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Background: The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer. Methods: Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed. Results: A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19–1.56, p<0.001) and HF (HR = 1.31, 95% CI 1.18–1.46, p<0.001). After propensity score matching, breast cancer patients with younger diagnosis age had significantly higher risks of MI and HF than controls without breast cancer. Conclusions: Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger age to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases. Funding: This study was supported by grants from the National Natural Science Foundation of China (82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2022 China Medical Board-open competition research grant (22-466). [ABSTRACT FROM AUTHOR]

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63–0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles. [ABSTRACT FROM AUTHOR]

Background: According to epidemiological studies, particulate matter 2.5 (PM2.5) is a significant contributor to cardiovascular disease (CVD). However, making causal inferences is difficult due to the methodological constraints of observational studies. In this study, we used two-sample Mendelian randomization (MR) to examine the causal relationship between PM 2.5 and the risk of CVD. Methods: Genome-wide association study (GWAS) statistics for PM2.5 and CVD were collected from the FinnGen and UK Biobanks. Mendelian randomization analyses were applied to explore the causal effects of PM2.5 on CVD by selecting single-nucleotide polymorphisms(SNP) as instrumental variables. Results: The results revealed that a causal effect was observed between PM2.5 and coronary artery disease(IVW: OR 2.06, 95% CI 1.35, 3.14), and hypertension(IVW: OR 1.07, 95% CI 1.03, 1.12). On the contrary, no causal effect was observed between PM2.5 and myocardial infarction(IVW: OR 0.73, 95% CI 0.44, 1.22), heart failure(IVW: OR 1.54, 95% CI 0.96, 2.47), atrial fibrillation(IVW: OR 1.03, 95% CI 0.71, 1.48), and ischemic stroke (IS)(IVW: OR 0.98, 95% CI 0.54, 1.77). Conclusion: We discovered that there is a causal link between PM2.5 and coronary artery disease and hypertension in the European population, using MR methods. Our discovery may have the significance of public hygiene to improve the understanding of air quality and CVD risk. [ABSTRACT FROM AUTHOR]

Aims: Cardiovascular disease is the leading cause of death worldwide. Anxiety disorders are common psychiatric conditions associated with cardiovascular outcomes. This two‐sample Mendelian randomization (MR) study investigated the causal relationship between anxiety disorders and coronary heart disease (CHD), myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). Methods: Single nucleotide polymorphisms (SNPs) associated with anxiety disorders (16 730 cases; 101 021 controls) were obtained from the UK Biobank genome‐wide association study (GWAS). Cardiovascular outcome data were derived from the FinnGen study (CHD: 21 012 cases and 197 780 controls; MI: 12 801 cases and 187 840 controls; HF: 23 397 cases and 194 811 controls; and AF: 22 068 cases and 116 926 controls). Inverse variance weighted (IVW), MR–Egger, weighted median, simple mode, and weighted mode analyses examined causality. Results: IVW analysis demonstrated significant causal relationships between anxiety disorders and increased risk of CHD [odds ratio (OR): 4.496; 95% confidence interval (CI): 1.777–11.378; P = 0.002], MI (OR: 5.042; 95% CI: 1.451–17.518; P = 0.011), and HF (OR: 3.255; 95% CI: 1.461–7.252; P = 0.004). No relationship was observed with AF (OR: 1.775; 95% CI: 0.612–5.146; P = 0.29). Other methods showed non‐significant associations. Two‐way analysis indicated no reverse causality. Conclusions: Anxiety disorders were causally associated with greater risk of CHD, MI, and HF but not AF among individuals of European descent. Further research on mediating mechanisms and in diverse populations is warranted. [ABSTRACT FROM AUTHOR]

Although uric acid-lowering agents such as xanthine oxidase inhibitors have potential cardioprotective effects, studies on their use in preventing cardiovascular diseases are lacking. We investigated the genetically proxied effects of reducing uric acid on ischemic cardiovascular diseases in a lipid-level-stratified population. We performed drug-target Mendelian randomization (MR) analyses using UK Biobank data to select genetic instruments within a uric acid-lowering gene, xanthine dehydrogenase (XDH), and construct genetic scores. For nonlinear MR analyses, individuals were stratified by lipid level. Outcomes included acute myocardial infarction (AMI), ischemic heart disease, cerebral infarction, transient cerebral ischemic attack, overall ischemic disease, and gout. We included 474,983 non-gout individuals with XDH-associated single-nucleotide polymorphisms. The XDH-variant-induced uric acid reduction was associated with reduced risk of gout (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.78–0.93; P < 0.001), cerebral infarction (OR, 0.86; 95% CI, 0.75–0.98; P = 0.023), AMI (OR, 0.79; 95% CI, 0.66–0.94; P = 0.010) in individuals with triglycerides ≥ 188.00 mg/dL, and cerebral infarction in individuals with low-density lipoprotein cholesterol (LDL-C) ≤ 112.30 mg/dL (OR, 0.76; 95% CI, 0.61–0.96; P = 0.020) or LDL-C of 136.90–157.40 mg/dL (OR, 0.67; 95% CI, 0.49–0.92; P = 0.012). XDH-variant-induced uric acid reduction lowers the risk of gout, AMI for individuals with high triglycerides, and cerebral infarction except for individuals with high LDL-C, highlighting the potential heterogeneity in the protective effects of xanthine oxidase inhibitors for treating AMI and cerebral infarction depending on the lipid profiles. [ABSTRACT FROM AUTHOR]

Over the years, numerous observational studies have substantiated that various dietary choices have opposing effects on CVD. However, the causal effect has not yet been established. Thus, we conducted a Mendelian randomisation (MR) analysis to reveal the causal impact of dietary habits on CVD. Genetic variants strongly associated with 20 dietary habits were selected from publicly available genome-wide association studies conducted on the UK Biobank cohort (n 449 210). Summary-level data on CVD were obtained from different consortia (n 159 836–977 323). The inverse-variance weighted method (IVW) was the primary outcome, while MR-Egger, weighted median and MR Pleiotropy RESidual Sum and Outlier were used to assess heterogeneity and pleiotropy. We found compelling evidence of a protective causal effect of genetic predisposition towards cheese consumption on myocardial infarction (IVW OR = 0·67; 95 % CI = 0·544, 0·826; P = 1·784 × 10−4) and heart failure (IVW OR = 0·646; 95 % CI = 0·513, 0·814; P = 2·135 × 10−4). Poultry intake was found to be a detrimental factor for hypertension (IVW OR = 4·306; 95 % CI = 2·158, 8·589; P = 3·416 × 10−5), while dried fruit intake was protective against hypertension (IVW OR = 0·473; 95 % CI = 0·348, 0·642; P = 1·683 × 10−6). Importantly, no evidence of pleiotropy was detected. MR estimates provide robust evidence for a causal relationship between genetic predisposition to 20 dietary habits and CVD risk, suggesting that well-planned diets may help prevent and reduce the risk of CVD. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification. Methods: After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections. Results: Participants aged 59 (51–64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid–base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results. Conclusions: Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated the joint effects of sleep traits on the risk of acute myocardial infarction (AMI). No previous study has used factorial Mendelian randomization (MR) which may reduce confounding, reverse causation, and measurement error. Thus, it is prudent to study joint effects using robust methods to propose sleep-targeted interventions which lower the risk of AMI. Methods: The causal interplay between combinations of two sleep traits (including insomnia symptoms, sleep duration, or chronotype) on the risk of AMI was investigated using factorial MR. Genetic risk scores for each sleep trait were dichotomized at their median in UK Biobank (UKBB) and the second survey of the Trøndelag Health Study (HUNT2). A combination of two sleep traits constituting 4 groups were analyzed to estimate the risk of AMI in each group using a 2×2 factorial MR design. Results: In UKBB, participants with high genetic risk for both insomnia symptoms and short sleep had the highest risk of AMI (hazard ratio (HR) 1.10; 95% confidence interval (CI) 1.03, 1.18), although there was no evidence of interaction (relative excess risk due to interaction (RERI) 0.03; 95% CI −0.07, 0.12). These estimates were less precise in HUNT2 (HR 1.02; 95% CI 0.93, 1.13), possibly due to weak instruments and/or small sample size. Participants with high genetic risk for both a morning chronotype and insomnia symptoms (HR 1.09; 95% CI 1.03, 1.17) and a morning chronotype and short sleep (HR 1.11; 95% CI 1.04, 1.19) had the highest risk of AMI in UKBB, although there was no evidence of interaction (RERI 0.03; 95% CI −0.06, 0.12; and RERI 0.05; 95% CI –0.05, 0.14, respectively). Chronotype was not available in HUNT2. Conclusions: This study reveals no interaction effects between sleep traits on the risk of AMI, but all combinations of sleep traits increased the risk of AMI except those with long sleep. This indicates that the main effects of sleep traits on AMI are likely to be independent of each other. [ABSTRACT FROM AUTHOR]

