Circulating endostatin has been linked to increased mortality, cardiovascular comorbidities, and renal impairment. However, its role as a cardiovascular risk marker in the general population remains largely unexplored. This study investigates the association between plasma endostatin and atherosclerosis, inflammation, and kidney function in a cohort of 5,026 randomly selected middle-aged individuals from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Plasma levels of endostatin, C-reactive protein (CRP), HbA1c, lipids, and creatinine were analyzed, and their associations with atherosclerosis and related markers were assessed. Coronary artery atherosclerosis was evaluated using coronary computed tomography. Blood pressure, body mass index, and waist circumference were measured, and medication use for diabetes, hyperlipidemia, and hypertension was recorded. Smoking habits were also documented. The following main results were significantly associated with endostatin. Severe coronary atherosclerosis was positively associated in men. Being on hypertensive medication or not, as reported by the participants at the interview at study inclusion, was significantly associated with endostatin. Hypertensive medication increased from 12% to 26% from the lowest to the highest quartile of endostatin. Waist circumference was positively associated, where endostatin increases, on average, 0.21±SD for a 1±SD increase of waist circumference. Kidney function, measured as eGFR, was negatively associated, where endostatin decreases, on average, 0.22±SD for a 1±SD increase in eGFR. Elevated endostatin levels were associated with advanced coronary atherosclerosis in men, antihypertensive treatment, systemic inflammation (increased CRP), increased waist circumference, and impaired kidney function (lower eGFR).

Background: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques.

Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques.

Results: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4–61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40–1.98, P < 0.001] and hsCRP [OR 2.25, (95% CI 1.89–2.60), P < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72–3.10), P < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05–1.38), P = 0.007.

Conclusion: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.

Background: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis.

Purpose: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT.

Material and methods: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured.

Patients: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0–1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants.

Interpretation: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC. 

Activated partial thromboplastin time (APTT) is widely practiced in preoperative screening. The value of using this test to predict the risk of perioperative bleeding is not well documented in Sweden. In this article, a literature review is performed to determine whether unselected APTT testing can predict abnormal perioperative bleeding. The current literature does not support coagulation screening with APTT in routine perioperative bleeding assessment, as preoperative screening with APTT has a low sensitivity for detection of clinically significant bleeding disorder. While a comprehensive bleeding history is crucial, the APTT test should only be performed on patients with a history of increased bleeding tendency. The conclusion of this literature review is that patients with a negative bleeding history do not require routine screening with APTT prior to surgery, which, if implemented, would lead to a more cost-effective perioperative routine.

APTT bör endast användas som screeningtest vid utredning av ökad blödningsbenägenhet.

APTT bör inte används rutinmässigt preoperativt som screeningtest för ökad blödningsrisk.

Normal APTT utesluter inte koagulationsrubbning.

Förlängd APTT är inte alltid relaterad till blödningsrisk.

There is a large inter-individual variation in response to clopidogrel treatment, and previous studies have indicated higher risk of thrombotic events in those with high residual platelet reactivity (HPR). Less is known about individual variation over time. The aim of this prospective cohort study was to investigate intra-individual variation in platelet reactivity. Platelet aggregation in whole blood was assessed in 77 patients, at 3 days, 8 days and 6 months after admission for acute myocardial infarction and loading dose of clopidogrel. All patients were treated with aspirin and clopidogrel through 6-month follow-up. We found a significant increase in median ADP-stimulated aggregation from third to eighth day (195 vs. 250 AU*min, p-value = 0.001) but not from day 8 to 6 months (250 vs. 223 AU*min, p-value = 0.666). There was no significant change in the overall rate of HPR (15.6% vs 20.8%, p-value 0.503) or low platelet reactivity (LPR) (37.7% vs 33.8%, p-value = 0.609) from day 8 to 6-month follow-up. In contrast, more than one in four changed HPR status, 15.6% from non-HPR to HPR and 10.4% HPR to non-HPR. A shift in LPR status appeared even more frequent, occurring in about one of three patients. In spite of similar median aggregation and rate of HPR during 6-month follow-up, about one in four of the patients changed HPR status and one in three changed LPR status. This may be important information for a concept of risk stratification based on a single aggregation value early after an acute coronary syndromes.

OBJECTIVE: To describe the dynamics of copeptin in open cardiac surgery during the perioperative course.

DESIGN: Prospective cohort study.

SETTING: Single tertiary hospital.

PARTICIPANTS: Twenty patients scheduled for open cardiac surgery procedures with cardiopulmonary bypass (CPB).

INTERVENTIONS: No intervention.

MEASUREMENTS AND MAIN RESULTS: Copeptin concentrations were measured pre-, peri-, and postoperatively until day 6 after surgery. Patients were analyzed as a whole cohort (n = 20) and in a restricted "normal cohort" consisting of patients with normal preoperative copeptin concentration (<10 pmol/L) and perioperative uneventful course (n = 11). In the whole cohort, preoperative copeptin concentration was 7.0 pmol/L (interquartile range: 3.1-11 pmol/L). All patients had an early rise of copeptin, with 80% having peak copeptin concentration at weaning from CPB or upon arrival in the intensive care unit. Patients in the "normal cohort" had copeptin concentration at weaning from CPB of 194 pmol/L (98-275), postoperative day 1, 27 pmol/L (18-31); and day 3, 8.9 pmol/L (6.3-12).

