Blood pressure control and treatment adherence in hypertensive patients with metabolic syndrome: protocol of a randomized controlled study based on home blood pressure telemonitoring vs. conventional management and assessment of psychological determinants of adherence (TELEBPMET Study).

BACKGROUND: Inadequate blood pressure control and poor adherence to treatment remain among the major limitations in the management of hypertensive patients, particularly of those at high risk of cardiovascular events. Preliminary evidence suggests that home blood pressure telemonitoring (HBPT) might help increasing the chance of achieving blood pressure targets and improve patient's therapeutic adherence. However, all these potential advantages of HBPT have not yet been fully investigated. METHODS/DESIGN: The purpose of this open label, parallel group, randomized, controlled study is to assess whether, in patients with high cardiovascular risk (treated or untreated essential arterial hypertension--both in the office and in ambulatory conditions over 24 h--and metabolic syndrome), long-term (48 weeks) blood pressure control is more effective when based on HBPT and on the feedback to patients by their doctor between visits, or when based exclusively on blood pressure determination during quarterly office visits (conventional management (CM)). A total of 252 patients will be enrolled and randomized to usual care (n = 84) or HBPT (n = 168). The primary study endpoint will be the rate of subjects achieving normal daytime ambulatory blood pressure targets (< 135/85 mmHg) 24 weeks and 48 weeks after randomization. In addition, the study will assess the psychological determinants of adherence and persistence to drug therapy, through specific psychological tests administered during the course of the study. Other secondary study endpoints will be related to the impact of HBPT on additional clinical and economic outcomes (number of additional medical visits, direct costs of patient management, number of antihypertensive drugs prescribed, level of cardiovascular risk, degree of target organ damage and rate of cardiovascular events, regression of the metabolic syndrome). DISCUSSION: The TELEBPMET Study will show whether HBPT is effective in improving blood pressure control and related medical and economic outcomes in hypertensive patients with metabolic syndrome. It will also provide a comprehensive understanding of the psychological determinants of medication adherence and blood pressure control of these patients. TRIAL REGISTRATION: Clinical Trials.gov: NCT01541566.

Evaluation of right ventricular function in patients with a previous episode of pulmonary embolism using tissue Doppler imaging.

New echocardiographic techniques including tricuspid annular plane systolic excursion (TAPSE) and pulsed tissue Doppler imaging (TDI) of the right ventricular wall have been assessed to better define right ventricular dysfunction (RVD) during the acute phase of pulmonary embolism (PE) in patients without significant tricuspidal insufficiency. Their application in patients with a previous history of PE may provide a better estimation of the incidence and clinical significance of long-term functional impairment of the right ventricle. In a case-control study, we compared the prevalence of RVD in a cohort of consecutive patients with previous PE and in age and sex-matched controls without PE. Exclusion criteria were moderate-severe left heart failure, moderate-severe mitral valve regurgitation, severe tricuspid insufficiency, or other causes of chronic pulmonary hypertension. Systolic and diastolic right ventricular functions were evaluated by measuring TAPSE and TDI of the right ventricular wall. Twenty-five patients with a previous first episode of PE and 25 controls were enrolled. Mean value of TAPSE was similar between patients with previous PE and controls (2.58 ± 0.33 and 2.53 ± 0.35 cm, P = ns). In patients with PE, the mean value of E″/A″ was significantly lower than in controls (0.89 ± 0.24 vs. 1.30 ± 0.39, P < 0.001), with 14 out of 25 cases having diastolic dysfunction as compared to only 3 out of 25 controls (P < 0.002). A high proportion of patients with previous PE have echocardiographic signs of RV diastolic dysfunction 6 months after the acute phase, even in the absence of symptoms, and in the presence of normal pulmonary pressures.

OSA, metabolic syndrome and CPAP: effect on cardiac remodeling in subjects with abdominal obesity.