Introduction: This analysis was conducted to assess the incidence of adverse clinical outcomes, healthcare resource use (HCRU), and the costs associated with systemic corticosteroid (SCS) use in adults with systemic lupus erythematosus (SLE) in the UK. Methods: We identified incident SLE cases using the Clinical Practice Research Datalink GOLD, Hospital Episode Statistics-linked healthcare, and Office for National Statistics mortality databases from January 1, 2005, to June 30, 2019. Adverse clinical outcomes, HCRU, and costs were captured for patients with and without prescribed SCS. Results: Of 715 patients, 301 (42%) had initiated SCS use (mean [standard deviation (SD)] 3.2 [6.0] mg/day) and 414 (58%) had no recorded SCS use post-SLE diagnosis. Cumulative incidence of any adverse clinical outcome over 10-year follow-up was 50% (SCS group) and 22% (non-SCS group), with osteoporosis diagnosis/fracture most frequently reported. SCS exposure in the past 90 days was associated with an adjusted hazard ratio of 2.41 (95% confidence interval 1.77–3.26) for any adverse clinical outcome, with increased hazard for osteoporosis diagnosis/fracture (5.26, 3.61–7.65) and myocardial infarction (4.52, 1.16–17.71). Compared to low-dose SCS (< 7.5 mg/day), patients on high-dose SCS (≥ 7.5 mg/day) had increased hazard for myocardial infarction (14.93, 2.71–82.31), heart failure (9.32, 2.45–35.43), osteoporosis diagnosis/fracture (5.14, 2.82–9.37), and type 2 diabetes (4.02 1.13–14.27). Each additional year of SCS use was associated with increased hazard for any adverse clinical outcome (1.15, 1.05–1.27). HCRU and costs were greater for SCS users than non-SCS users. Conclusions: Among patients with SLE, there is a higher burden of adverse clinical outcomes and greater HCRU in SCS versus non-SCS users. [ABSTRACT FROM AUTHOR]

Aims Treatment with sodium-glucose co-transporter 2 (SGLT2)-inhibitors reduces the risk of cardiovascular disease and mortality, but the mechanism is unclear. We hypothesized that a functional genetic variant in solute carrier family 5 member 2 (SLC5A2), known to be associated with familial renal glucosuria, would mimic pharmacological SGLT2-inhibition, and thus provide an opportunity to examine potential mediators of the effects on lower risk of cardiovascular disease and mortality. Methods and results We examined 112 712 individuals from the Copenhagen City Heart Study and Copenhagen General Population Study (CCHS + CGPS), 488 687 from the UK Biobank, and 342 499 from FinnGen, genotyped for SLC5A2 rs61742739, c.1961A > G; p.(Asn654Ser). The 2.0% heterozygotes and 0.01% homozygotes were pooled as carriers and compared with the 98% non-carriers. First, we examined the risk of cardiovascular disease and mortality; second, whether carrying the variant was associated with potential mediators of the effect; and third, whether identified potential mediators could explain the observed reduced risk of cardiovascular disease and mortality. In the CCHS + CGPS, carriers vs. non-carries had a 31% lower risk of heart failure, 21% lower risk of myocardial infarction, 16% lower risk of ischaemic heart disease, and 22% lower risk of all-cause mortality. Corresponding values in meta-analyses of the three studies combined were lower risk by 10%, 6%, 6%, and 10%, respectively. The SLC5A2 rs61742739 variant was not associated with a risk of ischaemic stroke or cardiovascular mortality. Of the lower risks observed in CCHS + CGPS, lower plasma glucose mediated 2.0%(P = 0.004) on heart failure, 3.1%(P = 0.09) on myocardial infarction, 4.1%(P = 0.02) on ischaemic heart disease, and 6.0%(P = 0.39) on all-cause mortality; corresponding values in the UK Biobank were 2.9%(P = 0.70), 1.5%(P = 0.77), 4.1%(P = 0.23), and 3.1%(P = 0.21), respectively. Conclusion A functional genetic variant in SLC5A2 , mimicking SGLT2-inhibition, was associated with a lower risk of heart failure, myocardial infarction, ischaemic heart disease, and all-cause mortality. These effects were at most minimally mediated through lower plasma glucose. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have shown that a potential relationship between anti-Helicobacter pylori (H. pylori) IgG levels and Myocardial Infarction (MI). Nevertheless, the evidence for the causal inferences remains disputable. To further clarify the relationship between anti-H. pylori IgG levels and MI and explore its pathogenesis, we conducted a Mendelian randomization (MR) analysis. Methods: In this study, we used two-sample Mendelian Randomization (MR) to assess the causality of anti-H. pylori IgG levels on MI and potential pathogenesis, 12 single nucleotide polymorphisms (SNPs) related to anti-H. pylori IgG levels were obtained from the European Bioinformatics Institute (EBI). Summary data from a large-scale GWAS meta-analysis of MI was utilized as the outcome dataset. Summary data of mediators was obtained from the FinnGen database, the UK Biobank, the EBI database, MRC-IEU database, the International Consortium of Blood Pressure, the Consortium of Within family GWAS. Inverse variance weighted (IVW) analysis under the fixed effect model was identified as our main method. To ensure the reliability of the findings, many sensitivity analyses were performed. Results: Our study revealed that increases of anti-H. pylori IgG levels were significantly related to an increased risk of MI (OR, 1.104; 95% CI,1.042-1.169; p = 7.084 × 10-4) and decreases in HDL cholesterol levels (β, -0.016; 95% CI, -0.026 to -0.006; p = 2.02 × 10-3). In addition, there was no heterogeneity or pleiotropy in our findings. Conclusion: This two-sample MR analysis revealed the causality of anti-H. pylori IgG levels on MI, which might be explained by lower HDL cholesterol levels. Further research is needed to clarify the results. [ABSTRACT FROM AUTHOR]

Objectives: There is conflicting evidence around the role of sex hormones with cardiovascular outcomes. The aim of this study was to examine the association of sex hormones with the risk of myocardial infarction (MI) in pre- and post-menopausal women, and men in the UK Biobank. Methods: The UK Biobank is a prospective population-based cohort study, that recruited over 500,000 (aged 40–69 years) women and men between 2006 and 2010. Sex specific cox regression models, estimating hazard ratios (HRs) and women to men ratio of HRs (RHR) with respective 95% confidence intervals (CI), were used to model the association of sex hormones [oestrogen, testosterone, oestrogen: testosterone (O/T) ratio, sex hormone–binding globulin (SHBG) and the free androgen index (FAI)], measured at study baseline, with incident MI for women and men. Results: Data were from 479,797 participants [264,282 (55.1%) women] without a history of MI at study baseline. Over 12.5 years of follow-up, there were 4,908 MI events in women and 10,517 in men. Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, a unit higher log-transformed O/T ratio was associated with a lower risk of MI 0.79 (0.65, 0.95) after adjustment for traditional CVD risk factors. The corresponding women to men RHR (95% CI) was 1.24 (0.99, 1.56). Higher SHBG (per unit) was also associated with a lower risk of MI in men 0.94 (0.89, 0.99), and not in women 1.02 (0.95, 1.09) after multiple adjustment, the corresponding women to men RHR (95% CI) was 1.09 (1.00, 1.18). Higher FAI was associated with a higher risk of MI in men 1.09 (1.02, 1.15), though not in women 0.97 (0.92, 1.02), the corresponding women to men RHR was 0.89 (0.82, 0.97). Finally, there were differential effects in the association of SHBG and FAI between pre- and post-menopausal women. Conclusions: A higher O/T ratio was associated with a lower risk of MI, and a higher FAI with a higher risk of MI after adjustment for CVD risk factors in men, but not in women. Thus, hormone ratios, rather than each alone, may play an important role in modulating the effect of MI. Plain Language Summary: There are conflicting findings surrounding the association of sex hormones and myocardial infarction (MI) (heart disease). In particular, high oestradiol levels in women are often thought to be protective and explain why the rates of heart disease are lower in women than men. For men, those with low levels of testosterone are often thought to be more prone to develop heart disease in their lifetimes. Our study presents a comprehensive analysis of the association of sex hormones (in isolation and also together via their ratios), in women and men using the large-scale UK Biobank. We found that neither oestrogen nor testosterone alone were associated with heart disease in women and men after accounting for cardiovascular risk factors, but the ratio of testosterone and oestrogen was associated with a lower risk of heart disease in men, though not in women. We also saw the association of sex hormone–binding globulin (SHBG), and free androgen index (FAI) (calculated by the ratio of total testosterone level to SHBG) with heart disease was different between women and men, and between pre- and post-menopausal women. This paper highlights the complex interplay between sex hormones with heart disease in the presence of age and cardiovascular risk factors. In particular the balance (ratio) of sex hormones maybe more important, rather than each in isolation, when exploring their association with heart disease. Highlights: Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, higher oestrogen/testosterone ratio was associated with a lower risk of MI after adjustment for traditional CVD risk factors. Higher SHBG was associated with a lower risk of MI in men, but not women overall. Higher FAI was associated with a higher risk of MI in men but not women overall. There were differential effects in SHBG and FAI between pre- and post-menopausal women. [ABSTRACT FROM AUTHOR]

Background Being breastfed is associated with lower cardiovascular risk factors but, to date, no studies have demonstrated a protective effect on cardiovascular disease (CVD). This study aims to address the limitations of previous studies, specifically insufficient statistical power and residual confounding, to determine if such association exists. Methods This is a population-based retrospective cohort study of 320 249 men and women aged 40–69 years. Breastfeeding status was self-reported. CVD and myocardial infarction (MI) events and deaths based via linkage to hospitalization and death records. Results Overall, 28 469 (8.4%) participants experienced a CVD event and 5174 (1.6%) experienced an MI. Following adjustment for sociodemographic, lifestyle and early life confounders, breastfeeding was associated with a reduced risk of CVD events (HR 0.97, 95% CI 0.94–1.00, P  = 0.041), CVD deaths (HR 0.91, 95% CI 0.84–0.98, P  = 0.017), MI events (HR 0.93, 95% CI 0.87–0.99, P  = 0.033) and MI deaths (HR 0.81, 95% CI 0.67–0.98, P  = 0.026). Conclusions Child health benefits of breastfeeding are well established. However, the benefits of breastfeeding may extend into later life reinforcing the need to encourage and support breastfeeding. [ABSTRACT FROM AUTHOR]

