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Although the association between sleep behavior and morbidity and mortality risk has been reported before, there is still uncertainty whether the observed associations are causal or confounding. Therefore, we investigated the causal relationships between sleep-behavioral traits and terminated healthspan risk using Mendelian randomization (MR). We conducted a one-sample MR analysis to evaluate causality between six sleep-behavioral traits (sleep duration, chronotype/morningness, napping, sleeplessness/insomnia, and getting up from bed) and risk of healthspan termination among 388, 909 UK Biobank (UKB) participants. Instrumental variables for sleep behaviors (N = 590) were obtained from recent genome-wide association studies (GWAS). We defined healthspan based on eight predominant health-terminating events associated with longevity (congestive heart failure, myocardial infarction, chronic obstructive pulmonary disease, stroke, dementia, diabetes, cancer, and death). We further constructed a sleep score and a weighted genetic risk score to increase the predictive ability of the sleep-behavioral traits. Cox regression models and Inverse Probability Treatment Weighting (IPTW) were implemented, followed by MR to assess causation. We used inverse-variance-weighted MR to estimate causal effects, and weighted-median and MR-egger for sensitivity analysis to test the pleiotropic effects. In IPTW, we observed a decreased risk of terminated healthspan for healthy sleep behaviors such as 'sleep duration 7-8h/d' (Hazard ratio, HR = 0.93; 95 % confidence interval, CI: 0.92–0.96; P < 0.001); 'morningness' (HR = 0.95; 95%CI: 0.93–0.98; P < 0.01); 'napping' (HR = 0.93; 95%CI: 0.91–0.94; P < 0.001); 'easy getting up from bed' (HR = 0.91; 95%CI: 0.88–0.93; P < 0.001); and, 'never/rarely experience sleeplessness/insomnia' (HR = 0.94; 95%CI: 0.92–0.96; P < 0.001). MR results further indicated causal associations between healthy sleep duration (OR = 0.98; 95%CI: 0.97–1.00; P = 0.036) and insomnia (OR = 1.02; 95%CI: 1.01–1.03; P < 0.001) with terminated healthspan. MR-egger did not suggest any potential pleiotropy. This study supports abnormal sleep duration and insomnia as potential causal risk factors for terminated healthspan. Thus, healthy sleep behavior is valuable for the extension of healthspan, and well-designed and tailored sleep health interventions are warranted. [ABSTRACT FROM AUTHOR]

Mendelian randomization confirmed multiple risk factors for primary events of coronary artery disease (CAD), but no such studies have been performed on recurrent major coronary events despite interesting insights derived from other designs. We examined the associations between genetically-influenced classical cardiovascular risk factors and the risk of recurrent major coronary events in a cohort of CAD patients. We included all first-time CAD cases (defined as angina pectoris, chronic ischemic heart disease or acute myocardial infarction) of European ancestry from the UK Biobank. Cases were followed till the end of follow-up, death or when they developed a recurrent major coronary event (chronic ischemic heart disease or acute myocardial infarction). Standardized weighted genetic risk scores were calculated for body mass index (BMI), systolic blood pressure, LDL cholesterol and triglycerides. From a total of 22,949 CAD patients (mean age at first diagnosis 59.8 (SD 7.3) years, 71.1% men), 12,539 (54.6%) reported a recurrent major coronary event within a period of maximum 17.8 years. One standard deviation higher genetically-determined LDL cholesterol was associated with a higher risk of a recurrent major coronary event (odds ratio: 1.08 [95% confidence interval: 1.05, 1.11]). No associations were observed for genetically-influenced BMI (1.00 [0.98, 1.03]), systolic blood pressure (1.01 [0.98, 1.03]) and triglycerides (1.02 [0.995, 1.05]). Despite the use risk-reducing medications following a first coronary event, this study provided genetic evidence that, of the classical risk factors, mainly high LDL cholesterol was associated with a higher risk of developing recurrent major coronary events. [Display omitted] • Most Mendelian randomization studies were performed on primary disease. • In atherosclerosis patients, LDL cholesterol associated with secondary disease. • Other classical cardiovascular disease did not associate with secondary disease. • LDL cholesterol should be mainly targeted to reduce secondary disease risk. [ABSTRACT FROM AUTHOR]

Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction(NIHR Health Informatics Collaborative:TROP-CABG study). Benedetto et al. The optimal timing of coronary artery bypass grafting (CABG) in patients with non-ST elevation myocardial infarction (NSTEMI) and the utility of pre-operative troponin levels in decision-making remains unclear. We investigated (a) the association between peak pre-operative troponin and survival post-CABG in a large cohort of NSTEMI patients and (b) the interaction between troponin and time-to-surgery. Our cohort consisted of 1746 patients (1684 NSTEMI; 62 unstable angina) (mean age 69 ± 11 years,21% female) with recorded troponins that had CABG at five United Kingdom centers between 2010 and 2017. Time-segmented Cox regression was used to investigate the interaction of peak troponin and time-to-surgery on early (within 30 days) and late (beyond 30 days) survival. Average interval from peak troponin to surgery was 9 ± 15 days, with 1466 (84.0%) patients having CABG during the same admission. Sixty patients died within 30-days and another 211 died after a mean follow-up of 4 ± 2 years (30-day survival 0.97 ± 0.004 and 5-year survival 0.83 ± 0.01). Peak troponin was a strong predictor of early survival (adjusted P = 0.002) with a significant interaction with time-to-surgery (P interaction = 0.007). For peak troponin levels <100 times the upper limit of normal, there was no improvement in early survival with longer time-to-surgery. However, in patients with higher troponins, early survival increased progressively with a longer time-to-surgery, till day 10. Peak troponin did not influence survival beyond 30 days (adjusted P = 0.64). Peak troponin in NSTEMI patients undergoing CABG was a significant predictor of early mortality, strongly influenced the time-to-surgery and may prove to be a clinically useful biomarker in the management of these patients. • In patients with NSTEMI undergoing CABG, pre-operative peak troponin level was a significant predictor of early mortality. • The relationship between troponin level and mortality was influenced by timing of CABG. • In patients with a pre-operative peak troponin >100 xULN, CABG within 10 days was associated with lower survival. • The interaction between troponin, timing of surgery and mortality should be discussed with NSTEMI patients undergoing CABG. [ABSTRACT FROM AUTHOR]

• A stochastic post COVID-19 was developed. • An eradication of Omicron variant as well as post COVID-19 with heart attack. • Persistence of the disease was presented. • The numerical simulation was obtained by utilizing real data. In this study, a latest version of COVID-19 pandemic is hand overed. A Stochastic post COVID-19 delayed model is developed to explore the spread of COVID-19 as well as omicron variant with the correlation of heart attack. This article provides an eradication of the COVID-19 and omicron variant as well as the population who have heart attack after post COVID-19 of these epidemic diseases. Then the existence and uniqueness of global positive solution are studied. Ensuing, In this article, we classify COVID-19 virus and omicron variant which go to extinction and become persistent in mean. By using Lyapunov function, the existence of ergodic stationary distribution are established. Later from the persistent disease as well as extinction, heart disease are ready to develop in the human body. By Eventually, an optimal control strategies are introduced in the form of stochastic post COVID-19 delayed model to control two different types of virus. Finally, the numerical simulation are presented to determine the behavior of dynamical system by utilizing the real data of United Kingdom. [ABSTRACT FROM AUTHOR]

Lack of physical activity (PA) and sarcopenia is a known risk factors for ischemic heart disease (IHD). However, considering their coexistence in the middle-aged and elderly population, the interaction of these two factors remains uncertain. Here, we investigated the interactive effects of PA and sarcopenia on IHD. We extracted 344,688 participants free of IHD at baseline from the UK Biobank. PA was classified into low, moderate, and high according to the International Physical Activity Questionnaire. Sarcopenia was identified in accordance with the European Working Group on Sarcopenia in Older People 2. Cox proportional hazard models were applied to estimate the effect of PA and sarcopenia on incident IHD and its subtypes. We also used objective PA data measured by wrist-worn devices to repeat these analyses. Over a median follow-up of 11.7 years, 24,809 (7.2%) participants developed incident IHD. Lack of PA was associated with a higher risk of IHD after adjusting for potential confounders. The hazard ratio (HR) was 1.09 (95% CI: 1.05–1.13) for individuals without sarcopenia and 1.29 (95% CI: 1.17–1.42) for those with sarcopenia. Regarding the joint effect, the combination of low PA and sarcopenia was associated with the highest risk of IHD, with an HR of 1.54 (95% CI: 1.44–1.66), and both additive and multiplicative interactions were significant (RERI 0.27, 95% CI: 0.14–0.39, p -interaction <0.01). For subtypes of IHD, the interaction was pronounced in acute myocardial infarction and chronic ischemic heart disease. These results suggest a synergistic interaction between lack of PA and sarcopenia on the risk of IHD. Findings from this study may help facilitate more effective primary prevention of IHD. [Display omitted] • Lack of physical activity (PA) and sarcopenia have synergistic interaction on ischemic heart disease (IHD). • The synergistic interaction is also found in subtypes of IHD. • Moderate volume of PA can provide beneficial protective effects. • Protective effects may only be achieved with moderate to high-intensity PA. [ABSTRACT FROM AUTHOR]

