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.

Identification of vulnerable carotid plaque with histologically validated CT-derived plaque maps.

OBJECTIVES: Ruptured carotid plaque causes stroke, but differentiating rupture-prone necrotic core from fibrous tissue with CT is limited by overlap of X-ray attenuation. We investigated the ability of CT-derived plaque maps created from ratios of plaque/contrast attenuation to identify histologically proven vulnerable plaques. METHODS: Seventy patients underwent carotid CT angiography and carotid endarterectomy. A derivation cohort of 20 patients had CT images matched with histology and carotid plaque components attenuation defined. In a validation cohort of 50 patients, CT-derived plaque maps were compared in 43 symptomatic vs 40 asymptomatic carotid plaques and accuracy detecting vulnerable plaques calculated. RESULTS: In 250 plaque areas co-registered with histology, the median attenuation (HU) of necrotic core 43(26-63), fibrous plaque 127(110-162) and calcified plaque 964 (816-1207) created significantly different ratios of plaque/contrast attenuation. CT-derived plaque maps revealed symptomatic plaques had larger necrotic core than asymptomatic (13.5%(5.9-33.3) vs 7.4%(2.3-14.3), p = 0.004) with large necrotic core predicting symptoms (area under ROC curve 0.68, p = 0.004). Twenty-four of 47 carotid plaques were histologically classified as most vulnerable (Starry-Type VI). Plaque maps revealed Type VI plaques had a greater necrotic core volume than Type IV/V plaques and a necrotic core/fibrous plaque ratio >0.5 distinguished Type VI plaques with sensitivity 75.0% (55.1-88.0) and specificity of 39.1% (22.2-59.2). CONCLUSIONS: Carotid plaque components can be differentiated by CT using a ratio of plaque/contrast attenuation. CT-derived plaque map volumes of necrotic core help distinguished the most vulnerable plaques. ADVANCES IN KNOWLEDGE: CT-derived plaque maps based on plaque/contrast attenuation may provide new markers of carotid plaque vulnerability.

SAIL study of stroke, systemic embolism and bleeding outcomes with warfarin anticoagulation in non-valvular atrial fibrillation (S4-BOW-AF).

Aims: In patients with non-valvular atrial fibrillation (NVAF) prescribed warfarin, the association between guideline defined international normalised ratio (INR) control and adverse outcomes in unknown. We aimed to (i) determine stroke and systemic embolism (SSE) and bleeding events in NVAF patients prescribed warfarin; and (ii) estimate the increased risk of these adverse events associated with poor INR control in this population. Methods and results: Individual-level population-scale linked patient data were used to investigate the association between INR control and both SSE and bleeding events using (i) the National Institute for Health and Care Excellence (NICE) criteria of poor INR control [time in therapeutic range (TTR) <65%, two INRs <1.5 or two INRs >5 in a 6-month period or any INR >8]. A total of 35 891 patients were included for SSE and 35 035 for bleeding outcome analyses. Mean CHA2DS2-VASc score was 3.5 (SD = 1.7), and the mean follow up was 4.3 years for both analyses. Mean TTR was 71.9%, with 34% of time spent in poor INR control according to NICE criteria.SSE and bleeding event rates (per 100 patient years) were 1.01 (95%CI 0.95-1.08) and 3.4 (95%CI 3.3-3.5), respectively, during adequate INR control, rising to 1.82 (95%CI 1.70-1.94) and 4.8 (95% CI 4.6-5.0) during poor INR control.Poor INR control was independently associated with increased risk of both SSE [HR = 1.69 (95%CI = 1.54-1.86), P < 0.001] and bleeding [HR = 1.40 (95%CI 1.33-1.48), P < 0.001] in Cox-multivariable models. Conclusion: Guideline-defined poor INR control is associated with significantly higher SSE and bleeding event rates, independent of recognised risk factors for stroke or bleeding.

Achievement of the ESC recommendations for secondary prevention of cardiovascular risk factors in high-risk patients with type 2 diabetes: A real-world national cohort analysis.

