SARS-CoV-2 and COVID-19: A Narrative Review.

The World Health Organisation has reported that the viral disease known as COVID-19, caused by SARS-CoV-2, is the leading cause of death by a single infectious agent. This narrative review examines certain components of the pandemic: its origins, early clinical data, global and UK-focussed epidemiology, vaccination, variants, and long COVID.

Angiogenesis, Metabolism, Endothelial and Platelet Markers in Diabetes and Cardiovascular Disease.

Introduction: Diabetes is a leading risk factor for cardiovascular disease (CVD), the pathophysiology of both being linked to metabolic, endothelial, renal, angiogenic and platelet abnormalities. We hypothesised that abnormalities in these systems are more adverse in those whose CVD is compounded by diabetes, compared to those with diabetes or CVD alone. Materials and methods: Serum or plasma from 66 patients with diabetes alone, 76 with CVD alone, and 70 with both diabetes and CVD i.e. diabetic cardiovascular disease, was probed for markers of angiogenesis [angiopoietin 1 and 2, vascular endothelial growth factor (VEGF) and endoglin], metabolic [soluble receptor for advanced glycation products (sRAGE), leptin, lipocalin-2, interleukin-8, and cystatin-C], the endothelium (von Willebrand factor, endothelial microparticles and soluble E selectin)], and the platelet (platelet microparticles and soluble P selectin) by ELISA, Luminex or flow cytometry. Results: VEGF (p = 0.04), von Willebrand factor (p = 0.001) and endothelial microparticles (p = 0.042) were all higher in diabetic cardiovascular disease than in diabetes alone and cardiovascular disease alone. Soluble E selectin was higher in diabetic cardiovascular disease than in diabetes alone (p = 0.045), whilst cystatin-C (p = 0.004) and soluble P selectin (p < 0.001) were higher in diabetes and diabetic cardiovascular disease than in cardiovascular disease alone. There were no differences in angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, or interleukin-8. Conclusion: Angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, interleukin-8, and cystatin-c cannot differentiate diabetes from cardiovascular disease, or both conditions combined. Our data point to a more adverse endothelial (von Willebrand factor, endothelial microparticles), and angiogenic profile (VEGF) in those with diabetic cardiovascular disease, supporting the view that this group should be targeted more aggressively.

Oxygen saturation in retinal vessels and their correlation with endothelial microparticles in diabetes mellitus and/or cardiovascular disease.

PURPOSE: Retinal oxygen supply is a critical requirement in ocular function, and when inadequate can lead to retinopathy. Endothelial dysfunction is a leading pathophysiology in diabetes and cardiovascular disease and may be assessed by endothelial microparticles (EMPs). We hypothesised links between retinal vessel oxygenation and EMPs, expecting these indices to be more adverse in those with both DM and CVD. METHODS: Plasma from 34 patients with diabetes mellitus alone (DM), 40 with cardiovascular disease (CVD) alone and 36 with DM plus CVD was probed for EMPs by flow cytometry, but also for vascular markers soluble E-selectin (sEsel) and von Willebrand factor (vWf) (both ELISA). Retinal vessel fractal dimension, lacunarity, calibres and oxygen saturation were assessed from monochromatic and dual wavelength imaging respectively, intra-ocular pressure by was measured by rebound tonometry (I-CARE). RESULTS: There was no difference in oxygenation (arterial p = 0.725, venous p = 0.264, arterio-venous difference 0.375) between the groups, but there were differences in EMPs (p = 0.049), vWf (p = 0.004) and sEsel (p = 0.032). In the entire cohort, and in diabetes alone, EMPs correlated with venous oxygenation (r = 0.24, p = 0.009 and r = 0.43, p = 0.011 respectively), while in DM + CVD, sEsel correlated with venous oxygenation (r = 0.55, p = 0.002) and with the arterial-venous difference (r = -0.63, p = 0.001). In multivariate regression analysis of vascular markers against retinal oximetry indices in the entire group, EMPs were positively linked to venous oxygenation (p = 0.037). CONCLUSIONS: Despite differences in systemic markers of vascular function between DM, CVD and DM + CVD, there was no difference in arterial or venous retinal oxygenation, or their difference. However, EMPs were linked to venous oximetry, and may provide further insight into the mechanisms underlying diabetes and diabetic retinopathy.