Mendelian randomization (MR) analysis was performed to explore the effect of psoriasis on lipid metabolism traits and myocardial infarction (MI) risk and to analyze the proportion of the mediatory effect of lipid metabolism traits. Publicly accessible summary-level data for psoriasis, lipid metabolism traits, and MI were provided by the genome-wide association studies (GWASs) of the FinnGen Biobank, UK Biobank, and CARDIoGRAMplusC4D, respectively. A two-sample MR was carried out to evaluate the association of psoriasis with lipid metabolism traits and MI. Furthermore, the current research focused on determining if the impact of psoriasis on MI is mediated by lipid metabolism traits. The outcomes of the random effect inverse-variance-weighted (IVW) technique indicated a substantial link between genetically predicted psoriasis and a higher risk of low-density lipoprotein (LDL) cholesterol (OR: 1.006, 95% CI: 1.005–1.007, p = 0.024), apolipoprotein B (OR: 1.018, 95% CI: 1.010–1.026, p = 0.015), lipoprotein A (OR: 1.006, 95% CI: 1.002–1.010, p = 0.039), and MI (OR: 1.066, 95% CI: 1.014–1.121, p = 0.012). The percentages of the mediatory effect of LDL cholesterol, apolipoprotein B, and lipoprotein A under psoriasis conditions on MI risk was 7.4%, 10.2%, and 4.1%, respectively. Psoriasis was causally linked to an elevated risk of lipid metabolism levels and MI. This study further demonstrated that LDL cholesterol, apolipoprotein B, and lipoprotein A mediated the effect of psoriasis on MI risk. And timely lipid-lowering treatment should be given to MI patients. [ABSTRACT FROM AUTHOR]

Background: The role of fatty acids in coronary heart disease (CHD) remains uncertain. There is little evidence from large-scale epidemiological studies on the relevance of circulating fatty acids levels to CHD risk. This study aims to examine the independent associations of the major circulating types of fatty acids with CHD risk. Methods: UK Biobank is a prospective study of adults aged 40–69 in 2006–2010; in 2012–2013, a subset of the participants were resurveyed. Analyses were restricted to 89,242 participants with baseline plasma fatty acids (measured using nuclear magnetic resonance spectroscopy) and without prior CHD. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the associations with incidence CHD, defined as the first-ever myocardial infarction, unstable angina pectoris, coronary-related death, or relevant procedure. And the major types of fatty acids were mutually adjusted to examine the independent associations. Hazard ratios were corrected for regression dilution using the correlation of baseline and resurvey fatty acids measures. Results: During a median follow-up of 11.8 years, 3,815 incident cases of CHD occurred. Independently of other fatty acids, CHD risk was positively associated with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA), inversely associated with omega-3 polyunsaturated fatty acids (PUFA), but there was no strong evidence of an association with omega-6 PUFA: HR per standard deviation higher were 1.14 (95% CI, 1.09–1.20), 1.15 (1.10–1.21), 0.91 (0.87–0.94), and 1.04 (0.99–1.09) respectively. Independently of triglycerides and cholesterol, the inverse association with omega-3 PUFA was not materially changed, but the positive associations with SFA and MUFA attenuated to null after adjusting for triglycerides levels. Conclusions: This large-scale study has quantitated the independent associations of circulating fatty acids with CHD risk. Omega-3 PUFA was inversely related to CHD risk, independently of other fatty acids and major lipid fractions. By contrast, independently of other fatty acids, the positive associations of circulating SFA and MUFA with CHD risk were mostly attributed to their relationship with triglycerides. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic placed the UK healthcare system under unprecedented pressure, and recovery will require whole-system investment in innovative, flexible and pragmatic solutions. Positioned at the heart of the healthcare system, ambulance services have been tasked with addressing avoidable hospital conveyance and reducing unnecessary emergency department and hospital attendances through the delivery of care closer to home. Having begun to implement models of care intended to increase 'see and treat' opportunities through greater numbers of senior clinical decision makers, emphasis has now been placed upon the use of remote clinical diagnostic tools and near-patient or point-of-care testing (POCT) to aid clinical decision making. In terms of POCT of blood samples obtained from patients in the pre-hospital setting, there is a paucity of evidence beyond its utility for measuring lactate and troponin in acute presentations such as sepsis, trauma and myocardial infarction, although potential exists for the analysis of a much wider panel of analytes beyond these isolated biomarkers. In addition, there is a relative dearth of evidence in respect of the practicalities of using POCT analysers in the pre-hospital setting. This single-site feasibility study aims to understand whether it is practical to use POCT for the analysis of patients' blood samples in the urgent and emergency care pre-hospital setting, through descriptive data of POCT application and through qualitative focus group interviews of advanced practitioners (specialist paramedics) to inform the feasibility and design of a larger study. The primary outcome measure is focus group data measuring the experiences and perceived self-reported impact by specialist paramedics. Secondary outcome measures are number and type of cartridges used, number of successful and unsuccessful attempts in using the POCT analyser, length of time on scene, specialist paramedic recruitment and retention, number of patients who receive POCT, descriptive data of safe conveyance, patient demographics and presentations where POCT is applied and data quality. The study results will inform the design of a main trial if indicated. [ABSTRACT FROM AUTHOR]

Background: The excess risk of cardiovascular disease associated with a wide array of infectious diseases is unknown. We quantified the short- and long-term risk of major cardiovascular events in people with severe infection and estimated the population-attributable fraction. Methods: We analyzed data from 331 683 UK Biobank participants without cardiovascular disease at baseline (2006–2010) and replicated our main findings in an independent population from 3 prospective cohort studies comprising 271 329 community-dwelling participants from Finland (baseline 1986–2005). Cardiovascular risk factors were measured at baseline. We diagnosed infectious diseases (the exposure) and incident major cardiovascular events after infections, defined as myocardial infarction, cardiac death, or fatal or nonfatal stroke (the outcome) from linkage of participants to hospital and death registers. We computed adjusted hazard ratios (HRs) and 95% CIs for infectious diseases as short- and long-term risk factors for incident major cardiovascular events. We also calculated population-attributable fractions for long-term risk. Results: In the UK Biobank (mean follow-up, 11.6 years), 54 434 participants were hospitalized for an infection, and 11 649 had an incident major cardiovascular event at follow-up. Relative to participants with no record of infectious disease, those who were hospitalized experienced increased risk of major cardiovascular events, largely irrespective of the type of infection. This association was strongest during the first month after infection (HR, 7.87 [95% CI, 6.36–9.73]), but remained elevated during the entire follow-up (HR, 1.47 [95% CI, 1.40–1.54]). The findings were similar in the replication cohort (HR, 7.64 [95% CI, 5.82–10.03] during the first month; HR, 1.41 [95% CI, 1.34–1.48] during mean follow-up of 19.2 years). After controlling for traditional cardiovascular risk factors, the population-attributable fraction for severe infections and major cardiovascular events was 4.4% in the UK Biobank and 6.1% in the replication cohort. Conclusions: Infections severe enough to require hospital treatment were associated with increased risks for major cardiovascular disease events immediately after hospitalization. A small excess risk was also observed in the long-term, but residual confounding cannot be excluded. [ABSTRACT FROM AUTHOR]

There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P < 1e−05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction. A genome-wide association study finds an inverse relationship between progression of coronary artery disease and retinal vasculature's complexity measured as fractal dimension, and validates a predictive model for myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated that the gut microbiota (GM) is associated with coronary artery disease (CAD), but the causality of these associations remains unestablished due to confounding factors and reverse causality. We conducted Mendelian randomization study (MR) to determine the causal effect of the specific bacterial taxa on CAD/myocardial infarction (MI) and identify the mediating factors involved. Methods: Two-sample MR, multivariable MR (MVMR) and mediation analysis were performed. Inverse-variance weighting (IVW) was the main method used to analyze causality, and sensitivity analysis was used to verify the reliability of the study. Causal estimates from CARDIoGRAMplusC4D and FinnGen databases were combined using the meta-analysis method, and repeated validation was conducted based on the UK Biobank (UKB) database. Confounders that may affect the causal estimates were corrected by MVMP and the potential mediation effects were investigated by using mediation analysis. Results: The study suggested that increased abundance of the RuminococcusUCG010 genus leads to a lower risk of CAD (OR, 0.88; 95% CI, 0.78, 1.00; p = 2.88 × 10-2) and MI (OR, 0.88; 95% CI, 0.79, 0.97; p = 1.08 × 10-2), with consistent results in both meta-analysis (CAD: OR, 0.86; 95% CI, 0.78, 0.96; p = 4.71 × 10-3; MI: OR, 0.82; 95% CI, 0.73, 0.92; p = 8.25 × 10-4) and repeated analysis of the UKB dataset (CAD: OR, 0.99; 95% CI, 0.99, 1.00, p = 2.53 × 10-4; MI: OR, 0.99; 95% CI, 0.99, 1.00, p = 1.85 × 10-11). Based on multiple databases, T2DM was proved as a mediating factor in the causal effect of RuminococcusUCG010 and CAD/MI, with an average mediation effect proportion of 20% on CAD and 17% on MI, respectively. Conclusion: This MR study provided suggestive genetic evidence that the higher the RuminococcusUCG010 abundance is, the lower the risk of CAD and MI, with T2DM playing a mediating effect. This genus may become a novel target in strategies for treating and preventing CAD and MI. [ABSTRACT FROM AUTHOR]

