Italian Society of Interventional Cardiology (GISE) and Italian Society of Arterial Hypertension (SIIA) Position Paper on the role of renal denervation in the management of the difficult-to-treat hypertension.

Renal denervation (RDN) is a safe and effective strategy for the treatment of difficult to treat hypertension. The blood pressure (BP)-lowering efficacy of RDN is comparable to those of many single antihypertensive medications and it allows to consider the RDN as a valuable option for the treatment of difficult to treat hypertension together with lifestyle modifications and medical therapy. A multidisciplinary team is of pivotal importance from the selection of the patient candidate for the procedure to the post-procedural management. Further studies are needed to investigate the effect of RDN on clinical outcomes and to better identify the predictors of BP response to RDN in order to recognize the patients who are more likely to benefit from the procedure.

Prevalence of pulmonary embolism among patients with recent onset of dyspnea on exertion. A cross-sectional study.

BACKGROUND: Exertional dyspnea is a frequently encountered complaint in clinical practice. However, the prevalence of pulmonary embolism (PE) among patients with dyspnea on exertion has not been reported. OBJECTIVE: The objective of this study was to assess the prevalence of objectively confirmed PE among consecutive patients visiting an emergency department because of recent onset of exertional dyspnea. METHODS: Patients aged ≤75 years with recent (<1 month) marked exertional dyspnea had a systematic workup for PE, irrespective of concomitant signs or symptoms of venous thromboembolism and alternative explanations for dyspnea. PE was excluded on the basis of a low pretest clinical probability and normal age-adjusted D-dimer. All other patients had computed tomography pulmonary angiography. An interim analysis after inclusion of 400 patients would stop recruitment if the 95% confidence interval (CI) of the PE prevalence had a lower limit exceeding 20%. RESULTS: The study was prematurely terminated after the inclusion of 417 patients. In 134 patients (32.1%), PE was excluded based on low clinical probability and normal D-dimer. PE was found in 134 (47.3%) of the remaining 283 patients, for an overall prevalence of 32.1% (95% CI, 27.8-36.8). PE was present in 40 of 204 (19.6%) patients without other findings suspicious for PE and in 94 of 213 patients (44.1%) with such findings. PE involved a main pulmonary artery in 37% and multiple lobes in 87% of the patients. CONCLUSION: The angiographic demonstration of PE is common in patients presenting with recent onset of marked exertional dyspnea, including 20% without other findings suggesting pulmonary embolism.

Assessment of respiratory function and exercise tolerance at 4-6 months after COVID-19 infection in patients with pneumonia of different severity.

BACKGROUND: The evaluation of COVID-19 systemic consequences is a wide research field in which respiratory function assessment has a pivotal role. However, the available data in the literature are still sparse and need further strengthening. AIM: To assess respiratory function 4-6 months after hospital discharge based on lung disease severity in patients who overcome COVID-19 pneumonia. METHODS: Patients hospitalised either in the Internal Medicine Department (IMD) for moderate to severe disease or in the Intensive Care Unit (ICU) for critical disease underwent spirometry with maximal flow-volume curve, lung volumes, lung diffusion capacity (DLCO ) and six-minute walking test (6-MWT). RESULTS: Eighty-eight patients were analysed: 40 from the IMD and 48 from the ICU. In both cohorts, there was a greater prevalence of male patients. In the IMD cohort, 38% of patients showed at least one altered respiratory parameter, while 62% in the ICU cohort did so (P < 0.05). Total lung capacity (TLC) and DLCO were the most frequently altered parameters: 15% and 33% from IMD versus 33% and 56% from ICU, respectively (P < 0.05). In IMD patients, 5% had only restrictive deficit, 22% had only lung diffusion impairment and 10% had both. In ICU patients, 6% had only restrictive deficit, 29% had only lung diffusion impairment and 27% had both (P < 0.05). ICU patients showed a higher frequency of abnormal 6-MWT (P < 0.05). CONCLUSION: Lung function tests and 6-MWT are highly informative tools for monitoring the negative consequences of COVID-19 pneumonia, which were more frequent and more complex in patients discharged from ICU.

Profile and management of hypertensive urgencies and emergencies in the emergency cardiology department of a tertiary hospital: a 12-month registry.

