Blood rheology, cardiovascular risk factors, and cardiovascular disease: The West of Scotland Coronary Prevention Study

The West of Scotland Coronary Prevention Study (WOSCOPS) showed that pravastatin reduced the risk of coronary heart disease (CHD) events in 6,595 middle-aged hypercholesterolaemic men aged 45-64 years without prior myocardial infarction followed for an average of 4.9 years. We hypothesised prospectively (a) that baseline levels of haemorheological variables were related to baseline and incident CHD and to mortality; and (b) that reduction in lipoproteins by pravastatin would lower plasma and blood viscosity, a potential contributory mechanism to CHD events. We therefore studied plasma and blood viscosity, fibrinogen, haematocrit, and blood cell counts at baseline and 1 year. At baseline, plasma and blood viscosity were related to risk factors, CHD measures, and claudication. On univariate analysis, baseline levels of all rheological variables (except platelet count) were related to incident CHD; CHD mortality; and total mortality. On multivariate analysis including baseline CHD and risk factors, plasma and blood viscosity, haematocrit and white cell count each remained significantly associated with incident CHD; while fibrinogen remained an independent predictor of mortality (all p<0.03). After one year, lipoprotein reduction by pravastatin was associated with significant reductions (about one quarter of a standard deviation) in plasma viscosity (mean difference 0.02 mPa.s, p<0.001) and in blood viscosity (mean difference 0.06 mPa.s, p<0.001), but was not associated with significant changes in other rheological variables. We therefore suggest that pravastatin therapy, which reduces elevated lipoproteins in hypercholesterolaemic men, may lower risks of CHD and mortality partly by lowering plasma and blood viscosity. Further studies are required to test this hypothesis

Long-term impact on healthcare resource utilization of statin treatment, and its cost effectiveness in the primary prevention of cardiovascular disease: a record linkage study

Aims: To assess the impact on healthcare resource utilization, costs, and quality of life over 15 years from 5 years of statin use in men without a history of myocardial infarction in the West of Scotland Coronary Prevention Study (WOSCOPS).<p></p> Methods: Six thousand five hundred and ninety-five participants aged 45–54 years were randomized to 5 years treatment with pravastatin (40 mg) or placebo. Linkage to routinely collected health records extended follow-up for secondary healthcare resource utilization to 15 years. The following new results are reported: cause-specific first and recurrent cardiovascular hospital admissions including myocardial infarction, heart failure, stroke, coronary revascularization and angiography; non-cardiovascular hospitalization; days in hospital; quality-adjusted life years (QALYs); costs of pravastatin treatment, treatment safety monitoring, and hospital admissions.<p></p> Results: Five years treatment of 1000 patients with pravastatin (40 mg/day) saved the NHS £710 000 (P < 0.001), including the cost of pravastatin and lipid and safety monitoring, and gained 136 QALYs (P = 0.017) over the 15-year period. Benefits per 1000 subjects, attributable to prevention of cardiovascular events, included 163 fewer admissions and a saving of 1836 days in hospital, with fewer admissions for myocardial infarction, stroke, heart failure and coronary revascularization. There was no excess in non-cardiovascular admissions or costs (or in admissions associated with diabetes or its complications) and no evidence of heterogeneity of effect over sub-groups defined by baseline cardiovascular risk.<p></p> Conclusion: Five years' primary prevention treatment of middle-aged men with a statin significantly reduces healthcare resource utilization, is cost saving, and increases QALYs. Treatment of even younger, lower risk individuals is likely to be cost-effective.<p></p&gt

