Circulating Metabolite Profiles and Risk of Coronary Heart Disease Among Racially and Geographically Diverse Populations.

BACKGROUND: Metabolomics may reveal novel biomarkers for coronary heart disease (CHD). We aimed to identify circulating metabolites and construct a metabolite risk score (MRS) associated with incident CHD among racially and geographically diverse populations. METHODS: Untargeted metabolomics was conducted using baseline plasma samples from 900 incident CHD cases and 900 age-/sex-/race-matched controls (300 pairs of Black Americans, White Americans, and Chinese adults, respectively), which detected 927 metabolites with known identities among ≥80% of samples. After quality control, 896 case-control pairs remained and were randomly divided into discovery (70%) and validation (30%) sets within each race. In the discovery set, conditional logistic regression and least absolute shrinkage and selection operator over 100 subsamples were applied to identify metabolites robustly associated with CHD risk and construct the MRS. The MRS-CHD association was evaluated using conditional logistic regression and the C-index. Mediation analysis was performed to examine if MRS mediated associations between conventional risk factors and incident CHD. The results from the validation set were presented as the main findings. RESULTS: Twenty-four metabolites selected in ≥90% of subsamples comprised the MRS, which was significantly associated with incident CHD (odds ratio per 1 SD, 2.21 [95% CI, 1.62-3.00] after adjusting for sociodemographics, lifestyles, family history, and metabolic health status). MRS could distinguish incident CHD cases from matched controls (C-index, 0.69 [95% CI, 0.63-0.74]) and improve CHD risk prediction when adding to conventional risk factors (C-index, 0.71 [95% CI, 0.65-0.76] versus 0.67 [95% CI, 0.61-0.73]; P<0.001). The odds ratios and C-index were similar across subgroups defined by race, sex, socioeconomic status, lifestyles, metabolic health, family history, and follow-up duration. The MRS mediated large portions (46.0%-74.2%) of the associations for body mass index, smoking, diabetes, hypertension, and dyslipidemia with incident CHD. CONCLUSIONS: In a diverse study sample, we identified 24 circulating metabolites that, when combined into an MRS, were robustly associated with incident CHD and modestly improved CHD risk prediction beyond conventional risk factors.

CPHEN-017: Comprehensive phenotyping of neutrophil extracellular traps (NETs) on peripheral human neutrophils.

With the recent discovery of their ability to produce neutrophil extracellular traps (NETs), neutrophils are increasingly appreciated as active participants in infection and inflammation. NETs are characterized as large, web-like networks of DNA and proteins extruded from neutrophils, and there is considerable interest in how these structures drive disease in humans. Advancing research in this field is contingent on developing novel tools for quantifying NETosis. To this end, we have developed a 7-marker flow cytometry panel for analyzing NETosis on human peripheral neutrophils following in vitro stimulation, and in fresh circulating neutrophils under inflammatory conditions. This panel was optimized on neutrophils isolated from whole blood and analyzed fresh or in vitro stimulated with phorbol 12-myristate 13-acetate (PMA) or ionomycin, two known NET-inducing agonists. Neutrophils were identified as SSChighFSChighCD15+CD66b+. Neutrophils positive for amine residues and 7-Aminoactinomycin D (7-AAD), our DNA dye of choice, were deemed necrotic (Zombie-NIR+7-AAD+) and were removed from downstream analysis. Exclusion of Zombie-NIR and positivity for 7-AAD (Zombie-NIRdim7-AAD+) was used here as a marker of neutrophil-appendant DNA, a key feature of NETs. The presence of two NET-associated proteins - myeloperoxidase (MPO) and neutrophil elastase (NE) - were utilized to identify neutrophil-appendant NET events (SSChighFSChighCD15+CD66b+Zombie NIRdim7-AAD+MPO+NE+). We also demonstrate that NETotic neutrophils express citrullinated histone H3 (H3cit), are concentration-dependently induced by in vitro PMA and ionomycin stimulation but are disassembled with DNase treatment, and are present in both chronic and acute inflammation. This 7-color flow cytometry panel provides a novel tool for examining NETosis in humans.

