Incidence Of Coronary Artery Disease Research Articles

Does the type of aortic pathology affect periprocedural outcomes in patients undergoing thoracic endovascular aortic repair?

Aim: To examine whether the type of aortic pathology affects periprocedural outcomes in patients undergoing thoracic endovascular aortic repair (TEVAR). Material and Methods: This retrospective observational cohort study included 47 TEVAR patients in total. Based on the kind of aortic pathology, the patients were categorized into three groups: Group 1 (n=23) included patients with type B aortic dissection (TBAD), Group 2 (n=14) included patients with descending thoracic aortic aneurysm (DTAA), and Group 3 (n=10) included patients with thoracic aortic mural thrombus (TAMT). Preprocedural basic clinical features, procedural data, and postprocedural outcomes and complications were compared between the groups. Results: The study population consisted of 36 males and 11 females, with a mean age of 62.48±14.2 years. Most of the patients in Groups 1 and 2 were male (82.6% and 92.8%), while 40% of the patients in Group 3 were male, and this difference was statistically significant. Compared to patients in other groups, individuals in Group 2 were significantly older and exhibited a higher incidence of chronic obstructive pulmonary disease and coronary artery disease. Group 3 required thromboembolectomy more frequently during the postprocedural period. In terms of other postprocedural outcomes, complications and mortality, there were no significant differences between the groups. Conclusion: Our study demonstrated that the type of aortic pathology did not significantly influence periprocedural outcomes in patients undergoing thoracic endovascular aortic repair (TEVAR). The TEVAR procedure can be effectively performed in suitable patients with various pathologies of the descending thoracic aorta.

Abstract 4118183: Anxiety disorder, depression and coronary artery disease: associations and modification by genetic susceptibility

Background: Associations of anxiety disorder and depression with coronary artery disease (CAD) are heterogeneous between populations. Research questions: How does genetic susceptibility to CAD alter the associations between anxiety and depression and incident CAD? Aims: To investigate how genetic susceptibility to CAD alters the associations of anxiety and depression with incident CAD, comparing and combining anxiety and depression. Methods: This is a prospective cohort study using UK Biobank. Diagnoses of anxiety disorder and depression before the baseline assessment were ascertained through linked hospital admission data. Incident CAD was ascertained through hospital admission and death certificate data after baseline. CAD polygenic risk score (PRS) was obtained from CARDIoGRAMplus4 and categorised into low, intermediate, and high. Cox proportional hazard models were used to examine associations between anxiety and depression and CAD. The product term of PRS and these mental health conditions, and the relative excess risk due to interaction (RERI), were used to investigate the presence of multiplicative and additive interactions, respectively. Results: Our study included 288,152 participants of whom 54.4% were female, with a mean age of 56.4 years. Both anxiety disorder (HR: 2.24, 95% CI: 1.86–2.70) and depression (HR: 2.04, 95% CI: 1.80–2.32) were associated with CAD after adjusting for sociodemographic confounders. There was an addictive interaction between depression and PRS (RERI: 0.86; 95% CI: 0.06–1.65) such that the association between depression and CAD was strongest among those with a high PRS whilst there was no such evidence for anxiety disorder. Anxiety only (HR 1.69, 95% 1.17–2.45), depression only (HR 2.01, 95% CI 1.62–2.49) and concomitant anxiety and depression (HR 3.51, 95% CI 2.26–5.45) were associated with CAD even among people with a low PRS. Lifestyle mediators attenuated all these associations across PRS categories. Conclusions: CAD genetic susceptibility might partly contribute to the clustering of depression and CAD but does not provide a full explanation, nor does it explain the association between anxiety disorder and CAD. Therefore, other mechanisms should be explored.

The Co-Existence of Hypovitaminosis D and Diabetes Mellitus Triples the Incidence of Severe Coronary Artery Disease in Women

Background and Aims: Hypovitaminosis D is involved in the development and progression of atherosclerosis, and it is more prevalent in women. The differential impact of hypovitaminosis D on the severity of coronary artery disease (CAD) between genders remains poorly understood. This study aims to address this literature gap. Methods: A total of 1484 consecutive patients with acute myocardial infarction (AMI) were enrolled in the study. Hypovitaminosis D was defined as vitamin D ≤ 20 ng/mL. CAD was defined as the presence of at least one coronary vessel stenosis > 50%, while severe CAD was defined as left main disease and/or three-vessel disease > 50%. Results: The mean age of the cohort was 66.3 (11.5) years, with a predominance of the male gender (71.8%). Vitamin D values were significantly lower in women than in men (15.7 [8.4–25.4] ng/mL vs. 17.9 [11–24.3] ng/mL, p = 0.01). A higher prevalence of severe CAD was observed in female patients with hypovitaminosis D compared to those without (33% vs. 19%, p < 0.01). This finding was not observed in men. Among women, hypovitaminosis D significantly increased the risk of severe CAD (OR: 1.85, p = 0.01), together with diabetes mellitus (DM) and older age, adjusted for GFR < 60 mL/min/1.73 m2, cholesterol and body mass index. Furthermore, women with both hypovitaminosis D and DM had more than three times the risk of severe CAD compared with women who lacked both (OR: 3.56, p = 0.02). Conclusions: In women, hypovitaminosis D increases the risk of severe CAD, and the co-existence of hypovitaminosis D and DM triples the incidence of severe CAD.