BACKGROUND: We evaluated whether obstructive sleep apnoea (OSA) and continuous positive airway pressure (CPAP) treatment influence left ventricular (LV) remodelling independently of abdominal obesity and metabolic syndrome (MetS). METHODS: Cardiorespiratory examination, 24-h BP monitoring and echocardiogram were performed in overweight/obese patients with increased abdominal adiposity and symptoms suggesting OSA : OSA/MetS (n.50), OSA/noMetS (n.22), noOSA/MetS (n.29), noOSA/noMets (n.16). The evaluation was repeated in 41 patients after ≥18 months of CPAP. RESULTS: Despite similar age, gender, BMI and 24-h BP, the 2 groups with MetS had greater LV remodelling (LV hypertrophy and diastolic dysfunction) than the 2 groups without MetS. From multiple regression analysis independent determinants for LV mass were MetS, 24-h systolic BP and age, for LV diastolic function were LV mass index, MetS and age. After CPAP, the 20 patients with decreased body weight showed diastolic BP decrease, LV hypertrophy regression and diastolic function improvement, whereas, despite similar respiratory improvement, BP and LV parameters were unchanged in the 21 patients with body weight unchanged/increased. CONCLUSION: In patients with increased abdominal adiposity, LV remodelling is not associated to OSA per se; chronic CPAP treatment does not influence LV remodelling whose regression is mainly linked to body weight decrease.

Plasma levels of matrix metalloproteinases and their inhibitors in hypertension: a systematic review and meta-analysis.

BACKGROUND: Hypertension is a major cause of cardiovascular remodeling. In the cardiovascular system, the remodeling of the extracellular matrix is controlled by the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs). The aim of this meta-analysis is to elucidate the behavior of plasma MMP and TIMP levels in hypertension and their relationship to cardiovascular remodeling. METHODS: MEDLINE and EMBASE databases were searched up to July 2011. Studies were considered eligible if they provided values of plasma MMPs and TIMPs in hypertensive patients. Given the high variability of the plasma biomarker values among studies, the standardized mean difference (SMD) was calculated. RESULTS: Ten studies provided plasma MMP-9; the SMD between 778 hypertensive patients and 669 controls was 1.95 units (P < 0.05). Thirteen studies provided plasma TIMP-1; the SMD between 851 hypertensive patients and 646 normotensive individuals was 1.92 units (P < 0.01). Three studies investigated whether plasma TIMP-1 predicted left ventricular (LV) remodeling; the SMD between 92 hypertensive patients with and 88 hypertensive patients without LV hypertrophy was 5.81 units (P < 0.05). As for diastolic heart failure (HF), five studies provided data for plasma MMP-2; the SMD between 321 hypertensive patients with and 334 hypertensive patients without HF was 2.36 units (P < 0.01). The heterogeneity among studies was high. CONCLUSIONS: These results suggest that MMP-2, MMP-9 and TIMP-1 may have a role as biomarkers of cardiovascular remodeling in hypertension. If these results are confirmed in prospective clinical studies, they could provide new tools to stratify cardiovascular risk in hypertensive patients.

Neutrophils and clinical outcomes in patients with acute coronary syndromes and/or cardiac revascularisation. A systematic review on more than 34,000 subjects.

Some studies have suggested that high levels of total white blood cell (WBC) count and C-reactive protein (CRP) may be considered as independent prognostic factors in patients with acute coronary syndromes (ACS) and/or after cardiac revascularisation by percutaneous coronary intervention or coronary artery bypass grafting surgery. Evidence on the role of neutrophils in cardiovascular disease is less compelling. Therefore, we conducted a systematic review of the literature with the aim of identifying all the available evidence to clarify the role of neutrophils (absolute or relative count, neutrophil/lymphocyte ratio) as a prognostic risk factor in patients with ACS and/or cardiac revascularisation. All published studies evaluating the role of neutrophils as a risk factor for clinical outcomes were assessed using the MEDLINE and EMBASE databases. Study selection, data extraction and validity assessment was performed independently by two reviewers. Twenty-one studies (17 of which had positive results) for a total of more than 34,000 patients were included. Ten of 13 studies in ACS patients found that neutrophils measured on-admission are related to mortality rate and/or to major adverse clinical events. A predictive value of neutrophils after cardiac revascularisation procedures was reported in seven out of eight studies. Most of the studies showed that neutrophils were independent predictors of cardiovascular outcomes when analysed concomitantly with other markers of inflammation (WBC, CRP). The findings of our systematic review highlight the potential application of this inexpensive and readily available inflammatory marker for risk stratification in patients with ACS and/or cardiac revascularisation.

Seasonal and monthly variability in the incidence of venous thromboembolism. A systematic review and a meta-analysis of the literature.