Background: Rotational atherectomy (RA) during PCI is linked to a higher likelihood coronary perforations (CP). However, the evidence base on incidence, predictors and outcomes of this complication in RA-PCI remains limited.Methods: Using the British Cardiac Intervention Society database, data were analysed on all RA-PCI procedures in UK 2007-2014. Descriptive statistics and multivariate logistic regressions were used to examine baseline, procedural and outcome associations.Results: During 10,980 RA-PCI procedures, 167 CPs were recorded (1.52%) with a stable annual incidence. Baseline and procedural covariates associated with higher rates of RA perforation were number of stents used, female gender, smoking, and left-main stenosis. CP was significantly associated with shock, DC cardioversion, heart block, transfusion, emergency surgery, periprocedural MI, in-hospital major bleed, acute kidney injury, dissection, side branch loss and in-hospital death. CP was also associated with higher rates of in-hospital MACCE (OR 12.22, 95% CI 7.67-19.47), 30-day mortality (OR 10.02, 95% CI 5.87-17.09) and 12-month mortality (OR 3.90, 95% CI 2.53-6.02).Conclusions: CP is more frequent in RA-PCI than all-comer PCI and is associated with a significant burden of morbidity and mortality. There are a limited number of baseline and procedural co-variates associated with CP in RA-PCI, making it difficult to predict. [ABSTRACT FROM AUTHOR]

This study examines whether neuroticism is differentially associated with risk of incident Alzheimer's disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD) using a prospective study design. Participants from the UK Biobank (N = 401,422) completed a self-report neuroticism scale in 2006–2010 and incident all-cause dementia, AD, VD, and FTD were ascertained using electronic health records or death records up to 2018. During an average follow-up of 8.8 years (3,566,123 person-years), there were 1798 incident of all-cause dementia, 675 AD, 376 VD, and 81 FTD. Accounting for age and sex, compared to individuals in the low quartile, individuals in the top quartile of neuroticism had higher risk of all-cause dementia (HR = 1.70; 95% CI: 1.49–1.93), AD (HR = 1.42; 1.15–1.75), VD (HR = 1.73; 1.30–2.29), but not FTD (HR = 0.89; 0.49–1.63). The associations with AD and VD were attenuated but remained significant after further accounting for education, household income, deprivation index, diabetes, hypertension, stroke, heart attack, ever smoker, physical activity, obesity, hemoglobin A1c, C-reactive protein, and low-density lipoprotein. The associations were not moderated by socioeconomic status. The findings were consistent in analyses that excluded cases that occurred within the first 5 years of follow-up. In conclusion, neuroticism is a robust predictor of incident AD and VD, but not FTD. This pattern suggests that the affective symptoms that distinguish dementia types may partly reflect premorbid differences in trait neuroticism. [ABSTRACT FROM AUTHOR]

The UK Simon Broome (SB) familial hypercholesterolaemia (FH) register previously reported 3-fold higher standardised mortality ratio for cardiovascular disease (CVD) in women compared to men from 2009 to 2015. Here we examined sex differences in CVD morbidity in FH by national linkage of the SB register with Hospital Episode Statistics (HES). Of 3553 FH individuals in the SB register (aged 20–79 years at registration), 2988 (52.5% women) had linked HES records. Standardised Morbidity Ratios (SMbR) compared to an age and sex-matched UK general practice population were calculated [95% confidence intervals] for first CVD hospitalisation in HES (a composite of coronary heart disease (CHD), myocardial infarction (MI), stable or unstable angina, stroke, TIA, peripheral vascular disease (PVD), heart failure, coronary revascularisation interventions). At registration, men had significantly (p < 0.001) higher prevalence of previous CHD (24.8% vs 17.6%), previous MI (13.2% vs 6.3%), and were commenced on lipid-lowering treatment at a younger age than women (37.5 years vs 42.3 years). The SMbR for composite CVD was 6.83 (6.33–7.37) in men and 7.55 (6.99–8.15) in women. In individuals aged 30–50 years, SMbR in women was 50% higher than in men (15.04 [12.98–17.42] vs 10.03 [9.01–11.17]). In individuals >50 years, SMbR was 33% higher in women than men (6.11 [5.57–6.70] vs 4.59 [4.08–5.15]). Excess CVD morbidity due to FH remains markedly elevated in women at all ages, but especially those aged 30–50 years. This highlights the need for earlier diagnosis and optimisation of lipid-lowering risk factor management for all FH patients, with particular attention to young women with FH. Image 1 • Males with familial hypercholesterolaemia (FH) had more cardiovascular disease (CVD) risk factors and were commenced on lipid-lowering therapy at a younger age, than females with FH. • Individuals with FH had excess rates of hospitalisations for CVD, compared to the general population of non-FH individuals. • Excess CVD morbidity due to FH was higher in women than men aged 30 years and over, but especially in those aged 30–50 years. [ABSTRACT FROM AUTHOR]

