Adherence to the Atrial fibrillation Better Care pathway and the risk of adverse health outcomes in older care home residents with atrial fibrillation: a retrospective data linkage study 2003-18.

BACKGROUND: The Atrial fibrillation Better Care (ABC) pathway is the gold-standard approach to atrial fibrillation (AF) management, but the effect of implementation on health outcomes in care home residents is unknown. OBJECTIVE: To examine associations between ABC pathway adherence and stroke, transient ischaemic attack, cardiovascular hospitalisation, major bleeding, mortality and a composite of all these outcomes in care home residents. METHODS: A retrospective cohort study of older care home residents (≥65 years) in Wales with AF was conducted between 1 January 2003 and 31 December 2018 using the Secure Anonymised Information Linkage Databank. Adherence to the ABC pathway was assessed at care home entry using pre-specified definitions. Cox proportional hazard and competing risk models were used to estimate the risk of health outcomes according to ABC adherence. RESULTS: From 14,493 residents (median [interquartile range] age 87.0 [82.6-91.2] years, 35.2% male) with AF, 5,531 (38.2%) were ABC pathway adherent. Pathway adherence was not significantly associated with risk of the composite outcome (adjusted hazard ratio, 95% confidence interval [CI]: 1.01 [0.97-1.05]). There was a significant independent association observed between ABC pathway adherence and a reduced risk of myocardial infarction (0.70 [0.50-0.98]), but a higher risk of haemorrhagic stroke (1.59 [1.06-2.39]). ABC pathway adherence was not significantly associated with any other individual health outcomes examined. CONCLUSION: An ABC adherent approach in care home residents was not consistently associated with improved health outcomes. Findings should be interpreted with caution owing to difficulties in defining pathway adherence using routinely collected data and an individualised approach is recommended.

Incident atrial fibrillation and adverse clinical outcomes during extended follow-up of participants recruited to the remote heart rhythm sampling using the AliveCor heart monitor to screen for atrial fibrillation: the REHEARSE-AF study.

Aims: Atrial fibrillation (AF) is an important risk factor for stroke, which is commonly asymptomatic, particularly in older patients, and often undetected until cardiovascular events occur. Development of novel technology has helped to improve detection of AF. However, the longer-term benefit of systematic electrocardiogram (ECG) screening on cardiovascular outcomes is unclear. Methods and results: In the original REHEARSE-AF study, patients were randomized to twice-weekly portable electrocardiogram (iECG) assessment or routine care. After discontinuing the trial portable iECG assessment, electronic health record data sources provided longer-term follow-up analysis. Cox regression was used to provide unadjusted and adjusted hazard ratios (HR) [95% confidence intervals (CI)] for clinical diagnosis, events, and anticoagulant prescriptions during the follow-up period. Over the median 4.2-year follow-up, although a greater number of patients were diagnosed with AF in the original iECG group (43 vs. 31), this was not significant (HR 1.37, 95% CI 0.86-2.19). No differences were seen in the number of strokes/systemic embolisms or deaths between the two groups (HR 0.92, 95% CI 0.54-1.54; HR 1.07, 95% CI 0.66-1.73). Findings were similar when restricted to those with CHADS-VASc ≥ 4. Conclusion: A 1-year period of home-based, twice-weekly screening for AF increased diagnoses of AF for the screening period but did not lead to increased diagnoses of AF or a reduction in cardiovascular-related events or all-cause death over a median of 4.2 years, even in those at highest risk of AF. These results suggest that benefits of regular ECG screening over a 1-year period are not maintained after cessation of the screening protocol.

Anticoagulation in older people with atrial fibrillation moving to care homes: a data linkage study.

