Cardiovascular Structural and Functional Parameters in Idiopathic Pulmonary Fibrosis at Disease Diagnosis.

INTRODUCTION: Prevalence of cardiac and vascular fibrosis in patients with Idiopathic Pulmonary Fibrosis (IPF) has not been extensively evaluated. AIM: In this study, we aimed to evaluate the heart and vessels functional and structural properties in patients with IPF compared to healthy controls. An exploratory analysis regarding disease severity in IPF patients has been done. METHODS: We enrolled 50 patients with IPF (at disease diagnosis before antifibrotic therapy initiation) and 50 controls matched for age and gender. Heart was evaluated through echocardiography and plasmatic NT-pro-brain natriuretic peptide that, together with patients' symptoms, allow to define the presence of Heart Failure (HF) and diastolic dysfunction. Vessels were evaluated through Flow Mediated Dilation (FMD - endothelial function) and Pulse Wave Velocity (PWV-arterial stiffness) RESULTS: Patients with IPF had a prevalence of diastolic disfunction of 83.8%, HF of 37.8% and vascular fibrosis of 76.6%. No statistically significant difference was observed in comparison to the control group who showed prevalence of diastolic disfunction, HF and vascular fibrosis of 67.3%, 24.5% and 84.8%, respectively. Disease severity seems not to affect PWV, FMD, diastolic dysfunction and HF. CONCLUSIONS: Patients with IPF early in the disease course do not present a significant CV fibrotic involvement when compared with age- and sex-matched controls. Bigger and adequately powered studies are needed to confirm our preliminary data and longitudinal studies are required in order to understand the time of appearance and progression rate of heart and vascular involvement in IPF subjects.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

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<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P=0.004) and 1.150 (95% CI, 1.021-1.295, P=0.02), respectively. CONCLUSIONS: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Secondary Prevention and Extreme Cardiovascular Risk Evaluation (SEVERE-1), Focus on Prevalence and Associated Risk Factors: The Study Protocol.

INTRODUCTION: Despite significant improvement in secondary CardioVascular (CV) preventive strategies, some acute and chronic coronary syndrome (ACS and CCS) patients will suffer recurrent events (also called "extreme CV risk"). Recently new biochemical markers, such as uric acid (UA), lipoprotein A [Lp(a)] and several markers of inflammation, have been described to be associated with CV events recurrence. The SEcondary preVention and Extreme cardiovascular Risk Evaluation (SEVERE-1) study will accurately characterize extreme CV risk patients enrolled in cardiac rehabilitation (CR) programs. AIM:  Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors. AIM: Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors. METHODS: We will prospectively enrol 730 ACS/CCS patients at the beginning of a CR program. Extreme CV risk will be retrospectively defined as the presence of a previous (within 2 years) CV events in the patients' clinical history. UA, Lp(a) and inflammatory markers (interleukin-6 and -18, tumor necrosis factor alpha, C-reactive protein, calprotectin and osteoprotegerin) will be assessed in ACS/CCS patients with extreme CV risk and compared with those without extreme CV risk but also with two control groups: 1180 hypertensives and 765 healthy subjects. The association between these biomarkers and extreme CV risk will be assessed with a multivariable model and two scoring systems will be created for an accurate identification of extreme CV risk patients. The first one will use only clinical variables while the second one will introduce the biochemical markers. Finally, by exome sequencing we will both evaluate polygenic risk score ability to predict recurrent events and perform mendellian randomization analysis on CV biomarkers. CONCLUSIONS: Our study proposal was granted by the European Union PNRR M6/C2 call. With this study we will give definitive data on extreme CV risk prevalence rising attention on this condition and leading cardiologist to do a better diagnosis and to carry out a more intensive treatment optimization that will finally leads to a reduction of future ACS recurrence. This will be even more important for cardiologists working in CR that is a very important place for CV risk definition and therapies refinement.

Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios.

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

Hypertensive emergencies and urgencies: a preliminary report of the ongoing Italian multicentric study ERIDANO.