Ischaemic heart disease and stroke are the leading causes of death worldwide at 119 per 100,000 and 85 per 100,000 population. For the USA, heart disease is leading cause of death at 165 per 100,000 population. In developed countries, strokes and acute myocardial infarction in the general population have fallen from smoking reduction, lifestyle modifications and therapeutic interventions including statins. In a population-based stroke study in the UK involving primary care practices, of in-hospital strokes 90% were ischaemic, and 37% occurred within 1 week of an operation. Approximately 50% of the patients were not on a statin. In the UK, there is a national screening initiative for the prevention of atherosclerotic cardiovascular disease (ASCVD) offered to people aged 40-74 yr old. The QRISK3 tool calculates the risk of developing heart disease or stroke over 10 yr, from which recommendations are made on interventions for the prevention of ASCVD up to age 84 yr, with similar screening and assessment tools in Europe and the US. If the QRISK3 score tool for calculating cardiovascular risk is considered sufficiently robust for population screening in primary care, should anaesthetists not use the same screening for secondary care? We present a case for statin use over the perioperative period, to reduce early vascular adverse events based on statins' early pleiotropic actions, using the primary care QRISK tool for screening of ASCVD risk. [ABSTRACT FROM AUTHOR]

Background: Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis.Objectives: This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time.Methods: This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440).Results: Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018).Conclusion: In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294). [ABSTRACT FROM AUTHOR]

Purpose: Inversed probability weighted (IPW) estimators are commonly used to adjust for time-fixed or time-varying confounders. However, in high-dimensional settings, including all identified confounders may result in unstable weights leading to higher variance. We aimed to develop a visualization tool demonstrating the impact of each confounder on the bias and variance of IPW estimates, as well as the propensity score overlap.Methods: A SAS macro was developed for this visualization tool and we demonstrate how this tool can be used to identify potentially problematic confounders of the association of statin use after myocardial infarction on one-year mortality in a plasmode simulation study using a cohort of 39,792 patients from the UK (1998-2012).Results: Through the tool's output, we can identify problematic confounders (two instrumental variables) and important confounders by comparing the estimated psuedo MSE with that from the fully adjusted model and propensity score overlap plot.Conclusion: Our results suggest that the analytic impact of all confounders should be considered carefully when fitting IPW estimators. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that beta blockers are associated with increased perioperative risk in hypertensive patients. We investigated whether beta blockers were associated with an increased risk in elderly patients with raised preoperative arterial blood pressure.Methods: We conducted a propensity-score-matched cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13), including 84 633 patients aged 65 yr or over. Conditional logistic regression models, including factors that were significantly associated with the outcome, were constructed for 30-day mortality after elective noncardiac surgery. The effects of beta blockers (primary outcome), renin-angiotensin system (RAS) inhibitors, calcium-channel blockers, thiazides, loop diuretics, and statins were investigated at systolic and diastolic arterial pressure thresholds.Results: Beta blockers were associated with increased odds of postoperative 30-day mortality in patients with systolic hypertension (defined as systolic BP >140 mm Hg; adjusted odds ratio [aOR]: 1.92; 95% confidence interval [CI]: 1.05-3.51). After excluding patients for whom prior data suggest benefit from perioperative beta blockade (patients with prior myocardial infarction or heart failure), rather than adjusting for them, the point estimate shifted slightly (aOR: 2.06; 95% CI: 1.09-3.89). Compared with no use, statins (aOR: 0.35; 95% CI: 0.17-0.75) and thiazides (aOR: 0.28; 95% CI: 0.10-0.78) were associated with lower mortality in patients with systolic hypertension.Conclusions: These data suggest that the safety of perioperative beta blockers may be influenced by preoperative blood pressure thresholds. A randomised controlled trial of beta-blocker withdrawal, in select populations, is required to identify a causal relationship. [ABSTRACT FROM AUTHOR]