Novel Mouse Model of Myocardial Infarction, Plaque Rupture, and Stroke Shows Improved Survival With Myeloperoxidase Inhibition.

BACKGROUND: Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of death worldwide. Although most mouse models of atherosclerosis develop lesions in the aorta and carotid arteries, they do not develop advanced coronary artery lesions. Moreover, they do not undergo spontaneous plaque rupture with MI and stroke or do so at such a low frequency that they are not viable experimental models to study late-stage thrombotic events or to identify novel therapeutic approaches for treating atherosclerotic disease. This has stymied the development of more effective therapeutic approaches for reducing these events beyond what has been achieved with aggressive lipid lowering. Here, we describe a diet-inducible mouse model that develops widespread advanced atherosclerosis in coronary, brachiocephalic, and carotid arteries with plaque rupture, MI, and stroke. METHODS: We characterized a novel mouse model with a C-terminal mutation in the scavenger receptor class B, type 1 (SR-BI), combined with Ldlr knockout (designated SR-BI∆CT/∆CT/Ldlr-/-). Mice were fed Western diet (WD) for 26 weeks and analyzed for MI and stroke. Coronary, brachiocephalic, and carotid arteries were analyzed for atherosclerotic lesions and indices of plaque stability. To validate the utility of this model, SR-BI∆CT/∆CT/Ldlr-/- mice were treated with the drug candidate AZM198, which inhibits myeloperoxidase, an enzyme produced by activated neutrophils that predicts rupture of human atherosclerotic lesions. RESULTS: SR-BI∆CT/∆CT/Ldlr-/- mice show high (>80%) mortality rates after 26 weeks of WD feeding because of major adverse cardiovascular events, including spontaneous plaque rupture with MI and stroke. Moreover, WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice displayed elevated circulating high-sensitivity cardiac troponin I and increased neutrophil extracellular trap formation within lesions compared with control mice. Treatment of WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice with AZM198 showed remarkable benefits, including >90% improvement in survival and >60% decrease in the incidence of plaque rupture, MI, and stroke, in conjunction with decreased circulating high-sensitivity cardiac troponin I and reduced neutrophil extracellular trap formation within lesions. CONCLUSIONS: WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice more closely replicate late-stage clinical events of advanced human atherosclerotic disease than previous models and can be used to identify and test potential new therapeutic agents to prevent major adverse cardiac events.

The association between glycated hemoglobin levels and long-term prognosis in patients with diabetes and triple-vessel coronary disease across different age groups: A cohort study.

AIM: Our study aimed to investigate the correlation between glycated hemoglobin (HbA1c) and adverse prognostic events in patients with diabetes and triple-vessel coronary disease (TVD). METHODS: This study ultimately included 2051 patients with TVD and diabetes. Patients were categorized into five groups based on their HbA1c levels: < 6.0 %, 6.0-6.4 %, 6.5-6.9 %, 7.0-7.9 %, and ≥ 8.0 %. The primary endpoint was all-cause death, and the secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: The median follow-up time was 5.88 years. During this period, a total of 323 (15.7 %) all-cause deaths and 537 (26.2 %) MACCEs were recorded. The relationship between HbA1c and the risk of endpoint events showed a J-shaped pattern, with the lowest risk observed between 6.0 % and 6.4 %. Further analysis revealed a significant interaction between HbA1c and age. In the subgroup with age < 70 years, as HbA1c increased, the risk of endpoint events gradually rose. While in the subgroup with age ≥70 years, there was an L-shaped relationship between HbA1c and endpoint events, with the highest risk observed in patients with HbA1c < 6.0 %. CONCLUSION: Our study revealed variations in the relationship between HbA1c levels and endpoint events among patients with TVD and diabetes of different ages. In younger patients, elevated HbA1c levels were associated with a higher risk of death and MACCE, while in older patients, excessively low HbA1c levels (HbA1c < 6 %) were linked to a higher risk of death and MACCE.

