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Aim The study was aimed to evaluate the influence of gender on left ventricular (LV) remodeling in metabolic syndrome (MetS). Methods and results We enrolled 200 subjects without diabetes or overt cardiovascular diseases, never treated with anti-hypertensive drugs or statins: 60 men and 40 women with MetS matched by age, gender and 24 h systolic and diastolic blood pressure (BP) with 60 men and 40 women without MetS. The patients underwent blood tests, 24 h our BP monitoring, LV echocardiographic examination. LV mass indexed by eight 2.7 was significantly greater in men and women with MetS than without MetS. Compared with women without MetS, women with MetS had significantly higher posterior wall thickness and relative wall thickness, greater prevalence of LV concentric remodeling/hypertrophy and lower indices of LV diastolic function, whereas all these parameters were not significantly different between men with and without MetS. MetS was an independent predictor of relative wall thickness and LV mass index in women, but not in men. Conclusion The impact of MetS on LV remodeling is significantly influenced by gender: the effects of MetS are more pronounced in women, with development of LV concentric hypertrophy/remodeling and preclinical diastolic dysfunction.

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.

The high cardiovascular risk of HIV infected (HIV+) patients is still partly unexplained. We aimed to evaluate if HIV infection and highly active antiretroviral therapy (HAART) are linked per se to left ventricular (LV) remodelling, independently of blood pressure (BP) values. We enrolled 4 groups of patients matched by gender, age, body mass index and smoking habit: 30 HIV+ hypertensives, 30 HIV+ normotensives, 30 not-infected (HIV-) hypertensives and 30 HIV- normotensives. HIV+ patients were on chronic HAART. Hypertension was newly diagnosed (≤6 months) and never treated. Each patient underwent blood tests, 24-h BP monitoring and LV echocardiogram. The 4 groups had similar fasting glucose and cholesterol; triglycerides, HOMA index and prevalence of metabolic syndrome were higher in the HIV+ groups. Despite similar 24-h BP values, HIV+ hypertensives had greater LV mass and higher prevalence of preclinical diastolic dysfunction than HIV- hypertensives. Compared to HIV- normotensives, HIV+ normotensives had similar 24-h BP values, but greater LV mass and lower LV diastolic indices, similar to HIV- hypertensives, whose 24-h BP values were higher. Asymptomatic HIV infection and chronic HAART are associated with myocardial hypertrophy and preclinical diastolic dysfunction, independently of BP values.

Background Metabolic syndrome (MS) is associated with an increased risk of cardiovascular events. Recent studies have found a higher prevalence of the MS in patients with idiopathic venous thromboembolic events (VTE) compared to controls suggesting a role of the MS in the pathogenesis of VTE. The presence of MS was shown to further increase the risk of arterial cardiovascular diseases (CVD) in diabetic patients. Conversely, there are no studies that have compared the risk of VTE in diabetic patients with and without the MS. Methods A cross sectional study comparing the prevalence of arterial cardiovascular events and VTE in diabetic patients with and without the MS was conducted. Results Nine hundred and fifty three patients were included in the study; 85.7% of patients had MS. Patients with the MS had an increased prevalence of CVD as compared with those without (23.4% vs. 11.8%) and the MS was an independent predictor of CVD in diabetic patients (OR 3.16, 95%CI 1.78, 5.59) after multiple logistic regression analysis. The prevalence of VTE was higher in patients with the MS in comparison to patients without the MS, but this association was not statistically significant (3,43% vs 1.47%; OR 2.38, 95% CI 0.56, 10.10%). Conclusion Our study confirms the role of MS as an adjunctive cardiovascular risk factor in patients with diabetes. There is insufficient evidence to evaluate the role of the as an adjunctive risk factor for VTE in these patients. Further studies are necessary to confirm or refute these preliminary findings.

SummaryStatins 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.

SummarySeveral 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 nonnegligible 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.

The baroreflex control of circulation is always operating and modulates blood pressure and heart rate oscillations. Thus, the study of cardiovascular variability in humans is performed in a closed-loop model and the physiology of post-sinoaortic denervation is completely unknown in humans. We dissected for the first time the different components of systolic arterial pressure (SAP) and RR-interval spectra in a patient with 'baroreflex failure' (due to mixed cranial nerve neuroma) who represents a human model to investigate the cardiovascular regulation in an open-loop condition. Interactions among cardiovascular variability signals and respiratory influences were described using the multivariate parametric ARXAR model with the following findings: (1) rhythms unrelated to respiration were detected only at frequencies lower than classical low frequency (LF; Slow-LF, around 0.02 Hz) both in SAP an RR spectra, (2) small high-frequency (HF) modulation is present and related with respiration at rest and in tilt (but for SAP only) and (3) the Slow-LF fluctuations detected both in SAP and RR oscillate independently as the multivariate model shows no relationships between SAP and RR, and these oscillations are not phase related. Thus, we showed that in a patient with impaired baroreflex arc integrity the Slow-LF rhythms for RR have a central origin that dictates fluctuations on RR at the same rhythm but unrelated to the oscillation of SAP (which may be related with both peripheral activity and central rhythms). The synchronization in LF band is a hallmark of integrity of baroreflex arc whose impairment unmasks lower frequency rhythms in SAP and RR whose fluctuations oscillate independently.

