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.

Interventions to Address Cardiovascular Risk in Obese Patients: Many Hands Make Light Work.

Obesity is a growing public health epidemic worldwide and is implicated in slowing improved life expectancy and increasing cardiovascular (CV) risk; indeed, several obesity-related mechanisms drive structural, functional, humoral, and hemodynamic heart alterations. On the other hand, obesity may indirectly cause CV disease, mediated through different obesity-associated comorbidities. Diet and physical activity are key points in preventing CV disease and reducing CV risk; however, these strategies alone are not always sufficient, so other approaches, such as pharmacological treatments and bariatric surgery, must support them. Moreover, these strategies are associated with improved CV risk factors and effectively reduce the incidence of death and CV events such as myocardial infarction and stroke; consequently, an individualized care plan with a multidisciplinary approach is recommended. More precisely, this review explores several interventions (diet, physical activity, pharmacological and surgical treatments) to address CV risk in obese patients and emphasizes the importance of adherence to treatments.

Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies.

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Left Ventricular Mechano-Energetic Efficiency Identifies an Early Impairment of Myocardial Blood Flow in Arterial Hypertension.

BACKGROUND: Arterial hypertension causes cardiac functional and structural alterations. In hypertensive patients without flow-limiting epicardial coronary artery disease, we investigated possible relationships between positron emission tomography/computed tomography-derived myocardial blood flow (MBF) and echocardiographic parameters of left ventricular (LV) performance, including mechano-energetic efficiency indexed for myocardial mass (MEEi). METHODS: Seventy-eight hypertensive patients without flow-limiting epicardial coronary artery disease underwent echocardiography, including MEEi computation, and cardiac positron emission tomography/computed tomography with assessment of MBF/mass ratio at rest and after stress and myocardial flow reserve. The lowest MEEi tertile (MEEi<0.031 mL/s/g) was compared to the merged second and third tertiles (MEEi≥0.031). RESULTS: Patients in the lowest MEEi tertile were older, had higher systolic blood pressure and body mass index. They also had higher prevalence of LV hypertrophy, whereas lower resting and stress MBF/mass ratio. MEEi was significantly correlated with both resting (r=0.51; P<0.0001) and hyperemic (r=0.54; P<0.0001) MBF/mass ratios, whereas it was not related to myocardial flow reserve. Delta of MBF/mass ratio was lower in the lowest MEEi tertile than in the highest (P<0.0001). In separate multiple linear regression models, after adjusting for sex, systolic blood pressure, body mass index, prevalence of LV hypertrophy, left atrial volume index, and diuretic therapy, the association between LV MEEi and both hyperemic (beta coefficient=0.44; P=0.003) and resting (beta coefficient=0.35; P=0.008) MBF/mass ratio remained significant. CONCLUSIONS: In hypertensive patients without flow-limiting epicardial coronary artery disease, low values of MEEi could detect an early LV dysfunction involving an impairment of both resting and hyperemic MBF/mass ratios. MEEi has the advantage of simpler detection, cheaper costs than positron emission tomography/computed tomography, and a lack of radiation exposure. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02211365.

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.

Coronary disease in refractory cardiac arrest undergoing resuscitation with extracorporeal membrane oxygenation.