Abstract 4136498: Analysis of Cardiovascular Events in Cancer Survivors: A Comparative Study of Solid Tumors and Hematologic Malignancies at a Tertiary Cardiovascular Center

Background: Cardiovascular disease (CVD) and cancer represent the leading contributors of death worldwide. Although advancements in antineoplastic therapies have notably enhanced prognoses, CVD now emerges as the primary cause of mortality in this population. Ojective: To assess the occurrence of CVD in cancer survivors and investigate disparities based on their previous cancer diagnosis, categorized into solid tumors or hematological malignancies. Methods: A cross-sectional study was conducted, including adult oncology survivors who had previously undergone oncological treatment and were referred to our center between 2010 and 2023 due to the presentation of major adverse cardiovascular events (MACE). They were categorized into two groups: those with hematological cancer and those with solid tumors. We used Chi2 test to assess differences between categorical variables and the Wilcoxon rank-sum test to evaluate differences in continuous parameters. Statistical analysis was performed using R 4.0 and StataMP 14.1. Results: A total of 214 oncological patients were included (median age: 69 [IQR: 55-80], women: 53%), comprising 164 (76.6%) with solid tumors and 50 (23.4%) with hematological cancer. Baseline characteristics were mostly similar between the groups (Table 1), with diabetes being more prevalent in patients with solid tumors (26% vs 12%, p=0.036). The prevalence of heart failure was predominantly NYHA I and II in solid tumors and NYHA III in hematological cancer (p=0.002) (Table 2). The incidence of coronary artery disease (CAD) was the most common MACE in solid tumors (39% vs 34%), but this was not statistically significant (p=0.04). In hematological cancer, the most frequent MACE was myocardial dysfunction, showing a significant difference (46% vs 24%, p=0.002). Similarly, valvular heart disease (VHD) appeared more frequently in this group (38% vs 20%, p=0.01). The remaining MACEs did not show significant differences, nor did the count of MACEs upon hospital arrival. Conclusion: Myocardial dysfunction and VHD exhibited a higher incidence in hematological cancer compared to solid tumors. Conversely, the incidence of CAD was higher in the solid tumor group; however, similar to the occurrence of other MACEs, there was no significant difference between the two groups. These findings could emphasize the importance of closely monitoring specific cancer types to enhance prevention strategies but still need further analysis to also determine the exact etiologies.

Abstract 4133122: Integrative Metabolomic Analysis of Triglyceride-Independent Lipoprotein Lipase Pathway Mechanisms for Coronary Artery Disease

Background: Strong genetic evidence supports the associations between key genes in triglyceride (TG) metabolism via the lipoprotein lipase (LPL) pathway (i.e., LPL , APOC3 , and ANGPTL3 ) and coronary artery disease (CAD). Given sparse human genetic or clinical trial evidence for other TG-modulating pathways, it is unclear if CAD risk reduction is due to reductions in TG levels alone or a secondary mechanism of action. Aim: To determine if there are TG-independent mechanisms of CAD risk reduction specific to the LPL pathway using genomics and metabolomics. Methods: We assessed the genetic effects of LPL pathway genes (67, 46, and 17 SNPs for LPL , APOC3 , and ANGPTL3 , respectively) and non-LPL pathway genes (3462 SNPs) for TG levels and 168 metabolites. We identified metabolites with associated effects that were greater than the associated effects with TG levels for LPL pathway genes and showed heterogeneity compared to the effects for non-LPL pathway genes. Cox proportional-hazards models were used to evaluate the association of candidate metabolites measured at baseline with incident CAD in participants of the UK Biobank. Models were adjusted for age, sex, TG levels, BMI, prevalent type 2 diabetes, statin, and ten PCs of genetic ancestry. Results: Among 233,719 UK Biobank participants free of prevalent CAD and with metabolite measurements, the mean (SD) age was 57.1 (8.0) years, 105,111 (45.0%) were male, and all self-reported as white. Over a median (IQR) follow-up of 11.2 (10.5-11.9) years, there were 7992 (3.4%) incident CAD cases. There were 30, 6, and 93 metabolites with significantly greater genetic effects for LPL , APOC3 , and ANGPTL3 than what was observed with TG levels, respectively. Among 20 metabolites with heterogeneity for ≥2 LPL pathway genes compared to non-LPL pathway genes, multi-variable Cox regression revealed 19 significantly associated with CAD (P<3x10 -4 ). Conclusion: LPL pathway genes have convergent and distinct impacts across metabolites. While LPL and ANGPTL3 have large genetic effects on VLDL metrics, APOC3 may have genetic effects beyond lipoprotein metabolism that impact CAD risk. The extent to which these metabolites influence CAD risk beyond TG alterations requires further study.