AIM: To assess compliance with European Society of Cardiology (ESC) secondary prevention recommendations in a nationwide contemporary population with diabetes mellitus (DM) and coronary artery disease. METHOD: We conducted a retrospective observational study using linked health data in patients across Wales with DM undergoing percutaneous coronary intervention (2012-2017). The follow-up was for one year. We analysed the clinical characteristics, medications, target levels for HbA1c, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and blood pressure against the ESC prevention guidelines. RESULTS: Overall, 3478 patients with diabetes had available data at 1-year post-PCI. Only 43% had HbA1c levels <53 mmol/L, but 81% had blood pressure < 140/80 (current ESC targets). Prescribing frequency of the newer hypoglycaemic agents (glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors) was suboptimal, with a higher rate in patients with HbA1c ≥53 mmol/mol. Only 51% & 27% of the patients had LDL-C levels <1.8 &1.4 mmol/L (2016 & 2019 guidelines recommendations respectively), and 55% & 34% had non-HDL-C levels <2.6 & 2.2 mmol/L (2016 & 2019 guidelines respectively). Of the uncontrolled LDL-C patients, 42% (2016 target) and 35% (2019 target) were prescribed high-intensity statins. Females were more likely to have LDL-C targets above the recommended level. CONCLUSION: Achievement of ESC treatment goals in this very-high risk cohort for DM and hyperlipidaemia was far from optimal, with a low prescription rate of the guidelines-recommended therapy. Target goals for hypertension were met more frequently. An up-to-date analysis reflecting the current practice against the most recent guidelines is warranted.

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.

Investigating the feasibility of recruitment to an observational, quality-of-life study of patients diagnosed with atrial fibrillation (AF) who have experienced a bleed while anticoagulated: EQUAL-AF feasibility study protocol.

BACKGROUND: Oral anticoagulation therapies (OATs) are often prescribed in conjunction with medications to restore normal heart rate rhythm which can limit the risk of an atrial fibrillation (AF) related stroke and systemic thromboembolism. However, they are associated with the serious side effect of bleeding. Both clinically relevant nonmajor bleeding (CRNMB) and major bleeding while anticoagulated are believed to have a significant impact on patient quality of life (QoL). There is currently limited research into the effect bleeding has on QoL. The aim of this study is to evaluate the feasibility of identifying and recruiting patients diagnosed with AF, who are taking OATs and have recently experienced a bleed and collecting information on their QoL. METHODS: We will recruit a minimum of 50 patients to this cross-sectional, observational study. We will recruit from general practices, secondary care, and through an online AF forum. We will ask participants to complete three validated patient-reported outcome measures (PROMs), EQ5D, AFEQT, and PACT-Q, approximately 4 weeks following a bleed and again 3 months later. We will randomly select a subset of 10 participants (of those who agree to be interviewed) to undergo a structured interview with a member of the research team to explore the impact of bleeding on their QoL and to gain feedback on the three PROMs used. We will undertake a descriptive analysis of the PROMs and demographic data. We will analyse the qualitative interviews thematically to identify key themes. DISCUSSION: We aim to establish if it is possible to recruit patients and use PROMs to collect information regarding how patient QoL is affected when they experience either a clinically relevant non-major bleed (CRNMB) or major bleed while taking OATs for the management of AF. We will also explore the appropriateness, or otherwise, of the three identified PROMs for assessing quality of life following a bleed. PROMS: Three PROMs were selected following a literature review of similar QoL studies and using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for comparison. A review of the current literature produced no suitable validated PROM to record QoL experiences in patients who have been diagnosed with AF and have experienced a bleed while anticoagulated. As such, the EQ5D, AFEQT, and PACT-Q (part 2) were deemed most appropriate for use in this feasibility study. TRIAL REGISTRATION: The trial has been adopted onto the NIHR Portfolio (ID no. 47771) and registered with www. CLINICALTRIALS: gov (no. NCT04921176) retrospectively registered in June 2021.

Stroke in Older Adults Living in Care Homes: Results From a National Data Linkage Study in Wales.

OBJECTIVES: To determine the proportion of older people moving to care homes with a recent stroke, incidence of stroke after moving to a care home, mortality following stroke, and secondary stroke prevention management in older care home residents. DESIGN: Retrospective cohort study using population-scale individual-level linked data sources between 2003 and 2018 in the Secure Anonymized Information Linkage (SAIL) Databank. SETTING AND PARTICIPANTS: People aged ≥65 years residing in long-term care homes in Wales. METHODS: Competing risk models and logistic regression models were used to examine the association between prior stroke, incident stroke, and mortality following stroke. RESULTS: Of 86,602 individuals, 7.0% (n = 6055) experienced a stroke in the 12 months prior to care home entry. The incidence of stroke within 12 months after entry to a care home was 26.2 per 1000 person-years [95% confidence interval (CI) 25.0, 27.5]. Previous stroke was associated with higher risk of incident stroke after moving to a care home (subdistribution hazard ratio 1.83, 95% CI 1.57, 2.13) and 30-day mortality following stroke (odds ratio 2.18, 95% CI 1.59, 2.98). Severe frailty was not significantly associated with risk of stroke or 30-day mortality following stroke. Secondary stroke prevention included statins (51.0%), antiplatelets (61.2%), anticoagulants (52.4% of those with atrial fibrillation), and antihypertensives (92.1% of those with hypertension). CONCLUSIONS AND IMPLICATIONS: At the time of care home entry, individuals with history of stroke in the previous 12 months are at a higher risk of incident stroke and mortality following an incident stroke. These individuals are frequently not prescribed medications for secondary stroke prevention. Further evidence is needed to determine the optimal care pathways for older people living in long-term care homes with history of stroke.