BACKGROUND: Treatment decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) are complex in older care home residents. AIM: To explore factors associated with OAC prescription. DESIGN AND SETTING: Retrospective cohort study set in care homes in Wales, UK, listed in the Care Inspectorate Wales Registry 2017/18. METHOD: Analysis of anonymised individual-level electronic health and administrative data was carried out on people aged ≥65 years entering a care home between 1 January 2003 and 31 December 2018, provisioned from the Secure Anonymised Information Linkage Databank. RESULTS: Between 2003 and 2018, 14 493 people with AF aged ≥65 years became new residents in care homes in Wales and 7057 (48.7%) were prescribed OACs (32.7% in 2003 compared with 72.7% in 2018) within 6 months before care home entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per 1-year age increase, 95% confidence interval [CI] = 0.95 to 0.96 and aOR 0.91, 95% CI = 0.84 to 0.98, respectively). Conversely, prior venous thromboembolism (aOR 4.06, 95% CI = 3.17 to 5.20), advancing frailty (mild: aOR 4.61, 95% CI = 3.95 to 5.38; moderate: aOR 6.69, 95% CI = 5.74 to 7.80; and severe: aOR 8.42, 95% CI = 7.16 to 9.90), and year of care home entry from 2011 onwards (aOR 1.91, 95% CI = 1.76 to 2.06) were associated with higher odds of an OAC prescription. CONCLUSION: There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population.

Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.

OBJECTIVE: To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents. METHODS: Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality. RESULTS: There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P < 0.001). CONCLUSIONS: Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy.

Identifying unmet antithrombotic therapeutic need, and implications for stroke and systemic embolism in atrial fibrillation patients: a population-scale longitudinal study.

Aims: Guidelines recommend anticoagulation (AC) in atrial fibrillation (AF) to reduce stroke and systemic embolism (SSE) risk; however, implementation has been slow across many populations. This study aimed to quantify the potential impact of changing prevalence of AF, associated risk, and AC prescribing on SSE hospitalizations and death. Methods and results: We evaluated temporal trends of AF, CHA2DS2-VASc, antithrombotic prescriptions, SSE hospitalizations, death, and their associations between 2012 and 2018 in a longitudinal cohort of AF patients in Wales UK. Multi-state Markov models were used to estimate expected SSE rates given the AC coverage, adjusting for CHA2DS2-VASc scores. SSE rates were modelled for various past and future AC scenarios. A total of 107 137 AF patients were evaluated (mean age = 74 years, 45% female). AF prevalence increased from 1.75 to 2.22% (P-value <0.001). SSE hospitalizations decreased by 18% (2.34-1.92%, P-value <0.001). Increased AC coverage from 50 to 70% was associated with a 37% lower SSE rate, after adjustment for individual time-dependent CHA2DS2VASc scores. The observed AC increase accounted for approximately 80 fewer SSE hospitalizations per 100 000/year. If 90% AC coverage had been achieved since 2012, an estimated 279 SSE per 100 000/year may have been prevented. Our model also predicts that improving AC coverage to 90% over the next 9 years could reduce annual SSE rates by 9%. Conclusion: We quantified the relationship between observed AC coverage, estimating the potential impact of variation in the timing of large-scale implementation. These data emphasize the importance of timely implementation and the considerable opportunity to improve clinical outcomes in the Wales-AF population.

Associations between inflammation, coagulation, cardiac strain and injury, and subclinical vascular disease with frailty in older men: a cross-sectional study.

BACKGROUND: Inflammation, coagulation activation, endothelial dysfunction and subclinical vascular disease are cross-sectionally associated with frailty. Cardiac-specific biomarkers are less-well characterised. We assessed associations between these and frailty, in men with, and without, cardiovascular disease (CVD). METHODS: Cross-sectional analysis of 1096 men without, and 303 with, CVD, aged 71-92, from the British Regional Heart Study. Multinominal logistic regression was performed to examine the associations between frailty status (robust/pre-frail/frail) and, separately, C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), D-dimer, von Willebrand factor (vWF), high-sensitivity cardiac troponin-T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) (all natural log-transformed), and, in men without CVD, carotid intima-media thickness (CIMT), carotid-femoral pulse wave velocity (cfPWV), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), adjusted for age, renal function, BMI, social class, smoking, polypharmacy, cognition, multimorbidity and systolic blood pressure. Explanatory variables with p < 0.05 were carried forward into mutually-adjusted analysis. RESULTS: In men without CVD, higher CRP, IL-6, vWF, tPA, hs-cTnT, NT-proBNP, cfPWV, and lower DC were significantly associated with frailty; mutually-adjusted, log IL-6 (OR for frailty = 2.02, 95%CI 1.38-2.95), log hs-cTnT (OR = 1.95, 95%CI 1.24-3.05) and DC (OR = 0.92, 95%CI 0.86-0.99) retained associations. In men with CVD, higher CRP, IL-6, and hs-cTnT, but not vWF, tPA, NT-proBNP or D-dimer, were significantly associated with frailty; mutually-adjusted, log hs-cTnT (OR 3.82, 95%CI 1.84-7.95) retained a significant association. CONCLUSIONS: In older men, biomarkers of myocardial injury are associated with frailty. Inflammation is associated with frailty in men without CVD. Carotid artery stiffness is associated with frailty in men without CVD, independently of these biomarkers.