CONCLUSIONS: Regardless of cardiac surgical procedure and perioperative course, all patients had an early significant rise of copeptin concentrations, generally peaking at weaning from CBP or upon arrival in the intensive care unit. Among patients with normal copeptin concentration preoperatively and uneventful course, the postoperative copeptin concentrations decreased to normal values within 3-to-4 days after cardiac surgery. Furthermore, the restricted "normal cohort" generally tended to display lower levels of copeptin concentration postoperatively. Further studies may evaluate whether copeptin can be a tool in identifying risk patients in cardiac surgery.

Imaging methods based on time-lapse microscopy are important tools for studying the dynamic events that shape thrombus formation upon vascular injury. However, there is a lack of methods to translate the vast amount of visual data generated in such experiments into quantitative variables describing platelet movements that can be subjected to systematic analysis. In this study, we developed experimental and computational protocols allowing for a detailed mathematical analysis of platelet movements within a developing thrombus. We used a flow chamber-based model of thrombosis wherein a collagen strip was used to initiate platelet adhesion and activation. Combining the use of a platelet staining protocol, designed to enable identification of individual platelets, and image processing, we tracked the movements of a large number of individual platelets during thrombus formation and consolidation. These data were then processed to generate aggregate measures describing the heterogeneous movements of platelets in different areas of the thrombus and at different time points. Applying this model and its potential, to a comparative analysis on a panel of platelet inhibitors, we found that total platelet intra-thrombus movements are only slightly reduced by blocking the interactions between glycoproteins IIb/IIIa and Ib and their ligands or by inhibiting thromboxane synthesis or P2Y12 signalling. In contrast, whereas 30 to 40% of the platelets movements (for the CD42a-labelled platelets) and 20% (for the pro-coagulant platelets), within a thrombus, are contractile, i.e., towards the centre of the thrombus, this contractile component is almost totally abolished in the presence of agents inhibiting these pathways.

Platelet-derived polyphosphates (polyP), stored in dense granule and released upon platelet activation, have been claimed to enhance thrombin activation of coagulation factor XI (FXI) and to activate FXII directly. The latter claim is controversial and principal results leading to these conclusions are probably influenced by methodological problems. It is important to consider that low-grade contact activation is initiated by all surfaces and is greatly amplified by the presence of phospholipids simulating the procoagulant membranes of activated platelets. Thus, proper use of inhibitors of the contact pathway and a careful choice of materials for plates and tubes is important to avoid artefacts. The use of phosphatases used to degrade polyP has an important drawback as it also degrades the secondary activators ADP and ATP, which are released from activated platelets. In addition, the use of positively charged inhibitors, such as polymyxin B, to inhibit polyP in platelet-rich plasma and blood is problematic, as polymyxin B also slows coagulation in the absence of polyP. In conclusion we hope awareness of the above caveats may improve research on the physiological roles of polyP in coagulation. © 2016 Authors; published by Portland Press Limited.

Flow chambers are common tools used for studying thrombus formation in vitro. However, the use of such devices is not standardised and there is a large diversity among the flow chamber systems currently used, and also in the methods used for quantifying the thrombus development. It was the study objective to evaluate a new method for analysis and quantification of platelet thrombus formation that can facilitate comparison of results between research groups. Whole blood was drawn over a collagen patch in commercial Ibid or in-house constructed PDMS flow chambers. Five percent of the platelets were fluorescently labelled and z-stack time-lapse images were captured during thrombus formation. Images were processed in a Python script in which the number of platelets and their respective x-, y- and z-positions were obtained. For comparison with existing methods the platelets were also labelled and quantified using fluorescence intensity and thrombus volume estimations by confocal microscopy. The presented method was found less sensitive to microscope and image adjustments and provides more details on thrombus development dynamics than the methods for measuring fluorescence intensity and thrombus volume estimation. The platelet count method produced comparable results with commercial and PDMS flow chambers, and could also obtain information regarding the stability of each detected platelet in the thrombus. In conclusion, quantification of thrombus formation by platelet count is a sensitive and robust method that enables measurement of platelet accumulation and platelet stability in an absolute scale that could be used for comparisons between research groups.

Background The menstrual cycle exhibits a pattern of repeated inflammatory activity. The present study aims to evaluate inflammatory and endothelial markers during the two phases of a menstrual cycle. Methods The study cohort consisted of 102 women with regular menstrual cycles. Inflammatory and endothelial markers (interleukin-6 [IL-6], pentraxin-3 [PTX-3], hs-C reactive protein [hs-CRP], sE-selectin, sP-selectin, intracellular and vascular cell adhesion molecules [ICAM-1 and VCAM-1] and cathepsins L, B and S) were measured during the early follicular and the late luteal phase of a normal menstrual cycle. Results Pentraxin-3 (PTX-3) and hs-CRP were significantly higher during the follicular phase compared to the luteal phase (p &lt; 0.001 respectively p = 0.025). The other inflammatory and endothelial markers, with the exception of cathepsin B, were higher, albeit not significantly, during the follicular phase. Conclusions Inflammatory activity, expressed mainly by members of the pentraxin family, is higher during the early follicular compared to the luteal phase. This could be associated to menstruation but the exact mechanisms behind this pattern are unclear and might involve the ovarian hormones or an effect on hepatocytes.