AIMS: Currently there are scarce epidemiological data regarding prevalence, clinical phenotype, and therapy of hypertensive urgencies (HU) and emergencies (HE). The aim of this article was to record the prevalence, clinical characteristics, and management of patients with HU and HE assessed in an emergency department (ED) of a tertiary hospital. METHODS AND RESULTS: The population consisted of patients presenting with HE and HU in the ED (acute increase in systolic blood pressure (BP) ≥ 180 mmHg and/or diastolic BP ≥120 mmHg with and without acute target organ damage, respectively). Of the 38 589 patients assessed in the ED during a 12-month period, 353 (0.91%) had HU and HE. There were 256 (72.5%) cases presented as HU and 97 (27.5%) as HE. Primary causes for both HU and HE were stress/anxiety (44.9%), increased salt intake (33.9%), and non-adherence to medication (16.2%). Patients with HU reported mainly dizziness/headache (46.8%) and chest pain (27.4%), whereas those with HE presented dyspnoea (67%), chest pain (30.2%), dizziness/headache (10.3%), and neurological disorders (8.2%). In HE, the underlying associated conditions were pulmonary oedema (58%), acute coronary syndrome (22.6%), and neurological disorders/stroke (7.2%). All HE cases were hospitalized and received intensive healthcare, including dialysis. CONCLUSION: This 1-year single-centre registry demonstrates a reasonable prevalence of HU and HE contributing to the high volume of visits to the ED. Stress, increased salt intake and non-adherence were main triggers of HE and HU. Dizziness and headache were the prevalent symptoms of HU patients while heart failure was the most common underlying disease in patients with HE.

Serum Uric Acid and Kidney Disease Measures Independently Predict Cardiovascular and Total Mortality: The Uric Acid Right for Heart Health (URRAH) Project.

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 <60 ml/min) was significantly higher in patients with hyperuricemia and albuminuria (3.8, 22.1 and 19.1, respectively) as compared to those with only one risk factor or none (0.4, 2.8 and 3.1, respectively). Serum uric acid and eGFR significantly interact in determining cardiovascular and all-cause mortality. For each SUA increase of 1 mg/dl the risk for mortality increased by 10% even after adjustment for potential confounding factors included eGFR and the presence of albuminuria. Conclusions: hyperuricemia is a risk factor for cardiovascular and all-cause mortality additively to eGFR strata and albuminuria, in patients at cardiovascular risk.

The Vobarno Study.

The Vobarno Study represents the first observational study aimed to assess in a general population sample the relationship between parameters of cardiac and vascular structure (and function) and blood pressure values, measured in the clinic and during the 24 hours. In the frame of The Vobarno Study blood samples for hematochemistry and DNA extraction, clinic and 24-hour blood pressure measurements, cardiac and carotid ultrasound, and aortic stiffness were measured in all subjects, living in a small town (Vobarno) between Brescia and the Garda Lake (Italy), and randomly selected from electoral roles. In this sample of a general population an extensive evaluation of organ damage, including left ventricular (LV) mass and hypertrophy, LV systolic function, left atrial dimensions and aortic root diameters, carotid intima media thickness (IMT) and carotid plaques, carotid and aortic stiffness were performed. In this study subjects were included in a long follow-up, lasting 25 years, and cardiovascular morbility and mortality were assessed up to 2019. This will allow to update the information related to cardiovascular morbidity and mortality in the study cohort. The present paper will report the results of some analyses performed, exploring epidemiological and clinical aspects of target organ damage.

Factors associated with survival in older patients affected by COVID-19: A retrospective cohort study.

AIM: Mortality is high in Coronavirus disease 2019 patients with pre-existing comorbidities and advanced age. Associated complications have added to the negative prognosis. Nevertheless, many have fully recovered, even among the most fragile. Factors associated with their survival was investigated. METHODS: Retrospective study of patients aged ≥90 years admitted for COVID-19 to the Internal Medicine wards of two hospitals in Lombardy, Italy. RESULTS: Among 34 patients with SARS-CoV-2 pneumonia, 33 (97.1%) had respiratory failure. Eighteen patients (52.9%) survived and 16 (47.1%) died during hospital stay. Survivors compared to deceased had a significantly longer hospitalization (19 vs. 10 days respectively; p = 0.02), a better PaO2:FiO2 ratio (241 vs. 171 respectively; p = 0.003), higher lymphocyte counts (p = 0.01) and lower serum LDH levels (p < 0.001) at admission. At multivariate analysis only higher PaO2:FiO2 was associated with survival (OR 1.06 [95%CI 1.0-1.03]; p = 0.02). Kaplan-Meier analysis showed a significant difference in event-free survival between patients treated or not with LMWH (p < 0.0001) and between those treated or not with beta-blockers (p = 0.008). Cox regression, performed in the subgroup of patients who received LMWH, did not show significant difference for sex (HR 2.7 [95% CI 0.53-14.3], p = 0.23), CCI (HR 0.7 [95% CI 0.37-1.45], p = 0.38), PaO2:FiO2 ratio (HR 0.98 [95% CI 0.97-1.0], p = 0.07), corticosteroid therapy (HR 0.99 [95% CI 0.22-4.5], p = 0.99) and beta-blocker therapy (HR 2.8 [95% CI 0.56-14,7], p = 0.21). CONCLUSIONS: Despite higher mortality in elderly, treatment with LMWH and betablockers might be associated with better survival. Dedicated studies are required to confirm our result.