Many studies showed that the occurrence of cardiovascular and cerebrovascular events exhibits a seasonal and monthly variation. Evidences of a seasonal and monthly variation in the incidence of venous thromboembolism (VTE) are more conflicting. We conducted a systematic review and a meta-analysis of the literature to assess the presence of an infradian rhythm of this disease. MEDLINE and EMBASE databases were searched up to January 2010. Monthly and seasonal variation in the incidence of VTE were analysed. We included studies analysing seasonal or monthly aggregation in the incidence of deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) with an objective diagnosis of VTE. Two authors independently reviewed and extracted data. Seventeen studies for a total of about 35,000 patients were included. Twelve studies analysed the seasonal variation and 10 studies the monthly variation of VTE. Our results showed a significantly increased incidence of VTE in winter (chi-square 146.04, p <0.001), with a relative risk (RR) of VTE of 1.143 (99% CI [1.141, 1.144]), and a significantly increased incidence of VTE in January (chi-square 232.57, p <0.001) with an RR of VTE of 1.194 (99% CI 1.186, 1.203). Subgroup analyses including only idiopathic venous thromboembolic events confirmed the results of principal analyses. In conclusion, our data support the presence of an infradian pattern in the incidence of venous thromboembolic events, with a significantly higher risk in Winter and in January. Future studies are needed to better clarify the mechanisms behind this pattern.

Lipid targets during statin treatment in dyslipidemic patients affected by nonalcoholic fatty liver disease.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is associated with both dyslipidemia and increased risk for cardiovascular disease. Despite the indication to treat in patients affected by both dyslipidemia and NAFLD, an undertreatment in statin therapy due to the potential liver damage is frequently observed. We sought to evaluate retrospectively the impact of statin on the lipid profile and on the achievement of low-density lipoprotein (LDL) cholesterol targets in relation to the National Cholesterol Education Program--Adult Treatment Panel III-cardiovascular risk in dyslipidemic patients presenting with a clinical--diagnosis of NAFLD and elevated liver enzymes before statin prescription. As a secondary endpoint, the authors investigated whether statin could be associated with changes of liver enzymes. METHODS: Forty-three patients with dyslipidemic NAFLD presenting with increased values of aspartate aminotransferase and/or alanine aminotransferase and/or γ-glutamyl-transferase at baseline were analyzed retrospectively as regard the lipid profile and liver enzymes (values reported before statin and during statin therapy). RESULTS: Total cholesterol, LDL and triglycerides were significantly reduced at follow-up (5.4 ± 5.4 months). The LDL target was achieved at the second visit in 30 patients (69.8%).The number of patients achieving the LDL target was significantly higher in low-risk group compared with moderate- and high-risk subjects. Liver enzyme levels showed no significant changes between baseline and follow-up. CONCLUSIONS: Statin treatment was effective (without changes in liver enzymes) in patients with dyslipidemia and NAFLD and therefore, affected by a profound alteration in lipoprotein metabolism. The number of patients achieving LDL target was related to the Adult Treatment Panel III risk classification, being higher in patients with lower risk.

Use of statins and recurrence of atrial fibrillation after catheter ablation or electrical cardioversion. A systematic review and meta-analysis.

Statins have important pleiotropic effects and have been shown to reduce vascular inflammation. Some evidence suggests that statins may have a role in the primary prevention of atrial fibrillation (AF), whereas little is know on the role of statins in patients with existing AF. We performed a meta-analysis of the literature to assess the effect of statins on the recurrence of AF after electrical cardioversion or ablation. MEDLINE and EMBASE databases were searched up to January 2010. Relative risks (RR) and 95% confidence intervals (CIs) were then calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of I² statistics. Sixteen studies were included in our systematic review. Statins did not reduce the risk of AF recurrence after ablation (four studies including 750 patients; RR, 1.04; 95% CI, 0.85-1.28, p=0.71; I² = 34%). Conversely, the use of statins was associated with a significantly reduced risk of AF recurrence after electrical cardioversion (12 studies including 1790 patients; RR, 0.78; 95% CI, 0.67-0.90, p=0.0003; I² = 34%). This reduction was not statistically significant when the analysis was restricted to randomised controlled trials (RCTs) only (five studies, 458 patients, RR, 0.76; 95% CI, 0.48-1.20). In conclusion, statins may lower the risk of AF recurrence after electrical cardioversion, but not ablation. However, this finding should be considered with caution, and larger RCTs are warranted to confirm our preliminary results.

Cytokine production from peripheral blood mononuclear cells and polymorphonuclear leukocytes in patients studied for suspected obstructive sleep apnea.