British Journal of Biomedical Science in 2019. What have we learned?

In 2019 the British Journal of Biomedical Science published 40 articles in the various disciplines that comprise biomedical science. These were one review, 22 original articles and 17 'In Brief' short reports. Of those citing original data, the majority were in cellular pathology (14 papers), clinical chemistry (9 papers), and microbiology (6 papers: 4 in bacteriology and 2 in virology). There were 3 papers in haematology and 2 in andrology, whilst 5 papers crossed traditional discipline boundaries (such as the molecular genetics of IL6, liver function tests, and hepatocellular carcinoma). Over two-thirds of papers used techniques in molecular genetics. The present report will summarise key aspects of these publications that are of greatest relevance to laboratory scientists.

Non-coding RNAs - A primer for the laboratory scientist.

Advances in molecular genetics have identified several species of RNA that fail to translate - hence the non-coding RNAs. The two major groups within this class of nucleic acids are microRNAs (miRNA) and long non-coding RNAs (lncRNA). There is growing body of evidence supporting the view that these molecules have regulatory effect on both DNA and RNA. The objective of this brief review is to explain the molecular genetic of these molecules, to summarize their potential as mediators of disease, and to highlight their value as diagnostic markers and as tools in disease management.

British Journal of Biomedical Science in 2018: what have we learned?

In 2018 the British Journal of Biomedical Science published one guideline (in reproductive science) and 40 research articles in the various disciplines the comprise biomedical science. The latter were 24 original articles and 16 'In Brief' short reports. Of these, 23 are of note to only one of the sub-disciplines (seven each to biochemists and microbiologists, six to cell pathologists, and one each to cytologists, immunologists and reproductive scientists). Reflecting the increasing complexity of laboratory science, thirteen papers crossed one boundary (three papers each relevant to biochemists and immunologists, and to haematologists and biochemists), whilst four papers were relevant to three or more disciplines. Indeed, biochemical techniques were used in 18 papers, microbiological techniques in 9, whilst histopathology was relevant to 11 papers. Notably, 20 papers used techniques in chromosome analysis and molecular genetics. The present report will summarise key aspects of these publications that are of greatest relevance to laboratory scientists.

Retinal vessel diameters and reactivity in diabetes mellitus and/or cardiovascular disease.

BACKGROUND: Retinal vessel calibre and vascular dilation/constriction in response to flicker light provocation may provide a measure distinguishing patients suffering from diabetes mellitus and/or cardiovascular disease. METHODS: One hundred and sixteen age and sex matched patients with diabetes mellitus (DM), cardiovascular disease (CVD) and both DM and CVD (DM + CVD) underwent systemic and intraocular pressure measurements. Retinal vessel calibres were assessed using a validated computer-based program to compute central retinal artery and vein equivalents (CRVE) from monochromatic retinal images. Vessel dilation and constriction responses to flicker light provocation were assessed by continuous retinal vessel diameter recordings. Plasma endothelial markers von Willebrand factor (vWf) and soluble E selectin (sEsel) were measured by ELISA. RESULTS: Retinal vessel calibres were comparable across groups but CRVE correlated significantly with disease duration in DM patients (r = 0.57, p < 0.001). Patients suffering DM only exhibited reduced arterial vasomotion at rest and reduced arterial constriction following flicker light induced vessel dilation compared to patients with CVD and those suffering both CVD + DM (p = 0.030). Patients suffering from CVD + DM exhibited significant differences between each flicker cycle in regards to arterial maximum constriction (p = 0.006) and time needed to reach arterial maximum dilation (p = 0.004), whereas the other two groups did not show such inconsistencies between individual flicker cycles. vWf was raised in CVD + DM compared to the other two groups (p ≤ 0.02), whilst sEsel was raised in CVD + DM compared to DM alone (p = 0.044). CONCLUSIONS: Dynamic retinal vascular calibres as obtained by continuous diameter measurements using flicker light provocation can reveal subtle differences between groups suffering from CVD with and without DM. This difference in reaction pattern and lack of arterial constriction in DM may provide a suitable marker to monitor progression.

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses.