Hypertensive urgencies (HU) and hypertensive emergencies (HE) are challenges for the Emergency Department (ED). A prospective multicentre study is ongoing to characterize patients with acute hypertensive disorders, prevalence of subclinical hypertension-mediated organ damage (HMOD), short- and long-term prognosis; this is a preliminary report. Patients admitted to the ED with symptomatic blood pressure (BP) ≥180/110 mmHg were enrolled. They were managed by ED personnel according to their clinical presentations. Subsequently they underwent clinical evaluation and subclinical HMOD assessment at a Hypertension Centre within 72 h from enrolment. 122 patients were included in this report. Mean age was 60.7±13.9 years, 52.5% were females. 18 (14.8%) patients were diagnosed with HE, 108 (88.5%) with HU. There were no differences in gender, BMI, and cardiovascular comorbidities between groups. At ED discharge, 66.7% and 93.6% (p = 0.003) of HE and HU patients, respectively, had BP < 180/110 mmHg. After 72 h, 34.4% of patients resulted normotensive; 35.2%, 22.1%, and 8.2% had hypertension grade 1, 2, and 3, respectively. Patients with uncontrolled BP at office evaluation had higher vascular HMOD (49.1 vs. 25.9%, p = 0.045). Cardiac (60 vs. 34%, p = 0.049), renal (27.8 vs. 9.6%, p = 0.010) and cerebral (100 vs. 21%, p < 0.001) HMOD was more frequent in HE compared to HU group. HE showed greater cardiac, renal, and cerebral subclinical HMOD, compared to HU. 72-hours BP control is not associated with different HMOD, except for vascular HMOD; therefore, proper comprehensive examination after discharge from the ED could provide added value in cardiovascular risk stratification of such patients. One third of patients with acute blood pressure rise evaluated to the ED resulted normotensive at office evaluation (<72 hours after discharge). Patients with hypertensive emergency showed greater cardiac, renal, and cerebral subclinical HMOD, compared to the patients with hypertensive urgency. BP: blood pressure; HMOD: hypertension-mediated organ damage; y.o.: years old; mo.: months.

Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project.

BACKGROUND: Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. METHODS: Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m2 and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol. RESULTS: Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR < 60 and micro- or macroalbuminuria of 16, 15 and 4%, respectively. Serum uric acid showed a trend towards higher values along with decreasing renal function. Both the prevalence of gout and the frequency of allopurinol use increased significantly with the reduction of eGFR and the increase in albuminuria. Hyperuricemia was independently related to male gender, eGFR strata, and signs of insulin resistance such as body mass index (BMI) and triglycerides. CONCLUSIONS: The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR < 60 ml/min the occurrence of hyperuricemia is about 10 times higher than in those with eGFR > 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria.

Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study.

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.

Continuous flow left ventricular assist devices do not worsen endothelial function in subjects with chronic heart failure: a pilot study.

AIMS: To evaluate endothelial function in subjects with left ventricular assist devices (LVADs), comparing them with subjects with chronic heart failure with reduced ejection fraction on the list for heart transplant (HT) and with HT patients with a normal systolic cardiac function to identify any differences. METHODS: We enrolled 28 subjects with LVAD, 55 subjects with HT, and 42 subjects with heart failure on the transplant list. The subjects underwent a general physical examination, assessment of laboratory blood parameters, and assessment of endothelial function through flow-mediated dilation (FMD) of brachial artery. RESULTS: The three groups were homogeneous as regards age, gender, smoke abuse, C-reactive protein (CRP) and FMD parameters (P = ns). In LVAD group percentage of FMD change showed an inverse correlation with CRP (rho: -0.5, P: 0.003), a well-known marker of inflammation and tissue damage. CONCLUSIONS: Continuous flow related to LVAD seems to not worsen endothelial function. Endothelial function was not affected by cardiovascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, and tobacco habit), by the functional status expressed by New York Heart Association class, by the left ventricular systolic function and by the presence or absence of ischaemic heart disease in all the populations analysed. CRP was the only factor able to influence percentage of FMD change in patient with LVAD, reinforcing the hypothesis that inflammation is the main determinant of endothelial function.