Abstract 4138517: Role of Coronary Computed Tomographic Angiography in Patients with Discordant Findings on Exercise Stress Echocardiography

Background: Exercise stress echocardiography is routinely used for risk stratification and diagnosis of myocardial ischemia in low-to-intermediate risk patients with suspected coronary artery disease (CAD). Discrepancies between exercise electrocardiography (EKG) and echocardiography (ECHO) are common in clinical practice. Prior literature suggests that patients with discordant stress test results generally have worse outcomes, though the extent of epicardial atherosclerotic disease remains unclear. Coronary computed tomographic angiography (CTA) has gained a class I recommendation for the assessment of atherosclerotic burden per ACC/AHA chest pain guidelines. Using non-invasive fractional flow reserve (CT-FFR), the functional significance of lesions can also be assessed. This study investigates the incidence and burden of CAD in patients with discordant exercise echocardiography findings. Methods: Patients aged 18 or older who had exercise echocardiography followed by CTA from January 1, 2013, to January 31, 2023, were retrospectively enrolled in this study and categorized into two discordant result groups: EKG+/ECHO- or EKG-/ECHO+. Those who failed to achieve the target heart rate or had a paced rhythm/left bundle branch block on baseline EKG were excluded. CTA findings were classified as no CAD, non-obstructive CAD (<50% stenosis), obstructive CAD (≥50% stenosis), and obstructive CAD with FFR+ (<0.75). Results: The study included 198 patients, the majority female (56.0%), with a mean age of 61 ±10 years. Among them, 159 (80.3%) were EKG+/ECHO- and 39 (19.7%) were EKG-/ECHO+ (Table 1). In the EKG+/ECHO- group, 55 (34.6%) had no CAD, 48 (30.2%) had non-obstructive CAD, and 56 (35.2%) had obstructive CAD, out of which 19 (33.9%) were FFR+. In the EKG-/ECHO+ group, 13 (33.3%) had no CAD, 17 (43.6%) had non-obstructive CAD, and 9 (23.2%) had obstructive CAD of which 3 (33.3%) was FFR+. There was no statistically significant difference in the degree of CAD between the two cohorts. Conclusions: The majority of patients with discordant results on exercise echocardiography were found to have CAD. There was no significant difference in the degree of disease between the EKG+/ECHO- or EKG-/ECHO+ groups. Overall, discordant results on exercise echocardiography should not be discounted and warrant further evaluation. CTA provides important information that can impact the diagnosis and further medical management of patients with chest pain and suspected CAD.

Abstract 4143289: Contemporary and Genomic Cardiovascular Risk Factors Have Explanatory Power Similar to Traditional Risk Factors for Incident Myocardial Infarction

Background: Modifiable cardiovascular risk factors (CRF) have been proposed to be responsible for 80-90% of the risk for incident coronary artery disease (CAD). However, these studies were conducted prior to the era of preventive medications, novel biomarkers, and genetic risk scores. The relative contributions of traditional and contemporary CRF in light of secular trends in worsening cardiometabolic health globally have not been assessed. Hypothesis: Including genetic risk scores and contemporary biomarkers will enhance discrimination and explainability of myocardial infarction (MI) incidence prediction. Methods: The UKBiobank was used to identify traditional CRF (hypertension, diabetes, dyslipidemia, smoking, waist-to-hip ratio (WHR), diet, exercise, alcohol intake and socioeconomic deprivation), and contemporary/genetic CRF (lipoprotein(a), high-sensitivity C-reactive protein [hsCRP], familial hypercholesterolemia [FH] variants, and polygenic risk score for CAD [PRS CAD ]). Incident MI was defined as first-time MI diagnosis or coronary revascularization. Base model discrimination was assessed using C-statistics from Cox proportional hazards models. Percent contribution of each risk factor was calculated by explanatory power lost via Nagelkerke R 2 after removal of the CRF from the full model. Population attributable risks (PAR) were additionally assessed for each model and CRF individually. Results: Over a median [IQR] follow-up of 11.0 [9.6, 12.5] years, 17409/299707 (5.8%) of participants developed incident CAD. C-statistics sequentially increased from base model to traditional CRF to contemporary/genetic CRF model with PAR of 84.3% (95% CI 82.4%-86.5%) ( Table 1 ). Among CRFs, hypertension (C 0.74, R 2 loss 15.2%, PAR 32.5%) and PRS CAD (C 0.72, R 2 loss 12.4%, PAR 38.4%) most strongly explained MI incidence by all 3 indices. Based on discriminability, ApoB:ApoA1 ratio (C 0.71, R 2 loss 3.4%), presence of diabetes (C 0.71, R 2 loss 2.2%), and log(hsCRP) (C 0.71, R 2 loss 1.82%) were subsequently prioritized. PAR analyses included prevalence in prioritization where WHR, presence of diabetes, and log(lipoprotein(a)) levels rose higher. Conclusions: The addition of genetic risk factors and contemporary biomarkers to explanatory models for CAD shows previously underappreciated importance of contemporary CRFs such as PRS, hsCRP, and lipoprotein(a) alongside traditional CRFs such as hypertension, dyslipidemia and presence of diabetes.