PURPOSE: To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease. METHODS: Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index. RESULTS: Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p < 0.05). Arterial reaction time was linked to serum creatinine (p = 0.036) and eGFR (p = 0.039); venous reaction time was linked to creatinine clearance (p = 0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p < 0.001 and p = 0.003, respectively) and the dilatation amplitude (p = 0.038 and p = 0.048, respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p = 0.004) and dilatation amplitude (p = 0.017), vWf was linked to the maximum constriction response (p = 0.016), and creatinine clearance to the baseline diameter fluctuation (p = 0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p = 0.022). CONCLUSIONS: Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses.

Laboratory assessment of anti-thrombotic therapy in heart failure, atrial fibrillation and coronary artery disease: insights using thrombelastography and a micro-titre plate assay of thrombogenesis and fibrinolysis.

As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p < 0.05). In multivariate regression analysis, only microplate assay indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p < 0.001) in aspirin users. Three microplate assay indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk.

Effects of propofol and isoflurane on haemodynamics and the inflammatory response in cardiopulmonary bypass surgery.

Cardiopulmonary bypass (CPB) causes reperfusion injury that when most severe is clinically manifested as a systemic inflammatory response syndrome. The anaesthetic propofol may have anti-inflammatory properties that may reduce such a response. We hypothesised differing effects of propofol and isoflurane on inflammatory markers in patients having CBR Forty patients undergoing elective CPB were randomised to receive either propofol or isoflurane for maintenance of anaesthesia. CRP, IL-6, IL-8, HIF-1α (ELISA), CD11 and CD18 expression (flow cytometry), and haemoxygenase (HO-1) promoter polymorphisms (PCR/electrophoresis) were measured before anaesthetic induction, 4 hours post-CPB, and 24 hours later. There were no differences in the 4 hours changes in CRP, IL-6, IL-8 or CD18 between the two groups, but those in the propofol group had higher HIF-1α (P = 0.016) and lower CD11 expression (P = 0.026). After 24 hours, compared to the isoflurane group, the propofol group had significantly lower levels of CRP (P < 0.001), IL-6 (P < 0.001) and IL-8 (P < 0.001), with higher levels CD11 (P = 0.009) and CD18 (P = 0.002) expression. After 24 hours, patients on propofol had increased expression of shorter HO-1 GT(n) repeats than patients on isoflurane (P = 0.001). Use of propofol in CPB is associated with a less adverse inflammatory profile than is isofluorane, and an increased up-regulation of HO-1. This supports the hypothesis that propofol has anti-inflammatory activity.

Edoxaban versus placebo, aspirin, or aspirin plus clopidogrel for stroke prevention in atrial fibrillation. An indirect comparison analysis.

As non-valvular atrial fibrillation (AF) brings a risk of stroke, oral anticoagulants (OAC) are recommended. In 'real world' clinical practice, many patients (who may be, or perceived to be, intolerant of OACs) are either untreated or are treated with anti-platelet agents. We hypothesised that edoxaban has a better net clinical benefit (NCB, balancing the reduction in stroke risk vs increased risk of haemorrhage) than no treatment or anti-platelet agents. We performed a network meta-analysis of published data from 24 studies of 203,394 AF patients to indirectly compare edoxaban with aspirin alone, aspirin plus clopidogrel, and placebo. Edoxaban 30 mg once daily significantly reduced the risk of all stroke, ischaemic stroke and mortality compared to placebo and aspirin. Compared to aspirin plus clopidogrel, there was a lower risk of intra-cranial haemorrhage (ICH). Edoxaban 60 mg once-daily had a reduced risk of any stroke and systemic embolism compared to placebo, aspirin, and aspirin plus clopidogrel. Mortality rates for both edoxaban doses were estimated to be lower compared to any anti-platelet, and significantly lower compared to placebo. With overall reduced risk of ischemic stroke and ICH, both edoxaban doses bring a NCB of mean (SD) 1.68 (0.15) saved events per 100 patients per year compared to anti-platelet drugs in a clinical trial population. The NCB was demonstrated to be lower, at 0.77 (0.12) events saved (p< 0.01) when modeled to data from a 'real world' cohort of AF patients. In conclusion, edoxaban is likely to provide even better protection from stroke and ICH than placebo, aspirin alone, or aspirin plus clopidogrel in both clinical trial populations and unselected community populations. Both edoxaban doses would also bring a positive NCB compared to anti-platelet drugs or placebo/non-treatment based on 'real world' data.

The influence of age and metformin treatment status on reported gastrointestinal side effects with liraglutide treatment in type 2 diabetes.