Protein Intake and Physical Activity in Newly Diagnosed Patients with Acute Coronary Syndrome: A 5-Year Longitudinal Study.

Cardiovascular disease is one of the most common causes of hospitalization and is associated with high morbidity and mortality rates. Among the most important modifiable and well-known risk factors are an unhealthy diet and sedentary lifestyle. Nevertheless, adherence to healthy lifestyle regimes is poor. The present study examined longitudinal trajectories (pre-event, 6-, 12-, 24-, 36-, and 60-month follow-ups) of protein intake (fish, legumes, red/processed meat) and physical activity in 275 newly-diagnosed patients with acute coronary syndrome. Hierarchical Generalized Linear Models were performed, controlling for demographic and clinical variables, the season in which each assessment was made, and the presence of anxiety and depressive symptoms. Significant changes in protein intake and physical activity were found from pre-event to the six-month follow-up, suggesting the adoption of healthier behaviors. However, soon after the six-month follow-up, patients experienced significant declines in their healthy behaviors. Both physical activity and red/processed meat intake were modulated by the season in which the assessments took place and by anxiety symptoms over time. The negative long-term trajectory of healthy behaviors suggests that tailored interventions are needed that sustain patients' capabilities to self-regulate their behaviors over time and consider patient preference in function of season.

Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study.

OBJECTIVE: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension. METHODS: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ±â€Š65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders. RESULTS: A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively. CONCLUSION: The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).

Thoracic radiotherapy as a risk factor for heart ischemia in subjects treated with chest irradiation and chemotherapy and without classic cardiovascular RISK factors.

BACKGROUND AND PURPOSE: Radiation Induced Heart Disease (RIHD) represents a late effect of chest irradiation, contributing in increasing mortality rate in oncological patients by affecting pericardium, myocardium, valvs and coronaries. Currently, regarding the risk of Coronary Artery Disease (CAD), a cardiological screening involving exercise stress electrocardiography after 5-10 years from radiotherapy is advised. We sought to determine the rate of ischemia at exercise stress electrocardiography in a population of patients without cardiovascular risk factors who sustained radiotherapy, using a cohort of patients presenting with at least one cardiovascular risk factor as control group. DESIGN AND METHODS: A population of 115 patients who sustained chest irradiation (and associated chemotherapy), presenting without classic cardiovascular risk factors or typical symptoms suggesting CAD, was evaluated with exercise stress electrocardiography. 135 patients with at least one risk factor for cardiovascular disease candidate to stress testing for primary prevention or for atypical symptoms served as control group. RESULTS: The cohort of irradiated patients without classical cardiovascular risk factors is younger (48.7 ± 10.1 vs 60.5 ± 10.8 years, p < 0.001) and presents a lower percentage of males when compared with the control group. In this latter group 25.9% of subjects has diabetes, 62.9% dyslipidaemia, 67.4% hypertension and 19.2% actively smoke. Despite this important differences regarding classic cardiovascular risk factors, no significant differences were found in the number of positive exercise stress electrocardiography (10.4 vs 5.9%, p = ns). CONCLUSIONS: Chest irradiation represents a strong cardiovascular risk factor. In fact, prevalence of positive ECG-stress test is not different (nor higher and nor lower) in irradiated subjects without cardiovascular risk and not irradiated patients with classic cardiovascular risk.

Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study.

OBJECTIVE: The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men. METHODS: The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ±â€Š66.9 months. RESULTS: A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P < 0.01), but not in men. CONCLUSION: The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.