Achievement of European Society of Cardiology/European Atherosclerosis Society lipid targets in very high-risk patients: Influence of depression and sex.

AIMS: To explore differences in the use of lipid lowering therapy and/or achievement of lipid guideline targets in patients with and without prior depression and influence of sex in very high-risk coronary patients. METHODS & FINDINGS: A retrospective observational cohort study was conducted using individual-level linked electronic health record data in patients who underwent percutaneous coronary intervention (2012-2017) in Wales. The cohort comprised of 13,781 patients (27.4% female), with 26.1% having prior depression. Lipid levels were recorded in 10,050 patients of whom 25% had depression. History of depression was independently associated with not having lipids checked (OR 0.79 95%CI 0.72-0.87 p<0.001). Patients with prior depression were less likely to achieve targets for low density lipoprotein cholesterol (LDL-C <1.8mmol/l), non-high density lipoprotein cholesterol (non-HDL-C <2.6mmol/l) and triglycerides (<2.3mmol/l) than patients without depression (OR 0.86 95%CI 0.78-0.96 p = 0.007, OR 0.80 95%CI 0.69-0.92 p = 0.003 & OR 0.69 95CI% 0.61-0.79 p<0.001 respectively). Females were less likely to achieve targets for LDL-C and non-HDL-C than males (OR 0.55 95%CI 0.50-0.61 p<0.001 & OR 0.63 95%CI 0.55-0.73 p<0.001). There was an additive effect of depression and sex; females with depression were not only least likely to be tested (OR 0.74 95%CI 0.65-0.84 p<0.001) but also (where levels were known) less likely to achieve LDL-C (OR 0.47 95%CI 0.41-0.55 p<0.001) and non-HDL-C targets (OR 0.50 95%CI 0.41-0.60 p<0.001). It was not possible to look at the influence of medication adherence on achievement of lipid targets due to limitations of the use of anonymised routinely-held clinical care data. CONCLUSION: Patients with prior depression were less likely to have their lipids monitored and achieve guideline targets within 1-year. Females with depression are the least likely to be tested and achieve lipid targets, suggesting not only a greater risk of future events, but also an opportunity to improve care.

Ultrasound- Versus Fluoroscopy-Guided Strategy for Transfemoral Transcatheter Aortic Valve Replacement Access: A Systematic Review and Meta-Analysis.

[Figure: see text].

Subclinical cardiovascular disease and risk of incident frailty: The British Regional Heart Study.

BACKGROUND/OBJECTIVES: Subclinical cardiovascular disease (CVD) is cross-sectionally associated with frailty, but the relationship between subclinical CVD and incident frailty has not been reported. We aimed to assess this prospective association. DESIGN: Longitudinal analysis of data from the British Regional Heart Study, a prospective cohort study. PARTICIPANTS: 1057 men, aged 71-92 years, robust or pre-frail at baseline, and without a clinical diagnosis of CVD. MEASUREMENTS: Participants underwent baseline measurement of carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (CIMT), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), and had questionnaire-based frailty assessment after three years. Frailty status was based on the Fried phenotype. Multivariate logistic regressions examined associations between incident frailty and tertile of cfPWV, CIMT, DC, and ABPI group (<0.9, 0.9-1.4, ≥1.4). RESULTS: 865 men were examined and completed the 3 year follow-up questionnaire, of whom 78 became frail. Adjusted for age, prefrailty, body mass index, diabetes, smoking, atrial fibrillation, blood pressure, renal function, and incident CVD, higher CIMT was associated with greater odds of incident frailty (2nd tertile OR 1.62, 95% CI 0.78-3.35, 3rd tertile OR 2.61, 95% CI 1.30-5.23, p = 0.007, trend p = 0.006). cfPWV showed a weaker, non-significant association (2nd tertile OR 1.79, 95% CI 0.85-3.78, 3rd tertile OR 1.73, OR 0.81-3.72, p = 0.16, trend p = 0.20). There was no clear association between incident frailty and DC or ABPI. In subgroup analyses, CIMT was significantly associated with incident frailty in men ≥80 years (3rd tertile OR 6.99, 95%CI 1.42-34.5), but not in men aged 75-80 or < 75 years. CONCLUSION: Subclinical CVD, as measured by CIMT, is associated with greater risk of incident frailty in older men over three year follow-up, independent of the development of clinically-apparent stroke, heart failure, or myocardial infarction, and may be a modifiable risk factor for frailty. This association may be stronger in very old age.