Effect of direct renin inhibition on vascular function after long-term treatment with aliskiren in hypertensive and diabetic patients.

OBJECTIVE: We tested the hypothesis that chronic treatment with the direct renin inhibitor aliskiren improves vascular function in resistance and conduit arteries of type two diabetic and hypertensive patients. METHOD: Sixteen patients with mild essential hypertension and with a previous diagnosis of noninsulin-dependent diabetes mellitus were included in the study. Patients were then randomized to aliskiren (150 mg once daily, n = 9), or ramipril (5 mg once daily, n = 7). Each patient underwent a biopsy of the subcutaneous tissue and small arteries were dissected and mounted on a pressurized micromyograph to evaluate endothelium dependent vasorelaxation in response to acetylcholine ±â€ŠN omega-nitro-L-arginine methyl ester hydrochloride in vessels precontracted with norepinephrine. Endothelial function has been quantified also in large conduit arteries by flow-mediated dilation. RESULTS: A similar office blood pressure-lowering effect was observed with the two drugs, although changes in DBP were not statistically significant in the ramipril group. Aliskiren significantly improved endothelium-dependent relaxation in subcutaneous resistance arteries, as well as increased flow-mediated dilation in conduit arteries, whereas the effects induced by ramipril did not reach statistical significance. Only aliskiren significantly increased the expression of p1177-endothelial nitric oxide synthase in the endothelium. Both aliskiren and ramipril had a negligible effect on markers of oxidative stress. CONCLUSION: Aliskiren restored endothelial function and induced a more prompt peripheral vasodilation in hypertensive and diabetic patients possibly through the increased production of nitric oxide via the enhanced expression and function of the active phosphorylated form of endothelial nitric oxide synthase.

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).

Atrial fibrillation as presenting sign of primary aldosteronism: results of the Prospective Appraisal on the Prevalence of Primary Aldosteronism in Hypertensive (PAPPHY) Study.

BACKGROUND: Despite hyperaldosteronism being suggested as predisposing to arrhythmias, the relationship between atrial fibrillation and primary aldosteronism remains uncertain. Therefore, we tested the hypothesis that atrial fibrillation is a presentation of primary aldosteronism in hypertensive patients with unexplained atrial fibrillation. DESIGN AND METHODS: The Prospective Appraisal on the Prevalence of Primary Aldosteronism in Hypertensive (PAPPHY) Study recruited consecutive patients with atrial fibrillation and an unambiguous diagnosis of arterial hypertension at three referral centers for hypertension. RESULTS: In a cohort entailing 411 atrial fibrillation patients, we identified 18% (age 61 ±â€Š11 years; 32% women), who showed no known cause of the arrhythmia. A thorough diagnostic work-up allowed us to identify primary aldosteronism in 73 of these patients, i.e. 42% [95% confidence interval (CI) 31.8-53.9]. Subtyping of primary aldosteronism demonstrated that surgically curable forms of primary aldosteronism accounted for 48% of the cases (95% CI 31.9-65.2). The high prevalence of primary aldosteronism was confirmed at sensitivity analyses. CONCLUSION: These results provided compelling evidence that primary aldosteronism is highly prevalent in hypertensive patients with unexplained atrial fibrillation. Accordingly, they suggest that patients with no identifiable cause of the arrhythmia should be screened for primary aldosteronism to identify those who can be cured or markedly improved with target treatment. CLINICAL TRIAL REGISTRATION: :: https://clinicaltrials.gov, Identifier: NCT01267747.

Carotid stiffness is significantly correlated with wall-to-lumen ratio of retinal arterioles.