Cardiovascular Remodeling after Endovascular Treatment for Thoracic Aortic Injury.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) currently represents the gold standard of treatment for thoracic aortic injury (TAI). Nevertheless, there is an ongoing debate surrounding its safety and subsequent cardiovascular effects. Our aim is to assess heart and vascular structure and function remodeling after TEVAR in TAI young patients. METHODS: We evaluated 20 patients (18 men, age 41 ± 14 years, 11 treated with Gore CTAG, 9 with Medtronic Valiant) with office and 24-hr blood pressure (BP) with specific vascular stiffness analysis (Mobil-O-Graph), aortic diameters (computed tomography scan) and left ventricular mass index (LVMI echocardiogram). Evaluation was done after a median time of 5.0 ± 3.5 years from the trauma. RESULTS: After TAI 12 patients (55%) developed hypertension. When patients were divided according to treating time, those treated for more than 3 years show higher LVMI, PWV, and ascending aorta dilatation. CONCLUSIONS: Our study shows that TEVAR for TAI is associated with heart and vascular remodeling. The presence of TEVAR modifies aortic functional properties and could induce an increase in BP that can promote aortic and cardiac damage, even in young patients.

In healthy normotensive subjects age and blood pressure better predict subclinical vascular and cardiac organ damage than atherosclerosis biomarkers.

PURPOSE: Only few studies evaluated biomarkers useful for defining the cardiovascular risk of a subject in a pre-clinical condition (i.e. healthy subjects). In this context we sought to determine the relationships of Plasminogen activator inhibitor type 1 (PAI-1), P-Selectin, Tissue Inhibitors Metalloproteinases type 1 (TIMP-1) and Cystatin-C with subclinical Target Organ Damage (TOD) in normotensive and normoglycemic subjects without known cardiovascular and kidney diseases. MATERIALS AND METHODS: 480 blood donors participated at the present analysis. TOD was evaluated as Pulse Wave Velocity (PWV), Left Ventricular Hypertrophy (LVH) and Intima Media Thickness (IMT) and carotid plaque presence) grouped together under carotid TOD. RESULTS: 3.1% of the subjects showed a PWV higher than 10 m/sec with those subjects exerting significantly lower values of P-Selectine (0.068 ± 0.015 vs 0.08 ± 0.036 mg/L, p = .014). 8.8% of the subjects showed carotid TOD that was associated with higher Cystatin-C values (0.67 ± 0.17 vs 0.63 ± 0.14 mg/L, p = .045). Finally 23.8% of the subjects showed LVH with no significant differences regarding biomarkers. Despite some significant correlations between biomarkers and TOD, at the multivariate analysis none came out to be as significant predictor of the assessed TOD. CONCLUSIONS: in normotensive and normoglycemic healthy subjects, the evaluated biomarkers of atherosclerotic process didn't show any significant association with cardiac, carotid and vascular TOD while age and BP are its principal predictors.

Association Between Atrial, Ventricular and Vascular Morphofunctional Alterations in Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) represents a risk of non-fatal and cardiovascular events. The aim of the present study was to evaluate simultaneously left and right atrial and ventricular function, as well as arterial stiffness, in RA patients. METHODS: This cross-sectional study included 55 consecutive RA patients and 55 healthy age and gender-matched controls. Blood pressure and arterial stiffness were assessed in all participants, who also underwent a complete echocardiographic examination. RESULTS: RA patients were treated with steroid therapy (52.7%), methotrexate (66.6%) and biological therapy (54.5%). Disease activity score revealed low average RA activity. Augmentation index was significantly higher in RA patients (32.2 ± 8.6 vs. 28.4 ± 8.9%, P = 0.02). Left atrial volume was also higher among RA patients (23.1 ± 8.2 vs. 20.1 ± 7.1 ml/m2, P = 0.04), whereas mitral and tricuspid E/A ratios were significantly lower in RA individuals (0.90 ± 0.24 vs. 1.03 ± 0.35, P = 0.02; 1.07 ± 0.31 vs. 1.27 ± 0.35, P = 0.003, respectively). Tissue Doppler systolic and diastolic velocities were similar between the observed groups. Arterial stiffness index showed significant correlation with disease duration (r = 0.29; P = 0.03). Tissue Doppler-derived transmitral late diastolic velocity (A') showed significant correlation with index of disease activity in the RA patients. CONCLUSIONS: Our results showed that left and right ventricular diastolic function and arterial stiffness were significantly deteriorated in the RA patients comparing with controls. The assessment of left and right ventricular diastolic function, as well as vascular function, should be an essential part of clinical evaluation in the RA patients.

