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The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07–6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04–1.27], p < 0.001 and HR 1.25 [1.09–1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

Background Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional‐based Italian cohort. Methods and Results Among 14 189 subjects aged 18 to 95 years followed‐up for 11.2 (5.3–13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high‐density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid‐lowering drugs. During 139 375 person‐years of follow‐up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8–103.3, sensitivity 76.6, specificity 34.1, P

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan–Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

Abstract The effect of metabolic syndrome (MetS) and clusters of its components on central blood pressure (CBP) has not been well characterized. We aimed to describe the effect of MetS and clusters of its components on CBP in a large population and to identify whether this effect differs in men and women. We studied 15,609 volunteers (43% women) from 10 cohorts worldwide who participated in the Metabolic syndrome and Artery REsearch Consortium. MetS was defined according to the NCEP-ATP III criteria (GHTBW, glucose, high-density lipoprotein cholesterol, triglyceride, blood pressure, waist circumference). CBP was measured noninvasively and acquired from pulse wave analysis by applanation tonometry. MetS was associated with a 50% greater odds of having higher CSBP. After controlling for age, male sex, non HDL cholesterol, diabetes mellitus, and mean arterial pressure, only specific clusters of MetS components were associated with a higher CSBP; and some of them were significant in women but not in men. We identified “risky clusters” of MetS variables associated with high CSBP. Future studies are needed to confirm they identify subjects at high risk of accelerated arterial aging and, thus, need more intensive clinical management.

Malignant hypertension (MH) is characterized by severe hypertension (usually grade 3) associated with fundoscopic changes (flame hemorrhages and/or papilledema), microangiopathy and disseminated intravascular coagulation. In addition encephalopathy, acute heart failure and acute deterioration in renal function may be present. The term “malignant” reflects the very poor prognosis for this condition if untreated. When severe hypertension is associated with hypertension-mediated organ damage (HMOD) a life-threatening situation that requires immediate but careful intervention occurs (hypertensive emergency). In the last few years an increase in the number of patients with malignant hypertension has been observed, especially among those patients with black ethnicity. Limited access to treatment and the poor adherence to anti-hypertensive therapy may contribute to the development of hypertensive emergencies. It is considered appropriate to study patients in order to rule out thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. In fact, the microvascular damage caused by malignant hypertension can favor intravascular hemolysis like Thrombotic Microangiopathies (TMs). TMs may present in three different clinical conditions: typical hemolytic uremic syndrome (HUS), atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). TMs can arise in the context of other pathological processes, including malignant hypertension.

Background: Thyroid storm is a rare, life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis and can be precipitated by several factors. We described a thyroid storm precipitated by a long-term treatment using homeopathic medicine containing iodine. Case presentation: A 55-year-old Italian woman was admitted to our Sub-Intensive Care Unit with the diagnosis of congestive heart failure and thyrotoxicosis. She has been diagnosed with Graves’ disease two years before; she refused conventional therapy and in the preceding six months had been using phytotherapeutic and homeopathic medicine. We found serum and urine iodine levels consistent with severe intoxication by iodine (serum iodine: 42100 mcg/L and urinary iodine: 4223 mcg/L, respectively). After a few hours, the patient went into cardiac arrest. She was subjected to invasive ventilation, dialyzed with continuous veno-venous hemofiltration and treated with vasoactive amines. Conclusion: The high level of iodemia manifested in our patient - around a thousand times greater than the normal range and itself associated with fatal outcomes - was caused by long-term homeopathic treatment. This long-term treatment has two consequences: first, iodine load-precipitated hyperthyroidism in thyroid storm, and secondly, it prevents us from treating patients with inorganic iodide.

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan–Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (≥4.7 mg/dL) and CVM (≥5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12–1.40], p < 0.001) and CVM (1.31 [1.11–1.74], p < 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12–1.43], p < 0.001) and hypertriglyceridemia (1.31 [1.02–1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23–1.73], p < 0.001) and hypertriglyceridemia (HR 1.31 [0.99–1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels.