AIMS: Because re-establishment of spontaneous circulation (ROSC) in patients with cardiac arrest is frequently not achieved by conventional cardiopulmonary resuscitation (C-CPR), selected patients may undergo resuscitation with extracorporeal membrane oxygenation (E-CPR). We compared angiographic features and percutaneous coronary intervention (PCI) between patients undergoing E-CPR and those with ROSC after C-CPR. METHODS AND RESULTS: Forty-nine consecutive E-CPR patients undergoing immediate coronary angiography admitted between August 2013 and August 2022 were matched to 49 patients with ROSC after C-CPR. Multivessel disease (69.4% vs. 34.7%; P = 0.001), ≥ 50% unprotected left main (ULM) stenosis (18.4% vs. 4.1%; P = 0.025), and ≥1 chronic total occlusion (CTO) (28.6% vs. 10.2%; P = 0.021) were more often documented in E-CPR group. There was no significant differences in the incidence, features, and distribution of acute culprit lesion which was present in >90%. Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) (27.6 vs. 13.4; P = 0.002) and GENSINI (86.2 vs. 46.0; P = 0.001) scores were increased in E-CPR group. Optimal cut-off predicting E-CPR was 19.75 for SYNTAX (sensitivity 74%, specificity 87%) and 60.50 (sensitivity 69%, specificity 75%) for GENSINI score. More lesions were treated (1.3 vs. 1.1 lesions/patient; P = 0.002) and stents implanted (2.0 vs. 1.3/patient; P < 0.001) in E-CPR group. Final TIMI three flow was comparable (88.6% vs. 95.7%; P = 0.196) but residual SYNTAX (13.6 vs. 3.1; P < 0.001) and GENSINI (36.7 vs. 10.9; P < 0.001) scores remained increased in E-CPR group. CONCLUSION: Extracorporeal membrane oxygenation patients have more multivessel disease, ULM stenosis, and CTO but similar incidence, features, and distribution of acute culprit lesion. Despite more complex PCI, revascularization is less complete.

Prognostic Stratification of Clinically Stable Patients with Heart Failure by Echocardiographic Pressure/Volume Loop Model.

BACKGROUND: Pressure/volume (P/V) loops provide useful information on left ventricular performance and prognosis in patients with heart failure (HF) but do not lend themselves to routine clinical practice. The authors developed a noninvasive method to compute individualized P/V loops to predict adverse clinical outcomes in patients with stable HF, which the authors believe can be used clinically. METHODS: A derivation cohort (n = 443 patients) was used to develop an echocardiography P/V loop model, using brachial arterial pressure and trans-thoracic two-dimensional Doppler echocardiographic data. Each patient's P/V loop was depicted as an irregular pentagon, and a centroid was derived for each loop. The centroid distance (CD) from a reference centroid (derived from 101 healthy control subjects) was computed. This model was prospectively applied to 435 patients who constituted the validation cohort. The study end point was a composite of cardiac death or hospitalization for HF among study patients. RESULTS: In the derivation cohort, CD was threefold greater among patients who experienced adverse events than those who did not. During a follow-up period of 30 months (15-45 months), event rates were 35% (72 of 206 patients) and 12% (29 of 237 patients P < .001), respectively, among patients with CD > 33 mL/mm Hg and those with CD ≤33 mL/mm Hg (prognostic cutoff derived by receiver operating characteristic analysis). Multivariate Cox analysis identified CD as an independent predictor of adverse outcome (hazard ratio, 1.61; 95% CI, 1.03-2.50) independently of left ventricular end-diastolic volume, pulmonary capillary wedge pressure, and left ventricular ejection fraction. These conclusions were confirmed in the validation cohort. CONCLUSIONS: The authors propose a method to create a noninvasive P/V loop and its centroid. These data provide useful pathophysiologic and prognostic information in patients with HF.

Rationale and proposal for cardio-oncology services in Italy.

In the last 20 years, a substantial improvement in the efficacy of cancer treatment has induced a progressive increase in cancer survival, with an obvious parallel increase in morbidity and mortality related to the adverse effects of anticancer therapy, in particular, cardiovascular complications. In relation to the peculiar aspects related to cardiac and vascular toxicity, clinical management of patients should be ideally reserved for experts in the field of this novel medical discipline, which has been defined as cardio-oncology. The rationale for this choice corresponds to the aim of identifying patients more prone to developing cardiovascular damage, prevent overt cardiotoxicity and conduct active surveillance of treated patients for early identification of cardiac and vascular involvement during short- and long-term follow-up. Due to the burden of treated cancer patients, the development of dedicated cardio-oncology services has become one of the main goals of contemporary medicine, needed to accomplish the peculiar mission of guiding the patients through the narrow path of cancer survival without the expense of cardiovascular damage. The main purpose of cardio-oncology services is to provide dedicated cardiologic care to cancer patients affected by concomitant (subclinical or overt) cardiovascular diseases, either preexisting the cancer onset or acquired during and after the time course of anticancer therapy. In this article, we describe a possible spoke-hub model of cardio-oncology services, which could be appropriately applied in Italy. Rationale, organization, definition of referral criteria, strategies, interventional programs, long-term surveillance and home assistance of this model are described and discussed.

