Achille Venco

Eradication of Helicobacter pylori Infection in Primary Low-Grade Gastric Lymphoma of Mucosa-Associated Lymphoid Tissue

Low-grade gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is an uncommon tumor with an indolent natural history and prolonged confinement to the site of origin. Its morphologic appearance is characterized by prominent and often multifocal lymphoepithelial lesions showing dense, diffuse infiltrates of centrocyte-like cells within the lamina propria [1]. B-cell monoclonality can often be shown by either immunocytochemical or molecular methods [2]. A close association has been suggested between gastric MALT lymphoma and the presence of certain strains of Helicobacter pylori, which are found in more than 90% of patients with gastric MALT lymphoma [3]. Regression of this lymphoma after eradication of H. pylori was reported in 5 of 6 patients who received antibiotic therapy [2]. We analyzed the effects of antibiotic therapy for H. pylori infection in 26 patients with low-grade gastric MALT lymphoma. Our patients were from a geographic area (southern Switzerland and northern Italy) where the incidence of gastric tumors appears to be uncommonly high [4, 5]. Many patients with primary gastric lymphoma reside in northeastern Italy [6], a region geographically close and environmentally similar to the area in which our patients reside. Reasons for these disease clusters are not known. Methods Twenty-six patients (14 women, 12 men; median age, 60 years [range, 21 to 76 years]) with histologic diagnoses of localized (stage IE), primary, B-cell, low-grade gastric MALT lymphoma and H. pylori infection (diagnosed using endoscopic biopsy specimens) were entered into our study. Almost all patients had a prolonged history (as long as 4 years) of gastric symptoms before diagnosis of H. pylori infection, and most of them had already been given antacid medication, motility stimulant agents, or both. Before patients received treatment for H. pylori infection, the following staging procedures were done: physical examination, routine laboratory tests, chest radiographs, abdominal ultrasound or computed tomographic scans, endoscopic gastric biopsy specimens, and bone marrow biopsy specimens. Patients were treated for H. pylori infection for 2 weeks with amoxicillin (500 mg three times daily) plus metronidazole (400 mg three times daily) and colloidal bismuth (120 mg four times daily; 13 patients) or omeprazole (20 mg twice daily; 13 patients). Twenty patients were treated immediately after diagnosis of H. pylori infection, and 6 were treated after an observation period of several months (median, 5 months; range, 3 to 36 months) without endoscopic and histologic changes of the MALT lymphoma. One patient had a brief response to first-line combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP regimen), but the patient later had a local relapse. This patient still had histologic characteristics of low-grade gastric MALT lymphoma when treatment for H. pylori infection was given. To reevaluate the condition of the patients after treatment for H. pylori infection, biopsy specimens were obtained from any abnormal area in the stomach and randomly obtained from the rest of the stomach. These multiple (range, 8 to 20 specimens), random biopsy specimens of the gastric mucosa were obtained within 6 months of treatment (3 months for 19 patients, 4 months for 4 patients, and 6 months for the remaining 3 patients); patients were reevaluated every 3 to 6 months thereafter. The patients with persistent H. pylori infection had additional treatment for 2 weeks with a different regimen: omeprazole (20 mg twice daily), metronidazole (400 mg three times daily), and azithromycin (500 mg daily for 3 consecutive days every week). Restaging with chest radiographs and abdominal ultrasound was done again after 1 year. In 9 patients, a bone marrow biopsy specimen was obtained again after 6 months. Histologic responses were graded according to the histologic scoring system recently proposed for the diagnosis of gastric MALT lymphoma [2]. We considered a post-treatment score of 2 or less to be evidence of lymphoma regression. Binomial exact 95% CIs were calculated for outcome percentages. Results Complete eradication of H. pylori was initially achieved in 21 patients (81%; 95% CI, 61% to 93%); in the remaining 4 patients, second-line antibiotic treatment was needed to eradicate the microorganism. The overall eradication rate was therefore 96% (25 of 26 patients; 95% CI, 80% to 99%). After treatment for