Risk Factors For Coronary Disease Research Articles

The intersection of allergy and acute coronary syndrome: a type II Kounis syndrome case report.

This case report discusses a rare occurrence of type II Kounis syndrome, characterised by an acute myocardial infarction triggered by an allergic reaction. The patient, a young adult male, experienced urticaria soon after eating oysters, which quickly escalated to severe chest discomfort. Despite lacking typical cardiac risk factors, the electrocardiogram showed indications of ST-elevation myocardial infarction. This condition was further complicated by ventricular fibrillation, necessitating urgent life-saving measures. This case demonstrates the intricate and often overlooked relationship between hypersensitivity reactions and cardiovascular events. It highlights the necessity for increased vigilance and rapid diagnostic and treatment approaches in handling Kounis Syndrome, especially in emergency situations. The case underscores the importance of considering allergic causes in acute cardiac scenarios, particularly in patients who do not have standard risk factors for coronary artery disease.

Modeling the Impact of Extracellular Vesicle Cargoes in the Diagnosis of Coronary Artery Disease

Objectives: We aimed to assess the relationship among circulating extracellular vesicles (EVs), hypoxia-related proteins, and the conventional risk factors of life-threatening coronary artery disease (CAD) to find more precise novel biomarkers. Methods: Patients were categorized based on coronary CT angiography. Patients with a Segment Involvement Score > 5 were identified as CAD patients. Individuals with a Segment Involvement Score < 5 were considered control subjects. The characterization of EVs and analysis of the plasma concentration of growth differentiation factor-15 were performed using multicolor or bead-based flow cytometry. The plasma protein levels of glycogen phosphorylase, muscle form, clusterin, and carboxypeptidase N subunit 1 were determined using an enzyme-linked immunosorbent assay. Multiple logistic regression was used to determine the association of the biomarkers with the CAD outcome after accounting for established risk factors. The analysis was built in three steps: first, we included the basic clinical and laboratory variables (Model 1), then we integrated the plasma protein values (Model 2), and finally, we complemented it with the circulating EV pattern (Model 3). To assess the discrimination value of the models, an area under (AUC) the receiver operating curve was calculated and compared across the three models. Results: The area under the curve (AUC) values were 0.68, 0.77, and 0.84 in Models 1, 2, and 3, respectively. The variables with the greatest impact on the AUC values were hemoglobin (0.2 (0.16–0.26)) in Model 1, carboxypeptidase N subunit 1 (0.12 (0.09–0.14)) in Model 2, and circulating CD41+/CD61+ EVs (0.31 (0.15–0.5)) in Model 3. A correlation analysis showed a significant impact of circulating CD41+/CD61+ platelet-derived EVs (p = 0.03, r = −0.4176) in Model 3. Conclusions: Based on our results, the circulating EV profile can be used as a supportive biomarker, along with the conventional laboratory markers of CAD, and it enables a more sensitive, non-invasive diagnostic analysis of CAD.

Abstract 4122710: Impact of cigarette smoking on long-term clinical outcomes in patients with coronary chronic total occlusion lesions

Cigarette smoking is a significant risk factor for coronary artery disease (CAD). However, evidence regarding on the long-term clinical effects of smoking in the Asian population with chronic total coronary occlusion (CTO) is insufficient. This study aimed to assess the effects of smoking on 5-year (median follow-up period 4.2 ± 1.5 years, interquartile range 4.06-5.0 years) clinical outcomes in patients with CTO lesions who had undergone percutaneous coronary intervention (PCI) or medical treatment (MT). We enrolled 681 consecutive patients with CTO who had undergone diagnostic coronary angiography and subsequent PCI or MT. Patients were categorized into smokers (n = 304) and non-smokers (n = 377). The primary endpoint encompassed major adverse cardiovascular events (MACE), including a composite of all-cause death, myocardial infarction (MI), and revascularization over a 5-year period. Propensity score matching (PSM) analysis was used to adjust for potential baseline confounders. After PSM analysis, two propensity-matched groups (200 pairs, n = 400) were generated, and the baseline characteristics of both groups were balanced. The smokers exhibited a higher cardiovascular risk of MACE (29.5% vs. 18.5%, p = 0.010) and non-target vessel revascularization (17.5 vs. 10.5%, p = 0.044) than those of the non-smokers(Table 1). In a landmark analysis using Kaplan-Meier (KM) curvesat the 1-year, the smokers had significantly higher rate of MACE in early period (up to 1-year) (18.8% and 9.2%, p=0.008) compared with non-smokers(Figure 1). Cox hazard regression analysis by propensity score-adjustedwith , revealed that smoking was independently associated with an increased risk of MACE. The findings indicate that smoking is a strong cardiovascular risk factor in patients with CTO, regardless of treatment strategies (PCI or MT) (Figure 2). In addition, in a subgroup analysis, the risk of MACE was most prominently elevated in the group of smokers who underwent PCI.