Low Awareness of Cardiovascular Risk Factor Among Patients Admitted in Cardiac Rehabilitation Unit.

INTRODUCTION: Cardiovascular diseases (CVD) are still the leading cause of death and disability worldwide despite the availability of well-established and effective preventive strategies. AIM: We aim to assess patients awareness of the main modifiable cardiovascular risk factors in a population with recent acute coronary syndrome (ACS) admitted in cardiac rehabilitation unit. METHODS: 50 patients with recent ACS have been recruited. We used a 9-items questionnaire about awareness of CV risk factors and eating habits. RESULTS: Many patients underestimate the role of physical activity (PA), cigarette smoking and diabetes as main CV risk factors. Although the importance of good eating habits as cardiovascular protector is well known, only few participants declare a healthy balanced diet. CONCLUSIONS: This study revealed low awareness of common CV risk factors among patients with recent ACS. Individual training plans and the use of technological development to improve awareness and adherence are needed especially in high risk population.

Autocrine Bradykinin Release Promotes Ischemic Preconditioning-Induced Cytoprotection in Bovine Aortic Endothelial Cells.

The aims of this study were to assess whether ischemic preconditioning (PC) induces bradykinin (Bk) synthesis in bovine aortic endothelial cells (bAECs) and, if so, to explore the molecular mechanisms by which this peptide provides cytoprotection against hypoxia. PC was induced by exposing bAECs to three cycles of 15 min of hypoxia followed by 15 min of reoxygenation. Bk synthesis peaked in correspondence to the early and late phases of PC (10-12 M and 10-11 M, respectively) and was abolished by a selective tissue kallikrein inhibitor, aprotinin. Stimulation with exogenous Bk at concentrations of 10-12 M and 10-11 M reduced the cell death induced by 12 h of hypoxia by 50%. Pretreatment with HOE-140, a Bk receptor 2 (BKR2) inhibitor, in bAECs exposed to 12 h of hypoxia, abrogated the cytoprotective effect of early and late PC, whereas des-Arg-HOE-140, a Bk receptor 1 (BKR1) inhibitor, affected only the late PC. In addition, we found that PC evoked endocytosis and the recycling of BKR2 during both the early and late phases, and that inhibition of these pathways affected PC-mediated cytoprotection. Finally, we evaluated the activation of PKA and Akt in the presence or absence of BKR2 inhibitor. HOE-140 abrogated PKA and Akt activation during both early and late PC. Consistently, BKR2 inhibition abolished cross-talk between PKA and Akt in PC. In bAECs, Bk-synthesis evoked by PC mediates the protection against both apoptotic and necrotic hypoxia-induced cell death in an autocrine manner, by both BKR2- and BKR1-dependent mechanisms.

Arterial blood gas analysis utility in predicting lung injury in blunt chest trauma.

BACKGROUND: thoracic trauma is one of the leading causes of death in all age groups and accounts for 25-50 % of all traumatic injuries. With the term lung injury in blunt chest trauma, we identified a spectrum of conditions: lung contusion, pneumothorax and haemothorax. The aim of this study was to evaluate the utility of arterial blood gas analysis parameters in predicting lung injury in blunt chest trauma. METHODS: we included 51 patients presenting to the Emergency Department of "C.T.O." Hospital in Naples [Italy] for blunt chest trauma. The patients were assigned to the Lung Injury Group or to the Non-Lung Injury Group basing on CT scan findings. For each patient, we calculated the alveolar-arterial oxygen gradient [AaDO2], the AaDO2 augmentation, the arterial partial pressure of oxygen deficit [PaO2 Deficit] and the ratio between arterial partial pressure of oxygen and fraction of inspired oxygen [P/F]. Areas under the curve [AUC] and receiver operating characteristic [ROC] curve were used to compare the performance of each different test in relation to the detection of lung injury in blunt chest trauma. RESULTS: patients with lung injury had lower oxygen saturation, arterial partial pressure of oxygen, P/F and higher PaO2 Deficit, AaDO2, AaDO2 augmentation than patients without lung injury. PaO2 Deficit, AaDO2 and AaDO2 augmentation showed a good accuracy to predict lung injury in blunt chest trauma. CONCLUSION: our study demonstrates that the combination of different arterial blood gas analysis variables may be a fast approach for identifying patients with lung injury in the setting of blunt chest trauma in the Emergency Department.