Background: Smoking is a well-documented risk for acute ST-segment elevation myocardial infarction (STEMI). The differential effect between sexes has yet to be quantified.Objectives: The purpose of this study was to differentiate the effect of smoking on increased risk of STEMI between sexes.Methods: For this retrospective ecological cohort study, all patients at a U.K. tertiary cardiothoracic center who presented between 2009 and 2014 with acute STEMI were combined with population data to generate incidence rates of STEMI. Age-standardized incidence rate ratios (IRRs) using the Poisson distribution were calculated comparing STEMI rates between smokers and nonsmokers stratified by sex and 3 age groups (18 to 49, 50 to 64, and >65 years).Results: A total of 3,343 patients presented over 5,639,328 person-years. Peak STEMI rate for current smokers was in the 70 to 79 years age range for women (235 per 100,000 patient-years) and 50 to 59 years (425 per 100,000 patient-years) in men. Smoking was associated with a significantly greater increase in STEMI rate for women than men (IRR: 6.62; 95% confidence interval [CI]: 5.98 to 7.31, vs. 4.40; 95% CI: 4.15 to 4.67). The greatest increased risk was in women age 18 to 49 (IRR: 13.22; 95% CI: 10.33 to 16.66, vs. 8.60; 95% CI: 7.70 to 9.59 in men). The greatest risk difference was in the age 50 to 64 years group, with IRR of 9.66 (95% CI: 8.30 to 11.18) in women and 4.47 (95% CI: 4.10 to 4.86) in men.Conclusions: This study quantifies the differential effect of smoking between sexes, with women having a significantly increased risk of STEMI than men. This information encourages continued efforts to prevent smoking uptake and promote cessation. [ABSTRACT FROM AUTHOR]

Abstract Background The effect of individual saturated fatty acids (SFAs) on serum cholesterol levels depends on their carbon-chain length. Whether the association with myocardial infarction (MI) also differs across individual SFAs is unclear. We examined the association between consumption of individual SFAs, differing in chain lengths ranging from 4 through 18 carbons, and risk of MI. Methods We used data from 22,050 and 53,375 participants from EPIC-Norfolk (UK) and EPIC-Denmark, respectively. Baseline SFA intakes were assessed through validated, country-specific food frequency questionnaires. Cox regression analysis was used to estimate associations between intakes of individual SFAs and MI risk, for each cohort separately. Results During median follow-up times of 18.8 years in EPIC-Norfolk and 13.6 years in Denmark, respectively, 1204 and 2260 MI events occurred. Mean (±SD) total SFA intake was 13.3 (±3.5) en% in EPIC-Norfolk, and 12.5 (±2.6) en% in EPIC-Denmark. After multivariable adjustment, intakes of C12:0 (lauric acid) and C14:0 (myristic acid) inversely associated with MI risk in EPIC-Denmark (HR upper versus lowest quintile: 0.80 (95%CI: 0.66, 0.96) for both SFAs). Intakes in the third and fourth quintiles of C4:0–C10:0 also associated with lower MI risk in EPIC-Denmark. Moreover, substitution of C16:0 (palmitic acid) and C18:0 (stearic acid) with plant proteins resulted in a reduction of MI risk in EPIC-Denmark (HR per 1 energy%: 0.86 (95%CI: 0.78, 0.95) and 0.87 (95%CI: 0.79, 0.96) respectively). No such associations were found in EPIC-Norfolk. Conclusion The results from the present study suggest that the association between SFA and MI risk depends on the carbon chain-length of the SFA. Highlights • The associations of dietary saturated fatty acids with myocardial infarction seems to depend on their carbon chain-length. • Short- to medium chained saturated fatty acids and the odd-chain SFAs with 15 and 17 carbons were inversely or not associated to myocardial infarction risk. • Substituting the longer-chain saturated fatty acids C16:0 and C18:0 with plant proteins inversely associated with myocardial infarction risk. [ABSTRACT FROM AUTHOR]