Abstract 4124039: Aging-Associated Protein Medin Induces Human Coronary Artery Endothelial Proinflammatory and Prothrombotic Activation

Background: Age is the most important risk factor for coronary artery disease (CAD), independent of traditional risk factors such as hypertension, diabetes (DM), hyperlipidemia and smoking, through poorly understood mechanisms. Medin, a cleavage product of MFGE8 protein that forms the most common human amyloid, accumulates in the vasculature with age, including the coronary arteries. Although medin amyloid has been implicated in various diseases such as Alzheimer’s disease, vascular dementia and aortic aneurysms, its role in CAD remains unknown. Medin was shown to induce changes characteristic of vascular aging, such as endothelial and smooth muscle dysfunction in human donor cerebral arteries. Medin also induced proinflammatory activation of human brain microvascular endothelial cells through NFκB activation . Aims: To determine the effects of medin on pro-inflammatory and prothrombotic activation of human coronary artery endothelial cells (HCAECs). Methods: Primary HCAECs (passages 6-8) were exposed for 20 hours to physiologic doses of recombinant medin (0.5, 1 and 5 µM) and gene expression of pro-inflammatory proteins (IL-6, IL-8, IL-1b and intercellular adhesion molecule (ICAM)-1), prothrombotic protein (plasminogen activator inhibitor (PAI)-1) and anticoagulant membrane protein thrombomodulin were quantified using rtPCR and compared. Separately, HCAECs were exposed to medin (0.5, 1 and 5 µM) with or without small molecule specific inhibitor of NFκB (RO106-9920, 10 uM) for 20 hours and protein expression of IL-6 in conditioned media was measured using ELISA. Results: Medin caused dose-dependent increases in gene expressions of pro-inflammatory cytokines IL-6, IL-8, IL-1b, ICAM-1 (Figure 1 A-D). Medin caused a dose-dependent increase in PAI-1 and a dose-dependent decrease in thrombomodulin (Fig. 1 E-F). Co-treatment with RO106-9920 prevented medin-induced increase in IL-6 protein expression (Fig. 1G). Conclusions: Medin induces pro-inflammatory and prothrombotic activation of human coronary artery endothelial cells. The proinflammatory activation is likely NFκB-dependent. Medin is a promising potential novel mediator of CAD and vascular aging.

Abstract 4137895: Serum High-density Lipoprotein-Associated Paraoxonase-1 Levels Predict Recurrent Cardiovascular Events after Stent Implantation in Patients with Stable Angina Pectoris