Percutaneous Coronary Intervention of Left Main Disease: Outcome After 1-year Follow-up at a Tertiary Hospital in Vietnam.

Background: Left main (LM) coronary artery disease (CAD) is a severe condition that can lead to severe outcomes. Treatment options include medication, coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI). Recent advancements in PCI techniques position it as a viable alternative to CABG for LM revascularisation. Methods: This prospective observational study evaluated outcomes after PCI for LM CAD, encompassing in-hospital and post-discharge mortality, in a single-centre registry in Vietnam. Results: Our research involved 59 patients who underwent PCI for LM lesions, with an average age of 66.7 ±1.5 years, who were divided into two groups based on presentation diagnosis - acute coronary syndrome or chronic coronary syndrome. After PCI, one individual was diagnosed with contrast-induced nephropathy and one with cardiac shock. There were two cases of in-hospital mortality in the acute coronary syndrome group and one in the chronic coronary syndrome group giving a rate of major adverse cardiac and cerebrovascular events (MACCE) of 5.1%. After a 12-month follow-up, the MACCE rate increased to 18.6%. Triple vessel coronary artery disease and troponin I elevation exhibited significant associations with adverse in-hospital outcomes (p<0.05). Conclusion: PCI for LM coronary artery disease is considered a safe treatment option, demonstrating relatively favourable in-hospital and mid-term outcomes. It presents a viable alternative for patients in need of revascularisation, particularly in cases where CABG is not the preferred choice. Clinical indicators, such as triple vessel coronary artery disease and elevated troponin I levels, may serve as predictors of adverse outcomes during hospitalisation.

Outcomes Following Percutaneous Coronary Intervention in Patients With Multivessel Disease Who Were Recommended for But Declined Coronary Artery Bypass Graft Surgery.

BACKGROUND: Patients may prefer percutaneous coronary intervention (PCI) over coronary artery bypass graft (CABG) surgery, despite heart team recommendations. The outcomes in such patients have not been examined. We sought to examine the results of PCI in patients who were recommended for but declined CABG. METHODS AND RESULTS: Consecutive patients with stable ischemic heart disease and unprotected left main or 3-vessel disease or Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score >22 who underwent PCI after heart team review between 2013 and 2020 were included. Patients were categorized into 3 groups according to heart team recommendations on the basis of appropriate use criteria: (1) PCI-recommended; (2) CABG-eligible but refused CABG (CABG-refusal); and (3) CABG-ineligible. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. The study included 3687 patients undergoing PCI (PCI-recommended, n=1718 [46.6%]), CABG-refusal (n=1595 [43.3%]), and CABG-ineligible (n=374 [10.1%]). Clinical and procedural risk increased across the 3 groups, with the highest comorbidity burden in CABG-ineligible patients. Composite events within 1 year after PCI occurred in 55 (4.1%), 91 (7.0%), and 41 (14.8%) of patients in the PCI-recommended, CABG-refusal, and CABG-ineligible groups, respectively. After multivariable adjustment, the risk of the primary composite outcome was significantly higher in the CABG-refusal (hazard ratio [HR], 1.67 [95% CI, 1.08-3.56]; P=0.02) and CABG-ineligible patients (HR, 3.26 [95% CI, 1.28-3.65]; P=0.004) groups compared with the reference PCI-recommended group, driven by increased death and stroke. CONCLUSIONS: Cardiovascular event rates after PCI were significantly higher in patients with multivessel disease who declined or were ineligible for CABG. Our findings provide real-world data to inform shared decision-making discussions.

Prospective Deep Learning-based Quantitative Assessment of Coronary Plaque by CT Angiography Compared with Intravascular Ultrasound.