Aims: Prognosis for ST‐segment elevation myocardial infarction (STEMI) is worse when heart failure is present on admission. Understanding clinical practice in different health systems can identify areas for quality improvement initiatives to improve outcomes. In the absence of international comparison studies, we aimed to compare treatments and in‐hospital outcomes of patients admitted with ST elevation myocardial infarction (STEMI) by heart failure status in two healthcare‐wide cohorts. Methods and results: We used two nationwide databases to capture admissions with STEMI in the United Kingdom (Myocardial ischemia National Audit Project, MINAP) and Japan (Japanese Registry of All Cardiac and Vascular Diseases‐Diagnostic Procedure Combination, JROAD‐DPC) between 2012 and 2017. Participants were stratified using the HF Killip classification into three groups; Killip 1: no congestive heart failure, Killip 2–3: congestive heart failure, Killip 4: cardiogenic shock. We calculated crude rate and case mix standardized risk ratios (CSRR) for use of treatments and in‐hospital death. Patients were younger in the United Kingdom (65.4 [13.6] vs. 69.1 [13.0] years) and more likely to have co‐morbidities in the United Kingdom except for diabetes and hypertension. Japan had a higher percentage of heart failure and cardiogenic shock patients among STEMI during admission than that in the United Kingdom. Primary percutaneous coronary intervention (pPCI) rates were lower in the United Kingdom compared with Japan, especially for patients presenting with Killip 2–3 class heart failure (pPCI use in patients with Killip 1, 2–3, 4: Japan, 86.2%, 81.7%, 78.7%; United Kingdom, 79.6%, 58.2% and 79.9%). In contrast, beta‐blocker use was consistently lower in Japan than in the United Kingdom (61.4% vs. 90.2%) across Killip classifications and length of hospital stay longer (17.0 [9.7] vs. 5.0 [7.4] days). The crude rate of in‐hospital mortality increased with increasing Killip class group. Both the crude rate and CSRR was higher in the United Kingdom compared with Japan for Killip 2–3 (15.8% vs. 6.4%, CSRR 1.80 95% CI 1.73–1.87, P < 0.001), and similar for Killip 4 (36.9% vs. 36.3%, CSRR 1.11 95% CI 1.08–1.13, P < 0.001). Conclusions: Important differences in the care and outcomes for STEMI with heart failure exist between the United Kingdom and Japan. Specifically, in the United Kingdom, there was a lower rate of pPCI, and in Japan, fewer patients were prescribed beta blockers and hospital length of stay was longer. This international comparison can inform targeted quality improvement programmes to narrow the outcome gap between health systems. [ABSTRACT FROM AUTHOR]

Background: Understanding the effects of risk factor burden and genetic predisposition on the long-term risk of atrial fibrillation (AF) is important to improve public health initiatives. However, the 10-year risk of AF considering risk factor burden and genetic predisposition is unknown. Methods: A total of 348,904 genetically unrelated participants without AF at baseline from the UK were categorized into three groups: index ages 45 years (n = 84,206), 55 years (n=117,520), and 65 years (n=147,178). Optimal, borderline, or elevated risk factor burden was determined by body mass index, blood pressure, diabetes mellitus, alcohol consumption, smoking status, and history of myocardial infarction or heart failure. Genetic predisposition was estimated using the polygenic risk score (PRS), constructed using 165 predefined genetic risk variants. The combined effects of risk factor burden and PRS on the risk of incident AF in 10 years were estimated for each index age. Fine and Gray models were developed to predict the 10-year risk of AF. Results: The overall 10-year risk of AF was 0.67% (95% CI: 0.61–0.73%) for index age 45 years, 2.05% (95% CI: 1.96–2.13%) for index age 55 years, and 6.34% (95% CI: 6.21–6.46%) for index age 65 years, respectively. An optimal risk factor burden was associated with later AF onset regardless of genetic predisposition and sex (P < 0.001). Significant synergistic interactions were observed for risk factor burden with PRS at each index age (P < 0.05). Participants with an elevated risk factor burden and high PRS had the highest 10-year risk of AF in reference to those who had both an optimal risk factor burden and a low PRS. At younger ages, optimal risk burden and high PRS might also lead to later onset of AF, compared to the joint effect of elevated risk burden and low/intermediate PRS. Conclusions: Risk factor burden together with a genetic predisposition is associated with the 10-year risk of AF. Our results may be helpful in selecting high-risk individuals for primary prevention of AF and facilitating subsequent health interventions. [ABSTRACT FROM AUTHOR]

Background. Ischaemia with nonobstructive coronary arteries is most commonly caused by coronary microvascular dysfunction but remains difficult to diagnose without invasive testing. Myocardial blood flow (MBF) can be quantified noninvasively on stress perfusion cardiac magnetic resonance (CMR) or positron emission tomography but neither is routinely used in clinical practice due to practical and technical constraints. Quantification of coronary sinus (CS) flow may represent a simpler method for CMR MBF quantification. 4D flow CMR offers comprehensive intracardiac and transvalvular flow quantification. However, it is feasibility to quantify MBF remains unknown. Methods. Patients with acute myocardial infarction (MI) and healthy volunteers underwent CMR. The CS contours were traced from the 2-chamber view. A reformatted phase contrast plane was generated through the CS, and flow was quantified using 4D flow CMR over the cardiac cycle and normalised for myocardial mass. MBF and resistance (MyoR) was determined in ten healthy volunteers, ten patients with myocardial infarction (MI) without microvascular obstruction (MVO), and ten with known MVO. Results. MBF was quantified in all 30 subjects. MBF was highest in healthy controls (123.8 ± 48.4 mL/min), significantly lower in those with MI (85.7 ± 30.5 mL/min), and even lower in those with MI and MVO (67.9 ± 29.2 mL/min/) (P < 0.01 for both differences). Compared with healthy controls, MyoR was higher in those with MI and even higher in those with MI and MVO (0.79 (±0.35) versus 1.10 (±0.50) versus 1.50 (±0.69), P = 0.02). Conclusions. MBF and MyoR can be quantified from 4D flow CMR. Resting MBF was reduced in patients with MI and MVO. [ABSTRACT FROM AUTHOR]

Background: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation. Methods: Across 25 hospitals in the United Kingdom, 342 patients with COVID-19 and an elevated troponin level (COVID+/troponin+) were enrolled between June 2020 and March 2021 and had a magnetic resonance imaging scan within 28 days of discharge. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin-) and 113 patients without COVID-19 or elevated troponin level matched by age and cardiovascular comorbidities (COVID-/comorbidity+). Regression modeling was performed to identify predictors of major adverse cardiovascular events at 12 months. Results: Of the 519 included patients, 356 (69%) were men, with a median (interquartile range) age of 61.0 years (53.8, 68.8). The frequency of any heart abnormality, defined as left or right ventricular impairment, scar, or pericardial disease, was 2-fold greater in cases (61% [207/342]) compared with controls (36% [COVID+/troponin-] versus 31% [COVID-/comorbidity+]; P <0.001> P <0.001> P <0.01)> P <0.001),> P =0.10). Using the Lake Louise magnetic resonance imaging criteria, the prevalence of probable recent myocarditis was 6.7% (23/342) in cases compared with 1.7% (2/113) in controls without COVID-19 (P =0.045). During follow-up, 4 patients died and 34 experienced a subsequent major adverse cardiovascular event (10.2%), which was similar to controls (6.1%; P =0.70). Myocardial scar, but not previous COVID-19 infection or troponin, was an independent predictor of major adverse cardiovascular events (odds ratio, 2.25 [95% CI, 1.12-4.57]; P =0.02). Conclusions: Compared with contemporary controls, patients with COVID-19 and elevated cardiac troponin level have more ventricular impairment and myocardial scar in early convalescence. However, the proportion with myocarditis was low and scar pathogenesis was diverse, including a newly described pattern of microinfarction. Registration: URL: https://www.isrctn.com ; Unique identifier: 58667920. What Is New? * This study is the first large, multicenter, prospective, case-control study investigating the nature and extent of myocardial injury in patients hospitalized with COVID-19 and elevated cardiac troponin level imaged within 28 days of discharge with core laboratory analyses. * Patients with COVID-19 had a much lower prevalence of probable recent myocarditis than previously reported. * In patients with COVID-19, we identified a new pattern of microinfarction on cardiac magnetic resonance imaging, highlighting the prothrombotic nature of this disease. * Among hospitalized patients with COVID-19 and elevated cardiac troponin level, the presence of scar was independently associated with cardiovascular outcomes at 12 months. What Are the Clinical Implications? * We identified a lower prevalence of probable recent myocarditis than previously described and higher proportions of myocardial infarction and microinfarction in COVID-19. Myocardial scar was independently associated with cardiovascular outcomes. This is important to facilitate appropriate management decisions. [ABSTRACT FROM AUTHOR]

Aims Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken. Methods and resuts Patients treated with surgical or percutaneous repair of PIVSD (2010–2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6–14) vs. surgical 9 (4–22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64–77) vs. 67 (61–73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37–2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01–2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01–1.47), P = 0.043] were independently associated with long-term mortality. Conclusion Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery. [ABSTRACT FROM AUTHOR]

BACKGROUND. Spontaneous coronary artery dissection (SCAD) is a cause of myocardial infarction, especially in younger women without cardiovascular risk factors. Patient management and diagnostics are still largely based on retrospective and observational studies. Most patients with SCAD report chest pain and have elevated biomarkers with ECG findings. SCAD can lead to cardiogenic shock, ventricular arrhythmias and cardiac arrest, and is commonly associated with fibromuscular dysplasia (FMD). Genetic associations are still in their infancy with this disease process. METHODS. An Invitae 29 gene aortopathy panel was performed on a mother with a thoracic aortic aneurysm and her daughter who presented with SCAD and was noted to have FMD. RESULTS. The patient and her mother were both noted to have a heterozygous mutation of the Biglycan (BGN) gene (Variant c.1030T > G (p.Tyr344His)) of undetermined significance. An extensive literature review was performed, including a review of the UK Biobank. This is the first case to our knowledge showing a possible link between the BGN mutation and SCAD/FMD. CONCLUSIONS. The BGN mutation has been recognized to be correlated with aortic aneurysm and aortic dissection. It has not yet been explored to be associated with SCAD/FMD. This paper highlights the potential link between the BGN gene and SCAD/FMD. Further research looking at this association is warranted. [ABSTRACT FROM AUTHOR]

