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Rapid identification and localization of an acute coronary occlusion are vital to prevent myocardial damage, yet reliance on ST-segment ECG criteria misses many acute occlusion myocardial infarctions (OMI) and triggers unnecessary acute angiographies. Here, we present a trained and validated deep learning model using 540,372 emergency ECGs paired with definitive catheterization outcomes. The model has a C-statistic of ≥0.95 for OMI and ≥0.87 for non-OMI infarctions and can localize culprit lesions in the three main coronary branches, which can guide the angiographer. Performance is similar across age, sex, and ECG hardware subgroups. Obviating dependence on ST-elevations and troponins, this model for the identification and localization of OMI has the potential to shorten the time to reperfusion of an acute coronary occlusion and save resources. Because human oversight of OMI detection on the ECG is limited, randomized clinical trials with patient-relevant outcomes are warranted.

Disruptions in gut microbiome are implicated in cardiometabolic disorders and other health outcomes. Antibiotics are known gut microbiome disruptors, but their long-term consequences remain underexplored. Here we combined individual-level data from the Swedish Prescribed Drug Register with fecal metagenomes of 14,979 adults to examine the association between oral antibiotic use over 8 years and gut microbiome. In multivariable confounder-adjusted regression models, antibiotic use <1 year before fecal sampling was associated with the greatest reduction in species diversity, but significant associations were also observed for use 1-4 and 4-8 years earlier. Clindamycin, fluoroquinolones and flucloxacillin accounted for most of the associations with the abundance of individual species. Use of these antibiotics 4-8 years earlier was associated with altered abundance of 10-15% of the species studied; penicillin V, extended-spectrum penicillins and nitrofurantoin were associated with only a few species. Similar results were found comparing one antibiotic course 4-8 years before sampling versus none in the past 8 years. These findings indicate that antibiotics may have long-lasting consequences for the gut microbiome.

Background:

The elevated risk of cardiovascular disease (CVD) in inflammatory bowel disease (IBD) has been increasingly recognized. Although inflammation is implicated in both IBD and CVD, the IBD-CVD association through the mediation of systemic inflammation remains underexplored.

Objective:

To evaluate the associations between IBD and incident CVD and examine the mediating role of inflammatory biomarkers.

Design:

A sex- and age-matched cohort study.

Methods:

Using data from the UK Biobank, the study included 1494 participants with a first-ever diagnosis of IBD from 1999 to the recruitment date (2006–2010), and 14,940 matched reference individuals. The primary outcome was any CVD, whereas secondary outcomes included 7 major CVD categories and 19 specific CVD entities. Fifteen inflammatory biomarkers and indices measured at recruitment were included, serving as proxies of underlying inflammatory status. Cox proportional hazard model estimated the adjusted hazard ratios (HRs) and 95% confidence intervals (CI) of associations between IBD and CVD and between inflammatory biomarkers and CVD. Model-based mediation analyses were conducted to explore the potential mediating role of inflammatory biomarkers in IBD-CVD associations.

Results:

Compared with reference individuals, patients with IBD had an increased risk of any CVD (HR = 1.34, 95%CI 1.20, 1.49), ischemic heart disease (HR = 1.20, 95%CI 1.02, 1.41), heart failure (HR = 1.61, 95%CI 1.28, 2.02), arrhythmias (HR = 1.34, 95%CI 1.13, 1.59), atrial fibrillation (HR = 1.34, 95%CI 1.11, 1.62), other supraventricular arrhythmia (HR = 1.83, 95%CI 1.12, 2.99), and venous thromboembolism (HR = 1.74, 95%CI 1.38, 2.21). The mediation proportion was generally higher in Crohn’s disease and in CVD subtypes (ischemic heart disease, heart failure, and arrhythmias) than in venous thromboembolism.

Conclusion:

IBD is associated with various CVD outcomes, and inflammatory biomarkers mediate their associations, suggesting that reducing inflammation may help alleviate cardiac burden in patients with IBD.

BACKGROUND: Large between-person differences in blood pressure (BP) responses to sodium reduction, potassium supplementation, and potassium-enriched salt have been suggested by prior studies. However, limitations in research designs and misinterpretation of findings mean that overestimation of true between-person variation in response is likely.

METHODS: Systolic BP (SBP) response during a 4-week run-in period on potassium-enriched salt was measured for 608 individuals. Participants were defined as apparently sensitive if SBP fell and apparently resistant if SBP was unchanged or rose. The effect of potassium-enriched salt compared with regular salt on SBP was then compared for apparently sensitive versus apparently resistant groups over a subsequent 12-month postrandomization period. A linear mixed model was used to determine how background within-person BP variability contributed to apparent between-person differences in BP response.