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.

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Achievement of European guideline-recommended lipid levels post-percutaneous coronary intervention: A population-level observational cohort study.

AIMS: European Society of Cardiology/European Atherosclerosis Society 2019 guidelines recommend more aggressive lipid targets in high- and very high-risk patients and the addition of adjuvant treatments to statins in uncontrolled patients. We aimed to assess (a) achievement of prior and new European Society of Cardiology/European Atherosclerosis Society lipid targets and (b) lipid-lowering therapy prescribing in a nationwide cohort of very high-risk patients. METHODS: We conducted a retrospective observational population study using linked health data in patients undergoing percutaneous coronary intervention (2012-2017). Follow-up was for one-year post-discharge. RESULTS: Altogether, 10,071 patients had a documented LDL-C level, of whom 48% had low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/l (2016 target) and (23%) <1.4 mmol/l (2019 target). Five thousand three hundred and forty patients had non-high-density lipoprotein cholesterol (non-HDL-C) documented with 57% <2.6 mmol/l (2016) and 37% <2.2 mmol/l (2019). In patients with recurrent vascular events, fewer than 6% of the patients achieved the 2019 LDL-C target of <1.0 mmol/l. A total of 10,592 patients had triglyceride (TG) levels documented, of whom 14% were ≥2.3 mmol/l and 41% ≥1.5 mmol/l (2019). High-intensity statins were prescribed in 56.4% of the cohort, only 3% were prescribed ezetimibe, fibrates or prescription-grade N-3 fatty acids. Prescribing of these agents was lower amongst patients above target LDL-C, non-HDL-C and triglyceride levels. Females were more likely to have LDL-C, non-HDL-C and triglyceride levels above target. CONCLUSION: There was a low rate of achievement of the new European Society of Cardiology/European Atherosclerosis Society lipid targets in this large post-percutaneous coronary intervention population and relatively low rates of intensive lipid-lowering therapy prescribing in those with uncontrolled lipids. There is considerable potential to optimise lipid-lowering therapy further through statin intensification and appropriate use of novel lipid-lowering therapy, especially in women.

Epilepsy, antiepileptic drugs, and the risk of major cardiovascular events.

OBJECTIVE: This study was undertaken to determine whether epilepsy and antiepileptic drugs (including enzyme-inducing and non-enzyme-inducing drugs) are associated with major cardiovascular events using population-level, routinely collected data. METHODS: Using anonymized, routinely collected, health care data in Wales, UK, we performed a retrospective matched cohort study (2003-2017) of adults with epilepsy prescribed an antiepileptic drug. Controls were matched with replacement on age, gender, deprivation quintile, and year of entry into the study. Participants were followed to the end of the study for the occurrence of a major cardiovascular event, and survival models were constructed to compare the time to a major cardiovascular event (cardiac arrest, myocardial infarction, stroke, ischemic heart disease, clinically significant arrhythmia, thromboembolism, onset of heart failure, or a cardiovascular death) for individuals in the case group versus the control group. RESULTS: There were 10 241 cases (mean age = 49.6 years, 52.2% male, mean follow-up = 6.1 years) matched to 35 145 controls. A total of 3180 (31.1%) cases received enzyme-inducing antiepileptic drugs, and 7061 (68.9%) received non-enzyme-inducing antiepileptic drugs. Cases had an increased risk of experiencing a major cardiovascular event compared to controls (adjusted hazard ratio = 1.58, 95% confidence interval [CI] = 1.51-1.63, p < .001). There was no notable difference in major cardiovascular events between those treated with enzyme-inducing antiepileptic drugs and those treated with non-enzyme-inducing antiepileptic drugs (adjusted hazard ratio = .95, 95% CI = .86-1.05, p = .300). SIGNIFICANCE: Individuals with epilepsy prescribed antiepileptic drugs are at an increased risk of major cardiovascular events compared with population controls. Being prescribed an enzyme-inducing antiepileptic drug is not associated with a greater risk of a major cardiovascular event compared to treatment with other antiepileptic drugs. Our data emphasize the importance of cardiovascular risk management in the clinical care of people with epilepsy.

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.