AIM: Treatment of type 2 diabetes with glucagon-like peptide-1 (GLP-1) receptor agonists may be limited by gastrointestinal side effects (GISE) in some patients. Risk factors for developing GISE are not known. We analysed patient characteristics that were associated with GISE among patients treated with the GLP-1 receptor agonist liraglutide. METHODS: Data was obtained from an audit database of liraglutide use based in clinical practice in the UK. Patients were grouped into those who did not report GISE, those who reported GISE but continued liraglutide and those who discontinued liraglutide due to GISE within 26 weeks of treatment. Baseline variables of age, diabetes duration, HbA1c, weight, BMI, blood pressure, lipids, gender, ethnicity, alanine transaminotransferase, estimated glomerular filtration rate (eGFR) and diabetes treatment types were tested for possible associations with GISE outcome. Significant variables in univariate analyses were entered into ordinal logistic regression analyses. RESULTS: A total of 4442 patients were suitable for analysis. A total of 3905 (87.9%) did not report GISE, 297 (6.7%) and 240 (5.4%) had GISE and continued and discontinued treatment, respectively. Age, weight, eGFR, metformin status and insulin status were associated with GISE outcome in univariate analyses (P all <0.05). In the final regression model, age (adjusted OR 1.15 [95%CI 1.05,1.26], P=0.002) and non-metformin use (adjusted OR 0.76 [95%CI 0.60,0.96], P=0.020) were associated with worse GISE outcome. CONCLUSION: Older age and non-metformin use were associated with more significant GISE leading to discontinuation of liraglutide treatment. The reasons for these findings are unclear and warrant further investigation.

Development and validation of a new assay for assessing clot integrity.

INTRODUCTION: Research and routine laboratory assessment of clot integrity can be time consuming, expensive, and cannot be batched as it is generally performed in real time. To address these issues, we developed and validated a micro-titre based assay to quantify thrombogenesis and fibrinolysis, the purpose being to assess patients at risk of cardiovascular events by virtue of hypercoagulability. In further validation, thrombogenesis results were compared to similar indices from the thrombelastograph (TEG). METHODS: Our assay determines three indices of thrombogenesis (lag time to the start of thrombus formation (LT), rate of clot formation (RCF), and maximum clot density (MCD)) and two of fibrinolysis (rate of clot dissolution (RCD) and time for 50% of the clot to lyse (T50)). Plasma was tested fresh and again after being frozen at -70°C. Some samples were tested immediately, others after being left at room temperature for up to 24h. RESULTS: The intra-assay coefficients of variation (CVs) of the three thrombogenesis measures (LT, RCF, MCD) and two fibrinolysis measures (RCD, T50) varied between 2.7 and 12.0% in fresh plasma and between 1.3% and 10.8% in frozen plasma respectively. Similarly, the inter-assay coefficients of variation of the thrombogenesis and fibrinolysis measures were 4.9-10.8% in fresh plasma and 2.2-6.5% in frozen plasma respectively. TEG assays intra- and inter assay CVs were around 25%. There were no significant differences in all plate assay indices up to 6h at room temperature. Certain plate assay thrombogenesis data were comparable to TEG indices after analysis by Pearson's correlation. The reagent processing cost per sample is £15 for TEG and £2 for the plate assays. CONCLUSION: Our micro-titre based assay assessing plasma thrombogenesis and fibrinolysis has good intra- and inter-assay CVs, can assess plasma up to 6h after venepuncture, is more efficient (in terms of throughput) and is more economical than that of the TEG.

Increased pre-surgical numbers of endothelial progenitor cells and circulating endothelial cells in colorectal cancer fail to predict outcome.