Background Sex hormone-binding globulin (SHBG), testosterone and oestradiol have been associated with many diseases in observational studies; however, the causality of associations remains unestablished. Methods A phenome-wide Mendelian randomization (MR) association study was performed to explore disease outcomes associated with genetically proxied circulating SHBG, testosterone and oestradiol levels by using updated genetic instruments in 339 197 unrelated White British individuals (54% female) in the UK Biobank. Two-sample MR analyses with data from large genetic studies were conducted to replicate identified associations in phenome-wide MR analyses. Multivariable MR analyses were performed to investigate mediation effects of hormone-related biomarkers in observed associations with diseases. Results Phenome-wide MR analyses examined associations of genetically predicted SHBG, testosterone and oestradiol levels with 1211 disease outcomes, and identified 28 and 13 distinct phenotypes associated with genetically predicted SHBG and testosterone, respectively; 22 out of 28 associations for SHBG and 10 out of 13 associations for testosterone were replicated in two-sample MR analyses. Higher genetically predicted SHBG levels were associated with a reduced risk of hypertension, type 2 diabetes, diabetic complications, coronary atherosclerotic outcomes, gout and benign and malignant neoplasm of uterus, but an increased risk of varicose veins and fracture (mainly in females). Higher genetically predicted testosterone levels were associated with a lower risk of type 2 diabetes, coronary atherosclerotic outcomes, gout and coeliac disease mainly in males, but an increased risk of cholelithiasis in females. Conclusions These findings suggest that sex hormones may causally affect risk of several health outcomes. [ABSTRACT FROM AUTHOR]

Spontaneous coronary artery dissection (SCAD) is an infrequent cause of nonobstructive ischemic heart disease in previously healthy young women and therefore is not usually considered in differential diagnoses. The overall incidence of SCAD in angiographic series is between 0.28 and 1.1%, with a clear predominance in young, healthy women (70%) of whom approximately 30% are in the postpartum period. In the United Kingdom, between 2008 and 2012, SCAD was the cause of 27% of acute myocardial infarctions during pregnancy, with a prevalence of 1.81 per 100,000 pregnancies. Regarding the mechanism of arterial obstruction, this may be due to the appearance of an intramural hematoma or to a tear in the intima of the arteries, both spontaneously. Although multiple diagnostic methods are available, it is suggested to include an appropriate anamnesis, an electrocardiogram in the first 10 min after admission to the service or the onset of symptoms, and subsequently, a CT angiography of the coronary arteries or urgent coronary angiography if the hemodynamic status of the patient allows it. Treatment should be individualized for each case; however, the appropriate approach is generally based on two fundamental pillars: conservative medical treatment with antiplatelet agents, beta-blockers, and nitrates, and invasive treatment with percutaneous coronary intervention for stent implantation or balloon angioplasty, if necessary. [ABSTRACT FROM AUTHOR]

We wanted to assess if "Explainable AI" in the form of extreme gradient boosting (XGBoost) could outperform traditional logistic regression in predicting myocardial infarction (MI) in a large cohort. Two machine learning methods, XGBoost and logistic regression, were compared in predicting risk of MI. The UK Biobank is a population-based prospective cohort including 502 506 volunteers with active consent, aged 40 to 69 years at recruitment from 2006 to 2010. These subjects were followed until end of 2019 and the primary outcome was myocardial infarction. Both models were trained using 90% of the cohort. The remaining 10% was used as a test set. Both models were equally precise, but the regression model classified more of the healthy class correctly. XGBoost was more accurate in identifying individuals who later suffered a myocardial infarction. Receiver operator characteristic (ROC) scores are class size invariant. In this metric XGBoost outperformed the logistic regression model, with ROC scores of 0.86 (accuracy 0.75 (CI ±0.00379) and 0.77 (accuracy 0.77 (CI ± 0.00369) respectively. Secondly, we demonstrate how SHAPley values can be used to visualize and interpret the predictions made by XGBoost models, both for the cohort test set and for individuals. The XGBoost machine learning model shows very promising results in evaluating risk of MI in a large and diverse population. This model can be used, and visualized, both for individual assessments and in larger cohorts. The predictions made by the XGBoost models, points toward a future where "Explainable AI" may help to bridge the gap between medicine and data science. [ABSTRACT FROM AUTHOR]

Severe mental illnesses (SMI), including major depressive (MDD), bipolar (BD), and schizophrenia spectrum (SSD) disorders have multifactorial risk factors and capturing their complex etiopathophysiology in an individual remains challenging. Regional vulnerability index (RVI) was used to measure individual's brain‐wide similarity to the expected SMI patterns derived from meta‐analytical studies. It is analogous to polygenic risk scores (PRS) that measure individual's similarity to genome‐wide patterns in SMI. We hypothesized that RVI is an intermediary phenotype between genome and symptoms and is sensitive to both genetic and environmental risks for SMI. UK Biobank sample of N = 17,053/19,265 M/F (age = 64.8 ± 7.4 years) and an independent sample of SSD patients and controls (N = 115/111 M/F, age = 35.2 ± 13.4) were used to test this hypothesis. UKBB participants with MDD had significantly higher RVI‐MDD (Cohen's d = 0.20, p = 1 × 10−23) and PRS‐MDD (d = 0.17, p = 1 × 10−15) than nonpsychiatric controls. UKBB participants with BD and SSD showed significant elevation in the respective RVIs (d = 0.65 and 0.60; p = 3 × 10−5 and.009, respectively) and PRS (d = 0.57 and 1.34; p =.002 and.002, respectively). Elevated RVI‐SSD were replicated in an independent sample (d = 0.53, p = 5 × 10−5). RVI‐MDD and RVI‐SSD but not RVI‐BD were associated with childhood adversity (p <.01). In nonpsychiatric controls, elevation in RVI and PRS were associated with lower cognitive performance (p < 10−5) in six out of seven domains and showed specificity with disorder‐associated deficits. In summary, the RVI is a novel brain index for SMI and shows similar or better specificity for SMI than PRS, and together they may complement each other in the efforts to characterize the genomic to brain level risks for SMI. [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]

Aims: Previous studies investigated the associations between sleep traits and cardiac diseases, but the evidence for the causal inferences was unclear. This study aimed to explore the causal relationship between sleep and cardiac diseases by virtue of Mendelian randomization (MR). Methods and results: Summary‐level data for exposure variables (sleep duration, chronotype, and insomnia) and outcome variables (ischaemic heart disease, atrial fibrillation, myocardial infarction, and heart failure) were derived from UK Biobank. Data from the FinnGen consortium was used as a robustness check. In MR analysis, the inverse variance weighted (IVW) method was applied to infer causality between exposure and outcome. MR‐Egger regression was used to identify pleiotropy, and MR‐PRESSO outlier test was used to remove the pleiotropy of the genetic instruments. Based on UK Biobank, MR analysis suggested that sleep duration was weakly associated with atrial fibrillation (OR = 0.9999, 95% CI: 0.9998–0.9999) and ischaemic heart disease (OR = 0.9997, 95% CI: 0.9995–0.9998). Insomnia was associated with ischaemic heart disease (OR = 1.0117, 95% CI: 1.0051–1.0183) and myocardial infarction (OR = 1.0049, 95% CI: 1.0019–1.0079). No associations were found between chronotype and cardiac diseases (P > 0.05). We did not find pleiotropy except for insomnia with ischaemic heart disease and myocardial infarction using MR‐Egger regression, and MR‐PRESSO analysis consistent with IVW. Finally, we obtained the same direction as with UK Biobank using the FinnGen data. Conclusions: Sleep duration and insomnia might be the potential causal risk factors of cardiac diseases. As the OR was small, these associations are probably not clinically relevant. Further validation studies are needed. [ABSTRACT FROM AUTHOR]

Background: Measurement of fractional flow reserve (FFR) has an established role in guiding percutaneous coronary intervention. We tested the hypothesis that, at the stage of diagnostic invasive coronary angiography, systematic FFR-guided assessment of coronary artery disease would be superior, in terms of resource use and quality of life, to assessment by angiography alone.Methods: We performed an open-label, randomized, controlled trial in 17 UK centers, recruiting 1100 patients undergoing invasive coronary angiography for the investigation of stable angina or non-ST-segment-elevation myocardial infarction. Patients were randomized to either angiography alone (angiography) or angiography with systematic pressure wire assessment of all epicardial vessels >2.25 mm in diameter (angiography+FFR). The coprimary outcomes assessed at 1 year were National Health Service hospital costs and quality of life. Prespecified secondary outcomes included clinical events.Results: In the angiography+FFR arm, the median number of vessels examined was 4 (interquartile range, 3-5). The median hospital costs were similar: angiography, £4136 (interquartile range, £2613-£7015); and angiography+FFR, £4510 (£2721-£7415; P=0.137). There was no difference in median quality of life using the visual analog scale of the EuroQol EQ-5D-5L: angiography, 75 (interquartile range, 60-87); and angiography+FFR, 75 (interquartile range, 60-90; P=0.88). The number of clinical events was as follows: deaths, 5 versus 8; strokes, 3 versus 4; myocardial infarctions, 23 versus 22; and unplanned revascularizations, 26 versus 33, with a composite hierarchical event rate of 8.7% (48 of 552) for angiography versus 9.5% (52 of 548) for angiography+FFR (P=0.64).Conclusions: A strategy of systematic FFR assessment compared with angiography alone did not result in a significant reduction in cost or improvement in quality of life.Registration: URL: https://www.Clinicaltrials: gov; Unique identifier: NCT01070771. [ABSTRACT FROM AUTHOR]