AGE-RELATED CHARACTERISTICS OF ISCHEMIC HEART DISEASE INCIDENCE IN UKRAINE: A TWO-CENTER STUDY

Purpose of this study is to investigate the age-related characteristics of the incidence of coronary heart disease in Ukraine, considering sex differences. Materials and Methods: The study included patients with coronary heart disease who underwent coronary artery bypass surgery on a beating heart (n = 3,674), comprising 3,061 males and 613 females. The average age of the participants was 60.6 ± 0.8 years. The analysis was based on data obtained from primary medical documentation, including medical histories, anamnestic information, and extracts from patients’ outpatient cards. The research design categorized participants by age group according to the World Health Organization age classification and by sex. Results: The article presents the incidence rates of coronary artery disease based on patient age groups, classified according to the World Health Organization, and sex. The distribution of patients by age groups was analyzed while considering sex, and the frequencies and average ages of the patients were determined. It was found that the incidence of coronary artery disease was highest among the most prevalent age groups in Ukraine's population: middle-aged and elderly patients. The frequency of early postoperative mortality was 0.6%, and it correlated with age-related incidence rates of coronary heart disease. Notably, early postoperative mortality was significantly higher in age groups with the highest incidence of coronary heart disease, specifically among middle-aged and elderly patients (p = 0.03, χ² = 4.69). Conclusions: In this retrospective two-center study of patients with coronary heart disease, it was determined that male patients were affected five times more frequently than female patients. The most common age groups for patients with coronary heart disease were identified as middle-aged and elderly. Early postoperative mortality following coronary artery bypass surgery on a beating heart was found to be 0.6%, with the highest rates observed in elderly (54.6%) and middle-aged (31.8%) patients. The frequency ratios demonstrated statistical significance favoring elderly patients (p = 0.03, χ² = 4.69). The frequency of early postoperative mortality was significantly higher among male patients (p = 0.0001, χ² = 40.33).

FOXO3 Longevity Genotype Mitigates Risk Posed by Hypertension on Incident Coronary Artery Disease in Middle-aged Men: Kuakini Honolulu Heart Program.

This study tested whether carriage of the longevity-associated G-allele of FOXO3 SNP rs2802292 (TG/GG) protects against incident coronary artery disease (CAD) in men with hypertension. Subjects were American men residing on Oahu having Japanese (n=5415) or Okinawan (n=897) ancestry and free of CAD at baseline (1965-1968) when aged 45-68 years. During follow-up there were 1,629 incident CAD cases. Adjusting for age and cardiovascular disease risk factors, the main effect Cox model showed that in men of Japanese ancestry, hypertension was a strong predictor of CAD (HR 1.61; 95% CI 1.44-1.80), P<0.0001), but TG/GG genotype was not associated with CAD (HR 0.92; 95% CI = 0.82-1.02; p=0.11). A full Cox model showed the interaction of TG/GG with hypertension was significant (β = -0.23, p=0.038). Stratified by hypertension status, TG/GG genotype TG/GG had a protective effect against CAD in each group (HR 0.83; 95% CI 0.71-0.96; p=0.021 in men of Japanese heritage, and HR 0.66; 95% CI 0.43-1.01; p=0.054 in men of Okinawan heritage). No association with CAD was seen in normotensive men having either Japanese (HR 1.04; 95% CI 0.89-1.22; p=0.61) or Okinawan (HR 0.95; 95% CI 0.66-1.38; p=0.79) heritage. The present prospective study found longevity associated FOXO3 genotype did not independently affect risk of CAD in all men. Rather, it was associated with protection against incident CAD in men with hypertension. Hypertensive middle-aged men with FOXO3 TT genotype may merit particular attention in CAD prevention programs.

Triggering type and long-term survival following ST segment elevation-myocardial infarction treated with primary percutaneous coronary intervention.

Physical and emotional stress are recognized triggers of acute coronary syndromes, including ST segment elevation-myocardial infarction (STEMI). We have previously shown that identifiable triggers precede symptoms in over one-third of STEMI patients and inversely correlate with the extent of coronary artery disease (CAD). This study aims to investigate the association between trigger type (physical vs. emotional) and long-term mortality in STEMI patients treated with primary percutaneous coronary intervention (PCI). This retrospective, single-center observational study included all patients admitted with an STEMI diagnosis from January 2008 to December 2013. Physical and emotional triggers were identified retrospectively from patient records. Mortality data were obtained from the Israeli Ministry of Health. Of 1345 consecutive STEMI patients treated with primary PCI, mortality data were available for 1267 patients (median age: 61 years). A trigger preceding symptoms onset was identified in 36.5% of patients, with 85% experiencing physical stress and 15% emotional stress. Triggered STEMI patients tended to be younger with fewer comorbidities and lower incidence of multiple vessel CAD compared with nontriggered patients. Notably, emotionally triggered STEMI patients exhibited improved long-term survival compared with those without emotional triggers or with physical triggers. predictor of enhanced long-term survival post-PCI compared with physical triggering. Emotional triggering was identified as an independent. Patients with emotionally triggered STEMI showed less extensive CAD and improved long-term survival following PCI compared with those with physically triggered STEMI. These findings highlight the importance of considering both the presence and type of trigger in the management of STEMI patients and their long-term prognosis.

Hypertensive Disorders of Pregnancy Increase the Risk for Myocardial Infarction: APopulation-Based Study.

Angiographic evidence of the anatomy of coronary arteries and the type of coronary artery lesions in women with a history of hypertensive disorders of pregnancy (HDP) are poorly documented. This study sought to determine the role of a history of HDP as a unique risk factor for early coronary artery disease (CAD) and type of acute coronary syndrome (ACS) (ie, atherosclerotic vs myocardial infarction with nonobstructive coronary arteries [MINOCA]) in women who underwent coronary angiography. This study used a population-based cohort of parous female patients with incident CAD who underwent coronary angiography and age-matched control subjects. The SYNTAX (Synergy between PCI [percutaneous coronary intervention] with TAXUS [Boston Scientific] and Cardiac Surgery) score was assessed to determine the complexity and degree of CAD; MINOCA was diagnosed in the presence of clinical acute myocardial infarction in the absence of obstructive coronary disease. A total of 506 parous female Olmsted County, Minnesota (USA) residents had incident CAD and angiographic data from November 7, 2002 to December 31, 2016. Women with HDP were younger than normotensive women at the time of the event (median: 64.8 years vs 71.8 years; P=0.030). There was a strong association between HDP and ACS (unadjusted P=0.018). Women with HDP compared with women with normotensive pregnancies were more likely to have a higher SYNTAX score (OR: 2.28; 95%CI: 1.02-5.12; P=0.046), and MINOCA (OR: 2.08; 95%CI: 1.02-4.25; P=0.044). A history of HDP is associated with CAD earlier in life and with a future risk for myocardial infarction with both obstructive and nonobstructive coronary arteries. This study underscores the need for timely detection and treatment of nonobstructive disease, in addition to traditional risk factors.