Background: Poor clinical outcomes for patients undergoing hemodialysis (HD) after drug-eluting stent (DES) implantation have been reported. High-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease, and its anti-oxidant property has been attributed mainly to the HDL-bound enzyme paraoxonase-1 (PON-1). Myeloperoxidase (MPO), a pro-oxidant enzyme released from activated neutrophils, has been shown to alter the atheroprotective function of HDL to a dysfunctional form. The aim of this study was to investigate the relationship between plasma MPO and serum PON-1 levels after implantation of DES in patients with stable angina pectoris (SAP) with and without HD. Methods: Serum PON-1 concentrations and PON-arylesterase activity were measured in 183 patients with SAP after DES implantation (HD group, n=37; non-HD group, n=146) with a sandwich ELISA method. Cardiovascular events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction, cerebral infarction and other non-fatal events including unstable angina pectoris or coronary revascularization. Results: Serum PON-1 concentrations and PON-arylesterase activity were significantly lower in the HD group than in the non-HD group (PON-1 concentrations, P<0.0001; PON-arylesterase activity, P<0.0001). In addition, plasma MPO in patients undergoing HD were significantly higher than in patients not undergoing HD (P<0.0001). Moreover, plasma MPO showed a significant inverse correlation with serum PON-1 concentrations and PON-arylesterase activity (concentration: R= -0.24, P=0.0013; arylesterase-activity: R=-0.24, P=0.0014). Cardiovascular event rates were significantly higher in the HD group than in the non-HD group (67.6% vs. 43.8%, P<0.01). Kaplan-Meier survival analysis showed that the low-PON-1 group (<58.0 mg/mL, median) had a significantly worse outcome than the high-PON-1 group ( P =0.013). Multivariate analysis showed that a low serum PON-1 concentration was the only independent predictor of cardiovascular events (odds ratio, 1.93; 95% confidence interval, 1.10 to 3.40, P =0.024). Conclusions: These findings demonstrate that plasma MPO have a significant inverse correlation with PON-1 in patients undergoing HD and suggest that an imbalance between pro-oxidants and anti-oxidants may contribute to the progression and destabilization of human coronary atherosclerotic lesions in patients with SAP who undergo HD following DES implantation.

Isolation and assessment of probiotic potential of Acidipropionibacterium acidipropionici C03B-STR from goat milk with cholesterol-lowering capability.

Elevated levels of cholesterol or triglycerides in the blood are one of the major risk factors for coronary heart disease, which is the foremost leading cause of death across the world. The aims of this study were to isolate and verify the potential probiotic strain and cholesterol-lowering capability from goat milk. The C03B-STR isolate had a broad-spectrum antibacterial property and exhibited remarkable bacteriostatic activity against Klebsiella pneumoniae ATCC 13883 (27.00 ± 1.73mm), Pseudomonas aeruginosa ATCC 27853 (19.33 ± 0.57mm) and Staphylococcus aureus ATCC 10832 (19.00 ± 1.00mm) by agar well diffusion assay. This isolate is closely related to the 16S rDNA sequence of Acidipropionibacterium acidipropionici. Acidipropionibacterium acidipropionici C03B-STR can survive under acidic conditions (60.51 ± 0.02% of survival rate at pH 3.0 for 3h) and was as bile-tolerant strain (> 80% of survival rate at 0.30% bile salts after 3h of incubation). Furthermore, it showed significantly high cell surface hydrophobicity (74.36 ± 0.23%) and aggregation capability (> 83%) (p ≤ 0.05) but displayed low to moderate co-aggregation ability (44-61%). This strain can also be regarded as strongly adhesive (73.69 ± 0.74%) and inhibit pathogen attachment to the Caco-2 cell lines (39.20 ± 0.59-69.01 ± 0.29%). A. acidipropionici C03B-STR appeared to be safe (non-haemolytic) and controllable (sensitive to various antibiotics). Notably, it had the potential to suppress cholesterol uptake in Caco-2 cells (approximately 45%) and also reduced cholesterol level above 84% during the exponential phase under acidic conditions. Thus, A. acidipropionici C03B-STR from goat milk may be a promising novel potential cholesterol-lowering probiotic strain for application in functional foods and biotherapeutics.

Recent studies confirm the utility of the omega-3 index.

The Omega-3 Index (O3I) was proposed 20 years ago as not only a marker of body omega-3 fatty acid status, but more importantly, as a risk factor for fatal coronary heart disease. The purpose of this review is to document the continued and growing use of this metric in nutrition research. Of the 456 citations to the O3I in PubMed, 58 have appeared in the last 18 months. Several of these articles are reviewed, and they underscore the widespread use of the metric. Although the O3I was originally developed in the cardiovascular field, it has since been used in the study of a remarkably large number of health conditions, all of which appear to be favorably impacted by higher levels of tissue omega-3 fatty acids as reflected by the O3I.