As people age they are at increased risk of cardiovascular disease, the leading cause of mortality and morbidity worldwide. Understanding cardiovascular ageing is essential to preserving healthy ageing and preventing serious health outcomes. This collection of papers published in Age and Ageing since 2011 cover key themes in cardiovascular ageing, with a separate collection on stroke and atrial fibrillation planned. Treating high blood pressure remains important as people age and reduces strokes and heart attacks. That said, a more personalised approach to blood pressure may be even more important as people age to lower blood pressure to tight targets where appropriate but avoid overtreatment in vulnerable groups. As people age, more people experience blood pressure drops on standing (orthostatic hypotension), particularly as they become frail. This can predispose them to falls. The papers in this collection provide an insight into blood pressure and orthostatic hypotension. They highlight areas for further research to understand blood pressure changes and management in the ageing population. Inpatient clinical care of older people with heart attacks differs from younger people in UK national audit data. People aged over 80 had improved outcomes in survival after heart attack over time, but had lower rates of specialist input from cardiology compared with younger people. This may partly reflect different clinical presentations, with heart attacks occurring in the context of other health conditions, frailty and multimorbidity. The care and outcomes of acute and chronic cardiovascular disease are impacted by the frailty and health status of an individual at baseline. The research included in this collection reinforces the wide variations in the ageing population and the necessity to focus on the individual needs and priorities, and provide a person-centred multidisciplinary approach to care. [ABSTRACT FROM AUTHOR]

Background: The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer., Methods: Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed., Results: A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19-1.56, p<0.001) and HF (HR = 1.31, 95% CI 1.18-1.46, p<0.001). After propensity score matching, breast cancer patients with younger diagnosis age had significantly higher risks of MI and HF than controls without breast cancer., Conclusions: Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger age to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases., Funding: This study was supported by grants from the National Natural Science Foundation of China (82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2022 China Medical Board-open competition research grant (22-466)., Competing Interests: JL, YP, WZ, DG, YW, WX, FZ No competing interests declared, (© 2024, Liang et al.)

Background Associations between human herpesviruses (HHVs) and cardiovascular disease/mortality have been reported, but evidence is inconsistent. We investigated associations between 3 common herpesviruses and (1) incident stroke or myocardial infarction (MI) and (2) all-cause mortality. Methods We included participants from the UK Biobank Infectious Disease pilot study with valid serum antibody (IgG) measurements taken at cohort entry (2006–2010) for herpes simplex virus type 1 (HSV1), varicella zoster virus (VZV), and cytomegalovirus (CMV). Linked hospital and mortality records up to December 30 2019 provided information on rates of (1) incident first stroke or MI and (2) all-cause mortality. Hazard ratios (HRs) from Cox proportional hazards regression models were used to assess relationships between (1) HHV seropositivity, (2) HHV titer and incident stroke/MI, and death outcomes. Fully adjusted models accounted for sociodemographic information (age, sex, ethnicity, education, deprivation quintile, birthplace, population density), baseline comorbidities (including diabetes and hypertension), smoking status, body mass index, and serum cholesterol. Results Of 9429 study participants (56% female, 95% White, median age 58 years), 41% were seropositive for all 3 HHVs. Human herpesvirus seropositivity was not associated with stroke/MI (fully adjusted HRs and 95% confidence intervals [CIs]: HSV1 = 0.93 [CI, 0.72–1.22], VZV = 0.78 [CI, 0.51–1.20], CMV = 0.91 [CI, 0.71–1.16]) or all-cause mortality (HSV1 = 1.21 [CI, 1.00–1.47], VZV = 0.79 [CI, 0.58–1.07], CMV = 0.90 [CI, 0.76–1.06]). Human herpesvirus titers were not associated with outcomes. Conclusions In this mostly White UK Biobank subset, neither HHV seropositivity nor titers were associated with stroke/MI or all-cause mortality. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to replicate existing international (US and UK) mortality indices using Irish data. We developed and validated a four-year mortality index for adults aged 50 + in Ireland and compared performance with these international indices. We then extended this model by including additional predictors (self-report and healthcare utilization) and compared its performance to our replication model.Methods: Eight thousand one hundred seventy-four participants in The Irish Longitudinal Study on Ageing were split for development (n = 4,121) and validation (n = 4,053). Six baseline predictor categories were examined (67 variables total): demographics; cardiovascular-related illness; non-cardiovascular illness; health and lifestyle variables; functional variables; self-report (wellbeing and social connectedness) and healthcare utilization. We identified variables independently associated with four-year mortality in the development cohort and attached these variables a weight according to strength of association. We summed the weights to calculate a single index score for each participant and evaluated predicted accuracy in the validation cohort.Results: Our final 14-predictor (extended) model assigned risk points for: male (1pt); age (65-69: 2pts; 70-74: 4 pts; 75-79: 4pts; 80-84: 6pts; 85 + : 7pts); heart attack (1pt); cancer (3pts); smoked past age 30 (2pts); difficulty walking 100 m (2pts); difficulty using the toilet (3pts); difficulty lifting 10lbs (1pts); poor self-reported health (1pt); and hospital admission in previous year (1pt). Index discrimination was strong (ROC area = 0.78).Discussion: Our index is predictive of four-year mortality in community-dwelling older Irish adults. Comparisons with the international indices show that our 12-predictor (replication) model performed well and suggests that generalisability is high. Our 14-predictor (extended) model showed modest improvements compared to the 12-predictor model. [ABSTRACT FROM AUTHOR]

Personality is a strong determinant for several health-related behaviours and has been linked to the development of cardiovascular diseases. However, the reports of personality's mediating role have been inconsistent with no data available from large population-based cohorts. The study aimed to create proxies for the Big Five personality traits, extraversion, agreeableness, conscientiousness, openness and neuroticism, to examine the longitudinal relationship between personality and myocardial infarction in the UK Biobank. The study sample comprised of 484,205 participants (55% female, 45% male, mean age 56.4 ± 8.1 years) from UK Biobank cohort with a mean follow-up of 7 years. The personality proxies sociability, warmth, diligence, curiosity and nervousness were created using self-reported data on psychological factors, mental health and social support, to match the facets of the Big Five traits. As neuroticism is the only Big Five personality trait available in the UK Biobank, it was included to validate the personality proxies. Myocardial infarction outcome information was collected from hospital records, death registries or was self-reported. Logistic regression and Cox proportional hazard regression were used to estimate odds ratio (OR) and hazard ratios (HR), respectively with 95% confidence intervals (CI) adjusted for demographics (age, sex, socioeconomic status, ethnicity), health-related factors (BMI, diabetes, systolic and diastolic blood pressure) and lifestyle factors (alcohol intake, smoking, and moderate-to-vigorous physical activity). Diligence was found to be significantly associated with lower prevalent myocardial infarction [OR: 0.87; (CI 0.84–0.89)] and lower incident myocardial infarction [HR: 0.88; (CI 0.85–0.92)]. Sociability was also protective against prevalent [OR: 0.89; (CI 0.87–0.92)] and incident [HR: 0.90; (CI 0.87–0.93)] myocardial infarction. Conversely, nervousness inferred a higher risk for both prevalent [OR: 1.10; (CI 1.08–1.12)] and incident [HR: 1.07; (CI 1.04–1.09)] myocardial infarction during follow-up. Sex-stratified analyses revealed that nervousness significantly increases the risk for incident myocardial infarction among women [HR: 1.13; (CI 1.08–1.19)] compared to men [HR: 1.05; (CI 1.02–1.08)]. By using our created proxies, we were able to investigate the impact of personality on the development of myocardial infarction. Persons with higher levels of diligence and sociability mimicking predominantly conscientiousness and extraversion personalities respectively are less likely to experience myocardial infarction, while personalities predominantly characterised by nervousness pose higher risk for developing myocardial infarction. These initial findings invite further validation of the use of the personality proxies in UK Biobank cohort. [ABSTRACT FROM AUTHOR]