H. pylori infection, the median follow-up was 12 months (range, 3 to 36 months). One patient, treated after an observation period of 36 months without clinical or histologic change, showed persistent gastric infection and unchanged lymphoma features on biopsy specimens obtained 3 months after treatment. The patient received additional antibiotic treatment but has not been reevaluated with endoscopy. All but one of the patients were symptomatic at presentation; the main symptoms were pain (60% of patients), dyspepsia (30% of patients), and nausea and vomiting (7% of patients). One patient presented with gastrointestinal hemorrhage. Symptoms disappeared in 77% of patients or markedly diminished after antibiotic treatment. At the endoscopic evaluation done before treatment, 11 patients had gastric ulcers, 9 had endoscopic evidence of gastritis, and the remaining 6 had abnormal, congestive (hyperemic) gastric mucosa. In all patients, these endoscopic features improved after eradication of H. pylori infection and all of the ulcers healed, but only one patient had a complete recovery of the gastric mucosa. Histologic regression of the MALT lymphoma (Table 1) was observed in 15 patients (60%; CI, 39% to 79%) after H. pylori eradication, including the 1 patient who relapsed after chemotherapy. Five patients had complete disappearance of any histologic evidence of lymphoma (histologic score, 0 to 1), and 10 patients had residual lymphoid follicles but no longer had lymphoepithelial lesions (histologic score, 2). Three patients showed persistent suspicious, probably reactive, lymphoid infiltrate in the lamina propria (histologic score, 3) and were considered to have not responded to treatment. The other patients showed no change or only partial improvement in the lymphoma histologic pattern in repeat gastric biopsy specimens. Table 1. Effects of Helicobacter pylori Eradication on Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Our study suggests that regression of the lymphoma may require a prolonged period. Only 8 patients showed histologic regression on the first biopsy specimen after antibiotic treatment, but when endoscopic specimens were obtained again 3 or more months later, regression was clearly evident in 7 additional patients. At a median follow-up of 12 months, all patients were alive and 14 of 15 responders, including the 1 patient who relapsed after chemotherapy, were free of lymphoma. A bone marrow specimen from 1 patient showed evidence of relapse shortly thereafter, with a response duration of only 4 months; however, no evidence of MALT lymphoma was found in repeat gastric biopsy specimens (histologic score, 2). Discussion A strong causal relation between H. pylori infection and gastritis, duodenal ulcer, or both has been shown; moreover, increasing epidemiologic and histopathologic evidence indicates a link between H. pylori infection and gastric tumors, both carcinomas [7] and lymphomas [3, 8]. Further, the ability of H. pylori to stimulate cellular proliferation in low-grade gastric MALT lymphoma has been reported [9], and eradication of H. pylori may inhibit the growth of the lymphoma [2]. The rarity of extra-abdominal spread low-grade gastric MALT lymphoma may also be partially explained by the role of H. pylori in the pathogenetic process [9]. Our data confirm, in a larger series of patients, the recent observations that eradication of H. pylori can lead to a regression of the lymphoma [2, 10] and further support the concept of a causal correlation between H. pylori infection and gastric lymphoma. The case of low-grade gastric MALT lymphomas is not the only one in which a bacterial infection has been implicated in the pathogenesis of a lymphoma. Antibacterial therapy has already been reported to be useful in the treatment of -chain disease (a small-intestinal lymphoma) [11], providing indirect evidence that bacteria may have a pathogenetic role in lymphomas. Only careful, prolonged follow-up will ascertain whether treatment for H. pylori can definitely cure gastric MALT lymphoma. Currently, this represents one of the many questions in the treatment of gastric lymphoma (others include those about the necessity for surgery and role of chemotherapy) [12]. Our data show that for low-grade MALT gastric lymphoma, an antibiotic treatment designed to eradicate H. pylori appears to be mandatory before further therapeutic options are considered. An international randomized trial will soon investigate whether it is beneficial to add cytotoxic chemotherapy to such an antibiotic treatment.