Objective Angiotensin II, through the activation of angiotensin II type 1 receptors, plays a crucial role in atherosclerosis. Statins may interfere with the effects of angiotensin II. Methods We have investigated the expression of angiotensin II type 1 receptor, angiotensin II type 2 receptor and angiotensinogen on circulating monocytes and T-lymphocytes from subjects at high risk for vascular events before and during simvastatin treatment, and healthy controls. In-vitro experiments were also performed to assess the ability of simvastatin to interfere with angiotensin II signalling. Results In comparison with controls, high-risk subjects had similar angiotensin II type 1 receptor expression on the cell membranes but significantly higher angiotensin II type 1 receptor mRNA levels at least in monocyte subsets whereas their expression on T cells was similar. Angiotensin II type 2 receptor mRNA expression was higher than controls in both monocytes and T lymphocytes. No differences were observed in angiotensinogen expression on monocytes while T lymphocytes of high-risk subjects show higher expression. One-month treatment of high-risk subjects with simvastatin resulted in a reduction of angiotensin II type 1 receptor mRNA without affecting angiotensin II type 2 receptor whereas angiotensinogen mRNA expression was reduced at least in monocytes. Incubation in vitro with simvastatin reduces the expression of angiotensin II type 1 receptor mRNA levels on monocytes from untreated subjects. Conclusion Simvastatin induces down-regulation of the angiotensin II type 1 receptor, interferes with angiotensin II activity in immune cells and contributes to the anti-inflammatory profile of statins that can explain the therapeutic effects of these drugs.

Reciprocal translocation t(9;22) is central to the pathogenesis of chronic myeloid leukemia. Some authors have suggested that Alu repeats facilitate this process, but supporting analyses have been sparse and often anecdotal. The purpose of this study was to analyze the local structure of t(9;22) translocations and assess the relevance of interspersed repeat elements at breakpoints. Collected data have been further compared with the current models of DNA recombination, in particular the single-strand annealing (SSA) and the nonhomologous end joining (NHEJ) processes. We developed a protocol for the rapid characterization of patient-specific genomic junctions and analyzed 27 patients diagnosed with chronic myeloid leukemia. Sequence analysis revealed microhomologies at the junctions of 21 patients of 27, while interspersed repeats were of relevance (P < 0.05) in at least 16 patients. These findings are more frequent than expected and give an indication that the main mechanisms involved in the t(9;22) translocation are the SSA and NHEJ pathways, both playing a role. Furthermore, our report is consistent with microhomologies facilitating the joining of DNA ends in the translocation process, and with both Alu and a variety of other repeat sequences pairing nonhomologous chromosomes during the SSA pathway. V C 2008 Wiley-Liss, Inc.

To evaluate in type 2 diabetes mellitus the relationship between masked hypertension (MH) and left ventricular (LV) morpho-functional characteristics.Using 24-hour BP monitoring and echocardiography, we evaluated 71 type 2 diabetic patients, without overt cardiac disease and never treated with antihypertensive drugs: 45 normotensive subjects with clinic BP130/85 mmHg and 26 sustained hypertensives (SH)(clinic BPor = 140 and/or 90 mmHg and 24-hour BPor =125 and/or 80 mmHg), matched for age, gender, BMI and duration of diabetes with clinically normotensive patients. MH was diagnosed with clinic BP130/85 mmHg and 24-hour BPor =125 and/or 80 mmHg.Among clinically normotensive patients, 21 (47%) had MH and 24 were true normotensive (NT, 24-hour BP125/80 mmHg). LV mass increased from NT to MH to SH (p0.001); the parameters of LV diastolic function were similar between MH and SH and significantly lower than in NT.In type 2 diabetic patients with clinic BP130/85 mmHg, MH is frequent and is associated with LV remodelling characterized by increased myocardial mass and preclinical impairment of LV diastolic function; the remodelling is qualitatively and for some aspects also quantitatively similar to that found in sustained hypertensive patients. Therefore it would be useful to look for MH in diabetic subjects with clinic BP130/85 mmHg, who, following the guidelines, are not entitled to antihypertensive treatment: the finding of MH could identify a subgroup of patients at higher cardiovascular risk and therefore needing a prompt antihypertensive treatment.

Background: Elevated blood pressure levels that are associated with hypalgesia and hypothyroidism have major influences on the cardiovascular system. The potential modulation of pain sensitivity by thyroid hormones is largely undetermined. Moreover, a few experimental studies show that peripheral benzodiazepine receptors (PBRs), which may be altered in hypothyroidism, seem to be related with pain perception. Methods: Dental pain threshold and tolerance were evaluated in 19 patients followed for differentiated thyroid carcinoma (1) in severe short-term hypothyroidism (phase 1) and (2) during thyroid stimulating hormone-suppressive LT 4 treatment (phase 2). PBR expression (cytofluorimetric evaluation) on peripheral blood mononuclear cells was also investigated in the 2 phases. Results: Pain perception differed throughout the study, the dental pain threshold was higher in phase 1 (P < 0.05) whereas pain tolerance was higher but not significantly (P = 0.07). Although the systolic blood pressure was higher during hypothyroidism (P < 0.01), no relationship was found between blood pressure changes and pain sensitivity variations. Moreover, the multiple regression analysis showed an independent association of the clinical phase with pain sensitivity (r = -2.61, P = 0.029), while accounting for systolic blood pressure. The intensity of PBRs was significantly higher in the first phase of the study (P = 0.047) whereas the ratio did not significantly differ. However, no relationship was observed between pain sensitivity and PBRs. Discussion: In conclusion, in athyreotic patients, the pain sensitivity is related to the thyroid status and is independent of the increase in blood pressure induced by thyroid hormone deprivation. The PBRs do not seem to have major influence on pain sensitivity changes in hypothyroidism.

