SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions

Aims The aim of this study was to derive and validate the SCORE2-Older Persons (SCORE2-OP) risk model to estimate 5- and 10-year risk of cardiovascular disease (CVD) in individuals aged over 70 years in four geographical risk regions.Methods and results Sex-specific competing risk-adjusted models for estimating CVD risk (CVD mortality, myocardial infarction, or stroke) were derived in individuals aged over 65 without pre-existing atherosclerotic CVD from the Cohort of Norway (28 503 individuals, 10 089 CVD events). Models included age, smoking status, diabetes, systolic blood pressure, and total- and high-density lipoprotein cholesterol. Four geographical risk regions were defined based on country-specific CVD mortality rates. Models were recalibrated to each region using region-specific estimated CVD incidence rates and risk factor distributions. For external validation, we analysed data from 6 additional study populations {338 615 individuals, 33 219 CVD validation cohorts, C-indices ranged between 0.63 [95% confidence interval (CI) 0.61-0.65] and 0.67 (0.64-0.69)}. Regional calibration of expected-vs.-observed risks was satisfactory. For given risk factor profiles, there was substantial variation across the four risk regions in the estimated 10-year CVD event risk.Conclusions The competing risk-adjusted SCORE2-OP model was derived, recalibrated, and externally validated to estimate 5- and 10-year CVD risk in older adults (aged 70 years or older) in four geographical risk regions. These models can be used for communicating the risk of CVD and potential benefit from risk factor treatment and may facilitate shared decision-making between clinicians and patients in CVD risk management in older persons.Cardiolog

Fistula diameter correlates with echocardiographic characteristics in stable hemodialysis patients

Aims and background: Left ventricular hypertrophy (LVH) is a common finding in hemodialysis patients. The aim of the present study was to investigate if the diameter of the distal radiocephalic fistula could influence left ventricular variables in stable hemodialysis patients. Methods: Nineteen patients were investigated. Measurements of the diameter of the arteriovenous (AV) fistula were performed in 4 different locations. The patients were investigated using M-mode recordings and measurements in the 2D image. Doppler ultrasound was also performed. Transonic measurements were performed after ultrasound investigation. Results: Fistula mean and maximal diameter correlated with left ventricular characteristics. Fistula flow correlated neither with the left ventricular characteristics nor with fistula diameters. Conclusions: The maximal diameter of the distal AV fistula seems to be a sensitive marker of LVH in stable hemodialysis patients

Prolonged dual antiplatelet therapy in stable coronary disease: Comparative observational study of benefits and harms in unselected versus trial populations

Objective To estimate the potential magnitude in unselected patients of the benefits and harms of prolonged dual antiplatelet therapy after acute myocardial infarction seen in selected patients with high risk characteristics in trials. Design Observational population based cohort study. Setting PEGASUS-TIMI-54 trial population and CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records). Participants 7238 patients who survived a year or more after acute myocardial infarction. Interventions Prolonged dual antiplatelet therapy after acute myocardial infarction. Main outcome measures Recurrent acute myocardial infarction, stroke, or fatal cardiovascular disease. Fatal, severe, or intracranial bleeding. Results 1676/7238 (23.1%) patients met trial inclusion and exclusion criteria ("target" population). Compared with the placebo arm in the trial population, in the target population the median age was 12 years higher, there were more women (48.6% v 24.3%), and there was a substantially higher cumulative three year risk of both the primary (benefit) trial endpoint of recurrent acute myocardial infarction, stroke, or fatal cardiovascular disease (18.8% (95% confidence interval 16.3% to 21.8%) v 9.04%) and the primary (harm) endpoint of fatal, severe, or intracranial bleeding (3.0% (2.0% to 4.4%) v 1.26% (TIMI major bleeding)). Application of intention to treat relative risks from the trial (ticagrelor 60 mg daily arm) to CALIBER's target population showed an estimated 101 (95% confidence interval 87 to 117) ischaemic events prevented per 10 000 treated per year and an estimated 75 (50 to 110) excess fatal, severe, or intracranial bleeds caused per 10 000 patients treated per year. Generalisation from CALIBER's target subgroup to all 7238 real world patients who were stable at least one year after acute myocardial infarction showed similar three year risks of ischaemic events (17.2%, 16.0% to 18.5%), with an estimated 92 (86 to 99) events prevented per 10 000 patients treated per year, and similar three year risks of bleeding events (2.3%, 1.8% to 2.9%), with an estimated 58 (45 to 73) events caused per 10 000 patients treated per year. Conclusions This novel use of primary-secondary care linked electronic health records allows characterisation of "healthy trial participant" effects and confirms the potential absolute benefits and harms of dual antiplatelet therapy in representative patients a year or more after acute myocardial infarction. © 2016 Published by the BMJ Publishing Group Limited

Metabolic and haemodynamic effects of increased circulating adrenaline in man. Effect of labetalol, an alpha and beta blocker.

To simulate increased sympathoadrenal activity adrenaline was infused in normotensive subjects to achieve plasma adrenaline concentrations similar to those seen after myocardial infarction or hypoglycaemia. Adrenaline was infused after pretreatment for five days with labetalol 200 mg twice daily or placebo given in a random order. The rise in systolic blood pressure and the fall in diastolic blood pressure observed after the infusion of adrenaline (0.06 micrograms/kg/min) were prevented by labetalol and no increase in blood pressure was seen. Adrenaline infusion after pretreatment with placebo caused a profound fall in the serum potassium concentration (4.12-3.20 mmol(mEq)/l). Pretreatment with labetalol completely blocked adrenaline induced hypokalaemia (3.92-3.95 mmol(mEq)/l). Adrenaline induced T wave flattening and QTc prolongation were also prevented by labetalol. Thus labetalol can prevent the electrocardiographic, haemodynamic, and hypokalaemic effects of increased circulating adrenaline in man. The combination of alpha and beta blockade appears to be required to block the haemodynamic effects of adrenaline, and labetalol may, therefore, be useful in controlling both the metabolic and circulatory responses during increased sympathoadrenal activity