Abstract Aims With increasing age, physical inactivity and sedentary behaviour levels increase, as does cardiovascular disease (CVD) incidence. We investigate how device-measured sedentary behaviour and physical activity (PA) are related to CVD onset in men aged 70+; whether the total volume of activity is more important than pattern. Methods and results Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978–80. In 2010–12, 3137 survivors were invited to complete questionnaires and wear an Actigraph GT3x accelerometer for 7 days. PA intensity was categorised as sedentary, light and moderate to vigorous (MVPA). Men were followed up for Myocardial Infarction, stroke and heart failure (ICD9 410–414, 430–438 and 428) morbidity and mortality from 2010 to 12 to June 2016. Hazard Ratios (HRs) for incident Cardiovascular Disease (CVD) were estimated. 1528/3137 (49%) men had sufficient accelerometer data. 254 men with pre-existing CVD were excluded. Participants' mean age was 78.4 (range 71–92) years. After median 4.9 years follow-up, 122 first CVD events occurred in 1181 men (22.7/1000 person-years) with complete data. For each additional 30 min in sedentary behaviour, light PA,10 min in MVPA, or 1000 steps/day, HRs for CVD were 1.09(95%CI 1.00, 1.19), 0.94(0.85, 1.04), 0.88(0.81, 0.96) and 0.86(0.78 to 0.95) respectively, adjusted for measurement-related factors, socio-demographics, health behaviours and disability. HRs for accumulating 150 min/week MVPA in bouts ≥1 min and bouts ≥10 min were 0.47(0.32 to 0.69), and 0.49(0.25, 0.98). Conclusions In older men, high volume of steps or MVPA rather than MVPA bouts was associated with reduced CVD risk. Highlights • Prospective studies report that self-reported physical activity protects against cardiovascular disease (CVD). • Yet, self-reported behaviours cannot easily be used to assess the value of the 10 min activity bouts specified in guidelines. • This is the first study of risk of fatal and non-fatal CVD based on device measured physical activity and sedentary behaviour. • Among 1181 men aged over 70 years, more time in moderate to vigorous physical activity and more steps reduced 5-year CVD risk. • The pattern of accumulating moderate to vigorous physical activity in 10 min bouts was not important for CVD risk. [ABSTRACT FROM AUTHOR]

Abstract Background Lower socioeconomic status (SES) has been associated with worse outcomes after acute myocardial infarction. Data for survival after ST-elevation myocardial infarction (STEMI) by SES in the current era of primary percutaneous coronary intervention (PCI) is more limited. Methods Data was collected for all patients with acute STEMI undergoing primary PCI at The South Yorkshire Cardiothoracic Centre, UK between 2009 and 2014. A Cox regression analysis was used to assess differences in survival by SES quartile (using an area-level measure). Results Of the 3126 STEMI patients, 2655 (84.9%) were first presentations of STEMI. Lower SES groups generally had a less favourable baseline cardiovascular risk factor profile, with higher rates of smoking (p = 0.001), diabetes (p = 0.007) and previous coronary heart disease (p = 0.025). With the exception of beta-blockers, the use of secondary preventative medications was similar between SES quartiles. Adjusting for age and gender, the most disadvantaged SES quartile trended to a non-significant increased mortality at 30 days (hazard ratio 1.35 (0.79–2.33)), 1 year (1.12 (0.76–1.65)), or 3 years (1.22 (0.88–1.70)) compared to the least disadvantaged SES quartile, but this was attenuated by adjusting for additional cardiovascular risk factors and medication use on discharge. Conclusions In this large study of unselected STEMI patients managed by primary PCI, we did not find any significant differences in survival by SES at 30 days, 1 year, or 3 years. Highlights • Lower socioeconomic status is associated with worse outcomes post-MI. • STEMI and NSTEMI are managed different, with urgent reperfusion needed for STEMI. • Lower socioeconomic groups have greater use of emergency services. • Data for survival after STEMI by socioeconomic status in the era of PCI is limited. • We did not find any significant differences in survival by SES. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the individual and combined associations of depression and low socioeconomic status (SES) with risk of major cardiovascular events (MCVE), defined as first-ever fatal or non-fatal stroke or myocardial infarction, in a large prospective cohort study.Methods: We used data from 466,238 UK Biobank participants, aged 40-69 years without cardiovascular disease, bipolar disorder or schizophrenia at baseline. We performed Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the individual and combined associations of depression and each of educational attainment, area-based deprivation and income with risk of MCVE. We assessed effect modification and explored interaction on the additive and multiplicative scale.Results: Depression, low education, high area-based deprivation and low income were individually associated with increased risks of MCVE (adjusted HR, 95% CI: 1.28, 1.19-1.38; 1.20, 1.14-1.27; 1.17, 1.11-1.23; and 1.22, 1.16-1.29, respectively). Depression was associated with increased risks of MCVE among individuals with high and low SES. Individuals with depression and each of low education, high area-based deprivation and low income were at particularly high risk of MCVE (HR, 95% CI: 1.50, 1.38-1.63; 1.63, 1.46-1.82; 1.31, 1.23-1.40, respectively). There was interaction between depression and area-based deprivation on multiplicative and additive scales but no interaction with education or income.Conclusion: Depression was associated with increased risks of MCVE among individuals with high and low SES, with particularly high risks among those living in areas of high deprivation. [ABSTRACT FROM AUTHOR]