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality.Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality.Results: After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and

The management of an acute hemolytic event in a patient suffering from favism is based on transfusion support to ensure adequate tissue oxygenation. If this measure could not be pursued, in case of severe anemia the risk of death from multiorgan failure would be relevant. Most of Jehovah’s Witness decline transfusion of whole blood and its main components, even in life-threatening situations. In this context, the treatment of severe anemia in these patients still represents a challenge from both medical and legal stand points. Authors report a case of a Jehovah’s Witness suffering from favism who refused blood transfusion, surviving a severe event of critical anemia associated with acute renal failure, thanks to the application of alternative therapies. It is essential that clinicians know the medico-legal aspects in such situations and are able to act promptly to support the patient’s vital functions, by complying with his/her wishes.

Objective: Altered coagulation parameters in COVID-19 patients is associated with a poor prognosis. We tested whether COVID-19 patients on chronic oral anticoagulants (cOACs) for thromboembolism prophylaxis could receive protection from developing more severe phenotypes of the disease.Approach and Results: We searched the database of the SARS-RAS study (Clinicaltrials.gov: NCT04331574), a cross-sectional observational multicenter nationwide survey in Italy designed by the Italian Society of Hypertension. The database counts 2,377 charts of Italian COVID-19 patients in 26 hospitals. We calculated the Charlson comorbidity index (CCI), which is associated with death in COVID-19 patients. In our population (n = 2,377, age 68.2 ± 0.4 years, CCI: 3.04 ± 0.04), we confirm that CCI is associated with increased mortality [OR: 1.756 (1.628-1.894)], admission to intensive care units [ICU; OR: 1.074 (1.017-1.134)], and combined hard events [CHE; OR: 1.277 (1.215-1.342)]. One hundred twenty-five patients were on cOACs (age: 79.3 ± 0.9 years, CCI: 4.35 ± 0.13); despite the higher CCI, cOACs patients presented with a lower risk of admissions to the ICU [OR 0.469 (0.250-0.880)] but not of death [OR: 1.306 (0.78-2.188)] or CHE [OR: 0.843 (0.541-1.312)]. In multivariable logistic regression, cOACs confirmed their protective effect on ICU admission and CHE. The CCI remains the most important risk factor for ICU admission, death, and CHE.Conclusions: Our data support a mechanism for the continuation of cOAC therapy after hospital admission for those patients who are on chronic treatment. Our preliminary results suggest the prophylactic use of direct cOACs in patients with elevated CCI score at the time of the COVID-19 pandemic even in absence of other risks of thromboembolism.

Objective: Antiangiogenic therapies (tyrosine kinase inhibitors-TKI and direct anti-VEGF monoclonal antibodies) are being increasingly used in the treatment of solid tumors; hypertension represents a common side effect of these agents. Several mechanisms are involved in the development of hypertension, including microvascular rarefaction and other microvascular alterations. Therefore, the aim of our study was to evaluate whether TKI and direct anti-VEGF agents may affect the structure of retinal arterioles or capillary density.Design and Methods: We investigated 20 patients with a diagnosis of cancer who underwent a treatment with either a TKI or an anti-VEGF antibody. Patients were submitted to ambulatory monitoring blood pressure for blood pressure evaluation. Basal and total capillary density were assessed by capillaroscopy whereas, retinal arteriole morphology was measured by Adaptive Optics. Patients were evaluated before starting the antiangiogenic therapy (T0) and re-evaluated after 3 (T3) and 6 (T6) months after treatment. Fourteen patients completed the study.Results: Systolic and diastolic blood pressure values were similar in all patients at T3 and T6 compared to T0. However, during the study antihypertensive treatment was optimized (increased dose and/or addition of drugs) in 57% of patients (n = 8). No differences were observed in retinal arteriole structural parameters and in large artery stiffness. Basal capillary density was reduced by antiangiogenic drugs after 3 or 6 months.Conclusions: Our data suggest that an increase of antihypertensive treatment is necessary in patients treated with a TKI or a direct VEGF inhibitor, confirming pro-hypertensive effects of these drugs. However, under adequate blood pressure control, microvascular structure seem to be partially preserved, since a worsening of basal capillary density but no changes in retinal arteriole morphology were observed.

