI (n = 29) had RR interval and arterial blood pressure (BP) continuously monitored. Baroreflex function was assessed by the slope of the regression of RR interval, and BP responses to graded (−10, −20 and −40 mmHg) neck suction stimulation, the slope of bradycardic or tachycardic responses to spontaneous increases or reductions of SBP (sequence analysis) and the baroreflex efficiency index. Pulse wave velocity (PWV) was also measured. Compared with controls, CHF patients had RR interval and BP reflex responses to neck suction reduced by −36 and −54%, respectively (P < 0.01). By contrast, no differences were found between CHF and CAD patients. Similar reductions were observed for the sequence analysis (P < 0.01) in both CHF and CAD patients. Multiple regression analysis showed that in CHF and CAD patients, PWV and SBP and not ejection fraction were correlated with BRS. Conclusion The baroreflex function is impaired in CHF patients, the extent and the degree of baroreflex impairment being similar to that of CAD patients without MI. In CHF and CAD patients, the baroreflex impairment correlates significantly with the increased PWV and not with ejection fraction.

Radiofrequency-based carotid wall tracking: a comparison between two different systems.

Objectives: A direct measurement of carotid stiffness implies an accurate assessment of changes in carotid diameter and pressure during cardiac cycle. Radiofrequency-based wall-tracking systems (WTS) are capable to track arterial wall movement with adequate spatial and temporal resolution, and to provide carotid pressure estimate from calibrated distension waveforms. The aim of the present study was to compare the values of carotid distension and beta-stiffness index acquired in the same population by two commercially available WTS, in order to determine whether their measures can be pooled in clinical studies. In addition, a local carotid pulse pressure (PP) obtained from calibrated distension waveforms was compared with that obtained from pressure waveforms. Methods: In 105 patients, right common carotid artery (CCA) systo-diastolic excursions were assessed during the same session and by the same operator both by WTS implemented in Esaote system (QAS, MyLab) and in Aloka system (E-track; Alpha 10). In 78 patients, carotid PP was also estimated by applanation tonometry. Results: Despite comparable blood pressure and heart rate values during the two acquisitions, CCA distension was significantly lower (363 ± 162 vs. 458 ± 176 &mgr;m, P < 0.0001) and beta-stiffness index (11.9 ± 5.5 vs. 9.4 ± 3.8, P < 0.0001) higher with Esaote as compared to Aloka. PP obtained from calibrated pressure and distension waveforms was comparable (42.6 ± 11.4 vs. 43.0 ± 10.7 mmHg, P = 0.51). Conclusions: The values of carotid distension and stiffness obtained by two different WTS are not interchangeable and cannot be merged into a common database. Calibrated distension curves may provide an acceptable estimate of local carotid pressure.

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.

Multiparametric carotid and cardiac ultrasound compared with clinical risk scores for the prediction of angiographic coronary artery disease: a multicenter prospective study.

Objective: Cardiovascular risk prediction is deemed fundamental and the assessment of organ damage is emerging as a potentially ‘downstream’ picture of individual risk. Our aim was to assess the feasibility and value of prediction of coronaropathy [coronary artery disease (CAD)] of integrated cardiovascular ultrasound examination. Methods: This multicenter study involved eight cardiology centers that enrolled 457 consecutive patients. Blood pressures, carotid intima–media thickness (cIMT), carotid pulse wave velocity (cPWV), semiquantitative score of cardiac calcifications, global myocardial longitudinal strain (GLS), and rest Doppler flow velocity on the left anterior descending (LAD) coronary artery were measured. After coronary angiography, patients were divided in CAD, n = 273, at least one coronary stenosis higher than 50%, and no CAD, n = 184. Results: CAD were older (65.9 ± 10.7 versus 63.1 ± 11.2 years, mean ± standard deviation, P = 0.01), and had higher blood pressure (137.0 ± 18.8/77.5 ± 11.1 versus 130.2 ± 17.4/75.1 ± 9.7 mmHg, P < 0.02), cIMT (791.4 ± 165.5 versus 712.0 ± 141.5 mcm, P < 0.0001), cPWV (median: 9 versus 8.1 m/s, P < 0.01), score of calcium (median, 2 versus 1, P < 0.0001), LAD velocity (median, 38 versus 36, P < 0.07), and lower GLS (−17.6 ± 4.3 versus −19.3 ± 5.1, P < 0.05) than no CAD. Score of calcium was feasible in the totality of patients, cIMT in 97%, cPWV in 86%, GLS in 88%, and LAD in 84%. A combination of at least three variables was measurable in 80% of the patients. All ultrasound parameters significantly predicted CAD. However, in a stepwise logistic regression, the only combined predictors of obstructive CAD were score of calcium, cIMT, and LAD velocity. Conclusion: In Echo-Lab, Rome, Italy, the integrated cardiovascular ultrasound study is feasible in a high percentage of patients. The combination of three parameters, that is, score of calcium, cIMT, and LAD velocity, has incremental predictive value for obstructive CAD.

Ultrasound carotid intima-media thickness, carotid plaque and cardiac calcium incrementally add to the Framingham Risk Score for the prediction of angiographic coronary artery disease: A multicenter prospective study☆ , ☆☆

Ultrasound carotid intima–media thickness, carotid plaque and cardiac calcium incrementally add to the Framingham Risk Score for the prediction of angiographic coronary artery disease: A multicenter prospective study☆☆☆ Nicola Gaibazzi ⁎, Fausto Rigo , Rita Facchetti , Scipione Carerj , Cristina Giannattasio , Antonella Moreo , Gianfrancesco Mureddu , Anna Paini , Elisabetta Grolla , Giacomo Faden , Francesca Cesana , Pompilio Faggiano g

Differential incremental value of ultrasound carotid intima–media thickness, carotid plaque, and cardiac calcium to predict angiographic coronary artery disease across Framingham risk score strata in the APRES multicentre study

AIMS According to recent data, more accurate selection of patients undergoing coronary angiography for suspected coronary artery disease (CAD) is needed. From the Active PREvention Study multicentre prospective study, we further analyse whether carotid intima-media thickness (cIMT), carotid plaques (cPL), and echocardiographic cardiac calcium score (eCS) have incremental discriminatory and reclassification predictive value for CAD over clinical risk score in subjects undergoing coronary angiography, specifically depending on their low, intermediate, or high class of clinical risk. METHODS AND RESULTS In eight centres, 445 subjects without history of prior CAD but with chest pain of recent onset and/or a positive/inconclusive stress test for ischaemia prospectively underwent clinically indicated elective coronary angiography after cardiac and carotid ultrasound assessments with measurements of cIMT, cPL, and eCS. The study population was divided into subjects at low (10%), intermediate (10-20%), and high (>20%) Framingham risk score (FRS). Ultrasound parameters were tested for their incremental value to predict CAD over FRS, in each pre-test risk category. No significant difference could be appreciated between the discrimination value of FRS and Diagnostic Imaging for Coronary Artery Disease score for the presence of CAD. eCS or cPL demonstrated significant incremental prediction over FRS, consistently in the three FRS categories (P < 0.01); this applied to both discrimination and reclassification, with the exception of high-risk subjects, in whom cPL was apparently not incremental over FRS, and eCS was only of borderline significance for better discrimination. CONCLUSIONS Ultrasound eCS and cPL assessments were significant predictors of angiographic CAD in patients without prior CAD but with signs or symptoms suspect for CAD, independently and incrementally to FRS, across all pre-test risk probability strata, although in high-risk subjects, only eCS maintained an incremental value. The use of cIMT was not significantly incrementally useful in any FRS risk category.