Hemostatic factors and risk of coronary heart disease in general populations: new prospective study and updated meta-analyses

<p>Background: Activation of blood coagulation and fibrinolysis may be associated with increased risk of coronary heart disease. We aimed to assess associations of circulating tissue plasminogen activator (t-PA) antigen, D-dimer and von Willebrand factor (VWF) with coronary heart disease risk.</p> <p>Design: Prospective case-control study, systematic review and meta-analyses.</p> <p>Methods: Measurements were made in 1925 people who had a first-ever nonfatal myocardial infarction or died of coronary heart disease during follow-up (median 19.4 years) and in 3616 controls nested within the prospective population-based Reykjavik Study.</p> <p>Results: Age and sex-adjusted odds ratios for coronary heart disease per 1 standard deviation higher baseline level were 1.25 (1.18, 1.33) for t-PA antigen, 1.01 (0.95, 1.07) for D-dimer and 1.11 (1.05, 1.18) for VWF. After additional adjustment for conventional cardiovascular risk factors, corresponding odds ratios were 1.07 (0.99, 1.14) for t-PA antigen, 1.06 (1.00, 1.13) for D-dimer and 1.08 (1.02, 1.15) for VWF. When combined with the results from previous prospective studies in a random-effects meta-analysis, overall adjusted odds ratios were 1.13 (1.06, 1.21) for t-PA antigen (13 studies, 5494 cases), 1.23 (1.16, 1.32) with D-dimer (18 studies, 6799 cases) and 1.16 (1.10, 1.22) with VWF (15 studies, 6556 cases).</p> <p>Conclusions: Concentrations of t-PA antigen, D-dimer and VWF may be more modestly associated with first-ever CHD events than previously reported. More detailed analysis is required to clarify whether these markers are causal risk factors or simply correlates of coronary heart disease.</p&gt

Development and validation of a clinical and computerised Decision Support System for Management of Hypertension (DSS-HTN) at a Primary Health Care (PHC) setting

Background: Hypertension remains the top global cause of disease burden. Decision support systems (DSS) could provide an adequate and cost-effective m

N-terminal pro-B-type natriuretic peptide and the prediction of primary cardiovascular events: results from 15-year follow-up of WOSCOPS

<b>Aims:</b>To test whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) was independently associated with, and improved the prediction of, cardiovascular disease (CVD) in a primary prevention cohort. <b>Methods and results:</b> In the West of Scotland Coronary Prevention Study (WOSCOPS), a cohort of middle-aged men with hypercholesterolaemia at a moderate risk of CVD, we related the baseline NT-proBNP (geometric mean 28 pg/mL) in 4801 men to the risk of CVD over 15 years during which 1690 experienced CVD events. Taking into account the competing risk of non-CVD death, NT-proBNP was associated with an increased risk of all CVD [HR: 1.17 (95% CI: 1.11–1.23) per standard deviation increase in log NT-proBNP] after adjustment for classical and clinical cardiovascular risk factors plus C-reactive protein. N-terminal pro-B-type natriuretic peptide was more strongly related to the risk of fatal [HR: 1.34 (95% CI: 1.19–1.52)] than non-fatal CVD [HR: 1.17 (95% CI: 1.10–1.24)] (P= 0.022). The addition of NT-proBNP to traditional risk factors improved the C-index (+0.013; P < 0.001). The continuous net reclassification index improved with the addition of NT-proBNP by 19.8% (95% CI: 13.6–25.9%) compared with 9.8% (95% CI: 4.2–15.6%) with the addition of C-reactive protein. N-terminal pro-B-type natriuretic peptide correctly reclassified 14.7% of events, whereas C-reactive protein correctly reclassified 3.4% of events. Results were similar in the 4128 men without evidence of angina, nitrate prescription, minor ECG abnormalities, or prior cerebrovascular disease. <b>Conclusion:</b> N-terminal pro-B-type natriuretic peptide predicts CVD events in men without clinical evidence of CHD, angina, or history of stroke, and appears related more strongly to the risk for fatal events. N-terminal pro-B-type natriuretic peptide also provides moderate risk discrimination, in excess of that provided by the measurement of C-reactive protein

Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank

Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006–2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05–1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation

Anticoagulant vs. antiplatelet therapy in patients with cryptogenic stroke and patent foramen ovale: an individual participant data meta-analysis

Aims The preferred antithrombotic strategy for secondary prevention in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) is unknown. We pooled multiple observational studies and used propensity score-based methods to estimate the comparative effectiveness of oral anticoagulation (OAC) compared with antiplatelet therapy (APT). Methods and results Individual participant data from 12 databases of medically treated patients with CS and PFO were analysed with Cox regression models, to estimate database-specific hazard ratios (HRs) comparing OAC with APT, for both the primary composite outcome [recurrent stroke, transient ischaemic attack (TIA), or death] and stroke alone. Propensity scores were applied via inverse probability of treatment weighting to control for confounding. We synthesized database-specific HRs using random-effects meta-analysis models. This analysis included 2385 (OAC = 804and APT = 1581) patients with 227 composite endpoints (stroke/TIA/death). The difference between OAC and APT was not statistically significant for the primary composite outcome [adjusted HR = 0.76, 95% confidence interval (CI) 0.52-1.12] or for the secondary outcome of stroke alone (adjusted HR = 0.75, 95% CI 0.44-1.27). Results were consistent in analyses applying alternative weighting schemes, with the exception that OAC had a statistically significant beneficial effect on the composite outcome in analyses standardized to the patient population who actually received APT (adjusted HR = 0.64, 95% CI 0.42-0.99). Subgroup analyses did not detect statistically significant heterogeneity of treatment effects across clinically important patient groups. Conclusion We did not find a statistically significant difference comparing OAC with APT; our results justify randomized trials comparing different antithrombotic approaches in these patient