RESULTS: Apparent between-person variability in SBP response during run-in was substantial (mean SBP response, -13.7 [SD, 19.3; range, -80 to +56.5] mm Hg). Run-in identified 477 individuals as apparently sensitive and 131 as apparently resistant. Mean effects on SBP of potassium-enriched salt compared with regular salt over 12 months post-randomization were -2.2 mm Hg for apparently sensitive and -7.2 mm Hg for apparently resistant individuals, with no difference between the 2 groups (P=0.068). The mixed models identified no contribution of apparent run-in sensitivity to the observed between-person differences in postrandomization BP responses to potassium-enriched salt.

CONCLUSIONS: Individuals classified as responsive or resistant to potassium-enriched salt during initial exposure did not differ in their response to subsequent exposure.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00145756.

IMPORTANCE: Risk stratification strategies in primary prevention of coronary events lack precision.

OBJECTIVE: To determine whether prediction of first coronary events is improved by adding information on coronary atherosclerosis from coronary computed tomography angiography (CCTA) to a model using the pooled cohort equation (PCE) risk score tool and the coronary artery calcification score (CACS).

DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study including individuals aged 50 to 64 years randomly recruited from the general population and examined at 6 university hospitals in Sweden from 2013 to 2018, with a median follow-up of 7.8 years. A sample of 30 154 individuals underwent cardiopulmonary imaging, physical examinations, routine laboratory tests, questionnaires, and/or functional tests. This study included 24 791 individuals without previous cardiovascular disease for whom high-quality CCTA images were available. Events were followed up via registers until September 2024.

EXPOSURES: The information used from the CCTA images was the extent of coronary atherosclerosis (segment involvement score), presence of noncalcified atherosclerosis, and presence of coronary obstructive disease (stenosis ≥50%).

MAIN OUTCOMES AND MEASURES: The outcome was a composite of first occurrence of nonfatal myocardial infarction or death from coronary heart disease.

RESULTS: During follow-up, 304 coronary events occurred. Segment involvement scores of 3 to 4 and greater than 4 and presence of noncalcified atherosclerosis were associated with hazard ratios of 2.71 (95% CI, 1.34-5.44), 5.27 (95% CI, 2.50-11.07), and 1.66 (95% CI, 1.23-2.22), respectively. In a model based on the PCE and CACS, CCTA-derived data improved risk discrimination (C statistic improved from 0.764 to 0.779; P = .004) and risk reclassification (net reclassification improvement of 0.133 [95% CI, 0.031-0.165]), conferred a net correct upward reclassification of 14.2% in those with events and incorrectly classified 1.6% of participants not experiencing an event into a higher-risk category. Because of the low event rate in the cohort, reclassification mainly occurred in the group classified as at low risk (<5%) according to the PCE.

CONCLUSIONS AND RELEVANCE: Information on coronary atherosclerosis from CCTA modestly improved risk prediction beyond traditional risk factors and CACS in identifying individuals at risk of coronary events and in need of primary prevention.

Ischemic heart disease (IHD) remains a leading cause of death worldwide, with dietary risks being its most significant modifiable factor. Here, using the Global Burden of Diseases, Injuries and Risk Factors Study 2023, we estimated the mortality and disability-adjusted life years from diet-related IHD across 204 countries. In 2023, a suboptimal diet was responsible for 4.06 million (95% uncertainty interval (UI) 0.74-6.22) IHD deaths and 96.84 million (18.82-142.52) IHD disability-adjusted life years. The global age-standardized death rate of IHD attributable to suboptimal diet decreased by 43.92% (95% UI 34.44-53.23) per 100,000 population from 1990 to 2023. Among dietary factors, low intake of nuts and seeds (9.87, 95% UI 2.84-17.12 deaths per 100,000 population), low whole grains (9.22, 4.73-13.67), low fruits (7.25, 1.54-13.34) and high sodium (7.15, 0.92-17.97) were primary contributors to IHD deaths. The burden was particularly pronounced in low- and middle-sociodemographic index countries. By disentangling dietary risk factors, we identified the portion of IHD burden directly modifiable through food interventions.

BACKGROUND: Resistant hypertension (RH), in which blood pressure remains elevated on ≥3 medications or controlled on ≥4 medications, increases the risk of adverse cardiovascular events nearly 50% more than primary hypertension. We sought to identify genetic drivers of RH in a reliable and generalizable manner.