PURPOSE: The relationship between obstructive sleep apnea (OSA) and atherosclerosis-related inflammation has been poorly investigated, particularly focusing on functional responses of immune cells playing a key role in atherogenesis and in comparison with control groups with similar cardiovascular risk factors which are known to be themselves associated with inflammation. We sought to determine cellular tumor necrosis factor-alpha (TNF-α) production from peripheral blood mononuclear cells (PBMCs) and interleukin (IL)-8 release from neutrophils (PMNs) in patients studied for suspected OSA. METHODS: Thirty-six consecutive patients who underwent a nocturnal complete cardiorespiratory evaluation for suspected OSA were initially evaluated. Serum, PBMCs, and PMNs were isolated (at baseline and after 12 weeks) from patients with apnea-ipopnea index (AHI) >20 (OSA group, n = 16) and from control patients with AHI <5 (nonOSA group, n = 11). All patients continued the same pharmacological therapy for 12 weeks; the OSA group was additionally treated with nocturnal continuous positive-airway-pressure ventilation (cPAP). RESULTS: The two groups had similar clinical characteristics (prevalence of hypertension, dyslipidemia, diabetes, and cardio-metabolic therapies) except for obesity. Resting and stimulated TNF-α production from PBMCs and IL-8 release from PMNs were similar in the two groups. Serum cytokines resulted within the normal range. In the OSA group, cPAP was not associated with changes in cellular responses. CONCLUSIONS: In patients showing similar prevalence of major cardiovascular risk factors and cardio-metabolic therapies, differing for the presence or absence of OSA, cytokine productions from PBMC and PMN were similar and were not modified during cPAP therapy. Studies designed to investigate OSA-associated inflammation should carefully match the control group subjects.

Safety of thrombolysis in cerebral venous thrombosis. A systematic review of the literature.

Several small series have suggested the efficacy of thrombolysis in patients with cerebral vein thrombosis (CVT). However, since no randomised controlled trials have compared the use of thrombolysis with anticoagulant treatment in these patients, the risk to benefit ratio of this approach remains uncertain. The aim of this study is therefore to assess the safety of thrombolysis in CVT estimating mortality and major bleeding complications. MEDLINE and EMBASE databases were searched up to June 2010. Two reviewers performed study selection independently. Studies providing data on mortality and/or on the incidence of major bleeding complications were potentially eligible for the study. Two reviewers independently extracted data on study and population characteristics, type, dose and administration route of thrombolytic treatment; use and dose of concomitant heparin. Weighted mean proportion of the mortality rate and of the rate of major and non-major bleeding complications were calculated. Fifteen studies for a total of 156 patients were included. Twelve patients died after thrombolysis (weighted mean 9.2%; 95% CI 4.3, 15.7%) and 15 patients had a major bleeding complication (weighted mean 9.8%; 95% CI 5.3, 15.6%). Twelve haemorrhages were intracranial (weighted mean 7.6%; 95% CI 3.5, 13.1%), and seven of these patients died (58.3%; 95% CI 32.0, 80.7%). Our results suggest that thrombolysis is associated with a non-negligible incidence of major bleeding complications, including intracranial bleeding potentially affecting patients outcome. Future studies are necessary to evaluate the safety of thrombolysis in comparison to more conservative strategies.

Effectiveness of barnidipine 10 or 20 mg plus losartan 50-mg combination versus losartan 100-mg monotherapy in patients with essential hypertension not controlled by losartan 50-mg monotherapy: A 12-week, multicenter, randomized, open-label, parallel-group study.