Qualitative exploration of awareness about risk factors and transformative behaviours among Pakistani patients with coronary artery disease

ObjectivesTo explore patients’ awareness of risk factors for coronary artery disease (CAD) and experiences of the behavioural modifications, they made during their recovery through in-depth semistructured interviews.DesignQualitative exploration was undertaken...

CYP2C19 Loss-of-Function is an Associated Risk Factor for Premature Coronary Artery Disease: A Case-Control Study.

Cytochrome P450 2C19 (CYP2C19) is a major enzyme involved in the biotransformation and metabolism of various substances. Loss-of-function of the CYP2C19 gene represents downregulation of CYP2C19 enzyme indication limited or no enzymatic function, which may be, in turn, associated with some disease susceptibility. The relationship between CYP2C19 polymorphisms and susceptibility to premature coronary artery disease (PCAD) is not fully understood. This study aimed to assess this relationship. This study included 635 PCAD patients, and 548 age-matched non-CAD individuals as controls, from November 2019 to August 2023. The CYP2C19 rs4244285 (681G > A, *2) and rs4986893 (636G > A, *3) were genotyped, and the distribution of CYP2C19 polymorphisms between patients and controls and the relationship between CYP2C19 polymorphisms and PCAD risk were analyzed. A total of 442 (37.4%), 543 (45.9%), and 198 (16.7%) individuals had CYP2C19 extensive metabolizer (EM) (*1/*1), intermediate metabolizer (IM) (*1/*2 and *1/*3), and poor metabolizer (PM) (*2/*2, *2/*3, and *3/*3) phenotypes, respectively. CYP2C19 *2/*2 genotype frequency was higher, *1/*1 genotype was lower in PCAD patients than controls. Individuals with CYP2C19 PM phenotype had higher triglyceride (TG) levels than those with CYP2C19 EM or IM phenotypes. Logistic regression analysis showed that body mass index (BMI) ≥24.0 kg/m2 (≥24.0 kg/m2 vs 18.5-23.9 kg/m2, odds ratio (OR): 1.326, 95% confidence interval (CI): 1.041-1.688, p = 0.022), smoking (OR: 1.974, 95% CI: 1.283-3.306, p = 0.002), hypertension (OR: 1.327, 95% CI: 1.044-1.687, p = 0.021), diabetes mellitus (OR: 1.390, 95% CI: 1.054-1.834, p = 0.020), CYP2C19 PM phenotype (PM phenotype vs EM phenotype, OR: 1.701, 95% CI: 1.200-2.411, p = 0.003), and CYP2C19 IM+PM phenotypes (IM+PM vs EM phenotype, OR: 1.369, 95% CI: 1.077-1.740, p = 0.010) were associated with PCAD. CYP2C19 PM or IM+PM phenotypes, overweight, smoking, hypertension, and diabetes mellitus were associated with PCAD.

Correlation between LDL/HDL-cholesterol ratio and long term prognosis after acute coronary syndrome and severity of coronary artery disease