Long-Term Effects of Radiotherapy on Arterial Stiffness in Breast Cancer Women.

Radiotherapy for breast cancer may expose heart and vessels to late radiation-induced complications. Although recent technical progress in radiation therapy (RT) has been associated with drastic reduction in cardiovascular (CV) mortality, the prolonged life expectancy of patients with cancer requires CV evaluation for many years. The aim of our study was to evaluate local changes in vascular and cardiac function because of previous breast RT. We enrolled 43 patients treated with RT 15 years ago for breast cancer. CV risk factors and atherosclerotic carotid damage were investigated in all women. We divided patients into 2 groups: R (n = 25) treated to right breast and L (n = 18) to left breast. All subjects were submitted to standard echocardiography and functional arteries evaluation by carotid-radial pulse-wave velocity (crPWV; Complior) and AIx (Sphygmocor; Atcor Medical). Global mean age was 69.5 ± 8 years old. CV risk factors were equally allocated in 2 groups. No patients had history of cardiac or artery disease. R had a significantly increased crPWV (9.9 ± 1.4 vs 8.9 ± 1.1, p = 0.001) on right arm compared with left arm, and in L group, crPWV was similarly higher on the left arm than on right arm (9.6 ± 1.5 vs 8.9 ± 1.4, p = 0.011). AIx was significantly increased in the ipsilateral arm only in L (32.1 ± 7.6 vs 28.3 ± 6.8, p = 0.05). Central blood pressure estimation was not different in the right and left arms. No correlations were found with hormone therapy or chemotherapy. Our data show a local arterial stiffening because of radiation that can be involved in increased CV risk in breast cancer-treated patients.

Asymptomatic aortic mural thrombus in a minimally atherosclerotic vessel.

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

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

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

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.

Persistence of arterial functional abnormalities after successful coronary revascularization.

BACKGROUND: In patients with myocardial ischemia and coronary atherosclerosis, arterial stiffness and endothelial function are impaired. Whether these alterations can be favorably affected by successful coronary revascularization is debated. METHODS: We studied 39 hospitalized patients 59.3 ± 3.2 years old (mean ± SEM). In 21 patients with angiographic evidence of significant coronary artery stenosis, revascularization procedures were performed (stenting n = 11 and bypass surgery n = 10). The remaining patients had no significant stenosis and thus served as controls. Prerevascularization measurements included carotido-femoral pulse wave velocity (PWV), radial artery flow-mediated vasodilatation and a complete echocardiographic examination. The same measurements were performed 6 months later. Pharmacological treatment consisted of different cardiovascular drugs and remained substantially unchanged over the 6-month follow-up period. RESULTS: With the exception of an increased left ventricular mass index (LVMI; 130 ± 5.3 versus 105.8 ± 7.2 g/m(2), P < 0.05) and a lower Em/Am (0.6 ± 0.01 and 0.8 ± 0.01 respectively, P < 0.05) observed in patients with coronary stenosis, all other hemodynamic, cardiac and vascular variables were similar in the two groups. Following the 6-month follow-up period, all variables remained substantially unchanged, with the exception, in revascularized patients, of a significant reduction in LVMI (-12%, P < 0.05) and an improvement in Tissue Doppler Imaging-measured diastolic function (Em/Am + 30%, P < 0.05). This was not associated, however, with any significant change in PWV and in flow-mediated vasodilatation. CONCLUSION: Cardiac revascularization has no effect on arterial function, assessed either as arterial stiffness or as flow-mediated vasodilatation. On the contrary, the improvement in coronary blood flow triggers local cardiac changes, namely, a reduction in LVMI and an improvement in diastolic function.