AIMS: Coronary computed tomography angiography provides noninvasive assessment of coronary stenosis severity and flow impairment. Automated artificial intelligence analysis may assist in precise quantification and characterization of coronary atherosclerosis, enabling patient-specific risk determination and management strategies. This multicenter international study compared an automated deep-learning-based method for segmenting coronary atherosclerosis in coronary computed tomography angiography (CCTA) against the reference standard of intravascular ultrasound (IVUS). METHODS AND RESULTS: The study included clinically stable patients with known coronary artery disease from 15 centers in the U.S. and Japan. An artificial intelligence (AI)-enabled plaque analysis service was utilized to quantify and characterize total plaque (TPV), vessel, lumen, calcified plaque (CP), non-calcified plaque (NCP), and low attenuation plaque (LAP) volumes derived from CCTA and compared with IVUS measurements in a blinded, core laboratory-adjudicated fashion. In 237 patients, 432 lesions were assessed; mean lesion length was 24.5 mm. Mean IVUS-TPV was 186.0 mm3. AI-enabled plaque analysis on CCTA showed strong correlation and high accuracy when compared with IVUS; correlation coefficient, slope, and Y intercept for TPV were 0.91, 0.99, and 1.87, respectively; for CP volume 0.91, 1.05, and 5.32, respectively; and for NCP volume 0.87, 0.98, and 15.24, respectively. Bland-Altman analysis demonstrated strong agreement with little bias for these measurements. CONCLUSIONS: Artificial intelligence enabled CCTA quantification and characterization of atherosclerosis demonstrated strong agreement with IVUS reference standard measurements. This tool may prove effective for accurate evaluation of coronary atherosclerotic burden and cardiovascular risk assessment.[ClinicalTrails.gov identifier: NCT05138289].

The ABCs of the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease.

BACKGROUND: The 2023 Multisociety Guideline for the Management of Chronic Coronary Disease (CCD) updates recommendations for CCD, formerly known as "stable ischemic heart disease." This condition encompasses a spectrum of coronary vascular pathologies from subclinical to clinical ischemic heart disease. HYPOTHESIS: The new "ABC" mnemonic offers clinicians a streamlined framework for applying Class One Recommendations (COR1) and integrating recent updates into CCD management. METHODS: A critical analysis of the 2023 CCD guidelines was conducted, with this review highlighting key elements. RESULTS: The review outlines crucial changes, including novel recommendations supported by current clinical evidence. The focus is on these developments, clarifying their importance for day-to-day clinical practice. CONCLUSIONS: The review encourages a synergistic approach between primary healthcare providers and cardiologists to develop comprehensive strategies for lifestyle modification and medication therapy in CCD care. Furthermore, it suggests that utilizing comprehensive risk assessment tools can refine medical decision-making, ultimately enhancing patient care and clinical outcomes.

Minimally Invasive Isolated and Hybrid Surgical Revascularization for Multivessel Coronary Disease: A Single-Center Long-Term Follow-Up.

INTRODUCTION: Some evidence suggests that surgical minimally invasive (MIDCAB) and hybrid coronary revascularization (HCR) are safe and potentially effective at short-term follow-up. Data on long-term outcomes are more limited and inconclusive. METHODS: Between February 2013 and December 2023, a total of 1997 patients underwent surgical coronary artery revascularization at our institution, of whom, 92 (4.7%) received left anterior mini-thoracotomy access (MIDCAB), either isolated (N = 78) or in combination with percutaneous coronary intervention (N = 14, HCR group). RESULTS: After a median follow-up of 75 months (range 3.1: 149 months), cardiac mortality was 0% while overall mortality was 3%, with one in-hospital mortality and two additional late deaths. Conversion to sternotomy happened in two patients (2.1%), and surgical re-explorations occurred in five patients (4.6%), of whom three for bleeding and two for graft failure. All patients received left internal mammary (LIMA) to left anterior descending artery (LAD) grafting (100%). In the HCR group, 10 patients (72%) showed percutaneous revascularization (PCI) after MIDCAB, showing PCI on a mean of 1.6 ± 0.6 vessels and implanting 2.1 ± 0.9 drug-eluting stents. CONCLUSIONS: MIDCAB, in isolation or in association with hybrid coronary revascularization, is associated with encouraging short- and long-term results in selected patients discussed within a dedicated heart-team.

Effectiveness of mobile health applications on clinical outcomes and health behaviors in patients with coronary heart disease: A systematic review and meta-analysis.