Objectives To compare management of patients with acute non-ST segment elevation myocardial infarction (NSTEMI) in three developed countries with national ongoing registries. Background Results from clinical trials suggest significant variation in care across the world. However, international comparisons in "real world" registries are limited. Methods We compared the use of in-hospital procedures and discharge medications for patients admitted with NSTEMI from 2007 to 2010 using the unselective MINAP/NICOR [England and Wales (UK); n=137,009], the unselective SWEDEHEART/RIKS-HIA (Sweden; n=45,069), and the selective ACTION Registry-GWTG/NCDR [United States (US); n=147,438] clinical registries. Results Patients enrolled among the three registries were generally similar except those in the US who were younger but had higher rates of smoking, diabetes, hypertension, prior heart failure, and prior MI than in Sweden or in UK. Angiography and percutaneous coronary intervention (PCI) were performed more often in the US (76% and 44%) and Sweden (65% and 42%) relative to the UK (32% and 22%). Discharge betablockers were also prescribed more often in the US (89%) and Sweden (89%) than in the UK (76%). In contrast, discharge statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and dual antiplatelet agents (among those not receiving PCI) were higher in the UK (92%, 79%, and 71%) than in the US (85%, 65%, 41%) and Sweden (81%, 69%, and 49%). Conclusions The care for patients with NSTEMI differed substantially among the three countries. These differences in care among countries provide an opportunity for future comparative effectiveness research as well as identify opportunities for global quality improvement. [ABSTRACT FROM AUTHOR]

Aim: Takotsubo cardiomyopathy (TCM) is increasingly being recognised in patients admitted with suspected acute coronary syndrome, as access to angiography and echocardiography is much quicker than before. We aimed to analyse the prevalence of typical TCM in patients admitted for primary percutaneous coronary intervention (PPCI) with suspected ST elevation myocardial infarction (STEMI) to a single tertiary centre in United Kingdom. Methods: All patients admitted to our unit with suspected STEMI from September 2009 to November 2011 were included for analysis. Results: Of the 1875 patients admitted, 17 patients (all female) with mean age of 69±11.9yrs were identified to have clinical features of typical TCM, thus giving an overall prevalence of 0.9% in PPCI admissions (3.2% prevalence in women). The admission ECG showed ST elevation in 14 patients (82%) and 3 had LBBB (18%). In the 16 patients who had raised hs Troponin (normal range <14), the mean level was 921±668 (median 778, range 110 to 2550) ng/L. Two patients survived cardiac arrest and one had apical thrombus on presentation. Left ventricular function was severely impaired (EF ≤30%) in 2 patients, whilst it was moderately impaired (EF 31–50%) in others. During a mean follow-up period of 22±7months (range 8–36months), there was no mortality or recurrence. Conclusion: This is the first observational study to report the prevalence of typical TCM in patients admitted for PPCI in “real-world” practice. Though this condition is not benign during the acute episode, there is a good survival outcome if managed appropriately during the acute phase. [ABSTRACT FROM AUTHOR]

Abstract: Aims: The present study aims to investigate patterns of beta-blocker usage in a national primary care cohort. Methods and results: This is a retrospective cohort study utilising the UK General Practice Research Database from 2004 to 2008. Inclusion criteria were (i) a first diagnosis of chronic heart failure (CHF), myocardial infarction (MI) or angina, and (ii) first-ever prescription of beta-blocker on or after 1st April 2004. Outcome measures were discontinuation of beta-blockers over time, initiation dosages, titration patterns, incidence of adverse events (AEs) and associated prescribing actions. A total of 12,493 patients (68.0% male; mean age 58.0±SD 17.6years) were included. Of these, 27% had discontinued beta-blockers within 1year of initiation, increasing to 39% by 2years and 50% by 3years. Persistence appeared to be greater in the MI cohort compared with angina or CHF cohorts. Beta-blocker dose at initiation averaged approximately 33% of guideline recommended target, rising to 40% in those who continued with therapy. Dyspnoea, fatigue and dizziness were the most common incident AEs at 98, 53 and 49 per 1000 patient years, with little difference between indications. Conclusion: A quarter of patients with cardiovascular disease who are commenced on a beta-blocker are no longer taking the drug by one year. This rises to 50% by three years, a finding that is consistent irrespective of whether the prescription is for prognostic (CHF or post MI) or symptomatic (angina) benefit. There is an urgent need to understand and address the prescribing difficulties of beta-blockers in these at-risk patients. [Copyright &y& Elsevier]