BACKGROUND: Increasing the dose or adding a second antihypertensive agent are 2 possible therapeutic choices when blood pressure (BP) is poorly controlled with monotherapy. OBJECTIVE: This study investigated the effectiveness and tolerability of barnidipine 10 or 20 mg added to losartan 50 mg versus losartan 100 mg alone in patients with mild to moderate essential hypertension whose BP was uncontrolled by losartan 50-mg monotherapy. METHODS: This was a 12-week, multicenter, randomized, open-label, parallel-group study. Eligible patients (aged 30-74 years) had uncontrolled hypertension, defined as office sitting diastolic BP (DBP) > or =90 mm Hg and/or systolic BP (SBP) > or =140 mm Hg, and mean daytime DBP > or =85 mm Hg and/or SBP > or =135 mm Hg. All were being treated with losartan 50 mg at enrollment. After a 1-week run-in period while taking losartan 50 mg, patients were randomly assigned to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg or losartan 100-mg monotherapy. At the end of this period, patients with uncontrolled BP had barnidipine doubled to 20 mg and continued for an additional 6 weeks, whereas patients not achieving control on treatment with losartan 100 mg were discontinued. Office BP was measured at each visit, whereas 24-hour ambulatory BP monitoring (ABPM) was performed at randomization and at the final visit (ie, after 12 weeks of treatment, or at 6 weeks for patients not controlled on losartan 100 mg). The intent-to-treat population included all randomized patients who received at least one dose of study treatment and had valid ABPM recordings at baseline and the final visit. The primary end point was the change in daytime DBP between baseline and 12 weeks of treatment, compared between the combination treatment and monotherapy. Adverse events (AEs) were evaluated during each study visit. RESULTS: A total of 93 patients were enrolled (age range, 30-75 years; 60% [56/93] men). After the 1-week run-in period, 68 patients were randomly assigned to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg (n = 34) or losartan 100-mg monotherapy (n = 34). A total of 53 patients were evaluable (barnidipine plus losartan, n = 28; losartan, n = 25). After 6 weeks of treatment, 18 patients in the combination treatment group (64.3%) had their dose of barnidipine doubled from 10 to 20 mg because BP was not normalized by treatment, whereas 8 patients in the losartan group (32.0%) were discontinued for the same reason. The between-treatment difference (losartan alone - combination treatment) for changes from baseline in daytime DBP was -1.7 mm Hg (95% CI, -5.8 to 2.4 mm Hg; P = NS). A similar result was observed for daytime SBP (-3.2 mm Hg; 95% CI, -8.1 to 1.7 mm Hg; P = NS). Likewise, no significant differences were found for nighttime values (mean [95% CI] DBP, 0.5 mm Hg [-3.7 to 4.7 mm Hg]; SBP, 1.5 mm Hg [-4.1 to 7.1 mm Hg]) or 24-hour values (DBP, -0.9 mm Hg [-4.8 to 2.9 mm Hg]; SBP, -1.6 mm Hg [-5.9 to 2.7 mm Hg]). Combination treatment was associated with a significantly higher rate of SBP responder patients (ie, <140 mm Hg or a reduction of > or =20 mm Hg) compared with monotherapy (82.1% [23/28] vs 56.0% [14/25]; P = 0.044). Drug-related AEs were reported in 4 patients taking combination treatment (total of 7 AEs, including 2 cases of peripheral edema and 1 each of tachycardia, atrial flutter, tinnitus, confusion, and polyuria) and in 2 patients taking losartan alone (total of 2 AEs, both tachycardia). CONCLUSIONS: This open-label, parallel-group study found that there was no significant difference in the BP-lowering effect of barnidipine 10 or 20 mg in combination with losartan 50 mg compared with losartan 100-mg monotherapy in these patients with essential hypertension previously uncontrolled by losartan 50-mg monotherapy. However, the percentage of responders for SBP was significantly higher with the combination. Both treatments were generally well tolerated. European Union Drug Regulating Authorities Clinical Trials (EudraCT) no. 2006-001469-41.

Statins, fibrates, and venous thromboembolism: a meta-analysis.

AIMS: The aim is to make a systematic review of the literature to assess the effect of lipid-lowering drugs on venous thromboembolism (VTE) occurrence. METHODS AND RESULTS: MEDLINE and EMBASE databases were searched to identify studies that evaluated the effect of lipid-lowering drugs, in particular statins and fibrates, on VTE risk until April 2009. A scoring system was used to divide studies into two quality categories. Odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated and pooled using a fixed and a random-effects model. Statistical heterogeneity was evaluated through the use of I(2) statistics. Three randomized controlled trials (RCTs), three cohort, and eight case-control studies were included in our systematic review, for a total of 863 805 patients. Statins use significantly reduced VTE risk [OR, 0.81; 95% CI, 0.66-0.99, random-effect model)]. There was a very high heterogeneity among the studies (I(2) > 80%). The use of fibrates was associated with a significant increase in the risk of VTE (OR, 1.58; 95% CI, 1.23-2.02), without heterogeneity (I(2) = 0%). Data on other lipid-lowering drugs were lacking. CONCLUSION: This meta-analysis of available literature suggests that statins may lower the risk of VTE, whereas fibrates may increase this risk. Due to several methodological limitations, this conclusion should be considered with caution, and additional, specifically designed RCTs are warranted.