Summary. Background: Information on the incidence of venous thromboembolism (VTE) following laparoscopic procedures is inadequate and there is currently no solid evidence to guide the use of thromboprophylaxis in this setting. Gynecologic laparoscopy is a common procedure, and is frequently performed in low-risk patients. To our knowledge, there are no clinical studies specifically designed to assess the incidence of VTE in this setting. Methods: In a prospective cohort study, consecutive patients undergoing gynecologic laparoscopy underwent compression ultrasonography (CUS) and clinical assessment to evaluate the incidence of clinically relevant VTE. CUS was performed 7 ± 1 and 14 ± 1 days postoperatively. A subsequent telephone contact was scheduled at 30 and 90 days. No patient received pharmacologic or mechanical prophylaxis. Patients with malignancy or previous VTE were excluded from the study. Results: We enrolled 266 consecutive patients; mean age was 36.3 years, range: 18–72. The most common indications for laparoscopy were ovarian cysts in 25.6% of patients, endometriosis in 21.0% of patients, unexplained adnexal masses in 12.4% of patients, and infertility in 7.5% of patients. The mean duration of the procedure was 60.5 min (range: 10–300 min). In particular, in 55.6% of patients the duration exceeded 45 min. There were neither episodes of CUS detected DVT (0/247; 0%, 95% CI 0–1.51%) or clinically relevant VTE after follow-up (0/256; 0%, 95% CI 0–1.48%). No patient died of fatal pulmonary embolism (0/266; 0%, 95% CI 0–1.42%). Conclusions: Gynecologic laparoscopy in non-cancer patients is a low-risk procedure for postoperative VTE.

Background: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial. Methods: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2). Results: The RR interval value (p < 0.01) and systolic blood pressure (p < 0.05) were higher in phase 1 than in phase 2. The low-frequency/high-frequency (LF/HF) ratio was significantly lower in the hypothyroid state (p < 0.05), with a higher HF component (p < 0.05). After adjusting for mean RR interval in the regression model, the difference between the power of RR interval oscillations calculated in the two states was greater for the LF band (p = 0.005) and it was borderline significant for the HF band (p = 0.052). The baroreflex gain αLF index was similar in the two phases. The stimulus-induced cellular production of norepinephrine and epinephrine in peripheral blood mononuclear cells was significantly higher in phase 2. Conclusion: The neurally-mediated influences on the sinus node and the study of intracellular catecholamine production suggest a reduced sympathoexcitation in hypothyroidism compared with the treatment phase. The early increase in blood pressure observed after thyroid hormone withdrawal is not due to impaired sensitivity of the baroreflex arc.

Summary. Objective: The results of recent studies have suggested that patients with idiopathic venous thromboembolism (VTE) might be at increased risk of asymptomatic atherosclerosis and cardiovascular events. The metabolic syndrome is a cluster of risk factors for atherosclerosis. Its impact on VTE is unknown. Methods: In a case–control study, consecutive patients with objectively confirmed deep vein thrombosis (DVT) and control subjects with objectively excluded DVT underwent clinical assessment for the presence of the metabolic syndrome according to the National Cholesterol Education Program criteria. The presence of known risk factors for DVT was documented. Patients with DVT secondary to cancer were excluded. The prevalence of the metabolic syndrome was compared between patients with idiopathic DVT and controls. Results: We enrolled 93 patients with a first episode of idiopathic DVT and 107 controls. The mean age was 65.1 and 63.7 years, respectively. The metabolic syndrome was diagnosed in 50.5% of patients with idiopathic DVT and in 34.6% of controls [odds ratio (OR) 1.93; 95% confidence interval (CI) 1.05, 3.56]. After adjustment for age, sex, body mass index, and smoke, the metabolic syndrome remained independently associated with idiopathic DVT (OR 1.94; 95% CI 1.04, 3.63). In patients with secondary DVT, the prevalence of the metabolic syndrome was 27%. Conclusions: The metabolic syndrome may play a role in the pathogenesis of idiopathic DVT and may act as link between venous thrombosis and atherosclerosis.