Influence of Maternal Lifestyle and Diet on Perinatal DNA Methylation Signatures Associated With Childhood Arterial Stiffness at 8 to 9 Years.

[Figure: see text].

Glucagon-like peptide-1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomised controlled trials.

AIM: To conduct a meta-analysis and systematic review to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on clinical biomarkers of inflammation and oxidative stress in patients with type 2 diabetes. METHODS: Medline, Embase and the Cochrane Library were searched for randomised controlled trials (RCTs) that examined changes with GLP-1RAs in a priori selected biomarkers of inflammation: C-reactive protein (CRP), adiponectin, tumour necrosis factor-alpha (TNFα), plasminogen activator inhibitor-1, interleukin-6, leptin; and of oxidative stress: malondialdehyde (MDA); 8-iso-prostaglandin F2α; and 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: We included 40 eligible RCTs (n = 6749) with a median follow-up of 6 months, a mean participant age of 53.1 years, 56.3% females, glycated haemoglobin (HbA1c) 55.6 mmol/mol, body mass index 28.8 kg/m2 and diabetes duration 7.46 years. Analysis of GLP-1RAs versus standard diabetes therapies or placebo revealed significant reductions in CRP, TNFα and MDA, and significant increases in adiponectin for (mean difference -0.54 mg/L [-0.75, -0.34]; standard mean difference [SMD] -0.39 [-0.62, -0.15]; SMD -0.84 [-1.61, -0.06] and SMD 0.30 [0.12, 0.49], respectively [95% confidence intervals]). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. Homeostatic model assessment of insulin resistance was also significantly correlated with a reduction in CRP, but HbA1c was not. CONCLUSIONS: There is strong evidence supporting clinically relevant anti-inflammatory and antioxidant effects of GLP-1RAs. This may be used to guide future targeted clinical use of GLP-1RAs and the development of medications seeking to target the cardioprotective properties of GLP-1RAs.

Single-lead ECGs (AliveCor) are a feasible, cost-effective and safer alternative to 12-lead ECGs in community diagnosis and monitoring of atrial fibrillation.

BACKGROUND: Community management of atrial fibrillation (AF) often requires the use of electrocardiographic (ECG) investigation. Patients discharged following treatment of AF with fast ventricular response (fast AF) can require numerous ECGs to monitor rate and/or rhythm control. Single-lead ECGs have been proposed as a more convenient and relatively accurate alternative to 12-lead ECGs for rate/rhythm management and also diagnosis of AF. We aimed to examine the feasibility of using the AliveCor single-lead ECG monitor for diagnosis and monitoring of AF in the community setting. METHODS: During the course of 6 months, this evaluation of a clinical service improvement pathway used the AliveCor in management of patients requiring (1) follow-up ECGs for AF with previously documented rapid ventricular rate or (2) ECG confirmation of rhythm where AF was suspected. Twelve AliveCor devices provided to the acute community medical team were used to produce 30 s ECG rhythm strips (iECG) that were electronically sent to an overreading physician. RESULTS: Seventy-four patients (mean age 82 years) were managed on this pathway. (1) The AliveCor was successfully used to monitor the follow-up of 37 patients with fast AF, acquiring a combined total of 113 iECGs (median 1.5 ±3.75 per patient). None of these patients required a subsequent 12-lead ECG and this approach saved an estimate of up to £134.49 per patient. (2) Of 53 patients with abnormal pulses, the system helped identify 8 cases of new onset AF and 19 cases of previously known AF that had reverted from sinus back into AF. CONCLUSIONS: We have demonstrated that the AliveCor system is a feasible, cost-effective, time-efficient and potentially safer alternative to serial 12-lead ECGs for community monitoring and diagnosis of AF.