Background: There are conflicting data regarding the benefits of omega-3 (n-3) fatty acids, most recently in patients with type 2 diabetes. Objective: Our goal was to evaluate the impact of licensed, highly purified n-3 fatty acids on all-cause mortality after myocardial infarction (MI). Methods: This was a retrospective, matched-cohort study using data from the General Practice Research Database. Patients initiating treatment with 1 g of n-3 fatty acids in the 90 days after first MI were identified and each matched to 4 nonexposed patients. Progression to death was compared using time-dependent Cox models to account for potential differences in exposure to other cardiovascular risk-modifying treatments. Results: A total of 2466 eligible subjects exposed to n-3 fatty acids were matched. The majority of patients had concurrent treatment with lipid-lowering therapies, antihypertensives, and antiplatelets after first MI, with subjects exposed to n-3 fatty acids having a greater likelihood of concurrent exposure. For those initiating n-3 fatty acids within 90 days of first MI, the adjusted hazard ratio (aHR) was 0.782 (95% CI, 0.641-0.995; P = 0.0159); for those initiating treatment within 14 days, the aHR was 0.680 (95% CI, 0.481-0.961; P = 0.0288). In patients with type 2 diabetes at baseline, the aHRs were 0.714 (95% CI, 0.454-1.124) and 0.597 (95% CI, 0.295-1.211) when initiation was within 90 and 14 days, respectively. Use of n-3 fatty acids resulted in a consistent survival benefit under a range of scenarios quantitatively consistent with the overall effect. Conclusion: After MI, early treatment with licensed n-3 fatty acids was associated with improvement in all-cause mortality in patients with and without type 2 diabetes, against a background of contemporary cardiovascular risk-modifying treatments. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The methodology for the critical assessment of medical interventions is well established. Regulatory agencies and institutions adhere, in principle, to the same standards. This consistency, however, is not always the case in practice. Study Design and Setting: Using the evaluation of the CAPRIE (Clopidogrel versus Aspirin in Patients at risk of Ischemic Events) trial by the British National Institute for Health and Clinical Excellence (NICE) and the German Institute for Quality and Efficiency in Health Care (IQWiG), we illustrate that there was no consensus for the interpretation of possible heterogeneity in treatment comparisons across subgroups. Results: The NICE concluded that CAPRIE demonstrated clinical benefit for the overall intention-to-treat (ITT) population with sufficient robustness to possible sources of heterogeneity. The IQWiG interpreted the alleged heterogeneity as implying that the clinical benefit only applied to the subgroup of patients with a statistically significant result irrespective of the results of the ITT analysis. Conclusion: International standards for the performance and interpretation of subgroup analyses as well as for the assessment of heterogeneity between strata are needed. [Copyright &y& Elsevier]

NRXN1 deletions are a confirmed risk factor for schizophrenia and ASD. The full phenotypic spectrum of consequences of these deletions has not been established. We tested 140,187 white British or Irish participants in the UK Biobank (aged 40–70) for the presence of deletions that intersect at least one exon of the NRXN1 gene 48 people (30 women and 18 men) carried such deletions (0.03%). Carriers had subtle cognitive deficits: on seven tests they showed differences of between 0 and 1 SD (Z-scores, corrected for age and gender), with only two of these reaching significance: Digit Symbol and Reaction Time tests. Carriers did not differ on their educational qualifications (e.g., 15 carriers went to college or university), their occupational attainment, income or subjective happiness and satisfaction with their health and financial situation. We tested over 30 health outcomes, such as heart attacks, diabetes, cancer or number of hospital admissions. There was no increase in any adverse health outcomes. There was no increase in major psychiatric disorders, and no carrier had developed schizophrenia or mania. There were slight reductions of some measures of physical fitness: carriers had slight increases in hip and waist circumference, and lower peak expiratory volume. Despite the only subtle differences and the lack of adverse health outcomes, NRXN1 deletion carriers had on average 0.7 fewer children than the rest of the participants (on average women in the Biobank had 1.82 children and men had 1.78 children). Nine of the 18 men and 13 of the 30 women had no children. The differences in both men and women were significant, confirming previous suggestions that carriers have reduced fecundity (Rees et al., 2011; Stefansson et al., 2014). Reduced fecundity appears to be present even among overall healthy middle-aged people who have escaped early neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

We explored the association between diagnosed rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and the risk of developing a first-time acute myocardial infarction (AMI) by conducting a population-based, case-control analysis using data from the United Kingdom-based General Practice Research Database (GPRD). Among 8,688 patients with AMI and 33,329 matched controls, the adjusted odds ratio (ORs) of AMI for subjects with RA was 1.47 (95% confidence interval [CI] 1.23 to 1.76), and in subjects with both RA and diagnosed hyperlipidemia, the OR was 7.12 (95% CI 4.16 to 12.18). The risk associated with SLE was 2.67 (95% CI 1.34 to 5.34). These results underline that RA and SLE increase the risk of AMI. [Copyright &y& Elsevier]