METHODS: We utilized FinnGen (discovery) and UKBB (UK Biobank, replication) data sets to identify potential genetic drivers of RH. Using standard RH definitions, we developed cohorts in each data set and performed genome-wide (genome-wide association studies) and transcriptome-wide association studies, as well as Mendelian randomization analysis to evaluate potential causal associations.

RESULTS: We replicated 5 genetic loci in CASZ1, WNT2B, KCNK3, LSP1, and near the EVX1/EVX1AS locus for RH. Of these, CASZ1 and WNT2B are strongly associated with aldosterone homeostasis, while KCNK3 and LSP1 are associated with pathways mediating vasodilation. EVX1/EVX1AS are involved in mesendodermal lineage differentiation during gastrulation. Gene- and pathway-based analyses identified associations with vascular and cardiac developmental pathways in addition to aldosterone synthesis and secretion pathways. Transcriptome-wide association study analyses identified 37 genes, of which the genetically regulated expression is associated with RH, with particularly strong tissue-specific associations with KCNK3. Finally, Mendelian randomization identified possible causal association for 4 vascular risk factors (CRP [C-reactive protein]), triglycerides, waist circumference, and body mass index) with RH, with strong associations with identified lead variants.

CONCLUSIONS: We identified distinct genetic variants associated with RH, including those implicating the role of hyperaldosteronism, highlighting distinct pathways and targets for more effectively treating RH.

Background: A reduction in kidney function cause metabolites that normally are cleared by the kidney to accumulate. These accumulated metabolites could potentially link kidney function to an increased risk of cardiovascular disease.

Aim: To assess the relationships between creatinine-based estimated glomerular filtration rate (eGFR) and the metabolome (791 endogenous metabolites) in the general population, as well as the cortisol to cortisone ratio.

Patients and methods: Three population-based cohorts, Epihealth, PIVUS and POEM (total n = 3,444), were used with a discovery/validation approach. Metabolomics was measured by mass spectroscopy. eGFR was calculated using the 2021 CKD-EPI creatinine-based equation. Multivariable linear regression was used to assess the correlations between each metabolite concentration and eGFR, adjusting for sex, % fat mass, cardiovascular risk factors and medications. The metabolites significant in the linear regression were analyzed using MultiVariable Mendelian Randomization (MVMR), adjusting for diabetes and BMI.

Results: Nighty-six metabolites were significantly associated to eGFR and had the same direction of association in both linear regression and MVMR. The vast majority of these associations were negative. Apart from creatinine, N-acetylalanine, N,N-dimethyl-pro-pro, N,N,N-trimethyl-alanylproline betaine (TMAP) were the top findings. Pathway enrichment analysis (Metaboloanalyst 6.0) found five significantly enriched pathways, two of which involved amino acid metabolism.

Conclusions: In a general population with only mild to moderately reduced kidney function, several metabolites were associated with kidney function, including the cortisol to cortisone ratio. This finding is of interest since several of these metabolites might link reduced kidney function to an increased risk of cardiovascular disease.

Background: Studies comparing treatment strategies based on initiation timing-such as starting PCSK9 inhibitor (PCSK9i) therapy sooner versus later after a myocardial infarction (MI)-are prone to immortal time bias. Clone-censor-weight methods can address these issues and allow the researcher to emulate a trial in which patients are assigned to protocols dictating when PCSK9i is initiated. This study aimed to evaluate the comparability of patients in a clone-censor-weight setup who initiated a PCSK9i within 12 months post-MI versus non-initiators.

Methods: We included adult patients hospitalized for MI in Sweden (2015-2021) and followed them for 3 years. We considered two treatment strategies: initiating PCSK9i within 12 months versus not initiating PCSK9i during the same period. We applied the clone-censor-weight method to address immortal time bias and assessed remaining bias using covariate balance metrics and negative control outcomes.

Results: The primary study sample included 38 627 episodes of MI, with 561 (1.5%) initiating PCSK9i treatment within 12 months. These patients were younger, had higher baseline LDL-C levels, and were more frequently treated with ezetimibe during their post-MI follow-up compared to non-initiators. Although clone-censor-weight estimation was free of immortal time bias, it faced challenges in achieving adequate balance of covariates due to the high rates of censoring (relatively small number of people initiating a PCSK9i in the first year) and strong association between covariates and censoring. Truncation of weights provided more stable estimates but at the expense of some covariate imbalances.

Conclusions: The clone-censor-weight method is a promising approach that allows researchers to answer questions about the effect of treatment policies. But practical guidance is needed to address problems that arise from small, highly imbalanced groups, which is common with most newly introduced treatments.