Objective: Mobile health applications (apps) have gained significant popularity and widespread utilization among patients with coronary heart disease (CHD). The objective of this study is to evaluate the effects of mHealth apps on clinical outcomes and health behaviors in patients with CHD. Methods: Databases were searched from inception until December 2023, including Cochrane Library, PubMed, EMBASE, Web of Science, CINAHL, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Service System (SinoMed), Wanfang Data, China Science and Technology Journal Database (VIP), for randomized controlled trials (RCTs) regarding the effectiveness of mHealth apps in patients with CHD. Two researchers conducted a comprehensive review of the literature, extracting relevant data and evaluating each study's methodological quality separately. The meta-analysis was performed utilizing Review Manager v5.4 software. Results: A total of 34 RCTs were included, with 5,319 participants. The findings demonstrated that using mHealth apps could decrease the incidence of major adverse cardiac events (RR = 0.68, P = 0.03), readmission rate (RR = 0.56, P < 0.001), total cholesterol (WMD = -0.19, P = 0.03), total triglycerides (WMD = -0.24, P < 0.001), waist circumference (WMD = -1.92, P = 0.01), Self-Rating Anxiety Scale score (WMD = -6.70, P < 0.001), and Self-Rating Depression Scale score (WMD = -7.87, P < 0.001). They can also increase the LVEF (WMD = 6.50, P < 0.001), VO2 max (WMD = 1.89, P < 0.001), 6-min walk distance (6MWD) (WMD = 19.43, P = 0.004), Morisky Medication Adherence Scale-8 score (WMD = 0.96, P = 0.004), and medication adherence rate (RR = 1.24, P = 0.03). Nevertheless, there is no proof that mHealth apps can lower low-density lipoprote in cholesterol, blood pressure, BMI, or other indicator (P > 0.05). Conclusion: Mobile health apps have the potential to lower the incidence of major adverse cardiac events (MACEs), readmission rates, and blood lipids in patients with CHD. They can also help enhance cardiac function, promote medication adherence, and alleviate symptoms of anxiety and depression. To further corroborate these results, larger-scale, multi-center RCTs with longer follow-up periods are needed.

Remnant cholesterol, LDL cholesterol, and apoB absolute mass changes explain results of the PROMINENT trial.

BACKGROUND AND AIMS: The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial. METHODS: Among 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design. Endpoint atherosclerotic cardiovascular disease (ASCVD) was cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization as defined in PROMINENT. RESULTS: In the PROMINENT trial, treatment with pemafibrate resulted in -7 mg/dL (-0.18 mmol/L; -18 %) change in remnant cholesterol, +10 mg/dL (+0.26 mmol/L; +12 %) LDL cholesterol, and +5 mg/dL (+0.05 g/L; +5 %) apolipoprotein B. In the CGPS mimicking PROMINENT, the estimated hazard ratios for ASCVD were 0.97 (95 % confidence interval: 0.94-0.99) for a -7 mg/dL (-0.18 mmol/L) change in remnant cholesterol, 1.04 (1.01-1.07) for a +10 mg/dL (+0.26 mmol/L) change in LDL cholesterol, and 1.02 (1.01-1.03) for a +5 mg/dL (+0.05 g/L) change in apolipoprotein B. When combining absolute changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B, the estimated hazard ratio for ASCVD was 1.05 (0.96-1.14) in the CGPS mimicking PROMINENT compared to 1.03 (0.91-1.15) in the PROMINENT trial. CONCLUSIONS: Absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B can explain results of the PROMINENT trial. The 3 mg/dL (0.08 mmol/L) higher total atherogenic cholesterol together with 5 mg/dL (0.05 g/L) higher apolipoprotein B seem to explain the trend toward more ASCVD in the pemafibrate arm.

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Characteristics of Patients With Acute Coronary Syndrome and Normal Electrocardiogram.