Ultrasound-mediated cardiovascular thrombolysis: from Sonothrombolysis to Sonoperfusion.

The incidence of coronary artery disease has been increasing in recent years, with acute myocardial infarction as its most severe onset. The major aim for clinical treatment is to restore myocardial blood supply with the recanalization of coronary circulation as early as possible, while the still existed issue of microcirculation thromboembolism has become a serious obstacle. Thus, thrombus elimination in coronary microcirculation is crucial and essential to improve the treatment outcome of acute myocardial infarction. In recent years, from sonothrombolysis to sonoperfusion, ultrasound-mediated cardiovascular thrombolysis can effectively solve the problem of vascular thromboembolism, including microcirculation thromboembolism, and the treatment method is expected to obtain satisfied thrombolytic treatment effect with microthrombus elimination in coronary microvessels and function recovery of terminal microcirculation, which has potential clinical value for the establishment of novel treatment for coronary thromboembolism. Therefore, this paper reviews ultrasound-mediated cardiovascular thrombolysis including sonothrombolysis and sonoperfusion for the application exploration in the treatment of coronary artery thromboembolism, the mechanism of action, and its research progress.

PERFIL DE PACIENTES SUBMETIDOS A TOMOGRAFIA DE CORONÁRIAS EM UM SERVIÇO DE IMAGEM CARDIOVASCULAR DE SERGIPE

Introduction: Computed tomography angiography (CT angiography) of the coronary arteries can identify coronary artery disease (CAD) in its early stages. CAD is characterized by a narrowing of the arterial lumen due to the accumulation of fatty plaques in its walls. Currently, the gold standard for diagnosis is coronary angiography, an invasive measure that seeks to visualize the arterial lumen. The aim of this study was to characterize an outpatient sample using CT angiography as a diagnostic method. Methodology: This cross-sectional, observational prevalence study was based on data collection at a clinic in the city of Aracaju, where the angiotomography results of 210 patients were analyzed, 115 females and 95 males, tabulated as absolute numbers, percentages and averages. Results: The correlation of gender and age with the presence of luminal reduction showed that men and older individuals had a higher degree of alterations on CT angiography. When assessed by territory, the Left Coronary Trunk (LCT) often showed no luminal reduction, with the Anterior Descending Trunk showing the most alterations. Men present more lesions in the Right Coronary and Anterior Descending. Conclusion: Several factors can influence the incidence of CAD, gender and age being among the most important, as shown by the higher incidence in older men than in women or in younger individuals with luminal reduction.

The association between periodontal disease and coronary artery disease: insights from imaging, observational and genome-wide data

Abstract Background Periodontal disease is the sixth most common disease worldwide. It has been suggested that it may be a contributory risk factor for coronary artery disease (CAD). From a public health perspective, prevention of periodontal disease is relatively straightforward and cost-effective: daily brushing, flossing and, where applicable, smoking cessation. Purpose This study utilises imaging, longitudinal and genomic data to characterise the association between periodontal disease and CAD. Methods 481,915 individuals from the UK Biobank were included in this study, 18.9% (n = 91,022) of whom had self-reported periodontal disease. For the imaging analysis, a maximum of 59,019 had paired cardiovascular magnetic resonance (CMR) data. Multivariable linear regression models were constructed to examine the association of periodontal disease on CMR outcomes with LV end-diastolic volume, LV mass, LV mass:volume ratio (MVR), LV ejection fraction, LV global longitudinal strain and native T1 values considered as prognostically important phenotypes. The relationship between periodontal disease and incident CAD was assessed using Cox proportional hazards regression models. To examine the relationship of genetically-determined periodontal disease on CAD, a de novo GWAS for periodontal disease was performed and a genome-wide polygenic risk score (PRS) was constructed. Results Periodontal disease was associated with a significantly higher LV MVR (effect size = 0.00233, 95% confidence interval [CI] = 0.0006, 0.004) and significantly lower LV native global T1 value (effect size = -0.86 ms, 95% CI = -1.63, -0.09). The presence of periodontal disease was independently associated with a significantly increased hazard of incident CAD (HR = 1.09, 95% CI = 1.07, 1.13) at a median follow-up time of 13.8 years (Figure 1). Each standard deviation increase in the periodontal disease PRS was associated with increased odds of CAD (OR = 1.03, 95% CI = 1.02, 1.05) (Figure 2). Conclusion Using an integrated approach across imaging, observational and genomic data, periodontal disease is independently associated with biomarkers of subclinical remodelling as well as incident CAD. These findings highlight the potential importance of periodontal disease in the broader context of cardiovascular disease prevention.