Diagnosis and management of venous thromboembolism: Results of a survey on current clinical practice.

BACKGROUND: The implementation of evidence from clinical studies into daily clinical practice is not a straightforward process. We developed a standardized questionnaire to explore clinical practice patterns in the management of VTE, in particular about the use of pre-clinical probability and D-dimer testing and on the home treatment of pulmonary embolism (PE). METHODS: The standardized questionnaire was sent to all 394 physician members of the Italian Society of Thrombosis and Haemostasis (SISET) by e-mail. The questionnaire contained three groups of questions: about general information, about the diagnostic process for both deep venous thrombosis (DVT) and PE, and about home-therapy of PE. RESULTS: One hundred and twenty-eight (32.5%) physicians responded the questionnaire. For DVT diagnosis 69 (54.3%) physicians answered that they always use the D-dimer test; 4 (3.1%) do never use it; whereas only 11 (8.7%) take notice of the D-dimer result before visiting the patients; 38 (29.9%) use only clinical judgment to assess pre-clinical probability of disease. For the diagnosis of PE 80 (66.1%) physicians always use the D-dimer test, whereas 3 (2.5%) do never use it; whereas 14 (11.7%) take notice of the D-dimer result before visiting the patients; 50 (41.3%) use only clinical judgment to assess pre-clinical probability. Sixty-six (59.5%) clinicians declared to treat patients with PE at home, when feasible. CONCLUSION: The diagnostic approach to VTE among expert physicians appears to be heterogeneous; in particular there is no widespread use of clinical prediction rules. The majority of expert physicians appear to consider the possibility of treating at home patients with PE.

Angiotensin type 1 receptor expression and interleukin-8 production in polymorphonuclear leukocytes of patients with peripheral arterial disease.

We investigated angiotensin type 1 receptor (AT1R) expression and interleukin-8 (IL-8) productions in polymorphonuclear leukocytes obtained from patients with peripheral arterial disease (PAD) undergoing femoral endarterectomy. Subjects at high cardiovascular risk (high-risk subjects, HRS) and healthy controls (HC) were also enrolled. To this end, patients with PAD were studied 1 month before surgery, at the time of surgery, and 3 and 6 months after surgery. Polymorphonuclear leukocytes were obtained from venous blood and evaluated for AT1R expression at messenger RNA (mRNA) and protein level and IL-8 production (by means of enzyme-linked immunosorbent assay). At baseline, AT1R membrane expression was similar in cells from patients with PAD, HRS, and HC, whereas AT1R mRNA was similar in patients with PAD and HC and higher in HRS. During the follow-up period, AT1R expression progressively decreased both on the cell membrane and at the mRNA level. Both resting and stimulated production of IL-8 was lower in patients with PAD in comparison to HC and HRS and did not change during the follow up period. In PAD patients, femoral endarterectomy is associated with reduction of AT1R expression however with no apparent effect on IL-8 production. The relevance of such effects for cardiovascular protection deserves consideration.

Incidence of chronic pulmonary hypertension in patients with previous pulmonary embolism.

INTRODUCTION: The true incidence of chronic thromboembolic pulmonary hypertension (CTPH) remains a matter of debate. Symptomatic CTPH is probably more common than previously reported, whereas the occurrence of asymptomatic CTPH has not been defined since very limited evidence on the incidence of asymptomatic CTPH diagnosed with echocardiography Doppler are currently available. We therefore carried out a prospective cohort study to assess the incidence of CTPH diagnosed with echocardiography Doppler in consecutive patients with a first episode of PE. METHODS: Consecutive patients with a first episode of PE were evaluated with Doppler transthoracic echocardiography within 6 to 12 months after the index event. Pulmonary hypertension was defined as a systolic pulmonary artery pressure > or =40 mmHg at rest in the presence of residual perfusion defects at perfusion scintigraphy. Presence of symptoms related to pulmonary hypertension was evaluated with a standardized questionnaire. RESULTS: Ninety-one patients (mean age 61.9+/-15.7 years; range 22-89; 39 men) were enrolled. Eight patients (8.8%; 95% CI 4.5,16.4) had CTPH: of these, 4 (4.4%; 95% CI 2.0, 9.3) were symptomatic. CONCLUSIONS: Asymptomatic CTPH is not an uncommon finding after PE. Larger prospective trials with a longer follow up should assess the prognostic significance of asymptomatic CPTH.