Introduction: There is increasing evidence supporting the use of intracoronary imaging to optimize the outcomes of percutaneous coronary intervention (PCI). However, there are no studies examining the impact of imaging on PCI outcomes in cases utilising rotational atherectomy (RA-PCI). Our study examines the determinants and outcomes of using intracoronary imaging in RA-PCI cases including 12-month mortality.Methods: Using the British Cardiac Intervention Society database, data were analysed on all RA-PCI procedures in the UK between 2007 and 2014. Descriptive statistics and multivariate logistic regressions were used to examine baseline, procedural, and outcome associations with intravascular imaging.Results: Intracoronary imaging was used in 1,279 out of 8,417 RA-PCI cases (15.2%). Baseline covariates associated with significantly more imaging use were number of stents used, smoking history, previous CABG, pressure wire use, proximal LAD disease, laser use, glycoprotein inhibitor use, cutting balloons, number of restenosis attempted, off-site surgery, and unprotected left main stem (uLMS) PCI. Adjusted rates of in-hospital major adverse cardiac/cerebrovascular events (IH-MACCE), its individual components (death, peri-procedural MI, stroke, and major bleed), or 12-month mortality were not significantly altered by the use of imaging in RA-PCI. However, subgroup analysis demonstrated a signal towards reduction in 12-month mortality in uLMS RA-PCI cases utilising intracoronary imaging (OR 0.67, 95% CI 0.44-1.03).Conclusions: Intracoronary imaging use during RA-PCI is associated with higher risk of baseline and procedural characteristics. There were no differences observed in IH-MACCE or 12-month mortality with intracoronary imaging in RA-PCI. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. Methods and findings: We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor. Conclusions: These multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation. Trial registration: ClinicalTrials.gov - NCT03507309 Amit Kaura and colleagues investigate whether mildly elevated high sensitivity C-reactive protein is associated with mortality risk in patients with suspected acute coronary syndromes. Author summary: Why was this study done?: C-reactive protein (CRP) is a protein produced by the liver and released into the bloodstream in response to inflammation. A blood test called a high-sensitivity C-reactive protein (hsCRP) accurately measures low levels of CRP. In patients presenting with a suspected heart attack, low levels of hsCRP on admission may prove useful in predicting death beyond using troponin, a marker of heart muscle damage. What did the researchers do and find?: In this study of 102,337 patients with suspected heart attack, a higher hsCRP level was associated with a higher risk of death. This relationship was independent of the troponin level in all patients with suspected heart attack and was further verified in those who were confirmed to have a heart attack. What do these findings mean?: These findings suggest that hsCRP is a clinically meaningful marker of risk of death in addition to troponin in patients with suspected heart attack. hsCRP has potential utility in selecting patients with heart attack for new treatments that target reducing inflammation. [ABSTRACT FROM AUTHOR]

The treatment of acute coronary occlusion with Primary PCI has been a major factor in improving outcomes of patients suffering STEMI in the last 15 years, and is the standard treatment for patients suffering STEMI in the UK. Treatment is beneficial for patients presenting within 12 hours of the onset of symptoms, with the goal being opening of the occluded artery within 150 min of the call for help. Opening of the occluded artery is typically completed with a drug-eluting stent followed by administration of antiplatelet medications for 12 months. Procedures are performed using the radial artery which is associated with improved outcomes compared to vascular access via the femoral artery. Evidence is growing to support full revascularisation including the treatment of severe narrowing in other blood vessels as well as the culprit vessel. [ABSTRACT FROM AUTHOR]

Gender captures social components beyond biological sex and can add valuable insight to health studies in populations. However, assessment of gender typically relies on questionnaires which may not be available. The aim of this study is to construct a gender metric using available variables in the UK Biobank and to apply it to the study of angina diagnosis. Proxy variables for femininity characteristics were identified in the UK Biobank and regressed on sex to construct a composite femininity score (FS) validated using tenfold cross-validation. The FS was assessed as a predictor of angina diagnosis before incident myocardial infarction (MI) events. The FS was derived for 315,937 UK Biobank participants. In 3059 individuals with no history of MI at study entry who had an incident MI event, the FS was a significant predictor of angina diagnosis prior to MI (OR 1.24, 95% CI 1.10–1.39, P < 0.001) with a significant sex-by-FS interaction effect (P = 0.003). The FS was positively associated with angina diagnosis prior to MI in men (OR 1.37, 95% CI 1.19–1.57, P < 0.001), but not in women. We have provided a new tool to conduct gender-sensitive analyses in observational studies, and applied it to study of angina diagnosis prior to MI. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies suggested that a reduction in estimated glomerular filtration rate (eGFR) or a supranormal eGFR value was associated with adverse cardiovascular risks. However, a previous Mendelian randomization (MR) study under the linearity assumption reported null causal effects from eGFR on myocardial infarction (MI) risks. Further investigation of the nonlinear causal effect of kidney function assessed by eGFR on the risk of MI by nonlinear MR analysis is warranted.Methods: In this MR study, genetic instruments for log-eGFR based on serum creatinine were developed from European samples included in the CKDGen genome-wide association study (GWAS) meta-analysis (N=567,460). Alternate instruments for log-eGFR based on cystatin C were developed from a GWAS of European individuals that included the CKDGen and UK Biobank data (N=460,826). Nonlinear MR analysis for the risk of MI was performed using the fractional polynomial method and the piecewise linear method on data from individuals of white British ancestry in the UK Biobank (N=321,024, with 12,205 MI cases).Results: Nonlinear MR analysis demonstrated a U-shaped (quadratic P value < 0.001) association between MI risk and genetically predicted eGFR (creatinine) values, as MI risk increased as eGFR declined in the low eGFR range and the risk increased as eGFR increased in the high eGFR range. The results were similar even after adjustment for clinical covariates, such as blood pressure, diabetes mellitus, dyslipidemia, or urine microalbumin levels, or when genetically predicted eGFR (cystatin C) was included as the exposure.Conclusion: Genetically predicted eGFR is significantly associated with the risk of MI with a parabolic shape, suggesting that kidney function impairment, either by reduced or supranormal eGFR, may be causally linked to a higher MI risk. [ABSTRACT FROM AUTHOR]

Purpose: Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the frequency of medication success among patients with COPD who initiated BGF using real-world data., Patients and Methods: Patients with a recorded diagnostic COPD code who started BGF with ≥2 prescriptions within 90-days were identified in the UK Optimum Patient Care Research Database and followed from first prescription until censoring at the end of follow-up (180-days), death, leaving database or end of data at 24/10/2022. The primary outcome was medication success at 90-days post-BGF initiation, defined as no major cardiac or respiratory event (ie no complicated COPD exacerbation, hospitalization for any respiratory event, myocardial infarction, new/hospitalized heart failure, and death) and no incidence of pneumonia. Medication success was also assessed at 180-days post-BGF initiation. Overall real-life medication success was claimed if the lower 95% confidence interval (CI) for the proportion of patients meeting the primary outcome was ≥70% (defined a priori)., Results: Two hundred eighty-five patients were included. Prior to BGF initiation, these patients often had severe airflow obstruction (mean ppFEV 1 : 54.5%), were highly symptomatic (mMRC ≥2: 77.9% (n = 205/263); mean CAT score: 21.7 (SD 7.8)), with evidence of short-acting β 2 -agonist (SABA) over-use (≥3 inhalers/year: 62.1%, n=179/285), repeat OCS prescriptions (≥2 courses/year: 33.0%, n = 95/285) and multiple primary care consultations (≥2 visits/year: 61.1%, n = 174/285). Overall, 39.6% of patients (n = 113/285) switched from previous triple therapies. Real-life medication success was achieved by 96.5% of patients (n = 275/285 [95% CI: 93.6, 98.3]) during 90-days treatment with BGF and by 91.8% (n = 169/184 [95% CI: 86.9, 95.4]) of patients at 180-days. The prescribed daily dose of SABA remained stable over the study period., Conclusion: The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events. These benefits were apparent after 90-days of treatment and sustained over 180-days., Competing Interests: Hana Müllerová, Stefan Franzén, Johann Castaneda, and Jonathan Marshall are employees of, and own stock in, AstraZeneca. Jeffrey Shi Kai Chan, Heath Heatley, Victoria Carter, John Townend, and Derek Skinner are employees of Observational and Pragmatic Research Institute. David Price has advisory board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, Teva Pharmaceuticals; consultancy agreements with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, Teva Pharmaceuticals; consultancy and lecture fees from Medscape, Inside Practice paid to Observational and Pragmatic Research Institute; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Chiesi, Viatris, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Viatris, Novartis, Regeneron Pharmaceuticals and Sanofi Genzyme, Teva Pharmaceuticals; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Novartis, Teva Pharmaceuticals; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. The authors report no other conflicts of interest in this work., (© 2024 Müllerová et al.)

Background: The implementation of preventive therapies among patients with stroke remains inadequately explored, especially when compared with patients with myocardial infarction (MI), despite sharing similar vascular risk profiles. We tested the hypothesis that participants with a history of stroke have a worse cardiovascular prevention profile in comparison to participants with MI., Methods and Results: In cross-sectional analyses within the UK Biobank and All of Us Research Program, involving 14 760 (9193 strokes, 5567 MIs) and 7315 (2948 strokes, 4367 MIs) participants, respectively, we evaluated cardiovascular prevention profiles assessing low-density lipoprotein (<100 mg/dL), blood pressure (systolic, <140 mm Hg; and diastolic, <90 mm Hg), statin and antiplatelet use, and a cardiovascular prevention score that required meeting at least 3 of these criteria. The results revealed that, within the UK Biobank, patients with stroke had significantly lower odds of meeting all the preventive criteria compared with patients with MI: low-density lipoprotein control (odds ratio [OR], 0.73 [95% CI, 0.68-0.78]; P <0.001), blood pressure control (OR, 0.63 [95% CI, 0.59-0.68]; P <0.001), statin use (OR, 0.45 [95% CI, 0.42-0.48]; P <0.001), antiplatelet therapy use (OR, 0.30 [95% CI, 0.27-0.32]; P <0.001), and cardiovascular prevention score (OR, 0.42 [95% CI, 0.39-0.45]; P <0.001). Similar patterns were observed in the All of Us Research Program, with significant differences across all comparisons ( P <0.05), and further analysis suggested that the odds of having a good cardiovascular prevention score were influenced by race and ethnicity as well as neighborhood deprivation levels (interaction P <0.05 in both cases)., Conclusions: In 2 independent national cohorts, patients with stroke showed poorer cardiovascular prevention profiles and lower adherence to guideline-directed therapies compared with patients with MI. These findings underscore the need to explore the reasons behind the underuse of secondary prevention in vulnerable stroke survivors.