Multi-modality deep learning model for prediction of chronic obstructive coronary artery disease

Abstract Background/Introduction The incidence of coronary artery disease (CAD) is on the rise with an increasing burden of stable ischemic heart disease (SIHD) and high prevalence of obesity, diabetes, hyperlipidemia, and other cardiovascular risk factors. Pre-test probability estimation for CAD based on demographic features and characterization of chest pain is insufficient to accurately assess whether further evaluation for CAD is warranted. Purpose To develop and validate a deep learning (DL) algorithm utilizing electrocardiogram (ECG) waveforms and clinical features to predict obstructive CAD. Methods Clinical data from subjects undergoing invasive angiography over a 4-year period at a quaternary care center exclusive of subjects who had concern for acute coronary syndromes were used for model training. ECGs obtained up to 5 years prior to angiography were included; ECGs were partitioned 8:1:1 for training, validation, and test datasets. Obstructive CAD was defined as receiving percutaneous coronary intervention during elective angiography. Convolutional neural network models were developed for ECG waveforms alone (DL-ECG), clinical features from standard risk scores (DL-Clinical), and the combination of ECG waveforms and clinical features (DL-ECG+Clinical); a commonly used pre-test probability estimation tool derived from the CAD Consortium study was used as a comparison (PTP). The models were evaluated based on area under the curve receiver operating characteristics (AUC). Shapley additive explanations (SHAP) analysis was performed to understand feature importance in the DL models. Results A total of 40,602 ECGs and 8,361 coronary angiograms from 7,201 patients were included in the analysis. The median age was 66 (IQR 56-75), 71.9% were men, 34.9% had hypertension, 30.6% had diabetes mellitus, and 39.0% had dyslipidemia. The PTP model (AUC 0.733 [0.717-0.750]) had similar performance as the DL-Clinical model (AUC 0.762 [0.746-0.778]). The DL-ECG model (AUC 0.741 [0.726-0.758]) had similar performance as both the clinical feature models. The DL-ECG+Clinical model (AUC 0.807 [0.793-0.822]) trained on ECG waveforms and clinical features had a superior performance (Figure 1). SHAP analysis for the DL-ECG+Clinical model revealed that ECG waveforms had the largest influence on the model’s output followed by age and chest pain type (Figure 2). Conclusions Multi-modality DL model utilizing ECG and commonly used features can improve prediction of obstructive CAD in SIHD compared to traditional pre-test probability estimates. Prospective research is warranted to determine whether incorporation of DL methods to ECG analysis effectively improves diagnosis and outcomes in obstructive CAD.Figure 1.Figure 2.

Vitamin K2 and the Vitamin-K-Cycle-Enzyme VKORC1L1 improve endothelial regeneration by inhibiting endothelial-mesenchymal transition, inflammatory cell activation and ferroptosis

Abstract Introduction Vascular inflammation is a crucial contributor to atherosclerosis, in which oxidative stress, endoplasmic reticulum (ER) stress and transition of endothelial to mesenchymal cells (EndMT) are of critical importance. Vitamin-K-antagonists (VKA) promote vascular dysfunction, while dietary vitamin K intake was proposed to reduce incidence of coronary artery disease, but the mechanisms remain unresolved. Key enzyme for regeneration of vitamin K is the Vitamin K epoxide reductase complex subunit 1 (VKORC1), which also represents the pharmacological target of VKA. VKOR-like1 (VKORC1L1) is an isoenzyme of VKORC1, which resides at the ER-membrane, exerts antioxidative properties and is involved in vitamin K maintenance. Aim of this study was to investigate the role of Vitamin K2 and the VKOR-enzymes in endothelial cell inflammation. Methods and Results In human coronary artery endothelial cells (HCAEC), Vitamin K2 improves endothelial regeneration by increasing proliferation and cell viability and by reducing both apoptosis and ferroptosis (relative viability: RSL3 0.11 ± 0.01 vs 0.32 ± 0.05 RSL3+K2-1µM vs. 0.44 ± 0.11 RSL3+K2-10µM, p&amp;lt;0.001). Moreover, Vitamin K2-supplementation inhibits EndMT by reducing expression of mesenchymal markers (Calponin, SM22; Fig.1). In silico analyses of the proteome of human coronary atherosclerosis revealed increased expression of VKORC1L1, but not of VKORC1. In vitro induction of oxidative stress and ER-Stress promoted time- and dose-dependent enhanced expression of VKORC1L1, without altering VKORC1 expression (H2O2: 2.3-fold vs. 0.8-fold after 40 minutes, p=0.04; tunicamycin: 1 μg/ml: 1.43-fold vs. 0.8-fold, p&amp;lt;0.01). Likewise, siRNA-mediated VKORC1L1 knockdown induces an inflammatory gene signature with upregulation of NFkB-signalling and endoplasmic reticulum stress (NF-κB: 1.95-fold ± 0.13, GRP78: 1.32-fold ± 0.04 vs. control, p&amp;lt;0.01). Furthermore, VKORC1L1 downregulation increased formation of reactive oxygen species (ROS) and reduced proliferation (EdU signal: 0.56 ± 0.02 vs. control, p &amp;lt; 0.01). In contrast, VKORC1-knockdown does not impair endothelial regeneration and function (Fig.2). Vitamin K2 reduces vascular inflammation and endoplasmic reticulum stress in the case of VKORC1-, but not VKORC1L1-knockdown. In addition, inducing EndMT resulted in a reduction of VKORC1L1, but not of VKORC1, while VKORC1L1-knockdown aggravates EndMT. Conclusion VKORC1 and its isoenzyme VKORC1L1 exhibit divergent effects on endothelial cell inflammation. Further studies are warranted to shed light on the regulation of the enzymes to improve our understanding regarding vascular side effects of VKA treatment and beneficial effects of vitamin K supplementation.