Oral Vitamin K Lowers the International Normalized Ratio More Rapidly Than Subcutaneous Vitamin K in the Treatment of Warfarin-Associated Coagulopathy: A Randomized, Controlled Trial

Context Giving vitamin K when stopping warfarin increases the rate at which the international normalized ratio (INR) returns to normal. Although many clinicians give vitamin K subcutaneously, it appears that oral vitamin K reduces INR more rapidly. Contribution This randomized, controlled trial compared oral with subcutaneous vitamin K for patients receiving warfarin who had an INR of 4.5 to 10.0 but no bleeding. Oral administration normalized the INR faster than the subcutaneous route. Clinical Implications Clinicians should consider oral administration when prescribing vitamin K for patients who become overanticoagulated while receiving warfarin. This study had limited power to evaluate bleeding or thrombotic episodes and did not include a group that simply discontinued warfarin. The Editors Warfarin-associated coagulopathy, characterized by excessive prolongation of the international normalized ratio (INR), is clinically important because of its associated risk for life-threatening bleeding complications (1, 2). Compared with the simple withholding of warfarin, use of low-dose oral vitamin K has been shown to produce a faster reduction in an elevated INR and a potential reduction in risk for bleeding (3-5). These observations, coupled with the high rate of major or fatal hemorrhage in patients presenting with INRs greater than 6.0 (1), has led to increased use of vitamin K for the treatment of warfarin-associated coagulopathy. In North America, subcutaneous administration is most common (6). However, preliminary evidence suggests that oral vitamin K is more effective than subcutaneous vitamin K (3, 7). We did a randomized, controlled trial to compare the efficacy of 1 mg of vitamin K administered orally and 1 mg of vitamin K administered subcutaneously for the treatment of asymptomatic patients with warfarin-associated coagulopathy. Our hypothesis was that oral vitamin K is more effective than subcutaneous vitamin K. Methods Study Design This multicenter, randomized, open-label, controlled trial involved patients who were receiving warfarin, were asymptomatic, and presented with an INR between 4.5 and 10. Eligible patients stopped receiving warfarin for at least 1 day and were randomly assigned to receive 1 mg of vitamin K either orally or subcutaneously. Warfarin therapy was restarted at the discretion of the treating physician when the INR had decreased into the therapeutic range. We chose the INR range for study inclusion (4.5 to 10) by surveying thrombosis experts and health care providers who frequently prescribe warfarin. The consensus was that risk for hemorrhage in patients with an INR less than 4.5 was low enough that such patients did not mandate intervention, but there was concern about the safety of giving only 1 mg of vitamin K to patients with an INR greater than 10. Patients Patients were identified at two teaching hospitals, one in Hamilton, Ontario, Canada, and one in Varese, Italy. The study was approved by the Institutional Review Boards of each center, and all patients provided written informed consent (Appendix Figure). Inclusion and exclusion criteria were identical to those in our previous studies (3). Briefly, eligible patients were those receiving warfarin with a target INR of 2.0 to 3.0 who presented with single INRs of 4.5 to 10.0 and did not require immediate normalization of their INR, have current hemorrhage, or have a high risk for hemorrhage. Randomization and Intervention Sealed, sequentially numbered, opaque envelopes were used to randomly assign eligible, consenting patients to receive oral or subcutaneous vitamin K. The ran domization sequence was generated from a random number table, was stratified by center, and was block randomized in groups of four. Subcutaneous vitamin K was given by injection in the abdominal wall, and oral vitamin K was given under observation. In Canada, vitamin K1 in liquid form (phytonadione for intravenous injection [Abbot, Montreal, Canada]) was used for both oral and subcutaneous administration. In Italy, oral phytomenadione liquid (Konakion, Roche, Milan) was given to patients assigned to oral therapy; the subcutaneous form was diluted to a concentration of 1 mg/mL. Outcomes International normalized ratio testing was mandated on the day after study drug administration and was optional thereafter. In Canada, INR testing was done by using Thromborel S (Dade-Behring, Mississauga, Canada) with instrument-specific International Sensitivity Index values of 1.23 to 1.28. In Italy, INR testing was done by using Innovin (Dade-Behring, Milan, Italy) with an instrument-specific International Sensitivity Index value of 1.03. Patients were evaluated by telephone or at a clinic visit 1 month after study enrollment to determine whether thromboembolic or bleeding events had occurred. Major bleeding was defined as bleeding that required a blood transfusion or hospitalization; all other bleeding events were classified as minor. All thromboembolic events required objective confirmation. Statistical Analysis The primary analysis was a comparison of the proportion of patients in each study group with INRs between 1.8 and 3.2 on the day after study drug administration; all patients were analyzed in the group to which they were assigned. This range of INRs was chosen because it is a range within which most physicians would be comfortable restarting warfarin therapy. Our a priori assumption was a success rate of 60% in patients assigned to receive oral vitamin K and a success rate of 20% in patients assigned to receive subcutaneous vitamin K (3, 7-9). With an error set at 0.05 and a power of 80%, we needed 54 patients to complete the study. The effectiveness of oral vitamin K compared with subcutaneous vitamin K was