Abstract Introduction Dyslipidaemia is an important correctable risk factor for coronary artery disease (CAD). Many studies have confirmed that the lower the low-density lipoprotein cholesterol (LDL-C) levels are, the lower is the CAD morbidity and mortality rates (1). However, many patients who achieved low levels of LDL-C still experience a major adverse cardiovascular event (MACE) because of the other residual risk factors. Therefore, there is a constant need for better stratification of patients who are at higher risk for novel MACE following their first acute coronary syndrome (ACS). Evidence increasingly suggests that the ratio of LDL-C/HDL-C might be a new and better marker of cardiovascular disease, as it simultaneously evaluates the levels of both LDL-C and HDL-C (2). Purpose The aim of this study was to investigate the prediction value of LDL-C/HDL-C ratio for long term prognosis after ACS as well as its correlation with CAD severity. Methods We included patients hospitalized at out centre with ACS from January 2017 to January 2024. Demographic data, data on LDL-C and HDL-C levels on admission and calculated Syntax score were used. Syntax score is a comprehensive angiographic scoring system which determines complexity by using coronary anatomy and lesion characteristics (3). Follow-up data were collected either by clinical follow-up visits or by telephone interviews. The MACE was defined as the composite of cardiovascular death, acute coronary syndrome and need for elective or urgent percutaneous or surgical revascularization. Results This registry-based study included 2471 patients with ACS, median age of 64 (interquartile range 56-73) years, 31% female. Total of 1099 patients (44%) had non-ST elevation ACS and 1372 (54%) had ST elevation myocardial infarction (STEMI). Median Syntax score was 13 (IQR 7-20.5), with 1494 (61%) patients having low Syntax score (≤16), 508 (21%) patients medium (16-22), and 448 (18%) high score (>22), respectively. Median follow up was 17 (3-27) months. LDL-C/HDL-C ratio correlated significantly with cardiovascular death, with weak coefficient (2.94 vs. 2.54 p<0.001; rho=0.102, p<.0001), however did not correlate with MACE (2.88 vs. 2.92, p=0.188, rho=0.06, p=0.77). This remained identical when tested for patients with STEMI and non-STE ACS. In addition, LDL-C/HDL-C ratio did not correlate with CAD severity as assessed with Syntax score (low 2.92 vs. medium 2.83 vs. high 2.86, p=0.597; rho=0.4, p=0.09). Conclusion Our data suggest that LDL-C/HDL-C ratio cannot be used as a relevant predictor of post-ACS long-term MACE or cardiovascular death, nor it can be correlated with CAD severity. Further studies are needed to establish the real value of LDL-C/HDL-C ratio as a post-ACS predictor.

Predictive value of Type D personality combined with unhealthy cardiovascular behaviors for the long-term adverse cardiovascular events in ACS patients

Abstract Background Acute coronary syndrome (ACS) has become a major public health problem worldwide due to its high morbidity and mortality. In addition to traditional risk factors, psychosocial factors play an important role in the development of ACS.Type D personality, as a combination of social inhibition and negative affect, has been defined as a psychological risk factor for coronary heart disease by the European Society of Cardiology.Meanwhile, ACS patients with Type D personality may have behaviors such as unhealthy dietary behaviors, less regular physical activity, and poorer self-management behaviors. Then, whether the combination of Type D personality and poor cardiovascular health behaviors can increase the risk of poor prognosis in patients with ACS requires further research. Purpose The aim of this study was to investigate the effect of Type D personality combined with poor cardiovascular health behaviors on long-term major adverse cardiovascular events(MACE) in patients with ACS. Methods A total of 18631 patients diagnosed with ACS between January 2017 and July 2023 were included in this study. Type D personality, cardiovascular health behaviors (smoking cessation, physical activity, average sleep duration at night, dietary assessment index, BMI, lipids, blood glucose, blood pressure) were assessed during the admission period, and were divided into poor, general, and ideal cardiovascular health with a cut-off score of 50 and 80.The binary logistic regression analysis was used to assese the effect of Type D personality combined with cardiovascular health score on the occurrence of MACE (stroke, reinfarction, revascularization, all-cause death). Results The median follow-up in this study was 37 months, and we found that a total of 3750 people had MACE during the follow-up period. The logistic regression result showed that compared with Type D personality (-) and cardiovascular health behaviors (poor) group, Type D personality (+) and cardiovascular health behaviors (poor) group (OR=1.451, 95%CI=1.055-1.995,P=0.022), Type D personality (+) and cardiovascular health behaviors (general) group (OR=1.425, 95%CI=1.092-1.858,P=0.009), Type D personality (-) cardiovascular health behavior (poor) group (OR=1.301, 95%CI=1.013-1.670, P=0.039) were independent risk factors for the occurrence of further adverse cardiovascular events. Conclusion Type D personality combined with unhealthy cardiovascular behavior individuals may be at high risk for MACE. Therefore, early assessment of Type D personality and cardiovascular health behaviors are needed, thereby reducing the incidence of MACE in ACS patients.

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.