Left Ventricular Mass in Hypertrophic Cardiomyopathy Assessed by 2D-Echocardiography: Validation with Magnetic Resonance Imaging.

We aim to validate echocardiographic left ventricular (LV) mass (echoLVM) in sixty-one patients with hypertrophic cardiomyopathy (HCM), using cardiac magnetic resonance measures (cmrLVM) as gold standard. cmrLVM was calculated using LV short-axis images, from base to apex, whereas echoLVM by LV epicardial minus LV endocardial volumes in 4 and 2 chamber views, using Simpson disk summation; trabeculae and papillary muscle were excluded in both cmrLVM and echoLVM. cmrLVM and echoLVM were not different by paired t test (145 ± 66 vs 147 ± 61; p = 0.240), and their correlation was good (r = 0.977; p < 0.0001). Intraclass correlation demonstrated reliability of echoLVM with cmrLVM (ρ = 0.987; Cls = 0.978-0.992; p < 0.0001). LV end-diastolic volume was higher by CMR than that by echo (137 ± 33 vs 85 ± 28 mL, p < 0.0001), resulting in a lower mass/volume ratio (1.1 ± 0.4 vs 1.8 ± 0.8, p < 0.0001). EchoLVM may be determined in patients with HCM. However, mass/volume ratio is higher by echocardiography than that by CMR.

Echocardiography in Low-Risk Hypertensive Patients.

Background It is debated whether echocardiography should be part of the diagnostic workup in all hypertensive patients. We identified some factors potentially associated with left ventricular hypertrophy (LVH) at echocardiography in untreated hypertensive patients. Methods and Results We studied 2150 patients without LVH at ECG. All patients underwent standard 12-lead ECG and echocardiography. Mean age was 48.7 years, and mean office blood pressure was 154/97 mm Hg. Prevalence of echocardiographic LVH (LV mass >47.0 g/m2.7 in women and >50.0 g/m2.7 in men) was 37.1%. We developed a nomogram based on 7 items (age, smoking, body mass index, office systolic and diastolic blood pressure, Cornell voltage, and chronic kidney disease) on the basis of a multivariable logistic regression analysis. We internally validated the model by bootstrap recalibration and obtained a calibration curve to assess agreement in the validation data set. Probability of LVH at echocardiography ranged from <10% (score, ≤100 points) to >90% (score, ≥180 points). Proportion of patients with LVH progressively increased with the total score (χ2=444.8; P<0.001). Prevalence of LVH was <2% and 90% at the lower 5th and upper 95th percentile of its distribution, respectively. Conclusions We developed and validated a novel score to assess the probability of LVH at echocardiography in hypertensive patients without LVH at ECG. The score may guide the appropriateness of echocardiographic study in low-risk hypertensive patients. Echocardiography appears most appropriate for score values >136 in men and >124 in women.

Severity of Coronary Atherosclerosis and Risk of Diabetes Mellitus.