BACKGROUD AND PURPOSE: Wall-to-lumen ratio of retinal arterioles (W/L ratio) might serve as an in-vivo parameter of microvascular damage. No study has investigated the relationship between carotid stiffness and W/L ratio of retinal arteries. Therefore, the aim of the current study was to assess the correlation between local carotid stiffness, as assessed by echotracking technique, and W/L ratio of retinal arterioles, as assessed by noninvasive flowmetry in normotensive patients and in patients with primary hypertension. METHODS: Two hundred and twenty-seven patients underwent renal arteries W/L ratio and local carotid-pulse wave velocity (carotid PWV) measurement. One hundred and fifteen patients had a diagnosis of primary hypertension, whereas 112 were normotensive patients. RESULTS: W/L ratio and carotid PWV were both related with clinic SBP (r = 0.17, P < 0.05; r = 0.50, P < 0.001), clinic pulse pressure (r = 0.22, P < 0.001; r = 0.55, P < 0.001), carotid SBP (r = 0.18, P < 0.05; r = 0.51, P < 0.001) and carotid pulse pressure (r = 0.24, P < 0.001; r = 0.56, P < 0.001). W/L ratio was correlated with carotid PWV (r = 0.18, P < 0.005). At multivariate analysis, carotid PWV remained independently associated with W/L ratio. CONCLUSION: In hypertensive and normotensive patients, carotid stiffness is significantly correlated with W/L ratio of retinal arteries, independently of possible confounders.

Obesity and ECG left ventricular hypertrophy.

AIM: Our aim was to investigate the prevalence and the prognostic significance for fatal and nonfatal cerebrovascular and cardiovascular events of different ECG criteria for left ventricular hypertrophy (LVH) in normal weight, overweight and obese patients in an adult Italian population. METHODS: A total of 18 330 adults (mean age 54 ±â€Š11 years, 55% women, 53% hypertensive patients) were analyzed from the Moli-sani cohort. Obesity was defined using the ATPIII criteria. ECG-LVH was defined according to 2013 ESC-ESH guidelines. RESULTS: The age and sex adjusted prevalence of ECG-LVH did not differ from normal weight patients to class 1-3 obesity patients, when Cornell-voltage criterion was used. In overweight and obese patients, as compared with normal weight patients, a progressively lower prevalence of ECG-LVH was observed when the Sokolow-Lyon index was used, whereas a higher prevalence was shown by using the aVL R-wave voltage (>11 and >5.7 mm) and the Cornell-voltage-QRS duration product. The incidence of cardiovascular events was significantly greater in patients with ECG LVH diagnosis by the Cornell voltage [hazard ratio 1.89, 95% confidence interval (CI) 1.05-3.39] and the Cornell product (hazard ratio 1.87, 95% CI 1.31-2.67). After adjusting for different confounders (age, sex, cigarette, hypertension, hypercholesterolemia, diabetes, income, education, occupational class and physical activity) and for BMI categories, only the Cornell product remained significantly associated with a higher incidence of cardiovascular events (hazard ratio 1.66; 95% CI 1.16-2.38). The predictive significance of different LVH criteria was assessed across BMI categories; after adjusting for confounders, no LVH criteria were significantly associated with an increased risk of cardiovascular events in obese patients; Cornell-product LVH remained an independent predictor of events in normal weight and overweight individuals (hazard ratio 2.63; 95% CI 1.10-6.28 and hazard ratio 2.72; 95% CI 1.52-4.25, respectively). CONCLUSION: Our results confirm that ECG LVH prevalence may differ according to the criteria used across BMI categories in a low cardiovascular risk cohort. The use of different LVH criteria according to BMI categories may improve cardiovascular risk stratification in a general population independently of several confounding factors.

Changes in albuminuria and cardiovascular risk under antihypertensive treatment: a systematic review and meta-regression analysis.