Ethnic disparity in the care and management of non-ST-segment elevation myocardial infarction and its impact on short-term and long-term survival: a long-term study of a national registry

Abstract Background Previous examination of data from the United Kingdom indicates no apparent ethnic disparity in the treatment of patients hospitalised with non-ST-segment elevation myocardial infarction (NSTEMI). However, it remains uncertain whether this lack of disparity results in similar long-term survival outcomes among ethnic minority groups, particularly those with multiple underlying risk factors for coronary artery disease, when compared to White patients. Purpose To assess the impact of quality of care on short-term and long-term survival among NSTEMI patients while examining disparities based on ethnicity. Methods We analysed records of 252,964 individuals diagnosed with NSTEMI from the Myocardial Ischaemia National Audit Project database spanning 2005 to 2019, alongside Office of National Statistics data for mortality. Among them, 233,158 were identified as White patients, while 19,806 were categorised as belonging to ethnic minority groups (Asian, Black, and mixed ethnicity). Propensity score matching was used to compare average treatment effects between cohorts while survival was compared using Cox regression model. Results Ethnic minorities were younger (median age in years) (66 vs. 73, P < 0.001), predominantly male (70% vs. 63%, P < 0.001), and exhibited a higher prevalence of cardiovascular risk factors such as diabetes (52% vs. 24%, P < 0.001), hypertension (67% vs. 54%, P < 0.001), hypercholesterolemia (49% vs. 34%, P < 0.001), and chronic renal dysfunction (13% vs. 8%, P < 0.001). Ethnic minorities more frequently underwent invasive coronary angiography (80% vs. 68%, P < 0.001), percutaneous coronary intervention (53% vs. 44%, P < 0.001), and coronary artery bypass grafting (5% vs. 4%, P < 0.001). After conducting propensity score matching, both cohorts had no significant differences in in-hospital all-cause mortality [odds ratio (OR) 1.13, confidence interval (CI) 0.89 – 1.43; P = 0.268], cardiac mortality (OR 1.20, CI 0.89 – 1.54; P = 0.209), one-year mortality (OR 1.01, CI 0.89 – 1.13; P = 0.893) and major adverse cardiovascular events (OR 1.21, CI 0.95 – 1.48; P = 0.108). However, upon conducting a five-year survival analysis, ethnic minorities had better survival rates than their White counterparts (Hazard ratio (HR) 0.89, CI 0.86-0.92; P < 0.001). Conclusions Despite ethnic minorities being at a higher risk for coronary artery disease, our findings indicate that they experience better five-year survival rates than White patients. This suggests equitable access to care and potentially a more aggressive treatment approach in this relatively young patient cohort.

Angina pectoris after coronary angiography or revascularization in pre- and postmenopausal women with coronary artery disease

Abstract Background Menopause is a known risk factor of coronary artery disease (CAD) in women. Earlier studies indicate that the incidence of angina pectoris (AP) increases with age. Some studies suggest that menopause would be a risk factor for AP in women with history of myocardial infarction (MI). However, the evidence is still incomplete. Purpose The aim of this study was to determine whether pre- or postmenopausal women are more symptomatic after revascularization using Canadian Cardiovascular Society (CCS) grading and New York Heart Association (NYHA) classification. We also wanted to evaluate whether the presence of type two diabetes (T2D) had an impact of the volume of the symptoms of CAD. Methods ARTEMIS Study contains 1,947 subjects with angiographically documented CAD with or without T2D (women 31.8%). Nondiabetic patients were matched with T2D patients for age, sex, prior MI and revascularization. Information of the menopause was from 610 women. Results Total of 584 women were at postmenopausal stage and only 26 were at premenopausal stage. The mean age of the premenopausal women was 57.5±10.8 years (P<0.001) and 69.4±7.5 years in postmenopausal women (P<0.001). Among premenopausal women 46.2% were active or ex-smokers and 26.8% of postmenopausal women still smoked or had smoked in the past (P=0.031). There was not statistically significant difference in other baseline characteristics: BMI, LDL or BNP levels, systolic or diastolic blood pressure, syntax score prior or after the revascularization and prevalence of prior MI. Over half of the postmenopausal women (57.4%, p<0.001) reported to suffer chest pain CCS grade ≥ 2 after the revascularization whereas only one fifth of the premenopausal women (23.1%, P<0.001) reported the same level of AP. T2D seemed to increase the symptoms of CAD as 33.3% of the premenopausal and 61.7% of the postmenopausal women with T2D reported AP with severity of CCS grade ≥ 2 (P=0.050). CCS 2 symptoms were reported by 45.7% of the postmenopausal and 19.2% of the premenopausal women, and CCS 3 symptoms by 11.6% of the postmenopausal women, yet only 3.8% of the premenopausal women (p=0.001 for both, respectively). Three quarter of the premenopausal women reported CCS 1 level of symptoms but only 42.6% of the postmenopausal women (P=0.003). Prevalence of each of CCS grade reported within pre- and postmenopausal women with and without T2D are shown in the Table 1. None of the premenopausal women reported NYHA ≥ 2 dyspnea, and the same level of shortness of breath was reported also only from 4.3 % of the postmenopausal women (p=0.005). Among postmenopausal women with T2D, NYHA ≥ 2 symptoms were more common, though statistical significance was not obtained (9.2%, P=0.196). Conclusion Postmenopausal women seem to experience more CAD-related symptoms after angiography or revascularization compared premenopausal women. Presence of T2D seems to associate with higher CCS grade after revascularization.