Sex-differences in the clinical features, managements and outcomes of early-onset atherosclerotic coronary artery disease in China

Abstract Background/Introduction There is an alarming rise in the incidence of atherosclerotic coronary artery disease (CAD) among young adults, particularly in young women. Sex disparities of early-onset CAD in the context of contemporary cardiovascular practice are not well understood. Purpose We aimed to delineate the differences in clinical profiles and prognosis between young men and women with established early-onset CAD. Methods This is a nationwide, hospital-based, longitudinal prospective cohort study. Young patients (aged ≥18 years and ≤ 45 years) with angiographically confirmed severe atherosclerotic obstructive coronary arteries (luminal narrowing ≥ 70%) were included from 38 hospitals across China between May 2017 and May 2020. Coronary risk factors, clinical features and treatments were compared between men and women at baseline. Participants were followed for 3 years. The outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction (MI), unplanned revascularization, and ischemic stroke. The Cox regression analyses were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for outcome. Results There were 1524 patients (female: 4.4%) included in this study. The female patients were older than the male patients (41.1±4.0 years for females vs. 39.6±4.4 years for males, p=0.006). They showed a lower prevalence of hypertension, lipid disorders, and smoking or drinking (all p&amp;lt;0.01). The female patients were less likely to have at least 1 modifiable risk factors (female: n=45 (67.2%) vs. male: n=1382 [94.6 %], p&amp;lt;0.001); they showed more favorable laboratory results at baseline, including lipids, serum creatinine and uric acid (all p&amp;lt;0.05) as compared to male patients. Besides, young females presented more often with stable angina on admission, whereas young males tended to present with acute MI (p&amp;lt;0.001). There was no significant sex difference in Gensini Score (p=0.15). Female patients were less likely to undergo revascularization procedures than male patients (73.1% vs. 85.3%, p=0.01). During the 3 years of follow-up, female patients were at a significantly higher risk of MACE compared to their male counterparts (13.4% vs. 5.8%, adjusted HR: 3.07, 95% CI:1.36–6.94, p=0.007) after adjusting for age, smoking, drinking, body mass index, hypertension, diabetes, dyslipidemia, diagnosis and revascularization. Conclusions Distinct sex disparities, unfavorable to young females, were documented among patients with early-onset CAD, with the largest gaps noted in the treatment and prognosis. Despite more favorable baseline profiles, young female patients had insufficient care and 3-fold greater risk for MACE compared to young males. These results highlight the need for strengthening the treatment strategies for this vulnerable disease entity.Figure 1

Coronary artery disease polygenic risk score in patients undergoing coronary angiography and risk of future revascularization

Abstract Background Coronary artery disease (CAD) polygenic risk score (PRS) is a strong predictor of incident CAD. The role of CAD PRS in patients with known or suspected CAD already presenting for invasive coronary angiography remains poorly understood. Purpose We aimed to (i) study the association between CAD PRS and coronary angiography traits, and (ii) determine whether CAD PRS can predict risk of future revascularization after an initial coronary angiogram. Methods Patients who underwent coronary angiography at a single hospital and were part of its biobank were included in the study. Participants were classified into 3 risk groups based on CAD PRS distribution–low (0-20%), intermediate (21-80%), and high (81-100%)–computed from a recently reported PRS comprised of 1,296,172 variants (GPSMult, PGS003725). Revascularization was defined as a composite of coronary artery bypass graft and percutaneous coronary intervention with a 3-month blocking window after the initial angiogram. Associations between coronary stenosis severity and burden, and CAD PRS were assessed using multinomial logistic regression adjusted for age, sex, and genetic ancestry. The cumulative incidence of revascularization was tested using Fine-Gray regression accounting for competing risk of all-cause mortality and compared across CAD PRS strata by log-rank test. Results Among 3,518 participants (29.90% female, mean age 63.29±12.14 years), 2,568 (73%) had angiographic evidence of CAD – 340 (13.24%) mild, 346 (13.47%) moderate, and 1,882 (73.29%) severe. Out of those with CAD, 844 (32.87%) presented with acute coronary syndromes (ACS) and 1,724 (67.13%) with stable CAD. CAD PRS was strongly associated with angiographic presence of CAD (OR 2.62, 95%CI 2.08-3.29) and this did not differ among patients presenting with ACS vs. stable CAD (Fig1A). The association was weakest for mild CAD (OR 1.14, 95%CI 0.77-1.68) and strongest for severe CAD (OR 3.04, 95%CI 2.40-3.84). Besides severity, CAD PRS was also strongly associated with angiographic burden of CAD with the strongest association observed for presence of left main coronary stenosis (OR 2.63, 95%CI 1.86-3.73). Each standard deviation increase in CAD PRS was associated with a 10-point increase in the Gensini score, a continuous measure of angiographic burden of CAD (p&amp;lt;2e-16) (Fig1B). Over a mean follow-up period of 9.26±5.81 years, 659 (18.73%) patients required revascularization at a mean period of 5.31±4.69 years. Risk of revascularization varied dramatically by CAD PRS; HR was 1.64 (95%CI 1.28-2.10, p=8.7e-5) for high vs. low CAD PRS (Fig2). CAD PRS remained predictive of future revascularization even after adjusting for the angiographic burden of CAD at baseline (HR 1.41, 95%CI 1.09-1.82, p=7.9e-3). Conclusion CAD PRS is strongly associated with severity and burden of CAD assessed on coronary angiography and is predictive of future risk of revascularization even after accounting for baseline disease burden.Figure 1.CAD PRS and angiographic traitsFigure 2.CAD PRS and revascularization