The renin-angiotensin system plays a key role in the regulation of cardiovascular functions and in particular angiotensin II type 1 receptor (AT1R)-operated pathways are involved in the modulation of inflammation in the vascular wall. In the present study we assessed the pattern of expression of AT1Rs on different human circulating leukocyte subsets. Venous blood was obtained from healthy male subjects. Leukocyte subsets were purified by immunomagnetic cell sorting or identified in whole blood using multiparametric cytometric analysis. RT-PCR analysis showed that AT1R mRNA was expressed in polymorphonuclear leukocytes (PMNs), monocytes, B-lymphocytes, and, to a lesser extent, T-lymphocytes. Flow cytometric analysis revealed that the frequency of expression of AT1Rs was: PMNs>monocytes>or=B-lymphocytes>>T-lymphocytes, while receptor density per positive cells was: PMNs>or=B-lymphocytes>T-lymphocytes>or=monocytes. AT1Rs are expressed on PMNs, monocytes, T- and B-lymphocytes, however the expression pattern is peculiar to each subset, possibly suggesting distinct roles in the various cell types. Investigating the expression and the functional role of AT1Rs on circulating leukocyte subsets, as well as their possible modifications in disease conditions before and after pharmacological treatments, is likely to provide novel clues to the comprehension of the mechanisms involved in the therapeutic efficacy of currently available agents.

Left ventricular (LV) diastolic dysfunction is a main feature of diabetic heart disease. The aim of this prospective study was to evaluate the influence of glycemic control on diastolic function in type 1 diabetes mellitus. Thirty-six normotensive (24-hour blood pressure130/80 mm Hg) subjects with inadequately controlled (glycated hemoglobin7%) type 1 diabetes, without clinically detectable heart disease, were enrolled. After the basal evaluation, insulin therapy was modified to improve glycemic control. Glycated hemoglobin, LV echocardiography, 24-hour blood pressure monitoring, and laboratory tests were repeated after 6 months in all patients and after 12 months in 27 patients. At the basal evaluation, LV anatomy and systolic function were normal in all, and diastolic function was impaired in 14 patients. After 6 months, the mean values of body mass index, 24-hour blood pressure, and LV anatomy and systolic function were unchanged; mean glycated hemoglobin was decreased (p0.001), and mean values of diastolic parameters were significantly improved. After 12 months, the mean values of all blood pressure, metabolic, and LV parameters were unchanged. Percent changes of diastolic parameters were inversely correlated with percent changes of glycated hemoglobin, considering changes from the basal to the 6-month evaluation, as well as changes from the 6- to the 12-month evaluation. In conclusion, in normotensive patients with type 1 diabetes, a close relation was found between glycemic control and LV diastolic function, which improves when glycemic control improves. Therefore, diastolic dysfunction can be prevented or reversed, at least partly, by tight glycemic control.

The study aimed to evaluate, over a 3-year period, the progression towards sustained hypertension and left ventricular (LV) changes in patients with isolated office (IO) hypertension (office BP140 and/or 90 mmHg, daytime BP130/80 mmHg). After 3 years from the basal evaluation, 38 subjects with basal normal BP and 42 subjects with basal IO hypertension underwent a second 24-h BP monitoring and echocardiography; 19 patients of the basal IO hypertension group were not revaluated because they had already developed ambulatory hypertension and were on antihypertensive treatment. At the second evaluation, the 38 normotensive subjects had unchanged BP and LV parameters; 25 IO hypertensives have developed sustained hypertension. Considering them together with the 19 patients already treated, 72% of 61 IO hypertensives developed ambulatory hypertension over a 3-year period. The patients who subsequently developed hypertension differed from the group who did not only for lower basal values of LV diastolic parameters; all the patients with basal LV hypertrophy and/or preclinical diastolic impairment subsequently developed sustained hypertension. In conclusion, IO hypertensive patients show a high rate of progression towards sustained hypertension. Basal LV hypertrophy and/or preclinical diastolic dysfunction were the only markers of a greater risk of becoming hypertensives.

SummaryPost-thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT). Little is known about prognostic factors that might identify patients at high risk for the development of PTS. Body mass index (BMI) has been previously reported to be associated to the development of PTS. The aim of this study was to assess the association between BMI and other anthropometric parameters and PTS in a general population of DVT patients.In a prospective cohort study, 83 consecutive patients with objective diagnosis of DVT underwent physical examination. BMI was recorded at baseline and at 12 months, and waist circumference was recorded at 12 months to assess individual patterns of body fat distribution. The presence of PTS at 12 months was ascertained using a validated clinical scale. Sixty-three patients (75.9%) were overweight or obese at 12 months, 60 (72.3%) had a weight gain over 1 year. Twenty patients developed PTS (24.1%). Mean BMI was significantly higher in patients who developed PTS than in patients who did not (29.6 and 27.2 Kg/m2, respectively, p = 0.022). A BMI of > 28 Kg/m2 predicted early onset of PTS (OR 3.54, 95% CI 1.07-12.08, p = 0.017). Neither patterns of fat distribution nor weight gain in 1 year were correlated with PTS (p = 0.918 and p = 0.775, respectively).BMI is significantly correlated with the development of PTS. Patients with DVT should be encouraged to avoid weight gain. Reducing patient weight might be an important strategy to prevent PTS.