Does the LPA genotype have a role in coronary artery disease risk beyond Lp(a) values?

Abstract Introduction High lipoprotein(a) [Lp(a)] concentrations are one of the most important genetically determined risk factors for coronary artery disease (CAD). Many functional single nucleotide polymorphisms (SNPs) of the LPA gene have pronounced effects on Lp(a) concentrations. Studies show that rs3798220 polymorphism is strongly associated with Lp(a) concentration and also with risk of CAD. Goal: To evaluate if LPA rs3798220 T>C is associated with CAD beyond its effect on Lp(a) levels. Methods We performed a case-control study with 3,157 individuals (1,721 CAD patents and 1,436 controls). The LPA rs3798220 T>C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). This variant has a minor allele frequency (MAF) <2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Laboratory analysis was performed, and Lp(a) biochemical levels were measured in the cases and controls. Chi-squared tests were used to determine differences by genotype in CAD association (in cases and controls). We also reported a multivariate logistic regression to test if this LPA variant is still independently associated with CAD after adjustment to Lp(a) levels and traditional risk factors for CAD. Results Wild-type genotype TT was increased in the group without CAD, whereas the genotype TC was higher in patients with CAD (p<0.0001). After multivariate logistic regression, adjusted for traditional risk factors, the TC genotype remained in the equation as an independent risk factor for CAD (OR=2.36; 95%CI: 1.54–3.61; p<0.0001). When the multivariate regression analysis is adjusted for traditional risk factors plus Lp(a) levels, the TC genotype remains in the equation as independently associated with CAD despite being substantially attenuated (OR=1.67; 95%CI: 1.07–2.60; p=0.025). Conclusion LPA rs3798220 T>C may be an independent risk factor for CAD beyond the effect of rising Lp(a) levels. Perhaps testing for the genetic determinants of Lp(a) relative to direct measurement of Lp(a) level could provide additional prognostic utility.

Traditional cardiovascular risk factors and coronary microvascular disease in women and men- a single center study

Abstract Introduction Coronary microvascular dysfunction (CMD) is a common, often missed, cause for effort intolerance and angina symptoms, and is associated with adverse clinical outcomes. Risk factors for the development of CMD have not been fully elucidated, and studies examining sex associated differences in traditional cardiovascular risk factors (TCRs) for obstructive coronary artery disease (CAD) in patients with CMD have yielded conflicting results. Although several non-invasive methods for the evaluation of CMD exist, currently, catheter-based invasive assessment is the gold standard for the diagnosis of coronary microvascular dysfunction. Purpose To examine the association between TCR and CMD and sex associated differences in TCR, in a prospective cohort of patients undergoing invasive microvascular function evaluation in a large tertiary medical center. Methods In this single center, prospective registry, we enrolled patients with non-obstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Measurements of microvascular function included CFR, IMR, RRR as well as FFR. Pathologic CFR was defined as <2.5 or <2. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models. Results Overall, 245 patients with non-obstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range [IQR]: 59,75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men in the entire cohort (59.0% vs. 57.0%; p=0.77). In 41 patients diagnosed with functional microvascular dysfunction there were more women than men (70.7% vs. 29%). When using a threshold of CFR<2.5 no association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (CFR) (β=-0.29; p<0.01 and β=-0.15; p=0.05, respectively) and lower resistive reserve ratio (RRR) (β=-0.28; p<0.01 and β=-0.17; p=0.04, respectively). When using a threshold of <2.0 for CFR similar results were found. Conclusion The prevalence of TCRs was similar in patients with and without CMD. In women, older age and previous IHD were associated with lower CFR and RRR values while no association between TCRs and indices of CMD was found in men. It is likely that there are other, currently unknown risk factors for CMD as well as unique risk factors for each of its endotypes, beyond TCRs. It is unclear which parameter of microvascular dysfunction is the most accurate, and whether different parameters should be used in women and men. Large-scale multi-center studies to further evaluate these issues are needed.Variables associated with CMDStudy inclusion process