Deciphering lipoprotein(a) atherogenicity with use of high-throughput proteomics

Abstract Background Accumulating observational and genetic evidence suggests that lipoprotein(a) [Lp(a)], is significantly more atherogenic than other apolipoprotein-B containing particles. Systemic inflammation is thought to mediate the atherogenic effects of Lp(a). Previous studies have predominantly focused on single inflammatory biomarkers, an approach that fails to capture the broader molecular response to elevated Lp(a) levels. Purpose The aim of this study was to derive a proteome-wide signature of plasma Lp(a) concentrations and subsequently identify the pathways through which Lp(a) influences the risk of coronary artery disease (CAD). Methods This study included 41,123 UK Biobank participants with baseline Lp(a) measurements who also underwent a proteomic assessment. Relative concentration of 2,920 proteins was quantified in EDTA plasma samples using a high-throughput proximity extension assay. Lp(a)-associated proteins were identified in linear regression models, adjusting for age, sex, body mass index, race, smoking status, estimated glomerular filtration rate, medication use, and apolipoprotein B. Proteins linked with Lp(a) concentration were then evaluated for their association with incident CAD risk using Cox proportional hazards models. Significant traits were further included in pathway enrichment analysis. Results Out of 2,920 analyzed proteins (Figure 1), 140 showed a positive association with Lp(a) concentration, while 336 exhibited a negative association after adjustment for multiple testing (False discovery rate &amp;lt; 0.05). The strongest positive associations were observed for apolipoprotein F, group 10 secretory phospholipase A, and C4b-binding protein beta chain. The strongest negative associations were observed for asporin, aminoacylase-1, and retinol-binding protein 5. Among 140 proteins positively associated with Lp(a), 49 were associated with an increased risk of CAD. Conversely, among the 336 proteins negatively associated with Lp(a), 10 were associated with a decreased risk of CAD. Pathway enrichment analysis (Figure 2) indicated that proteins linked with both Lp(a) levels and CAD risk predominantly upregulated pathways related to peptide-ligand receptor signalling, platelet degranulation, neutrophil degranulation, and cytosolic calcium response. Conversely, pathways related to HDL remodeling, PI3K/AKT, KIT, and nuclear receptor signalling were downregulated. Conclusions The greater atherogenic potential of Lp(a) may be attributable to the modulation of several molecular pathways, particularly those involving platelet and neutrophil responses, cell signalling, and lipoprotein metabolism.

The relationship between repeated measurements of HbA1c and risk of coronary events among the common haptoglobin phenotype groups: the Action for Health in Diabetes (Look AHEAD) study

BackgroundIn the ACCORD study, participants with the haptoglobin (Hp) 2–2 phenotype and glycated hemoglobin (HbA1c) ≥ 8.0% had a higher risk of coronary artery disease (CAD) compared to those with HbA1c 7.0–7.9%. However, this association was not observed in participants without the Hp2-2 phenotype. The optimal glycemic target for CAD prevention for the Hp phenotypes remains uncertain and may vary based on demographic and clinical factors.ObjectiveTo investigate how reaching clinically relevant HbA1c targets relates to the risk of CAD in different Hp phenotype groups among a diverse cohort of individuals with T2DM (the Look AHEAD study, HbA1c ≤ 11% at baseline).MethodsCox regression models with time-varying covariables were used to quantify the association between time-varying achieved HbA1c (< 6.5%, 6.5–6.9%, and ≥ 8.0% compared to 7.0-7.9%), updated at years 1–4, 6, 8, and 10, and incident CAD in the Hp2-2 (n = 1,587) and non-Hp2-2 (n = 2,944) phenotypes separately. Further pre-specified subgroup analyses by age, sex, history of cardiovascular disease (CVD), race, and diabetes duration were performed in each Hp phenotype group separately.ResultsCompared with HbA1c 7.0-7.9%, having HbA1c < 6.5% was associated with a 29% lower CAD risk among participants with the non-Hp2-2 phenotype (adjusted HR 0.71, 95% CI 0.55–0.90). In subgroup analyses, this association was present in participants with the non-Hp2-2 phenotype who were male (0.60, 0.44–0.83), who did not have a history of CVD (0.65, 0.47–0.90), who were aged ≥ 65 years (0.64, 0.44–0.94), who were White (0.68, 0.51–0.91), or who had diabetes duration > 10 years (0.58, 0.35–0.95). HbA1c ≥ 8.0% was associated with CAD risk only among participants with the Hp2-2 phenotype who had a history of CVD (1.79, 1.00-3.20). No associations were found between the other HbA1c targets and CAD risk when participants with the Hp2-2 phenotype were grouped together or divided into subgroups.ConclusionThe differences in our results compared to our previous findings may be due to variations in the study populations and factors associated with weight loss, making it difficult to draw definitive conclusions. Our current findings should be considered in the context of hypothesis generation, and ideally, will encourage additional research in this field.