INTRODUCTION: The endothelium and angiogenesis are therapeutic targets in cancer. Response to treatment may be assessed by laboratory plasma markers such as circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), von Willebrand factor (vWf), soluble E selectin, vascular endothelial growth factor (VEGF) and angiogenin. We hypothesised that these markers, obtained before surgery, would predict 2-year outcome after surgery with or without anti-angiogenic therapy for colorectal cancer (CRC). METHODS: We recruited 154 patients with CRC, of whom 51 were treated with surgery alone, 74 were treated with standard chemotherapy (5-fluorouracil) and 29 were treated with standard chemotherapy plus anti-VEGF therapy (Avastin). Peripheral blood was taken before surgery. CD34(+)/CD45(-)/CD146(+) CECs and CD34(+)/CD45(-)/CD309 [KDR](+) EPCs were measured by flow cytometry and plasma markers by ELISA. RESULTS: After a mean of 2.1 years follow-up (range 1.9-2.3 years), 52 of the patients (33.7 %) experienced a poor outcome (radiological and/or histological evidence of tumour spread or recurrence, or death [n = 26]). In univariate analysis, poor outcome was linked to Dukes' stage (p < 0.001), American Joint Committee on Cancer (AJCC) stage (p < 0.001), type of treatment (surgery alone, standard chemotherapy with or without anti-antigenic therapy) (p = 0.047), CECs (p < 0.02) and EPCs (p < 0.01). In subsequent binary logistic regression analysis, only Dukes' stage (hazard ratio 2.3, 95 % confidence interval 1.0-5.3, p = 0.047) and modified AJCC stage (4.62, 1.88-11.33, p < 0.001) predicted a poor outcome. CONCLUSION: Endothelial cell markers (CECs, EPCs, vWf, soluble E selectin) and growth factors (VEGF and angiogenin), measured before surgery, have nothing extra to offer in predicting 2-year outcome in colorectal cancer when compared to Dukes' or AJCC stage.

Effect of standard chemotherapy and antiangiogenic therapy on plasma markers and endothelial cells in colorectal cancer.

INTRODUCTION: The importance of the endothelium in angiogenesis and cancer is undisputed, and its integrity may be assessed by laboratory markers such as circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), plasma von Willebrand factor (vWf), soluble E selectin, vascular endothelial growth factor (VEGF) and angiogenin. Antiantigenic therapy may be added to standard cytotoxic chemotherapy as a new treatment modality. We hypothesised that additional antiangiogenic therapy acts in a contrasting manner to that of standard chemotherapy on the laboratory markers. METHODS: We recruited 68 patients with CRC, of whom 16 were treated with surgery alone, 32 were treated with surgery followed by standard chemotherapy (5-flurouracil), and 20 were treated with surgery followed by standard chemotherapy plus anti-VEGF therapy (Avastin). Peripheral blood was taken before surgery, and again 3 months and 6 months later. CD34(+)/CD45(-)/CD146(+) CECs and CD34(+)/CD45(-)/CD309[KDR](+) EPCs were measured by flow cytometry, plasma markers by ELISA. RESULTS: In each of the three groups, CECs and EPCs fell at 3 months but were back at pre-surgery levels at 6 months (P<0.05). VEGF was lower in both 3-and 6-month samples in the surgery-only and surgery plus standard chemotherapy groups (P<0.05), but in those on surgery followed by standard chemotherapy plus anti-VEGF therapy, low levels at 3 months (P<0.01) increased to pre-surgery levels at 6 months. In those having surgery and standard chemotherapy, soluble E selectin was lower, whereas angiogenin was higher at 6 months than at baseline (both P<0.05). CONCLUSIONS: We found disturbances in endotheliod cells regardless of treatment, whereas VEGF returned to levels before surgery in those on antiangiogenic therapy. These observations may have clinical and pathophysiological implications.

The association between postprandial urinary C-peptide creatinine ratio and the treatment response to liraglutide: a multi-centre observational study.