Experimental studies demonstrated that mineralocorticoid antagonists prevent or reverse myocardial fibrosis. Therefore, we tested the hypothesis that the aldosterone antagonist canrenone can improve left ventricular diastolic function in essential hypertension. Using digitized M-mode echocardiography and 24-hour blood pressure monitoring (ABPM), we realized a prospective, randomized, controlled study on 34 never-treated essential hypertensives with left ventricular diastolic dysfunction. Echocardiogram and ABPM were repeated after 6 months of effective antihypertensive treatment with ACE inhibitors and calcium antagonists (second evaluation) and then after a 6-month period with 17 patients randomly assigned to add canrenone 50 mg/d to the previous treatment (third evaluation). At the basal evaluation 32 patients had left ventricular concentric hypertrophy, and 2 patients had left ventricular concentric remodeling. All the patients had normal left ventricular systolic function. At the second evaluation blood pressure was reduced ( P P P

Patients starting oral anticoagulant therapy after heart valve replacement initially require a lower target international normalized ratio (INR) (2.0, range 1.5 to 2.6) because of a higher risk of bleeding until pericardial wires are removed. In a previous retrospective analysis, we observed a higher sensitivity to warfarin in these patients compared with nonsurgical patients. In a randomized clinical trial, we compared a fixed, lower dose of warfarin (2.5 mg) with the standard treatment consisting of a 5-mg loading dose, then adjusted to the target INR during the first 5 days of anticoagulation. INRs were measured daily, but the fixed dose was only modified on day 3 if the INR was1.5 or3.0. One hundred ninety-seven patients were considered eligible for the study. The 2 groups were well matched according to age, gender, body mass index, concomitant treatments, and type of valves implanted. The proportion of INRs2.6 during the study period was 42.5% in the 5-mg group and 26.2% in the 2.5-mg group (p0.05), and the proportion of INRs3.0 on day 3 was 23.9% and 9.5% (p0.05), respectively. In the 2.5-mg group, 35.7% of patients had an INR1.5 on day 3 and had the dose increased (vs 3.5%, p0.001); however, in the 5-mg group, 95.6% had the initial dose reduced, 49.6% had the dose withheld for at least 1 day, and the mean dose during the 5 days of study was 3.08 mg. Average time to achieve therapeutic range was higher in the 2.5-mg group (2.72 vs 1.98 days, p0.0001), but the approach to the targeted INR was more regular, and the gap between target and mean INR on day 5 was smaller. There were no bleeding or thromboembolic complications in either group. Thus, a lower loading dose of warfarin in patients after heart valve replacement reduces excessive anticoagulation and offers a more regular achievement of the therapeutic target by reducing the number of dose adjustments. Daily monitoring of the INR is still recommended.

Background: We studied the prevalence of atrial fibrillation within a large Italian inpatient population, and evaluated the use of antithrombotic therapy among these individuals. Methods: A prospective cross sectional study (Phase 1) with a 1-year follow-up period (Phase 2) was conducted at a single Italian centre. During Phase 1, we conducted a chart review of all inpatients on 5 separate days, each 1 month apart, between January and May 1999. During Phase 2, at 1-year of follow-up, patients or their families were contacted to document the occurrence of new clinical events, as well as current antithrombotic therapy use. Results: A total of 3121 patient charts were reviewed. The prevalence of atrial fibrillation was 7.2%. Of these 224 patients, 21.3% were on oral anticoagulants, 29.7% on antiplatelets, while 49% received neither. Patients on oral anticoagulants were significantly younger (mean age 72.3 years) than those on antiplatelets (mean age 80.6 years; p

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. (C) 2009 Elsevier Ltd. All rights reserved

OBJECTIVE: To evaluate the influence of obesity, per se or associated with hypertension, on left ventricular (LV) diastolic function. PATIENTS: Thirty-two obese newly-diagnosed never-treated hypertensives; 32 obese normotensives matched for age, sex and BMI with hypertensives; 32 lean newly diagnosed never-treated hypertensives and 32 lean normotensives, matched for age, sex and 24 h blood pressure (BP) with the obese subjects. METHODS: Twenty-four-hour ambulatory blood pressure monitoring and digitized M-mode LV echocardiograms. PARAMETERS EVALUATED: Twenty-four-hour, day-time and night-time BP and heart rate, percentage nocturnal BP fall; LV end-diastolic diameter index, septal and posterior wall thickness, LV mass index, peak shortening and lengthening rate of LV diameter, peak thinning rate of LV posterior wall. RESULTS: A main effect was found for obesity on LV diameter and LV mass and for hypertension on LV mass; LV systolic function was normal in all the subjects and similar among the four groups; LV diastolic function was significantly reduced in both obese groups with respect to lean ones. This difference persisted after correction of diastolic parameters for 24 h BP and heart rate, LV diameter and LV mass index and disappeared only after correction for body mass index. This latter was inversely related with diastolic parameters only in the obese groups. CONCLUSIONS: Obesity is associated with a preclinical impairment of LV diastolic function in both normotensives and hypertensives; the diastolic impairment is independent of haemodynamic factors, such as 24 h BP and heart rate, and bears no relation to LV geometry in normotensives and only little relation in hypertensives, having therefore to be ascribed to obesity itself.