Background: Patients with acute coronary syndrome (ACS) and normal electrocardiogram (ECG) may have an increased risk of late diagnosis and complications of the disease. Objective: To study the demographic, angiographic and echocardiographic characteristics of patients hospitalized for ACS in whom the ECG was normal on admission to the hospital. Methods: This retrospective study included patients who were hospitalized for ACS without ST-elevation between 2015 and 2023 and who had coronary artery disease (CAD) confirmed by coronary angiography. By further inspection of the electronic databases, patients with ACS who had a normal ECG on admission were filtered out and analyzed separately. Results: Of the total 3137 patients with suspected ACS without ST-elevation, 129 patients (4.1%) were diagnosed as having ACS with a normal ECG. In three patients a non-atherosclerotic cause for the ACS was found. A significantly higher proportion of patients had single-vessel (54.3%) compared to two-vessel (29.5%) and three-vessel (14%) CAD. In addition to a normal ECG, 5.7% of patients with single-vessel CAD and 3.5% of patients with multi-vessel CAD had normal troponin levels and normal regional LV systolic function on echocardiography. Conclusion: Less than 5% of hospitalized patients with ACS without ST-elevation had a normal ECG on admission. The majority of these patients have single-vessel CAD. In about 5% of patients with single-vessel CAD, neither elevated troponin levels nor LV asynergy are detected.

Variation in Health Status With Invasive vs Conservative Management of Chronic Coronary Disease.

BACKGROUND: The ISCHEMIA trial found that patients with chronic coronary disease randomized to invasive strategy had better health status than those randomized to conservative strategy. It is unclear how best to translate these population-level results to individual patients. OBJECTIVES: The authors sought to identify patient characteristics associated with health status from invasive and conservative strategies, and develop a prediction algorithm for shared decision-making. METHODS: One-year disease-specific health status was assessed in ISCHEMIA with the Seattle Angina Questionnaire (SAQ) Summary Score (SAQ SS) and Angina Frequency, Physical Limitations (PL), and Quality of Life (QL) domains (range 0-100, higher = less angina/better health status). RESULTS: Among 4,617 patients from 320 sites in 37 countries, mean SAQ SS was 74.1 ± 18.9 at baseline and 85.7 ± 15.6 at 1 year. Lower baseline SAQ SS and younger age were associated with better 1-year health status with invasive strategy (P interaction = 0.009 and P interaction = 0.004, respectively). For the individual domains, there were significant treatment interactions for baseline SAQ score (Angina Frequency, PL), age (PL, QL), anterior ischemia (PL), and number of baseline antianginal medications (QL), with more benefit of invasive in patients with worse baseline health status, younger age, anterior ischemia, and on more antianginal medications. Parsimonious prediction models were developed for 1-year SAQ domains with invasive or conservative strategies to support shared decision-making. CONCLUSIONS: In the management of chronic coronary disease, individual patient characteristics are associated with 1-year health status, with younger age and poorer angina-related health status showing greater benefit from invasive management. This prediction algorithm can support the translation of the ISCHEMIA trial results to individual patients. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Looking into the Eyes to See the Heart of Chronic Kidney Disease Patients.

In patients with chronic kidney disease (CKD), the main cause of morbidity and mortality is cardiovascular disease (CVD). Both coronary artery calcium scoring by computed tomography (CT) and optical coherence tomography (OCT) are used to identify patients at increased risk for ischemic heart disease, thereby indicating a higher cardiovascular risk profile. Our study aimed to investigate the utility of these techniques in the CKD population. In patients with CKD, OCT was used to measure the choroidal thickness (CHT) and the thickness of the peripapillary retinal nerve fiber layer (pRNFL). A total of 127 patients were included, including 70 men (55%) with an estimated glomerular filtration rate (eGFR) of 39 ± 30 mL/min/1.73 m2. Lower pRNFL thickness was found to be related to high-sensitivity troponin I (r = -0.362, p < 0.001) and total coronary calcification (r = -0.194, p = 0.032). In a multivariate analysis, pRNFL measurements remained associated with age (ß = -0.189; -0.739--0.027; p = 0.035) and high-sensitivity troponin I (ß = -0.301; -0.259--0.071; p < 0.001). Severe coronary calcification (Agatston score ≥ 400 HU) was related to a worse eGFR (p = 0.008), a higher grade of CKD (p = 0.036), and a thinner pRNFL (p = 0.011). The ROC curve confirmed that the pRNFL measurement could determine the patients with an Agatston score of ≥400 HU (AUC 0.638; 95% CI 0.525-0.750; p = 0.015). Our study concludes that measurement of pRNFL thickness using OCT is related to the markers associated with ischemic heart disease, such as coronary calcification and high-sensitivity troponin I, in the CKD population.