The aim of this study is to assess practice and effectiveness of Peripheral Venous Catheter (PVC) insertion and intravenous fluid administration in the Emergency Department (ED). A prospective study was conducted at a single primary ED in Brescia, Italy. 455 participants were included in the analysis. PVC were placed in 88 % of patients, 18 gauge catheters were the most frequently used (63%). In 360 patients PVC placement required one attempt. In 99 % of patients PVCs were used at least once. Fluid administration was considered appropriate in 23 patients. Out of 402 PVC placements, 244 were not necessary (in 225 patients PVCs were used only for blood samples withdrawal, and in 16 patients they were used for blood samples withdrawal, and inappropriate fluid administration). We concluded that a large number of PVC placements in the ED was potentially avoidable, and, when PVCs were used for IV fluid administration, the indication was often inappropriate. Physicians should carefully assess the real need of PVC placement in patients admitted to the ED and critically assess some issues of everyday practice, like PVC placement or IV fluids prescription, with evaluation of cost savings.

[This corrects the article DOI: 10.1371/journal.pone.0237297.].

BackgroundCritically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPLs) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-β2GPI), and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-β2GPI antibodies was not reported.ObjectiveTo evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-β2GPI antibodies.MethodsELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events.ResultsAnti-β2GPI IgG/IgA/IgM was the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM was detected in 5.7/6.6% by ELISA. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA. No association between thrombosis and aPL was found. Reactivity against domain 1 and 4-5 of β2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-β2GPI nor with thrombosis.ConclusionsaPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against β2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.

Measurement of “unattended” blood pressure (BP) may reduce or eliminate the “white coat effect”. Despite the possible advantages of this approach for BP measurement, only few studies analysed the relationship between unattended BP and cardiovascular events or with hypertension mediated organ damage (HMOD). The aim of our study was to evaluate the relationship between “attended” or “unattended” BP values and carotid-femoral pulse wave velocity (PWV) in 285 subjects undergoing a visit and assessment of arterial stiffness at an ESH Excellence Centre. Unattended BP (measured with the patient alone in the room, with an oscillometric device programmed to perform 3 BP measurements, at 1 minute intervals, after 5 minutes) and attended BP were measured with the same device, on the same day of the measurement of PWV, in random order. Results: Mean age was 63 ± 13 years, mean BMI 26 ± 4, 47% were female, 76% had hypertension (55% treated). Systolic unattended BP was lower as compared to attended SBP (124.4 ± 14.3 vs 130.9 ± 16.1 mmHg). PWV was similarly correlated with attended and unattended SBP values (r = 0.428 and r = 0.404, p < 0.0001, respectively). No difference for the prediction of increased arterial stiffness was observed at receiver operator curves (ROC) analysis: attended SBP area under the curve (AUC) 0.665, 95% CI 0.607–0.720 vs unattended SBP: AUC 0.651, 95% CI 0.593–0.706, p for the comparison = ns). Conclusion: Attended and unattended BP values are similarly correlated with PWV, the gold standard measure of arterial stiffness. These findings may provide further information on the clinical value of unattended BP.

Background: There is evidence of a closer relation between 24 hour aortic systolic blood pressure (aSBP) and left ventricular mass (LVM) compared with 24 hour brachial SBP. However, sample sizes are relatively small and there is some inconsistency in findings. We sought to address this by pooling data from 16 centers in Asia, Europe and Latin America to determine the relationship between LVM and brachial office, as well as brachial and aortic 24 hour ambulatory SBP. Methods: In all centers, brachial and aortic SBP was measured with the same validated oscillometric device, using a transfer function for aortic pressure, and mean/diastolic pressure calibration. LVM was determined by echocardiography. Results: We studied 2092 participants (972 women) with a mean age of 52 years. Mean brachial office BP was 137/84 mmHg, and mean 24 hour bSBP and aSBP was 126 [118;134] and 131 [120;137] mm Hg, respectively. Mean LVM indexed to body surface area was 88.4 g/m2, and 27.2% of participants had left ventricular hypertrophy (LVH). The correlation coefficients between LVM and brachial office SBP, 24 hour bSBP, and 24 hour aSBP were 0.24, 0.35, and 0.43, respectively (p < 0.001 for differences). The areas under the curve for prediction of LVH were 0.62, 0.67, and 0.70 for brachial office SBP, 24 hour bSBP, and 24 hour aSBP, respectively (p < 0.001 for differences). Conclusion: In this pooled analysis of international data, we demonstrate that aortic ambulatory SBP, measured with an oscillometric cuff, shows a significantly closer association with hypertensive cardiac organ damage (left ventricular mass and hypertrophy) than brachial office/brachial ambulatory systolic blood pressure.