The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis.

OBJECTIVES: Cardiovascular (CV) mortality in RA patients is 50% higher than in the general population. There is increasing recognition that systemic inflammation is a major driver of this. IL-6 is implicated in cardiovascular disease (CVD) in the general population but its role in CVD in RA is undefined. Of the two modes of IL-6 signalling, trans-signalling is pro-inflammatory whereas classical signalling is linked with inflammation resolution. This study examines the role of IL-6 trans-signalling in CVD in a mouse model and patients with RA. METHODS: Myography determined the effect of IL-6 trans-signalling blockade, using sgp130Fc, on aortic constriction in murine collagen-induced arthritis. Serum CCL2 and sVCAM-1 as soluble biomarkers of sIL-6R trans-signalling were investigated in a human cross-sectional study. An observational longitudinal study investigated the association between these biomarkers and progression of subclinical atherosclerosis in early RA by measuring carotid intima-media thickness (CIMT). RESULTS: sgp130Fc reduced arthritis severity, serum CCL2 and sVCAM-1 and restored vascular function in collagen-induced arthritis (CIA). In established RA, sVCAM-1 correlated with the 28-joint DAS (DAS28) and CV risk. In early RA, baseline DAS28 was associated with CIMT change at 6 months. CIMT 'rapid progressors' at 12 months had higher baseline sVCAM-1, haemoglobin A1c, cholesterol:high-density lipoprotein cholesterol ratio and LDL cholesterol. CONCLUSIONS: IL-6 trans-signalling plays a pivotal role in vascular dysfunction in CIA. In early RA, sVCAM-1 was associated with progression of subclinical atherosclerosis. Inflammation from RA onset in CVD-susceptible individuals may accelerate atherosclerosis. IL-6 trans-signalling blockade may be beneficial to RA patients and perhaps for atherosclerosis in the general population.

Diagnostic performance of virtual fractional flow reserve derived from routine coronary angiography using segmentation free reduced order (1-dimensional) flow modelling.

INTRODUCTION: Fractional flow reserve (FFR) improves assessment of the physiological significance of coronary lesions compared with conventional angiography. However, it is an invasive investigation. We tested the performance of a virtual FFR (1D-vFFR) using routine angiographic images and a rapidly performed reduced order computational model. METHODS: Quantitative coronary angiography (QCA) was performed in 102 with coronary lesions assessed by invasive FFR. A 1D-vFFR for each lesion was created using reduced order (one-dimensional) computational flow modelling derived from conventional angiographic images and patient specific estimates of coronary flow. The diagnostic accuracy of 1D-vFFR and QCA derived stenosis was compared against the gold standard of invasive FFR using area under the receiver operator characteristic curve (AUC). RESULTS: QCA revealed the mean coronary stenosis diameter was 44% ± 12% and lesion length 13 ± 7 mm. Following angiography calculation of the 1DvFFR took less than one minute. Coronary stenosis (QCA) had a significant but weak correlation with FFR (r = -0.2, p = 0.04) and poor diagnostic performance to identify lesions with FFR <0.80 (AUC 0.39, p = 0.09), (sensitivity - 58% and specificity - 26% at a QCA stenosis of 50%). In contrast, 1D-vFFR had a better correlation with FFR (r = 0.32, p = 0.01) and significantly better diagnostic performance (AUC 0.67, p = 0.007), (sensitivity - 92% and specificity - 29% at a 1D-vFFR of 0.7). CONCLUSIONS: 1D-vFFR improves the determination of functionally significant coronary lesions compared with conventional angiography without requiring a pressure-wire or hyperaemia induction. It is fast enough to influence immediate clinical decision-making but requires further clinical evaluation.

Associations of depression-anxiety and dyslipidaemia with subclinical carotid arterial disease: Findings from the Whitehall II Study.