We evaluated the relationship of microalbuminuria to hyperinsulinemia and family history of hypertension in 92 never-treated essential hypertensives (mean 24-h blood pressure140 or 90 mm Hg), with positive (F+) or negative (F-) family history of hypertension: 31 had microalbuminuria (MA+) (urinary albumin excretion [UAE], 30 to 300 mg/24 h) and 61 had normal (30 mg/24 h) UAE (MA-). Glucose and insulin values before and 30, 60, 90, and 120 min after an oral glucose load were measured together with an index of peripheral insulin activity (10(4)/ insulin x glucose values at glucose peak). Subjects with and without microalbuminuria did not differ with regard to age, sex, body mass index, and 24-h heart rate, whereas 24-h, daytime, and nighttime systolic and diastolic blood pressure were significantly higher in MA+ than MA- patients. The prevalence of positive family history of hypertension was similar between MA+ and MA-, as were fasting and stimulated glucose and insulin values and the index of peripheral insulin activity. Subdividing the patients on the basis of family history of hypertension (59 F+, 33 F-) UAE was not significantly different between F+ and F-. UAE did not correlate with glucose and insulin parameters. From our results, in never-treated hypertensives, microalbuminuria is associated with higher blood pressure values, but is related neither to genetic predisposition to hypertension, nor to hyperinsulinemia; therefore, impaired insulin sensitivity and microalbuminuria are two components of the hypertensive syndrome, largely independent of each other.

Presence of residual thromboemboli at least six months after a first episode of symptomatic pulmonary embolism: Do perfusion scintigraphy and angio-computed tomography agree?

Abstract —We investigated the influence of genetic predisposition to hypertension by studying the relation between insulin sensitivity and left ventricular (LV) mass and function in untreated lean and obese hypertensives. We selected 50 lean hypertensives with normotensive parents (negative family history of hypertension [F−]), 64 lean hypertensives with 1 or both parents hypertensive (positive family history of hypertension [F+]), 40 obese F− hypertensives, and 43 obese F+ hypertensives. The 4 groups were comparable regarding age, gender, 24-hour blood pressure profile, and known duration of hypertension. We measured glucose, insulin, and C-peptide during fasting and during an oral glucose tolerance test; LV morphology and function were assessed by digitized M-mode echocardiography. Glucose (fasting and test) levels were normal in all and similar among the 4 groups. Insulin and C-peptide (fasting and stimulated) levels were higher in obese hypertensives than in lean hypertensives; at similar body mass index, insulin and C-peptide levels were higher in F+ than in F− groups. Compared with lean hypertensives, obese hypertensives had greater LV mass index; LV systolic function was normal in all and similar among the groups. The indices of LV diastolic function were significantly lower in F+ than in F− groups. LV mass index did not correlate with metabolic parameters; the indices of LV diastolic function were inversely correlated with insulin area during test in only the 2 F+ groups. In conclusion, genetic predisposition to hypertension is associated with a reduced insulin sensitivity and affects the response of the myocardium to increased insulin levels, inducing a greater impairment of diastolic function. Insulin sensitivity and genetic predisposition to hypertension seem to have no influence on LV mass.

Objective To investigate dental pain perception in a large group of essential hypertensive subjects. Methods A total of 130 hypertensive patients together with 51 normotensive subjects were submitted to tooth-electrical stimulation to determine the dental pain threshold (occurrence of pulp sensation) and tolerance (time when the subject asked for the test to be stopped). Blood pressure was measured at rest, before pain perception evaluation, and during a 24 h period by ambulatory monitoring. Results The normotensive and hypertensive subjects differed with regard to pain threshold (P= 0.002) and tolerance (P=0.01). Pain perception variables were significantly correlated with both resting blood pressure and 24 h, diurnal and nocturnal arterial pressures, the correlation between pain threshold and 24 h systolic blood pressure being the most significant (r = 0.31, P

Introduction: The aim of this study was to determine whether the degree of blood pressure elevation and/or a genetic predisposition to hypertension have a major role in determining a reduced pain perception in hypertensives. The reasons underlying the relationship between blood pressure elevation and pain perception mechanisms are not completely understood. Methods: One hundred and four untreated hypertensive patients (65 subjects with and 39 without a positive parental history of hypertension) together with a control group of 42 subjects (20 normotensive offspring of normotensive parents, and 22 normotensive offspring of hypertensive parents) were submitted to standard blood pressure evaluation, 24-h blood pressure monitoring and dental pain perception evaluation. Results: Both pain threshold and tolerance were found to be higher in hypertensive than normotensive subjects (P

We evaluated the influence of family history of hypertension on insulin sensitivity in lean and obese hypertensive subjects (H): 40 lean [body mass index (BMI)or = 25 kg m-2] H with normotensive parents (F-), 50 lean H with one or two parents hypertensive (F+), 30 obese HF- (BMIor = 30 kg m-2) and 35 obese HF+. The four groups were comparable in terms of age, sex and ambulatory blood pressure values. We evaluated glucose, insulin and C-peptide before and 30, 60, 90 and 120 min after an oral glucose load, insulin sensitivity index (ISI, fasting glucose/insulin ratio), fasting insulin/C-peptide ratio (I/Cp). Glucose, fasting and during test, and I/Cp were similar among the four groups; insulin and C-peptide, fasting and stimulated, were significantly higher and ISI lower in obese H than in lean H; at similar BMI, insulin and C-peptide were significantly higher in F+ than in F-. Insulin directly correlated with night-time blood pressure only in lean HF-. The correlation between insulin and BMI was significantly closer in F-than in F+. In conclusion, family history of hypertension appears to play a relevant role in insulin sensitivity in hypertensive subjects also in the presence of obesity.