BackgroundThe global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide. Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women. Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease.Methods and findingsWe designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19. We analyzed information from 2378 charts of Italian patients certified for COVID-19 admitted in 26 hospitals. Three hundred ninety-five patients (16.6%) required ICU admission due to COVID19 infection, more frequently men (74%), with a higher prevalence of comorbidities (1,78±0,06 vs 1,54±0,03 pConclusionsOur study demonstrates that gender is the primary determinant of the disease's severity among COVID-19. Obesity is the condition more often observed among those admitted to ICU within both genders.Trial registrationClinicaltrials.gov: NCT04331574.

Abstract Background The aim of this survey was to evaluate attitudes and preferences for the clinical management of hypertension and hypertension-related cerebrovascular diseases (CVD) in Italy. Methods A predefined 16-item survey questionnaire was anonymously administered to a large community sample of general practitioners (GPs), trained by specialized physicians (SPs), who have been included in an educational program between January and November 2015. Results A total of 591 physicians, among whom 48 (8%) training SPs and 543 (92%) trained GPs, provided 12,258 valid answers to the survey questionnaire. Left ventricular hypertrophy was considered the most frequent marker of hypertension-related organ damage, whereas atrial fibrillation and carotid atherosclerosis were considered relatively not frequent (10–20%). The most appropriate blood pressure (BP) targets to be achieved in hypertensive patients with CVD were

It has been suggested that measurement of “unattended” blood pressure values may provide advantages over conventional BP measurement; some hypertension guidelines now suggest this approach as the preferred one for measuring office BP. Data on the relationship between unattended BP and cardiovascular events are less solid as compared to those obtained with attended BP; only few studies suggested that unattended BP might be more strictly correlated with hypertensive target organ damage than “attended” BP. Aim: to evaluate the relationship between “attended” or “unattended” BP values and target organ damage in 261 subjects attending the outpatient clinic of an ESH-Excellence-Centre.BP values were measured by the physician with an automated oscillometric device (OmronHEM9000Ai, mean of 3 measurements),after 5 minutes of rest;thereafter,the patient was left alone and unattended BP was measured automatically after 5 minutes(3 measurements at 1 minute interval). Results: mean age was 61 ± 16yrs, BMI 26.1 ± 4.2,60% female, 88% hypertensives (64% treated). Systolic unattended BP was lower as compared to attended SBP (130.1 ± 15.7 vs 138.6 ± 17.2 mmHg).Left ventricular mass index(LVMI) was similarly correlated with unattended and attended SBP(r = 0.132 and r = 0.133, p < 0.05,respectively). LVMI was similarly correlated with unattended and attended pulse pressure(PP)(r = 0.277 and r = 0.299, p < 0.05,respectively).Carotid IMT was significantly and similarly correlated with both attended and unattended BP values(CBMaxIMT:r = 0.172 and r = 0.153 for attended and unattended SBP, p < 0.05 and: r = 0.459 and r = 0.436 for attended and unattended PP, p

New chemotherapeutic drugs and radiation therapy have significantly improved cancer patient’s survival, although the cardiovascular (CV) side effects of cancer treatment are increasingly important. In previous studies, an increased risk of cerebrovascular complications such as stroke and transient ischemic attack was described in patients undergoing neck radiotherapy. Aim: To evaluate vascular carotid structural (IMT, plaque) and functional (carotid stiffness) damage, and changes in arterial stiffness (Carotido-femoral pulse wave velocity; cf- PWV) in Hodgkin Lymphoma survivors previously treated with radiotherapy. Patients and methods: We enrolled206 Hodgkin lymphoma survivors (mean age 54±14years, 51%males, mean follow-up of9±6years).CV risk factors were investigated and atherosclerotic carotid damage was assessed by standard carotid ultrasound evaluation for intima-media thickness (IMT) measurement (MeanMax- IMT, CBMax, Tmax; n = 167); in 141 patients radiofrequency-based carotid stiffness analysis (distensibility; distensibility coefficient, DC; compliance coefficient; CC) was also performed.Cf-PWV measurement were obtained in 154 patients. Results: A significant correlation between radiotherapy dose and: MeanMax-IMT (r = 0.20; p < 0.05), Tmax (r = 0.20; p < 0.05), distensibility (r = 0.24; p < 0.05), DC(r = 0.24; p < 0.05), CC(r = 0.24; p < 0.05) was observed. Patients were divided into 4 groups according to radiotherapy dose (Dose: 20–30; 31–36; 37–42;>42Gy). An increase in Tmax (1.27±0.61, 1.35±0.59, 1.46±0.69, 1.76±1.12 mm, p for trend 42Gy), as compared to all the other dose groups (9.7±2.3 vs 8.3±2.2,8.0±1.5 and 8.3±1.4, p < 0.05). Conclusions: In this large number ofHL survivors, carotid IMT, plaque prevalence and aortic and carotid stiffness were significantly related with radiotherapy doses. Carotid IMT, carotid and aortic stiffness were significantly higher in the irradiated carotid arteries, but only at doses >42Gy, suggesting that there may be a dose threshold for radiotherapy-induced carotid wall damage.