AIMS: There is mixed evidence for an association between depression and/or anxiety and carotid intima-media thickness, and limited information on the related role of dyslipidaemia. Here we report associations between depression and/or anxiety and intima-media thickness in the Whitehall II cohort, considering the moderating effects of sex and dyslipidaemia. METHODS: A total of 2822 men and 1112 women (61 ± 6 years) were studied during phase 7 (2002-2004) of the Whitehall II study. Intima-media thickness and lipid levels were assessed, and questionnaires (general health questionnaire and the Centre for Epidemiologic Studies depression scale) were completed. Linear regression was used to explore relationships between depression and/or anxiety and intima-media thickness and the moderating effects of sex and dyslipidaemia. RESULTS: A total of 1461 participants were categorised with depression and/or anxiety. The association between depression and/or anxiety and intima-media thickness differed between men and women so analyses were undertaken separately by sex. In men, intima-media thickness was significantly associated with dyslipidaemia (P = 0.002) but not depression and/or anxiety (P = 0.29). In women, both dyslipidaemia and depression and/or anxiety were independently associated with intima-media thickness (P = 0.028 and P = 0.031). The greatest intima-media thickness was in women with both depression and/or anxiety and dyslipidaemia. These results were replicated when the general health questionnaire score was substituted for depression and/or anxiety and non-high-density lipoprotein cholesterol for dyslipidaemia. CONCLUSIONS: Depression and/or anxiety is associated with increased intima-media thickness in women but not in men. Dyslipidaemia is associated with intima-media thickness in both men and women. Women with both depression and/or anxiety and dyslipidaemia are potentially at the greatest risk of cardiovascular disease.

Active Children Through Individual Vouchers Evaluation: A Mixed-Method RCT.

INTRODUCTION: Physical activity declines in adolescence, especially among those in deprived areas. Research suggests this may result from accessibility barriers (e.g., cost and locality). The Active Children Through Individual Vouchers Evaluation RCT aimed to improve the fitness and heart health of teenagers in Wales with the help of teenagers who co-produced the study. STUDY DESIGN: This study was a mixed-method RCT. SETTING/PARTICIPANTS: Before data collection, which took place at baseline, 6 months, and 12 months for both arms, 7 schools were randomized by an external statistician (4 intervention schools, n=524; 3 control schools, n=385). INTERVENTION: The Active Children Through Individual Vouchers Evaluation intervention included provision of activity vouchers (£20 per month), a peer mentoring scheme, and support worker engagement for 12 months between January and December 2017. Data analysis occurred February-April 2018. MAIN OUTCOME MEASURES: Data included measures of cardiovascular fitness, cardiovascular health (blood pressure and pulse wave analysis), motivation, and focus groups. RESULTS: The intervention showed a trend to improve the distance ran (primary outcome) and was significant in improving the likelihood of intervention teenagers being fit (OR=1.21, 95% CI=1.07, 1.38, p=0.002). There was a reduction in teenagers classified as having high blood pressure (secondary outcome) in the intervention group (baseline, 5.3% [28/524]; 12 months, 2.7% [14/524]). Data on where teenagers used vouchers and evidence from focus groups showed that teenagers wanted to access more unstructured, informal, and social activities in their local areas. CONCLUSIONS: Active Children Through Individual Vouchers Evaluation identified methods that may have a positive impact on cardiovascular fitness, cardiovascular health, and perspectives of activity. Consulting with teenagers, empowering them, and providing more local opportunities for them to take part in activities that are fun, unstructured, and social could positively impact teenage physical activity. TRIAL REGISTRATION: ISRCTN, ISRCTN75594310.

Predictors of cardiovascular health in teenagers (aged 13-14 years): a cross-sectional study linked with routine data.

Objective: To examine the predictors of cardiovascular health in teenagers (aged 13-14 years). Methods: Measures of arterial stiffness (augmentation index (AIx)), blood pressure and cardiovascular fitness were taken from 234 teenage children (n=152 boys) and subsequently linked to routine data (birth and general practice records, education data and hospital admission data). Deprivation at school and at individual level was measured at birth, at 1 year old, at 13 years old and at secondary school using the Welsh Index of Multiple Deprivation. Multivariate regression analysis determined associations between routinely collected data and cardiovascular measures. Results: Teenagers had higher AIx (2.41 (95% CI 1.10 to 3.72)), ran fewer metres (-130.08 m (95% CI -234.35 to -25.78)) in the Cooper Run Test if they attended a more deprived school. However, higher individual level deprivation was associated with greater fitness (199.38 m (95% CI 83.90 to 314.84)). Higher systolic blood pressure was observed in first born children (10.23 mm Hg (95% CI 1.58 to 18.88)) and in those who were never breastfed (4.77 mm Hg (95% CI 1.10 to 8.42)). Conclusions: Improving heart health in deprived areas requires multilevel action across childhood namely, active play and programmes that promote physical activity and fitness and, the promotion of breastfeeding. Recognition of the important early indicators and determinants of cardiovascular health supports further development of the evidence base to encourage policy-makers to implement preventative measures in young people.