Improvement of coronary stent visualization using ultra-high-resolution photon-counting detector CT.

OBJECTIVES: This study aimed to compare the image quality and diagnostic performance of standard-resolution (SR) and ultra-high-resolution (UHR) coronary CT angiography (CCTA) based on photon-counting detector CT (PCD-CT) of coronary stents and explore the best reconstruction kernel for stent imaging. METHODS: From July 2023 to September 2023, patients were enrolled to undergo CCTA using a dual-source PCD-CT system after coronary angioplasty with stent placement. SR images with a slice thickness/increment of 0.6/0.4 mm were reconstructed using a vascular kernel (Bv48), while UHR images with a slice thickness/increment of 0.2/0.2 mm were reconstructed using vascular kernels of six sharpness levels (Bv48, Bv56, Bv60, Bv64, Bv72, and Bv76). The in-stent lumen diameters were evaluated. Subjective image quality was also evaluated by a 5-point Likert scale. Invasive coronary angiography was conducted in 12 patients (25 stents). RESULTS: Sixty-nine patients (68.0 [61.0, 73.0] years, 46 males) with 131 stents were included. All UHR images had significantly larger in-stent lumen diameter than SR images (p < 0.001). Specifically, UHR-Bv72 and UHR-Bv76 for in-stent lumen diameter (2.17 [1.93, 2.63] mm versus 2.20 [1.93, 2.59] mm) ranked the two best kernels. The subjective analysis demonstrated that UHR-Bv72 images had the most pronounced effect on reducing blooming artifacts, showcasing in-stent lumen and stent demonstration, and diagnostic confidence (p < 0.001). Furthermore, SR and UHR-Bv72 images showed a diagnostic accuracy of 78.3% (95% confidence interval [CI]: 56.3%-92.5%) and 88.0% (95%CI: 68.8%-97.5%), respectively. CONCLUSION: UHR CCTA by PCD-CT leads to significantly improved visualization and diagnostic performance of coronary stents, and Bv72 is the optimal reconstruction kernel showing the stent struts and in-stent lumen. CLINICAL RELEVANCE STATEMENT: The significantly improved visualization of coronary stents using ultra-high resolution CCTA could increase the diagnostic accuracy for in-stent restenosis and avoid unnecessary invasive quantitative coronary angiography, thus changing the clinical management for patients after percutaneous coronary intervention. KEY POINTS: Coronary stent imaging is challenging with energy-integrating detector CT due to "blooming artifacts." UHR images using a PCD-CT enhanced coronary stent visualization. UHR coronary stent imaging demonstrated improved diagnostic accuracy in clinical settings.

Rationale for the Inclusion of ß-Blockers Among Major Antihypertensive Drugs in the 2023 European Society of Hypertension Guidelines.

We address the reasons why, unlike other guidelines, in the 2023 guidelines of the European Society of Hypertension ß-blockers (BBs) have been regarded as major drugs for the treatment of hypertension, at the same level as diuretics, calcium channel blockers, and blockers of the renin-angiotensin system. We argue that BBs, (1) reduce blood pressure (the main factor responsible for treatment-related protection) not less than other drugs, (2) reduce pooled cardiovascular outcomes and mortality in placebo-controlled trials, in which there has also been a sizeable reduction of all major cause-specific cardiovascular outcomes, (3) have been associated with a lower global cardiovascular protection in 2 but not in several other comparison trials, in which the protective effect of BBs versus the other major drugs has been similar or even greater, with a slightly smaller or no difference of global benefit in large trial meta-analyses and a similar protective effect when comparisons extend to BBs in combination versus other drug combinations. We mention the large number of cardiac and other comorbidities for which BBs are elective drugs, and we express criticism against the exclusion of BBs because of their lower protective effect against stroke in comparison trials, because, for still uncertain reasons, differences in protection against cause-specific events (stroke, heart failure, and coronary disease) have been reported for other major drugs. These partial data cannot replace global benefits as the main deciding factor for drug choice, also because in the general hypertensive population whether and which type of event might occur is unknown.