Using digitized M-mode echocardiograms, we evaluated the relationship between plasma atrial natriuretic factor (ANF) and morphofunctional characteristics of the left ventricle (LV) in 24 mild hypertensive men, never treated, with normal renal function. For each subject we collected a blood sample for plasma ANF evaluation and, immediately after, we recorded the LV echocardiogram. All the patients had normal LV diastolic diameter and systolic function; LV hypertrophy was present in 10 patients, 7 of whom had left atrial enlargement, and 13 patients had impaired LV diastolic function. ANF was similar between patients with and without LV hypertrophy, as well as between patients with and without left atrial enlargement, whereas ANF was significantly (P < .01) higher in patients with LV diastolic dysfunction than in patients with normal diastolic function. ANF was inversely correlated with both indices of diastolic function (peak lengthening rate and peak wall thinning rate), whereas it did not correlate with blood pressure, heart rate, end-systolic wall stress, and other LV parameters. In conclusion, from our results, ANF level in never-treated mild hypertensives is related neither to the degree of LV hypertrophy nor to the afterload, expressed as blood pressure or end-systolic wall stress, whereas it is mainly influenced by LV diastolic function: the diastolic impairment induces an increase in ANF level, probably through an increased atrial stretch.

Summary Purpose To conduct a serial evaluation of the cardiac effects of antineoplastic therapy with 5-fluorouracil (5-FU) and low-dose folinic acid. Patients and methods Sixteen patients with colon-rectal carcinoma, without cardiac disease, treated with 400 mg/ m2/dic of 5-FU and 20 mg/m2/die of folinic acid for five days, once a month, for six months. Parameters evaluated: blood pressure, ECG, two-dimensional and digitized M-mode echo-cardiograms before and after the first and fifth drug administrations of the first cycle, after the fifth drug administration of the second cycle, after the fifth drug administration of the sixth cycle and six months after the treatment. Results Blood pressure, heart rate, left ventricular (LV) diameter and LV mass index did not change; all of the patients showed a decrease in the peak shortening rate of the LV diameter, index of systolic function, and of the peak lengthening rate of the LV diameter and peak thinning rate of LV posterior wall, indexes of diastolic function, with abnormal values in 11 patients at the end of treatment. LV wall motion remained normal in all; two patients developed transient T wave inversion without chest pain and with normal cardiac enzymes and myocardial scintigraphy during dypiridamole stress test. Six months after the treatment all indexes of LV systolic and diastolic function had returned within the normal limits and were similar to pre-treatment values. Conclusions 5-FU and low-dose folinic acid treatment induced a decrease of LV systolic function and an impairment of diastolic function, that developed without symptoms and were transient and reversible.

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 ( 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

Abstract Although a hypertension-related hypalgesia has been described, the relation between pain perception and the 24-hour blood pressure trend is still unknown. The ambulatory blood pressure monitoring parameters and dental pain sensitivity were correlated in 67 male subjects. The pulpar test (graded increase of test current of 0 to 0.03 mA) was performed on three healthy teeth, and mean dental pain threshold (occurrence of pulp sensation) and pain tolerance (time when the subjects asked for the test to be stopped) were evaluated. Three groups of subjects with normal (n=34), intermediate (n=13), and high (n=20) blood pressure values were identified according to ambulatory monitoring results. Pain threshold differed among the three groups ( P P

BACKGROUND The term mantle cell lymphoma (MCL) describes a subtype of non-Hodgkin's lymphoma that includes those lymphomas previously defined as centrocytic lymphoma, intermediate lymphocytic lymphoma, and mantle zone lymphoma. Since MCL has only recently been recognised as a distinct entity, the clinical literature is sparse and very little information is available about its treatment. PATIENTS AND METHODS We retrospectively attempted to analyse the clinical features and outcome of 65 patients with mantle cell lymphoma (MCL) treated from 1979 to 1993 at two institutions in the same geographic area. Univariate (Log-rank test) and multivariate (Cox regression) analyses of the major prognostic factors were performed. RESULTS At the time of analysis the median follow-up was 49 months. Median age was 64 years with a range of 27-85 years. The male to female ratio was 2:1. Forty-seven patients (72%) had stage IV at presentation and 20 (31%) had B-symptoms at presentation. The patients usually presented with generalised adenopathy (78% of cases) and bone marrow involvement (58%). Serum LDH were analysed at diagnosis in 61 patients and found to be elevated in 30%. beta 2-Microglobulin was determined at presentation in 42 patients and was higher than normal in 54% of them. In comparison with the other subtypes of NHLs in our series, MCL appears to have a very poor survival pattern. The median overall survival was 42 months. The CR rate was 51% with a median DFS of 44 months. Good performance status, normal LDH, normal beta 2-microglobulin, younger age (< 65 years), and a low prognostic risk according to the International Index were significantly associated (p < 0.05) with a better outcome. CONCLUSIONS The characteristics of the patients in this study appear to be in general agreement with those in most of the previously reported series except for the somewhat lower rate of bone marrow infiltration observed in this series. Despite the limitations of a retrospective analysis and the lack of randomization between the treatment options, this study seems to suggest a survival advantage with anthracycline-containing regimens in some patients with MCL. However, this benefit was evident only for the patients with favourable International Index prognostic scores (i.e., low- and to low-intermediate-risk disease) who may already have a better prognosis. Patients with intermediate-high and high-risk disease according to the International Index have a poor prognosis regardless of the type of therapy given.