AIMS: The response to glucagon-like peptide 1 receptor agonist treatment may be influenced by endogenous ß-cell function. We investigated whether urinary C-peptide creatinine ratio assessed before or during liraglutide treatment was associated with treatment response. METHODS: A single, outpatient urine sample for urinary C-peptide creatinine ratio was collected 2 h after the largest meal of the day among two separate groups: (1) subjects initiating liraglutide (0.6 â†’ 1.2 mg daily) or (2) subjects already treated with liraglutide for 20-32 weeks. The associations between pretreatment and on-treatment urinary C-peptide creatinine ratio and HbA1c change at 32 weeks were assessed using univariate and multivariate analyses (the ratio was logarithm transformed for multivariate analyses). Changes in HbA1c according to pretreatment urinary C-peptide creatinine ratio quartiles are shown. RESULTS: One hundred and sixteen subjects (70 pretreatment, 46 on treatment) with Type 2 diabetes from 10 diabetes centres were studied. In univariate analyses, neither pretreatment nor on-treatment urinary C-peptide creatinine ratio correlated with HbA1c change (Spearman rank correlation coefficient, r = -0.17, P = 0.17 and r = -0.20, P = 0.19, respectively). In multi-linear regression analyses, entering baseline HbA1c and log urinary C-peptide creatinine ratio, pretreatment and on-treatment log urinary C-peptide creatinine ratio became significantly associated with HbA1c change (P = 0.048 and P = 0.040, respectively). Mean (sd) HbA1c changes from baseline in quartiles 1 to 4 of pretreatment urinary C-peptide creatinine ratio were -3 ± 17 mmol/mol (-0.3 ± 1.6%) (P = 0.52), -12 ± 15 mmol/mol (-1.1 ± 1.4%) (P = 0.003), -11 ± 13 mmol/mol (-1.0 ± 1.2%) (P = 0.002) and -12±17 mmol/mol (-1.1±1.6%) (P=0.016), respectively. CONCLUSIONS: Postprandial urinary C-peptide creatinine ratios before and during liraglutide treatment were weakly associated with the glycaemic response to treatment. Low pretreatment urinary C-peptide creatinine ratio may be more useful than higher values by predicting poorer glycaemic response.

Non-vitamin K antagonist oral anticoagulants (NOACs): a view from the laboratory.

Disadvantages with traditional anticoagulants (vitamin K antagonists and heparinoids) have led to the development on non-vitamin K antagonist oral anticoagulants (NOACs). These agents are set to replace the traditional anticoagulants in situations such as following orthopaedic surgery, in atrial fibrillation, and in the prevention and treatment of venous thromboembolism. Although superior to vitamin K antagonists and heparinoids in several aspects, NOACs retain the ability to cause haemorrhage and, despite claims to the contrary, may need monitoring. This review aims to summarise key aspects of the NOACs of relevance to the laboratory.

Inflammation does not influence arterial stiffness and pulse-wave velocity in patients with coronary artery disease.

Vascular function is an important pathophysiological factor in cardiovascular disease, and is influenced by many factors, one of the principles being hypertension. Developing evidence suggests that inflammation may be another risk factor. Vascular function and blood pressure haemodynamics can be assessed by arterial stiffness, pulse pressure and plasma markers. Testing the hypothesis of a relationship between inflammatory markers, hypertension and vascular function, we recruited 222 stable coronary artery disease outpatients, assessing inflammation with levels of high sensitivity CRP and interleukin-6 (IL-6), vascular function/arterial stiffness by pulse-wave velocity (PWV), augmentation (SphygmoCor system Artcor, Sidney, Australia), aortic and brachial artery pulse pressure, Von Willebrand factor (vWf) and soluble E-selectin (both enzyme-linked immunosorbent assay). In multivariate regression analysis, PWVs, augmentation indices and pulse pressures were linked with age, blood pressure and (some) with heart rate (all P<0.01), while vWf was associated with age (P=0.01). We conclude that, in patients with stable coronary artery disease, arterial stiffness and pulse pressure are related strongly and independently with age, blood pressure and heart rate, and that any effect of inflammation is minimal.

Matrix metalloproteinases and their tissue inhibitors in hypertension-related pregnancy complications.

Matrix metalloproteinases (MMPs) are a family of endopeptidases that degrade the components of the extracellular matrix (ECM) such as collagen, and thus contribute to the remodelling and the physiological homeostasis of the ECM and its blood supply. The activities of these enzymes are regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and it has been suggested that a balance between MMPs and TIMPs plays an important role in vascular remodelling, angiogenesis and vasodilatation in a number of physiological situations. It follows that, regarding a relationship between MMPs and TIMPs, an imbalance between these molecules may lead to pathology in a wide range of conditions, including hypertension, cancer and pulmonary disease, and in the pathophysiology of reproduction. Indeed, regarding the latter, abnormalities in the maternal peripheral vasculature have been proposed as being (partly) responsible for the effects of hypertension on pregnancy and the development of complications including pre-eclampsia and eclampsia. However, the associations between MMPs, TIMPs and disease may be simply of association, not of pathology. This brief review explores current literature on the role of abnormalities of the ECM in general, focusing on the pathogenesis of hypertension and its complications during pregnancy as a model of disordered angiogenesis and remodelling.