The Interplay between Dyslipidemia and Neighboring Developments in Coronary Artery Disease Progression: A Personalized Approach.

(1) Background: Estimates suggest that up to 10% of global annual cardiovascular deaths could be related to environmental factors. Not only air pollution components, but also noise exposure and climate changes, are highlighted as nontraditional causes of cardiovascular morbidity. The aim of this study was to identify possible urbanization risk factors for the progression of coronary artery disease in a group of patients with chronic coronary syndrome. (2) Method: There were 77 patients (50 (65%) males and 27 (35%) females) with a median age of 70 (60-74) years who underwent repetitive angiography due to chronic coronary syndrome between 2018 and 2022. The Gensini score was calculated for assessment of coronary artery disease advancement. Environmental factors including neighboring developments were taken into account in this analysis, including housing, commercial, and industrial developments within 300, 500, and 700 m distances (buffer) from the place of habitation. (3) Results: The multivariable analysis results for prediction of Gensini score progression in relation to 700 m buffer urbanization pointed out the significance of hyperlipidemia (OR: 4.24, 95% CI 1.34-13.39, p = 0.014), initial Gensini score (OR: 1.02, 95% CI 1.00-1.05, p = 0.112), and neighborhood housing (OR: 0.03, 95% CI 0.01-0.49, p = 0.025). (4) Conclusions: Hyperlipidemia and housing neighborhood can be regarded as possible factors for coronary disease progression in patients with chronic coronary syndrome with the use of optimal medical therapy.

Association of Traditional and Nontraditional Risk Factors in the Development of Strokes Among Young Adults by Sex and Age Group: A Retrospective Case-Control Study.

BACKGROUND: Despite women having fewer traditional risk factors (eg, hypertension, diabetes), strokes are more common in women than men aged ≤45 years. This study examined the contributions of traditional and nontraditional risk factors (eg, migraine, thrombophilia) in the development of strokes among young adults. METHODS: This retrospective case-control study used Colorado's All Payer Claims Database (2012-2019). We identified index stroke events in young adults (aged 18-55 years), matched 1:3 to stroke-free controls, by (1) sex, (2) age±2 years, (3) insurance type, and (4) prestroke period. All traditional and nontraditional risk factors were identified from enrollment until a stroke or proxy-stroke date (defined as the prestroke period). Conditional logistic regression models stratified by sex and age group first assessed the association of stroke with counts of risk factors by type and then computed their individual and aggregated population attributable risks. RESULTS: We included 2618 cases (52% women; 73.3% ischemic strokes) and 7827 controls. Each additional traditional and nontraditional risk factors were associated with an increased risk of stroke in all sex and age groups. In adults aged 18 to 34 years, more strokes were associated with nontraditional (population attributable risk: 31.4% men and 42.7% women) than traditional risk factors (25.3% men and 33.3% women). The contribution of nontraditional risk factors declined with age (19.4% men and 27.9% women aged 45-55 years). The contribution of traditional risk factors peaked among patients aged 35 to 44 years (32.8% men and 39.7% women). Hypertension was the most important traditional risk factor and increased in contribution with age (population attributable risk: 27.8% men and 26.7% women aged 45 to 55 years). Migraine was the most important nontraditional risk factor and decreased in contribution with age (population attributable risk: 20.1% men and 34.5% women aged 18-35 years). CONCLUSIONS: Nontraditional risk factors were as important as traditional risk factors in the development of strokes for both young men and women and have a stronger association with the development of strokes in adults younger than 35 years of age.