expressed by an odds ratio with a 95% CI. The numbers of clinical events were compared by using the Fisher exact test. Results Patients Patient enrollment began in April 2000 and was completed in February 2001. Fifty-one patients were screened for study enrollment; all were eligible, and all provided written informed consent. We did not achieve our a priori sample size of 54 patients; only after closing the study did we determine that we had enrolled only 51 patients. The 26 patients assigned to the oral vitamin K group had a mean age (SD) of 73 14 years. Fifty-eight percent were women, 8% had received warfarin therapy for fewer than 7 days, and 38% were inpatients at the time of enrollment. The mean INR on day 0 was 5.8 (range, 4.5 to 7.6). Nineteen (73%) were enrolled in Canada, and 7 (27%) were enrolled in Italy. The 25 patients in the subcutaneous vitamin K group had a mean age (SD) of 67 15 years. Forty-eight percent were women, 20% had received warfarin for less than 7 days, and 20% were inpatients at the time of enrollment. The mean INR on day 0 was 6.2 (range, 4.8 to 9.0). Seventeen patients (68%) were enrolled in Canada, and 8 patients (32%) were enrolled in Italy. This study was done without external funding from peer-review agencies or pharmaceutical companies, and the authors maintained complete control of all aspects of the investigation throughout its course. Outcomes All 51 patients had INR testing done on the day after study drug administration. No patients were excluded from the primary analysis. Fifteen of 26 patients (58%) who received oral vitamin K and 6 of 25 patients (24%) who received subcutaneous vitamin K had INRs of 1.8 to 3.2 on the day after study drug administration (odds ratio, 4.32 [95% CI, 1.13 to 17.44]; P = 0.015; number needed to treat for benefit, 3) (Figure). No patient who received oral vitamin K and 2 patients (8%) who received subcutaneous vitamin K had an increased INR on the day after study drug administration (the INR increased from 5.0 to 6.3 and from 5.6 to 6.9 in the 2 patients). Three patients (12%) who received oral vitamin K and no patients who received subcutaneous vitamin K had an INR less than 1.8 on the day after study drug administration (P > 0.2). The mean INRs were higher in the subcutaneous vitamin K group than in the oral vitamin K group on the second and third days after study drug administration (Table). Figure. International normalized ratio ( INR ) of patients receiving oral ( left ) and subcutaneous ( right ) vitamin K. Table. International Normalized Ratios No statistically significant difference was seen in the proportion of patients in Italy (3 of 7 [43%]) and Canada (12 of 19 [63%]) who achieved an INR of 1.8 to 3.2 on the day after oral vitamin K administration (relative risk, 1.26 [CI, 0.75 to 2.10]). In the subcutaneous vitamin K group, a trend was seen in favor of increased efficacy in the patients randomly assigned to study groups in Italy. Thus, 2 of 17 patients (12%) compared with 4 of 8 patients (50%) achieved the target INR (relative risk, 0.42 [CI, 0.13 to 1.34]). During the 1-month follow-up period, no episodes of thromboembolism or bleeding occurred. Five patients, all receiving oral vitamin K, died (P = 0.05). Three died of cancer, one died of progressive lung disease, and one died of unknown causes. Discussion This study provides evidence that oral vitamin K may be more effective than subcutaneous vitamin K in reestablishing a therapeutic INR in asymptomatic patients with warfarin-associated coagulopathy and an INR between 4.5 and 10. This observation is supported by an extensive body of literature suggesting that 1) oral vitamin K is effective for the treatment of warfarin-associated coagulopathy and 2) subcutaneous vitamin K does not produce reliable, rapid reductions in the INR (3, 4, 7-9). Our findings are likely to be valid because our study was randomized, no patients were excluded after enrollment, the primary outcome was available for all patients, the primary outcome was not subject to observer interpretation, and the results were both statistically significant and consistent with our previous results (3, 7). The results are probably generalizable. The inclusion

The metabolic syndrome and the risk of venous thrombosis: a case–control study

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.

Prevalence and Clinical History of Incidental, Asymptomatic Pulmonary Embolism: A Meta-Analysis

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.

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.

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.

Aldosterone Antagonist Improves Diastolic Function in Essential Hypertension

Abstract—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 <0.0001), left ventricular mass index decreased (P <0.0001), and diastolic function improved (P <0.0001). After randomization, the canrenone and control groups had similar 24-hour blood pressure and left ventricular morpho-functional characteristics. At the third evaluation, despite unchanged blood pressure and similar decrease of left ventricular mass index, the canrenone group, compared with control group, showed a significantly greater increase in left ventricular diastolic indices. In essential hypertension, a low dose of aldosterone antagonist added to antihypertensive treatment significantly improved left ventricular diastolic function. This improvement, not accounted for by changes in blood pressure and left ventricular mass, can be therefore ascribed to a direct action of the drug on the myocardium.

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.

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.

Body mass index is associated with the development of the post-thrombotic syndrome.

Post-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/m(2), respectively, p = 0.022). A BMI of > 28 Kg/m(2) 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.