Early Discontinuation of P2Y12 Antagonists and Adverse Clinical Events Post-Percutaneous Coronary Intervention: A Hospital and Primary Care Linked Cohort.

Background Early discontinuation of P2Y12 antagonists post-percutaneous coronary intervention may increase risk of stent thrombosis or nonstent recurrent myocardial infarction. Our aims were to (1) analyze the early discontinuation rate of P2Y12 antagonists post-percutaneous coronary intervention, (2) explore factors associated with early discontinuation, and (3) analyze the risk of major adverse cardiovascular events (death, acute coronary syndrome, revascularization, or stroke) associated with discontinuation from a prespecified prescribing instruction of 1 year. Method and Results We studied 2090 patients (2011-2015) who were recommended for clopidogrel for 12 months (+aspirin) post-percutaneous coronary intervention within a retrospective observational population cohort. Relationships between clopidogrel discontinuation and major adverse cardiac events were evaluated over 18-month follow-up. Discontinuation of clopidogrel in the first 4 quarters was low at 1.1%, 2.6%, 3.7%, and 6.1%, respectively. Previous revascularization, previous ischemic stroke, and age >80 years were independent predictors of early discontinuation. In a time-dependent multiple regression model, clopidogrel discontinuation and bleeding (hazard ratio=1.82 [1.01-3.30] and hazard ratio=5.30 [3.14-8.94], respectively) were independent predictors of major adverse cardiac events as were age <49 and ≥70 years (versus those aged 50-59 years), hypertension, chronic kidney disease stage 4+, previous revascularization, ischemic stroke, and thromboembolism. Furthermore, in those with both bleeding and clopidogrel discontinuation, hazard ratio for major adverse cardiac events was 9.34 (3.39-25.70). Conclusions Discontinuation of clopidogrel is low in the first year post-percutaneous coronary intervention, where a clear discharge instruction to treat for 1 year is provided. Whereas this is reassuring from the population level, at an individual level discontinuation earlier than the intended duration is associated with an increased rate of adverse events, most notably in those with both bleeding and discontinuation.

Carotid artery wave intensity in mid- to late-life predicts cognitive decline: the Whitehall II study.

AIMS: Excessive arterial pulsatility may contribute to cognitive decline and risk of dementia via damage to the fragile cerebral microcirculation. We hypothesized that the intensity of downstream-travelling pulsatile waves measured by wave intensity analysis in the common carotid artery during mid- to late-life would be associated with subsequent cognitive decline. METHODS AND RESULTS: Duplex Doppler ultrasound was used to calculate peak forward-travelling compression wave intensity (FCWI) within the common carotid artery in 3191 individuals [mean ± standard deviation (SD), age = 61 ± 6 years; 75% male] assessed as part of the Whitehall II study in 2003-05. Serial measures of cognitive function were taken between 2002-04 and 2015-16. The relationship between FCWI and cognitive decline was adjusted for sociodemographic variables, genetic and health-related risk factors, and health behaviours. Mean (SD) 10-year change in standardized global cognitive score was -0.39 (0.18). Higher FCWI at baseline was associated with accelerated cognitive decline during follow-up [difference in 10-year change of global cognitive score per 1 SD higher FCWI = -0.02 (95% confidence interval -0.04 to -0.00); P = 0.03]. This association was largely driven by cognitive changes in individuals with the highest FCWI [Q4 vs. Q1-Q3 = -0.05 (-0.09 to -0.01), P = 0.01], equivalent to an age effect of 1.9 years. Compared to other participants, this group was ∼50% more likely to exhibit cognitive decline (defined as the top 15% most rapid reductions in cognitive function during follow-up) even after adjustments for multiple potential confounding factors [odds ratio 1.49 (1.17-1.88)]. CONCLUSION: Elevated carotid artery wave intensity in mid- to late-life predicts faster cognitive decline in long-term follow-up independent of other cardiovascular risk factors.