Amplitude Changes during Ventricular Fibrillation: A Mechanistic Insight

Introduction: Clinically in ventricular fibrillation (VF), ECG amplitude, and frequency decrease as ischemia progresses and predict defibrillation success. In vitro ECG amplitude declines without ischemia, independent of VF frequencies. This study examines the contribution of cellular electrical activity and global organization to ECG amplitude changes during VF. Methods and Results: Rabbit hearts were Langendorff-perfused (40 mL/min, Tyrode’s solution) and loaded with RH237. During VF, ECG, and epicardial optical action potentials were recorded (photodiode array; 256 sites, 15 mm × 15 mm). After 60 s of VF, perfusion was either maintained, global ischemia produced by low-flow (6 mL/min), or solution [K+]o raised to 8 mM. Peak-to-peak amplitude was determined for all signals. During VF, in control, ECG amplitude decreased to a steady-state (∼57% baseline), whereas in low-flow steady-state was not reached with the amplitude continuing to fall to 33% of baseline by 600 s. Optically, LV amplitude declined more than RV, reaching significance in control (LV vs. RV; 33 ± 5 vs. 63 ± 8%, p < 0.01). During VF in 8 mM [K+]o, amplitude changes were more complex; ECG amplitude increased with time (105 ± 13%), whilst LV amplitude decreased (60 ± 15%, p < 0.001). Microelectrode studies showed amplitude reduction in control and 8 mM [K+]o (to ∼79 and ∼93% baseline, respectively). Evaluation of electrical coordination by cross-correlation of optical signals showed as VF progressed coordination reduced in control (baseline 0.36 ± 0.02 to 0.28 ± 0.003, p < 0.01), maintained in low-flow (0.41 ± 0.03 to 0.37 ± 0.005, p = NS) and increased in 8 mM [K+]o (0.36 ± 0.02 to 0.53 ± 0.08, p < 0.05). Conclusion: ECG amplitude decline in VF is due to a combination of decreased systolic activation at the cellular level and increased desynchronization of inter-cellular electrical activity

DNA-controlled assembly of protein-modified gold nanocrystals

The controlled assembly in solution of gold nanocrystals modified by attachment of complementary protein-DNA conjugates is described. The size of the aggregates formed can be controlled by the addition of single-stranded DNA, which quickly terminates the assembly process. The rate of formation of the aggregates can also be controlled by varying the salt concentration. Consequently, two distinct regimes of aggregation kinetics are observed. At low salt concentrations, aggregation is shown to be dependent on the rate of duplex formation between the modified gold nanocrystals, i.e., reaction-limited. At higher salt concentrations, aggregation is shown to be dependent only on the rate of diffusion of the nanocrystals, i.e., diffusion-limited. The results presented provide important insights into the rates of formation of nanocrystal assemblies. Moreover, the approach adopted is modular, requiring only the relevant biotin linker chemistry to be developed for a given nanoparticle, while also precluding unfavorable interactions between the DNA and the streptavidin-coated nanoparticle. The ability to control the rate of formation and size of nanocrystal aggregates assembled is important new knowledge. Application of this knowledge will inform future studies of nanocrystal assembly in solution involving different types of nanocrystals, which is of increasing technological significance.This research was supported by a grant from the Petroleum Research Fund (Grant No. PRF# 32879-ACS). The Authors also thank Dr. Hakan Rensmo for helpful discussions and express their gratitude for the services provided by D. Cottell and the staff at the Electron Microscopy Centre, National University of Ireland, Dublin.Peer reviewe

Data protection and tech startups: The need for attention, support, and scrutiny

Abstract: Though discussions of data protection have focused on the larger, more established organisations, startups also warrant attention. This is particularly so for tech startups, who are often innovating at the ‘cutting‐edge’—pushing the boundaries of technologies that typically lack established data protection best‐practices. Initial decisions taken by startups could well have long‐term impacts, and their actions may inform (for better or for worse) how particular technologies and the applications they support are implemented, deployed, and perceived for years to come. Ensuring that the innovations and practices of tech startups are sound, appropriate and acceptable should therefore be a high priority. This paper explores the attitudes and preparedness of tech startups to issues of data protection. We interviewed a series of UK‐based emerging tech startups as the EU's General Data Protection Regulation (GDPR) came into effect, which revealed areas in which there is a disconnect between the approaches of the startups and the nature and requirements of the GDPR. We discuss the misconceptions and associated risks facing innovative tech startups and offer a number of considerations for the firms and supervisory authorities alike. In light of our discussions, and given what is at stake, we argue that more needs to be done to help ensure that emerging technologies and the practices of the companies that operate them better align with the regulatory obligations. We conclude that tech startups warrant increased attention, support, and scrutiny to raise the standard of data protection for the benefit of us all

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

&lt;b&gt;Aims:&lt;/b&gt;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. &lt;b&gt;Methods and results:&lt;/b&gt; 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 &lt; 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. &lt;b&gt;Conclusion:&lt;/b&gt; 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