BACKGROUND: Increased urine albumin excretion (UAE) is a well known predictor of cardiovascular events in patients with primary hypertension. Whether a reduction in UAE is associated to an improvement in cardiovascular risk is at present unclear. We performed a systematic review and meta-regression analysis of available trials to investigate whether treatment-induced changes in UAE are related to cardiovascular outcome. METHODS: We searched MEDLINE, ISIWeb of Science, Cochrane Database and Scopus for studies including hypertensive patients, which reported cardiovascular events and UAE at baseline and at end of follow-up. RESULTS: In trials reporting pairwise comparisons between antihypertensive treatment for cardiovascular outcome (16 randomized controlled trials and 48 580 patients, mean follow-up 45 months, 5867 cardiovascular events) after adjustment for differences in achieved blood pressure, a relationship between changes in albuminuria and risk was evident in the presence of a relevant between-arms difference in albuminuria [relative risks (RR) pooled 0.45, confidence interval (CI) 0.23-0.85] but not when no improvement in UAE was found between randomized arms (RR pooled 1.04, 95% CI 0.86-1.26, P for difference between subgroups <0.001). Meta-regression analysis showed a relationship between changes in albuminuria and risk after adjustment for blood pressure variation under treatment (adj. coeff. 0.005, 95% CI 0.0005-0.0096, P = 0.033, R 34.8%). In studies reporting changes in cardiovascular events on the basis of UAE variations (six trials and 36 325 patients, mean follow-up 60 months, 3741 cardiovascular events), the overall adjusted RR of total cardiovascular events was 0.51 (95% CI 0.38-0.59, P = 0.000) for albuminuria regression/stable vs increase. CONCLUSION: Reduction in UAE under antihypertensive treatment is associated with reduced risk of clinical cardiovascular events. Our findings suggest that UAE changes may represent a valuable intermediate end point for cardiovascular events in primary hypertension.

Speckle tracking analysis: a new tool for left atrial function analysis in systemic hypertension: an overview.

Speckle tracking echocardiography (STE) is an imaging technique applied to the analysis of left atrial function. STE provides a non-Doppler, angle-independent and objective quantification of left atrial myocardial deformation. Data regarding feasibility, accuracy and clinical applications of left atrial strain are rapidly gathering. This review describes the fundamental concepts of left atrial STE, illustrates its pathophysiological background and discusses its emerging role in systemic arterial hypertension.

Trends in Prevalence, Awareness, Treatment, and Control of Blood Pressure Recorded From 2004 to 2014 During World Hypertension Day in Italy.

Estimates of blood pressure (BP) control in real life are not systematically collected in Italy. We evaluated trends in systolic/diastolic BP levels, as well as prevalence, awareness, treatment, and control rates of hypertension among adult individuals visiting open checkpoints during the 2004 to 2014 annual editions of World Hypertension Day. Hypertension was defined as BP level ≥140/90 mm Hg or use of antihypertensive medication, whereas BP control was defined as BP level <140/90 mm Hg. We included 10,051 individuals (53.2% female, age 56.2±16.8 years, body mass index 25.7±7.6 kg/m(2) , systolic/diastolic BP 131.9±18.6/79.1±10.5 mm Hg). Hypertension prevalence and treatment were substantially unchanged, whereas awareness appears to increase over time. Controlled hypertension in diagnosed treated patients increased from 50.0% in 2004-2010 to 55.5% in 2011-2012 towards 57.6% in 2013-2014. This analysis provides real-life snapshots of hypertension over the years in the occasion of World Hypertension Day, showing increased awareness and improved control rates among treated hypertensive patients attending open checkpoints during 2004 to 2014 in Italy.

The controversial relationship between exercise and atrial fibrillation: clinical studies and pathophysiological mechanisms.

Atrial fibrillation is the most common clinically significant arrhythmia observed both in the general population and in competitive athletes. The most important risk factors are all preventable by regular physical activity. However, although the benefits of moderate physical activity in controlling cardiovascular risk factors and decreasing the risk of atrial fibrillation have been extensively proved, concerns have arisen about the potential negative effects of vigorous exercise, particularly in endurance athletes. Furthermore, in a subset of patients with atrial fibrillation younger than 60 years, routine evaluation does not reveal any cardiovascular disease or any other known causal factor. This condition is called 'lone atrial fibrillation', and the potential mechanisms underlying this condition are speculative and remain to be clarified. Atrial ectopy, increased vagal tone, changes in electrolytes, left atrial dilatation, and fibrosis have been proposed among others as potential mechanisms. However, no convincing data still exist. Particularly, the increase in left atrial size represents in athletes a physiological adaptation to exercise conditioning and the presence of biatrial fibrosis has not been demonstrated in humans. Thus, contrary to patients with cardiovascular disorders, the atrial substrate seems to play a secondary role in healthy athletes. This review article analyzes the controversial relationship between atrial fibrillation and physical activity, with a particular attention on the pathophysiological mechanisms that could be responsible for atrial fibrillation in the athletic population.

Ventricular-vascular coupling in hypertension: methodological considerations and clinical implications.