BACKGROUND: Cardio-vascular target organ damage predicts the onset of type 2 diabetes mellitus (DM) in hypertensive patients. Whether an increased incidence of DM is also in relation to the severity of coronary atherosclerosis is unknown. OBJECTIVE: We evaluated the onset of DM in relation to the extent and severity of coronary atherosclerosis, using the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (SS), in patients with stable angina or acute coronary syndromes, referred for coronary angiography (CA). METHODS: Non-diabetic patients that underwent CA for the first time were included, and the SS was computed. Predictors of DM onset in low, medium, and high SSs were investigated. RESULTS: Five hundred and seventy patients were included, and the mean SS was 6.3 ± 7.6. During a median follow-up of 79 months (interquartile range (IQR): 67-94), 74 patients (13%) developed DM. The risk of DM onset was significantly higher in the patients with a medium or high SS (hazard ratio (HR)-95% confidence interval (CI): 16 (4-61), p < 0.0001; and 30 (9-105), p < 0.0001, vs low SS, respectively), even after adjustment for obesity, history of hypertension, impaired fasting glucose, and cardiovascular therapy. CONCLUSIONS: The severity and extent of the coronary atherosclerosis, evaluated by the SS, is a strong and independent predictor of the development of DM in patients, referred to CA.

Depressed Myocardial Energetic Efficiency Increases Risk of Incident Heart Failure: The Strong Heart Study.

An estimation of myocardial mechano-energetic efficiency (MEE) per unit of left ventricular (LV) mass (MEEi) can significantly predict composite cardiovascular (CV) events in treated hypertensive patients with normal ejection fraction (EF), after adjustment for LV hypertrophy (LVH). We have tested whether MEEi predicts incident heart failure (HF), after adjustment for LVH, in the population-based cohort of a "Strong Heart Study" (SHS) with normal EF. We included 1,912 SHS participants (age 59 ± 8 years; 64% women) with preserved EF (≥50%) and without prevalent CV disease. MEE was estimated as the ratio of stroke work to the "double product" of heart rate times systolic blood pressure. MEEi was calculated as MEE/LV mass, and analyzed in quartiles. During a follow-up study of 9.2 ± 2.3 years, 126 participants developed HF (7%). HF was preceded by acute myocardial infarction (AMI) in 94 participants. A Kaplan-Meier plot, in quartiles of MEEi, demonstrated significant differences, substantially due to the deviation of the lowest quartile (p < 0.0001). Using AMI as a competing risk event, sequential models of Cox regression for incident HF (including significant confounders), demonstrated that low MEEi predicted incident HF not due to AMI (p = 0.026), after adjustment for significant effect of age, LVH, prolonged LV relaxation, diabetes, and smoking habits with negligible effects for sex, hypertension, antihypertensive therapy, obesity, and hyperlipemia. Low LV mechano-energetic efficiency per unit of LVM, is a predictor of incident, non-AMI related, HF in subjects with initially normal EF.

Achievement of target SBP without attention to decrease in DBP can increase cardiovascular morbidity in treated arterial hypertension: the Campania Salute Network.

OBJECTIVES: Results of the SPRINT study have influenced recent guidelines on arterial hypertension, in the identification of target SBP, but scarce attention has been paid to the consequences on DBP. However, there is evidence that reducing DBP too much can be harmful. METHODS: We analyzed outcome in 4005 treated hypertensive patients (22% obesity, 8% diabetes and 21% current smoking habit) with target attended office SBP less than 140 mmHg, in relation to quintiles of DBP, cardiovascular risk profile and target organ damage (LV hypertrophy, carotid plaque and left atrial dilatation). Composite fatal and nonfatal cardiovascular event was the outcome variable in this analysis (stroke and myocardial infarction, sudden cardiac death, heart failure requiring hospitalization, transient ischemic attack, myocardial revascularization, de novo angina, carotid stenting and atrial fibrillation). RESULTS: Lower DBP was associated with greater proportion of women and diabetes, older age, decline in kidney function and greater values of LV mass index and left atrial volume and greater prevalence of carotid plaque (all 0.04 < P < 0.0001). The lowest quintile of DBP (74.1 ±â€Š3.7 mmHg) was associated with 1.49 higher hazard of composite cardiovascular events, independently of significant effect of older age, female sex, LV hypertrophy and borderline effect of left atrial dilatation (0.04 < P < 0.001). CONCLUSION: Increased risk associated with aggressive reduction of DBP should be balanced with the advantage of reducing aggressively SBP to predict the net benefit of antihypertensive treatment, especially in the oldest old individuals.