A non-invasive approach for the estimation of mechanical efficiency through the calculation of the ratio between stroke work and HR-pressure product has been recently proposed by de Simone et al. This index, which expresses the amount of blood pumped in a single beat in 1 second by the heart, may be easily obtained by echocardiography. The aim of our study was to evaluate the determinants of myocardial mechanoenergetic efficiency index (MEEi), calculated as stroke volume/heart rate and indexed to LV mass (MEEi = MEE/LVM) in a large general population sample in Northern Italy. Design and methods: We evaluated 478 subjects participating in a general population study in Northern Italy (Studio Vobarno). All subjects underwent a physical examination with measurement of clinic blood pressure (BP). In all subjects laboratory examinations, 24 hours blood pressure measurement, echocardiography, and assessment of carotid-femoral pulse wave velocity (PWV) were performed. Results: Subjects had a mean age of 58±10 years, a BMI of 26±4, 44% were males, 69% had arterial hypertension (55% treated). MEEi was lower in males and in patients with increased PWV. MEEi was inversely correlated with age, BMI, waist circumference, clinic and 24 hours BP, glucose, uric acid, triglycerides and directly correlated with HDL. MEEI was also inversely correlated with relative wall thickness (RWT) and PWV. At linear regression multivariate (?) analysis MEEi remained independently related to male gender (β = 0.16, p < 0.001), BMI (β = −0.13, p < 0.005), RWT (β = −0.56, p < 0.001) and PWV (β = −0.10, p < 0.05). Conclusions: In a large sample of general population in Northern Italy myocardial mechanoenergetic efficiency was inversely correlated with arterial stiffness, independently of multiple possible confounders.

Background: Comprehensive information on 24-hour profiles of pulsatile as well as steady-state hemodynamics in humans is not available yet. Methods: In 693 healthy individuals (352 men) free from antihypertensive drugs, we performed 24-hour blood pressure (BP) monitoring with a validated oscillometric brachial cuff (mobilograph, i.e.m., Stolberg, Germany). Brachial waveforms were acquired and processed with ARCSolver algorithms to derive information on central pressures, wave reflections, stroke volume and systemic vascular resistance. Nighttime/daytime difference (N/D) was defined as nighttime (01.00–06.00) minus daytime (09.00–21.00) values / daytime values. Patients were categorized as young (Y: 15–40 years; n = 187), middle-aged (M: 41–70 years; n = 446), and old (O: 71–94 years; n = 60). Results: Averaged 24-hour brachial BP was 123/78 (Y), 127/82 (M), and 126/74 (O) mm Hg. N/D for brachial SBP was −13% (Y), −12% (M), and −5% (O). N/D for heart rate was – 20% (Y), −17% (M), and −15% (O). N/D for central SBP was less pronounced: −4% (Y), −6% (M), and −0% (O). Brachial pulse pressure (PP) displayed small circadian variations, whereas central PP was higher at nighttime: N/D was 25% (Y), 14% (M), and 17% (O). Consequently, PP amplification was higher at daytime (N/D was −21% (Y), −16% (M), and −12% (O)), and was related to heart rate, age, and gender. Measures of wave reflections were higher at nighttime, with N/D related to age, heart rate, mean pressure, systemic vascular resistance and stroke volume. Conclusion: The circadian profiles we provide may serve as reference for cardiovascular diseases and drug studies.