The present review is addressed to analyse the complex interplay between left ventricle and arterial tree in hypertension. The different methodological approaches to the analysis of ventricular vascular coupling in the time and frequency domain are discussed. Moreover, the role of hypertension-related changes of arterial structure and function (stiffness and wave reflection) on arterial load and how ventricular-vascular coupling modulates the process of left ventricular adaptation to hypertension are analysed.The different interplay between vascular bed and left ventricle emerges as the pathophysiological basis for the development of the multiple patterns of ventricular structural adaptation in hypertension and provides a pathway for the interpretation of systolic and diastolic functional abnormalities observed in hypertensive patients. Targeting the therapeutic approach to improve ventricular-vascular coupling may have relevant impact on reversing left ventricular hypertrophy and improving systolic and diastolic dysfunction.

Assessment of flow-mediated dilation reproducibility: a nationwide multicenter study.

OBJECTIVE: Impaired flow-mediated dilation (FMD) is associated with cardiovascular risk factors and provides prognostic information. Despite the noninvasive nature of this technique, a major limitation to its widespread use is low reproducibility. The aim of this study was to evaluate impact of methodological standardization among different investigation sites on brachial artery FMD reproducibility. METHODS: Seven Italian centers recruited 135 healthy volunteers, aged 20-60 years. FMD was assessed by high-resolution ultrasound equipped with a stereotactic probe-holding device. Certified sonographers recorded brachial artery scans at baseline (day 1a), 1 h after (day 1b), and 1 month later (day 30). Endothelium-independent vasodilation (EIVD) to sublingual glyceril-trinitrate was recorded at day 1 and day 30. FMD and EIVD were blindly evaluated at the coordinating center by an automated edge detection system. The intra-session (day 1a versus 1b) and inter-session (day 1a versus 30) coefficients of variation were calculated. RESULTS: FMD was not significantly (P = 0.91) different at day 1a, day 1b and day 30 (6.52 ± 2.9, 6.42 ± 3.1, 6.57 ± 2.8%, respectively). The FMD intra-session coefficient of variation was 9.9 ± 8.4% (from 7.6 to 11.9% across centers). The FMD inter-session coefficient of variation was 12.9 ± 11.6% (from 11.6 to 16.1% across centers). Inter-session coefficient of variation for EIDV was 19.7 ± 16.8%. CONCLUSIONS: This study shows a homogeneous coefficient of variation for FMD among different centers. The inter-session coefficient of variation was similar to the intra-session coefficient of variation, representing the intrinsic FMD variability. We demonstrate for the first time that rigorous and standardized procedure may provide reproducible FMD assessment to study endothelial function in multicenter clinical trials.

Association of central and peripheral pulse pressure with intermediate cardiovascular phenotypes.

OBJECTIVE: We assessed the relationship between pulse pressure and intermediate cardiovascular phenotypes in a middle-aged cohort with high prevalence of hypertension. BACKGROUND: It has been suggested that central pulse pressure (cPP) is a better predictor of cardiovascular outcome than peripheral pulse pressure (pPP), particularly in the elderly. Yet, it is unclear if cPP provides additional prognostic information to pPP in younger individuals. METHODS: In 535 individuals we assessed cPP and pPP as well as the intermediate cardiovascular phenotypes pulse wave velocity (PWV; SphygmoCor, Complior, PulsePen), carotid intima-media thickness (C-IMT; carotid ultrasound), left-ventricular mass index (LVMI; echocardiography) and urinary albumin : creatinine ratio (ACR). cPP was derived noninvasively from brachial blood pressure by pulse wave analysis (PWA; SphygmoCor) based on radial pulse wave tonometry and a validated transfer function. RESULTS: The cohort contained 331 hypertensive participants of whom 84% were treated. The average age was 46 ±â€Š16 years. When compared to pPP, cPP had stronger associations with PWV (r = 0.471 vs. r = 0.372; P < 0.01), C-IMT (r = 0.426 vs. r = 0.235; P < 0.01) and LVMI (r = 0.385 vs. r = 0.189; P < 0.01), but equal association with ACR (r = 0.236 vs. r = 0.226; P = n.s.). In contrast, after adjustment for age, mean arterial pressure, heart rate and hypertension status there was no significant difference between cPP and pPP for prediction of PWV (adjusted R, 0.399 vs. 0.413; P = 0.066), C-IMT (adjusted R, 0.399 vs. 0.413; P = 0.487) and LVMI (adjusted R, 0.181 vs. 0.170; P = 0.094) in multivariate analysis. CONCLUSION: In our middle-aged cohort with high prevalence of hypertension cPP is more closely correlated with cardiovascular phenotypes than pPP. When adjusted for relevant cofactors, however, cPP does not provide additional information beyond pPP.