Background: Myocardial infarction (MI), stroke and diabetes share underlying risk factors and commonalities in clinical management. We examined if their combined impact on mortality is proportional, amplified or less than the expected risk separately of each disease and whether the excess risk is explained by their associated comorbidities.Methods: Using large-scale electronic health records, we identified 2,007,731 eligible patients (51% women) and registered with general practices in the UK and extracted clinical information including diagnosis of myocardial infarction (MI), stroke, diabetes and 53 other long-term conditions before 2005 (study baseline). We used Cox regression to determine the risk of all-cause mortality with age as the underlying time variable and tested for excess risk due to interaction between cardiometabolic conditions.Results: At baseline, the mean age was 51 years, and 7% (N = 145,910) have had a cardiometabolic condition. After a 7-year mean follow-up, 146,994 died. The sex-adjusted hazard ratios (HR) (95% confidence interval [CI]) of all-cause mortality by baseline disease status, compared to those without cardiometabolic disease, were MI = 1.51 (1.49-1.52), diabetes = 1.52 (1.51-1.53), stroke = 1.84 (1.82-1.86), MI and diabetes = 2.14 (2.11-2.17), MI and stroke = 2.35 (2.30-2.39), diabetes and stroke = 2.53 (2.50-2.57) and all three = 3.22 (3.15-3.30). Adjusting for other concurrent comorbidities attenuated these estimates, including the risk associated with having all three conditions (HR = 1.81 [95% CI 1.74-1.89]). Excess risks due to interaction between cardiometabolic conditions, particularly when all three conditions were present, were not significantly greater than expected from the individual disease effects.Conclusion: Myocardial infarction, stroke and diabetes were associated with excess mortality, without evidence of any amplification of risk in people with all three diseases. The presence of other comorbidities substantially contributed to the excess mortality risks associated with cardiometabolic disease multimorbidity. [ABSTRACT FROM AUTHOR]

Background: It is commonly assumed that high oestradiol levels in women are cardioprotective. We assessed the association between oestradiol and the risk of incident myocardial infarction (MI) in women.Methods: We used data from 263 295 female UK Biobank participants [mean age 56.2; standard deviation (SD) 8.0 years] without previous cardiovascular disease (CVD). Associations of oestradiol with age and other cardiovascular risk factors were assessed. Cox proportional hazards models estimated crude, ag- and multiple-adjusted hazard ratios (HR) for MI associated with oestradiol levels.Results: After a mean follow-up of 9 years, 2206 incident cases of MI had been recorded, including 230 events among the 57 204 women (mean age 48) with detectable oestradiol levels. In the unadjusted analyses, a unit higher in log-transformed oestradiol was associated with an HR [95% confidence interval (CI) for MI of 0.73 (0.58; 0.92)]. After adjusting for age, this HR became 0.94 (0.75; 1.17), and after further adjusting for classical CVD risk factors, it was 1.05 (0.83; 1.31. Results were similar in subgroup analyses defined by age, menopausal status, socioeconomic status, contraceptive pill use and the use of hormone replacement therapy. The multivariable-adjusted HR for the 171 431 women (mean age 59) with undetectable levels of oestradiol, compared with those with detectable levels, was 0.97 (0.92; 1.02).Conclusions: Higher levels of oestradiol were not associated with a decreased risk of MI. The presumed cardioprotective effects of oestradiol seem to be largely confounded by age and further confounded by other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Light-to-moderate alcohol consumption has been reported to be cardio-protective among apparently healthy individuals; however, it is unclear whether this association is also present in those with disease. To examine the association between alcohol consumption and prognosis in individuals with pre-existing cardiovascular disease (CVD), we conducted a series of meta-analyses of new findings from three large-scale cohorts and existing published studies.Methods: We assessed alcohol consumption in relation to all-cause mortality, cardiovascular mortality, and subsequent cardiovascular events via de novo analyses of 14,386 patients with a previous myocardial infarction, angina, or stroke in the UK Biobank Study (median follow-up 8.7 years, interquartile range [IQR] 8.0-9.5), involving 1640 deaths and 2950 subsequent events, and 2802 patients and 1257 deaths in 15 waves of the Health Survey for England 1994-2008 and three waves of the Scottish Health Survey 1995, 1998, and 2003 (median follow-up 9.5 years, IQR 5.7-13.0). This was augmented with findings from 12 published studies identified through a systematic review, providing data on 31,235 patients, 5095 deaths, and 1414 subsequent events. To determine the best-fitting dose-response association between alcohol and each outcome in the combined sample of 48,423 patients, models were constructed using fractional polynomial regression, adjusting at least for age, sex, and smoking status.Results: Alcohol consumption was associated with all assessed outcomes in a J-shaped manner relative to current non-drinkers, with a risk reduction that peaked at 7 g/day (relative risk 0.79, 95% confidence interval 0.73-0.85) for all-cause mortality, 8 g/day (0.73, 0.64-0.83) for cardiovascular mortality and 6 g/day (0.50, 0.26-0.96) for cardiovascular events, and remained significant up to 62, 50, and 15 g/day, respectively. No statistically significant elevated risks were found at higher levels of drinking. In the few studies that excluded former drinkers from the non-drinking reference group, reductions in risk among light-to-moderate drinkers were attenuated.Conclusions: For secondary prevention of CVD, current drinkers may not need to stop drinking. However, they should be informed that the lowest risk of mortality and having another cardiovascular event is likely to be associated with lower levels of drinking, that is up to approximately 105g (or equivalent to 13 UK units, with one unit equal to half a pint of beer/lager/cider, half a glass of wine, or one measure of spirits) a week. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes is 2-3 times more prevalent in people of South Asian and African/African Caribbean ethnicity than people of European ethnicity living in the UK. The former 2 groups also experience excess atherosclerotic cardiovascular disease (ASCVD) complications of diabetes. We aimed to study ethnic differences in statin initiation, a cornerstone of ASCVD primary prevention, for people with type 2 diabetes.Methods and Findings: Observational cohort study of UK primary care records, from 1 January 2006 to 30 June 2019. Data were studied from 27,511 (88%) people of European ethnicity, 2,386 (8%) people of South Asian ethnicity, and 1,142 (4%) people of African/African Caribbean ethnicity with incident type 2 diabetes, no previous ASCVD, and statin use indicated by guidelines. Statin initiation rates were contrasted by ethnicity, and the number of ASCVD events that could be prevented by equalising prescribing rates across ethnic groups was estimated. Median time to statin initiation was 79, 109, and 84 days for people of European, South Asian, and African/African Caribbean ethnicity, respectively. People of African/African Caribbean ethnicity were a third less likely to receive guideline-indicated statins than European people (n/N [%]: 605/1,142 [53%] and 18,803/27,511 [68%], respectively; age- and gender-adjusted HR 0.67 [95% CI 0.60 to 0.76], p < 0.001). The HR attenuated marginally in a model adjusting for total cholesterol/high-density lipoprotein cholesterol ratio (0.77 [95% CI 0.69 to 0.85], p < 0.001), with no further diminution when deprivation, ASCVD risk factors, comorbidity, polypharmacy, and healthcare usage were accounted for (fully adjusted HR 0.76 [95% CI 0.68, 0.85], p < 0.001). People of South Asian ethnicity were 10% less likely to receive a statin than European people (1,489/2,386 [62%] and 18,803/27,511 [68%], respectively; fully adjusted HR 0.91 [95% CI 0.85 to 0.98], p = 0.008, adjusting for all covariates). We estimated that up to 12,600 ASCVD events could be prevented over the lifetimes of people currently affected by type 2 diabetes in the UK by equalising statin prescribing across ethnic groups. Limitations included incompleteness of recording of routinely collected data.Conclusions: In this study we observed that people of African/African Caribbean ethnicity with type 2 diabetes were substantially less likely, and people of South Asian ethnicity marginally less likely, to receive guideline-indicated statins than people of European ethnicity, even after accounting for sociodemographics, healthcare usage, ASCVD risk factors, and comorbidity. Underuse of statins in people of African/African Caribbean or South Asian ethnicity with type 2 diabetes is a missed opportunity to prevent cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, myocardial injury is increasingly reported and associated with adverse outcomes. However, the pathophysiology, extent of myocardial injury and clinical significance remains unclear. Methods: COVID-HEART is a UK, multicentre, prospective, observational, longitudinal cohort study of patients with confirmed COVID-19 and elevated troponin (sex-specific > 99th centile). Baseline assessment will be whilst recovering in-hospital or recently discharged, and include cardiovascular magnetic resonance (CMR) imaging, quality of life (QoL) assessments, electrocardiogram (ECG), serum biomarkers and genetics. Assessment at 6-months includes repeat CMR, QoL assessments and 6-min walk test (6MWT). The CMR protocol includes cine imaging, T1/T2 mapping, aortic distensibility, late gadolinium enhancement (LGE), and adenosine stress myocardial perfusion imaging in selected patients. The main objectives of the study are to: (1) characterise the extent and nature of myocardial involvement in COVID-19 patients with an elevated troponin, (2) assess how cardiac involvement and clinical outcome associate with recognised risk factors for mortality (age, sex, ethnicity and comorbidities) and genetic factors, (3) evaluate if differences in myocardial recovery at 6 months are dependent on demographics, genetics and comorbidities, (4) understand the impact of recovery status at 6 months on patient-reported QoL and functional capacity. Discussion: COVID-HEART will provide detailed characterisation of cardiac involvement, and its repair and recovery in relation to comorbidity, genetics, patient-reported QoL measures and functional capacity. Clinical Trial registration: ISRCTN 58667920. Registered 04 August 2020. [ABSTRACT FROM AUTHOR]