A challenging diagnosis of dyspnea: A case report of contralateral reexpansion pulmonary edema.

Reexpansion pulmonary edema (RPE) is an uncommon complication of thoracentesis or chest drainage. It occurs in the ipsilateral or contralateral lung. Causes, pathogenesis and therapy are not well understood especially for contralateral RPE. We describe a case of fatal contralateral RPE in a 59-years-old woman with right lung cancer underwent ultrasound-guided thoracentesis for massive pleural effusion and severe dyspnea. Pathogenesis of contralateral RPE is probably multifactorial and in this case is mostly due to the overperfusion of the healthy lung and consequent capillary damage. The right therapy for this condition is not known.

Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis.

OBJECTIVE: Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS). METHODS: AVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account. RESULTS: More men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. CONCLUSION: In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT00092677.

Influence of Left Ventricular Stroke Volume on Incident Heart Failure in a Population With Preserved Ejection Fraction (from the Strong Heart Study).

At a given level of left ventricular (LV) systolic function, LV pump performance (assessed by stroke index [SVi]) may differ, depending on LV size. We evaluated whether low SVi may be considered a marker of risk for incident congestive heart failure (HF), independent of LV geometry and systolic function, assessed by ejection fraction (EF) or midwall fractional shortening (MFS), in a large population-based sample with normal EF. Clinical and echocardiographic data from the second Strong Heart Study (SHS) examination, including 2,885 American Indians (59 ± 8 years; 63% women) with normal EF (EF ≥51% in men and EF ≥55% in women) and without prevalent HF or significant valve disease, were analyzed. Low SVi was defined as SVi ≤22 ml/m2.04. Low SVi was more common among men and associated with lower body mass index, systolic blood pressure, LV mass index, left atrial dimension, EF, and MFS and with higher relative wall thickness. During a mean 12-year follow-up, 209 participants developed HF and 246 had acute myocardial infarction. In Cox regression analysis, low SVi was associated with higher risk of incident HF (hazard ratio 1.38; 95% confidence interval 1.06 to 1.80), independently of age, gender, body mass index, heart rate, hypertension, prevalent cardiovascular disease, left atrial dimension index, LV mass index, LV concentric geometry, EF or MFS, and abnormal wall motion, also accounting for myocardial infarction as a competing risk event. In conclusion, in the SHS, low SVi was associated with higher incident rate of HF, independently of LV geometry and systolic function and other major confounders.

Aortic root dimension and arterial stiffness in arterial hypertension: the Campania Salute Network.

OBJECTIVES: The relation between aortic root dimension (ARD) and measures of arterial stiffness is uncertain. Accordingly, we studied the relation between ARD and an estimate of arterial stiffness in 12 392 hypertensive patients (age 53 ±â€Š12 years, 43% women) free of prevalent cardiovascular disease and with ejection fraction at least 50%, from the Campania Salute Network Registry. METHODS: Echocardiographic ARD was measured and compared with the value predicted by age, sex and height by using a z-score. Arterial stiffness was assessed by the pulse pressure/stroke index. The highest population tertile of pulse pressure/stroke index was considered 'high arterial stiffness'. RESULTS: High arterial stiffness was more common in women than in men (P < 0.001) and associated with older age, diabetes, longer duration of hypertension and less frequent smoking habit (all P less than 0.01). Patients with high arterial stiffness had smaller ARD, higher carotid intima-media thickness and plasma cholesterol, and lower BMI and glomerular filtration rate (all P less than 0.01). In multivariable logistic analysis, high arterial stiffness was associated with both lower ARD z-score [OR 0.83 (95% confidence interval 0.79-0.88)] and higher carotid intima-media thickness [OR 1.36 (95% confidence interval 1.26-1.47); both P less than 0.0001], independent of significant associations with age, female sex, body size, DBP, heart rate, duration of hypertension, diabetes and smoking habit. CONCLUSION: Small ARD, together with atherosclerotic modifications of conduit arteries, is associated with increased 2-element Windkessel model of arterial stiffness in hypertension, independently of the significant effect of confounders.