Lipoprotein(a) (Lp(a)) is a complex serum lipoprotein consisting of a low-density lipoprotein core associated by a disulfide bond with apolipoprotein(a), a heterogenous glycoprotein that, due to its structural homology with plasminogen, competes for fibrin binding, inhibits tissue plasminogen activator, and ultimately impairs fibrinolysis. 1,2 It has been recognized that more than 90% of variation of plasma Lp(a) concentration is genetically regulated, with apolipoprotein(a) gene (LPA) being a major determinant. To date, several genetic variants in the LPA gene have been shown to influence Lp(a) plasma values, rs3798220 and rs10455872 polymorphisms accounting in particular for at least 40% of such variation. 3 Because of its dual nature (i.e., proatherosclerotic low-density lipoprotein-like and prothrombotic plasminogen-like), Lp(a) has been the subject of intense research over the past 20 years from both in vivo and in vitro studies that have analyzed its AbstractElevated plasma levels of lipoprotein(a) (Lp(a)) are associated with increased cardiovascular risk in several clinical studies. However, there is a lack of data supporting a positive association between elevated Lp(a) levels and venous thromboembolism (VTE). Thus, we conducted a systematic review of the literature to better clarify its role as a risk factor for VTE. Medline and the Embase (up to May 2015) electronic databases were used to identify potentially eligible studies. Studies measuring Lp(a) values in adult patients with deep vein thrombosis and/or pulmonary embolism and in a population of patients without a VTE were selected. Studies on patients with major venous thromboembolic events occurring at other unusual site, case reports, and case series were excluded. The odds ratios (ORs) of the association between high values of Lp(a) and VTE and the weighted mean difference (WMD) in Lp(a) levels in cases and in controls were calculated using a random-effect model. Results were presented with 95% confidence interval (CI). Fourteen studies for a total of more than 14,000 patients were finally included in our analysis. Lp(a) was slightly but significantly associated with an increased risk of VTE (OR: 1.56, 95% CI: 1.36, 1.79; 10 studies, 13,541 patients). VTE patients had significantly higher Lp(a) values compared with controls (WMD: 14.46 mg/L, 95% CI: 12.14, 16.78; 4 studies, 470 patients). Lp(a) appeared to be significantly associated with increased risk of VTE. However, Lp(a) levels were only slightly increased in VTE patients compared with controls.

Background and Purpose: Cerebral vein thrombosis (CVT) incidence is estimated to be >10 per 1 000 000 per year. Few population-based studies investigating case-fatality rates (CFRs) and pyogenic/nonpyogenic CVT incidence are available. We assessed trends in CVT incidence between 2002 and 2012, as well as adjusted in-hospital CFRs and incidence of hospital admissions for pyogenic/nonpyogenic CVT in a large Northwestern Italian epidemiological study. Methods: Primary and secondary discharge diagnoses of pyogenic/nonpyogenic CVT were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes 325, 671.5, and 437.6. Age, sex, vital status at discharge, length of hospital stay, and up to 5 secondary discharge diagnoses were collected. Concomitant presence of intracerebral hemorrhage (ICH) was registered, and comorbidities were assessed through the Charlson comorbidity index. Results: A total of 1718 patients were hospitalized for CVT (1147 females—66.8%; 810 pyogenic and 908 nonpyogenic CVT, 47.1% and 52.9%, respectively), with 134 patients (7.8%) experiencing a concomitant ICH. The overall incidence rate for CVT was 11.6 per 1 000 000 inhabitants with a sex-specific rate of 15.1 and 7.8 per 1 000 000 in females and males, respectively. CVT incidence significantly increased in women during time of observation ( P =0.007), with the highest incidence being at 40 to 44 years (27.0 cases per 1 000 000). In-hospital CFR was 3%, with no difference between pyogenic/nonpyogenic CVT. Patients with concomitant ICH had a higher in-hospital CFR compared with patients without ICH (7.5% versus 2.7%; odds ratio, 2.96 [95% CI, 1.45–6.04]). In-hospital CFR progressively increased with increasing Charlson comorbidity index ( P =0.003). Age (odds ratio, 1.03 [95% CI, 1.02–1.05]), Charlson comorbidity index ≥4 (odds ratio, 4.33 [95% CI, 1.29–14.52]), and ICH (odds ratio, 3.05 [95% CI, 1.40–6.62]) were independent predictors of in-hospital mortality. Conclusions: In a large epidemiological study, CVT incidence was found to be comparable to the one registered in population-based studies reported after the year 2000. CVT incidence increased among women over time. In-hospital CFR was low, but not negligible, in patients with concomitant ICH. Age, ICH, and a high number of comorbidities were independent predictors of in-hospital mortality. Pyogenic CVT was not a predictor of in-hospital CFR, although its high proportion was not confirmed by internal validation.

The HYPODD study has been registered at the Agenzia Italiana del Farmaco-Osservatorio sulla Sperimentazione Clinica del Farmaco (AIFA-OsSC) and EUDRACT sites (n° 2012-003514-14) and has been approved by the Ethical Committees of all the Centers involved in the study. The patients' recruitment is currently underway.

To predict the 3-months mortality in permanently bedridden medical non-oncologic inpatients. Patients and Methods: 2788 consecutive patients admitted in 5 Italian Internal Medicine units from January 2016 through January 2017 were prospectively screened; 644 oncologic patients were excluded; 2144 non-oncologic patients (1021 female) were followed-up for mortality for 6 months. Main outcome was 3-months mortality in permanently bedridden inpatients with at least 2 of: creatinine clearance < 35 ml/min; albumin < 2.5 g/dl; at least 2 hospital admissions in the previous 6 months. Advanced dementia and dysphagia were also recorded. Results: Mean age of the 2144 patients was 73.9 (SD, 14.9) years; 374 (17%) were permanently bedridden, 435 (20%) had a creatinine clearance < 35 ml/min, 217 (10%) albumin < 2,5 g/dl, 112 (5%) at least 2 hospital admissions in the previous 6 months. Seventy-seven (4%) patients were permanently bedridden with at least 2 of the above mentioned items, and 48 of them died within 3 months (62%) (p < 0.001;95% CI 51-73%). Regression coefficients of the variables associated with 3months mortality in multivariate analysis in 998 patients of unit 1 (training cohort) were used to create a simple score, which was validated in the 1146 patients of the other units (validation cohort) and performed well in predicting the 3-months mortality (https://www.ejcrim.com/beclap/). Conclusions: Approximately two out of three non-oncologic medical patients permanently bedridden having 2 of the abovementioned items are dead 3 months after index admission; a simple score including bedridden status, creatinine clearance, albumin, dysphagia, age and sex may help discuss management priorities.

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