Using digitized M-mode echocardiograms, we evaluated left ventricular (LV) anatomy and function at rest and during handgrip in 24 normotensive young adults with both parents hypertensive (HP+), each matched for age, sex, body weight, and body surface area with one normotensive adult with both parents normotensive (HP-). LV parameters were within the normal range in all HP+ and HP-. At rest, HP+ as compared to HP- had higher systolic and diastolic blood pressure (BP), septal and posterior wall thickness, and LV mass; LV diastolic diameter and end-systolic wall stress were similar in the two groups. Modified midwall fractional shortening, peak shortening rate of LV diameter and peak thickening rate of LV posterior wall, indices of LV systolic function, and peak lengthening rate of LV diameter and peak thinning rate of LV posterior wall, indices of ventricular relaxation, were significantly higher in HP+. Handgrip induced significant (P < .001) and percent-comparable increases of systolic and diastolic BP, heart rate, and cardiac output in HP+ and HP-; peak shortening and lengthening rates of LV diameter and peak thickening and thinning rates of LV posterior wall increased significantly in HP-, whereas in HP+ the value of the four parameters, higher at rest as compared to HP-, did not show any further increase. In conclusion, normotensive young adults with high genetic risk for hypertension have higher BP and thicker and overactive LV as compared to subjects with normotensive parents. Handgrip stimulates LV function in offspring of normotensives, but not the already hyperkinetic LV of hypertensive offspring.

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.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.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.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.

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.

Summary 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.

SummaryMany 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

SummarySome 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.

Case presentationDr. Mongiardi, Dr. Maresca: G.L. is a 64-year-old manon chronic oxygen therapy due to chronic obstructivepulmonary disease (COPD) in the setting of a bronchi-ectasic disease, referred to our hospital in September 2009because of a micturition-nocturnal-syncope preceded bydizziness. The patient had neither a personal history ofcoronary artery disease nor known cardiovascular riskfactors. In the emergency department (ED) the patientpresented preserved consciousness and mild dyspneadespite low flows of inhalatory O

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) 90 mm Hg and/or systolic BP (SBP) 140 mm Hg, and mean daytime DBP 85 mm Hg and/or SBP 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

Background/Aims: Recent data suggest a possibile benefit of lipid-lowering drugs, in particular statins, in preventing venous thromboembolism (VTE). The aim of this systematic review of the literature is to assess the effect of lipid-lowering drugs on VTE occurrence. Materials and methods: 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. Results: Three randomized controlled trials (RCTs), three cohort, and eight casecontrol 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. Conclusions: 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.

Context Recently, there has been an increasing number of reports of incidental pulmonary embolism (PE) in patients undergoing chest computer tomography (CT) for reasons other than the research of suspected PE. Natural history of incidental PE remains unclear. Objectives To estimate the prevalence of incidental PE, to assess potential factors associated with incidental PE, and to evaluated its clinical history. Data Sources MEDLINE, EMBASE databases (up to January 2009). Study Selection Studies were included if the prevalence of incidental PE was assessed using CT scanning. Data Extraction The prevalence of incidental PE in these patients was documented. Separate data for inpatients and outpatients and according to the reason for CT scanning were collected. Weighted mean proportion of the prevalence of incidental PE was calculated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to test the association with potential predictors of incidental PE. Results Twelve studies for a total of more than 10 thousand patients were included. The weighted mean prevalence of incidental PE was 2.6% (95% CI 1.9, 3.4). Hospitalization at the time of CT scanning and the presence of cancer were associated with a significantly increased risk of incidental PE (OR 4.27 and OR 1.80 respectively). Conclusions The prevalence of incidental PE is clinically relevant. Future studies are necessary to properly evaluate the clinical history of these patients.

Atherosclerotic calcifications are related to poor prognosis and all-cause mortality in large population studies.1 Moreover, vascular calcifications are inversely associated with the potential reduction of plaque volume in regression studies during statin treatment, which suggests that more calcified lesions are less likely to undergo positive remodeling.2 Recently, it has been suggested that calcification is a tightly regulated process of mineralization akin to bone formation.3 In plaques, the deposits consist of a nonhomogeneous composite that contains hydroxyapatite mineral nanocrystals embedded in a collagenous organic matrix, whereas at a nanoscale level, apatite crystals interact with cholesterol crystallites. In this context, mineralization may result from a basic template pattern generated by the organic …

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.

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. 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