Background: Carotid-femoral pulse wave velocity (aoPWV), the gold-standard measurement of arterial stiffness, has been found associated with cardiac and vascular organ damage. Less information is available with regard to the correlation between local carotid stiffness (CS) and cardiac and vascular preclinical damage. Aim: of the study was to analyse the correlation between aoPWV and CS and cardiac and vascular preclinical organ damage in a middle age general population in Northern Italy (Vobarno Study). Methods: 245 subjects (57%female, age 56±4 years) underwent laboratory examinations, clinic and 24 hours BP measurement, cardiac and carotid ultrasound, aoPWV measurement (Complior-system). CS was determined from the relative stroke change in diameter (measured with a high-resolution echotracking system) and carotid pulse pressure (measured with applanation tonometry) and was expressed in the same dimensions as pulse wave velocity (m/s). Results: Both aoPWV and CS were significantly related with age (r=0.29, p115 g/m2 in men and>95 g/m2 in women)as compared to subjects without LVH (9.1±1.5 vs 8.5±1.4 m/s, p

Background: It is was suggested that, in resistant hypertension, the presence of particularly pronounced microvascular alterations may contribute to explain the relative lack of response to treatment. Similarly, in diabetic patients, the persistence of an altered microvascular structure, despite the administration of multiple drug combination treatment, might partly explain the difficulty to reach target blood pressure values, especially for systolic blood pressure. Patients and methods: For this reason, we investigated a population of 94 treated essential hypertensive patients. Secondary forms of hypertension were excluded according to standard clinical evaluations and biochemical or instrumental assessment, and in all patients a 24-hour blood pressure monitoring was performed in order to exclude a white coat effect. In all patients, we evaluated small resistance arteries morphology by a wire micromyographic approach (Mulvany’s technique). A small amount of subcutaneous tissue was obtained by local biopsy or during election surgery and subcutaneous small resistance arteries were dissected and mounted on a myograph; the media to lumen ratio (M/L) was then measured. Sixteen patients had true resistant hypertension, and were compared with the remaining 78 patients with non-resistant hypertension. Results: The two groups were different in terms of mean age, pulse pressure/stroke volume, media to lumen ratio and internal diameter of small resistance arteries. Conclusion: Our data suggest that hypertensive patients with true resistant hypertension have greater microvascular structural alterations compared with non-resistant hypertensive patients. This could explain, at least in part, the resistance to pharmacological treatment and the high cardiovascular risk observed in these patients.

We present a case of fatal myocardial damage caused by zinc phosphide ingestion. It is a highly toxic poison that causes life-threatening complications (cardiac and respiratory acute failure above all) by its active metabolite phosphine. Phosphine toxicity’s case reports from Europe (and Italy), United States and western countries are rare. A 69-year-old man drunk a great amount of alcohol and unspecified amount of diluted zinc phosphide and was admitted to emergency department with a mild metabolic acidosis and acute respiratory failure. After gastro-intestinal decontamination, a transient improvement of his clinical conditions was observed. In the emergency medicine unit a sudden onset of severe bradycardia and hypotension appeared, electrocardiogram showed an increase in QRS duration with ST elevation in many leads; 2 min later a thirddegree atrio-ventricular block was evident. Bradycardia went into asystole and the patient had cardiac arrest. Despite all resuscitative maneuvers, 6 h after zinc phosphide ingestion the patient died. No antidote or specific therapy or management of this potentially lifethreatening poison are actually available, but only supportive and resuscitative measures.

Macrovasculature and microvasculature are interrelated, and may influence each other. Microvascular structure is not only the site of vascular resistance but probably also the origin of most of the wave reflections generating increased central systolic blood pressure. Some index of large artery stiffness seems to be related with the media to lumen ratio of subcutaneous small resistance arteries of hypertensive patients. In addition, both microvascular structural alterations and changes in the mechanical properties of large arteries represent potent predictors of prognosis. In addition, drugs that may improve microvascular structure may also correct alterations in the mechanical properties of large arteries In fact, while β-blocking agents and diuretics have a negligible effect on microvascular structure, renin-angiotensin system antagonists and calcium entry blockers have favorable actions, improving also large artery mechanics and possibly reducing central wave reflections.