Gene Expression Changes in CAD Patients Due to Smoking Using Matched Samples

Abstract Background Smoking is a well-known risk factor for coronary artery disease (CAD). However, the effects of smoking on gene expression in the blood of CAD patients in Hungary have not been extensively studied. Aim To identify differentially expressed genes associated with smoking in CAD patients. Methods Eleven matched samples, based on age and gender, were selected for analysis in this study. All patients were non-obese, non-alcoholic, non-diabetic, and non-hypertensive and had moderate to severe stenosis of one or more coronary arteries, confirmed by coronary angiography. Whole blood samples were collected using PAXgene tubes. Next-generation sequencing was employed using the NextSeq 500 system to generate high-throughput sequencing data for transcriptome profiling. The differentially expressed genes were analyzed using the R programming language. Results The median age of patients was 67 years (range: 54-75). RNA sequencing was performed on two groups: smokers and non-smokers. After quality control and filtering, gene expression data were obtained for all samples. Using DESeq2, we identified 279 differentially expressed genes with a p-value ≤ 0.05 and a log2 fold change ≥1. Of these genes, 160 were upregulated in the smokers, and 119 were downregulated compared to non-smokers. Gene ontology analysis revealed that the upregulated genes were enriched for pathways related to immune responses and activities (FDR< 0.03). Specifically, upregulated genes were involved in keratinocyte differentiation, cornification, and epidermis development. The downregulated genes were enriched for cell-cardiac muscle cell adhesion (FDR= 0.004) and epithelium development (FDR= 0.001) pathways. Conclusions This research illuminates smoking’s biological effects, aiding personalized medicine for predicting and treating smoking-related diseases. Key messages • Smoking alters gene expression in CAD patients’ blood, identifying 279 differentially expressed genes, revealing smoking’s biological effects. • The study underscores gene expression profiles’ role in personalized medicine, predicting smoking-related disease risks and tailoring CAD patient treatments.

Coronary artery plaque characteristics in smokers assessed by intracoronary multi-modality imaging: a NIRS-IVUS guided PROSPECT II substudy

Abstract Background Smoking is a risk factor for coronary artery disease and myocardial infarction. Purpose Among patients with myocardial infarction, we hypothesized smokers would have increased prevalence of nonculprit high-risk plaque characteristics as assessed by intracoronary multimodality imaged when compared to nonsmokers. Method This is a prespecified post-hoc analysis of the PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree). Altogether 898 patients with acute myocardial infarction with or without ST-segment elevation who after successful percutaneous coronary intervention had near-infrared spectroscopy and intravascular ultrasound imaging performed. Data on lesion location, plaque burden, and lipid content were collected. Current, former, and nonsmokers were examined regarding the presence of high-risk plaques in both culprit and nonculprit lesions as well as plaque location. High-risk plaque characteristics were defined as a maximum plaque burden (maxPB) of ≥70% and a maximum 4 mm lipid core burden index (maxLCBI4mm) of ≥324.7. Results Out of 886 patients with known smoking history, 32% were smokers, 32% former, and 37% nonsmokers. Smokers were younger (median age: smokers 59.0; former 65.5; nonsmokers 64.0 years, p<0.001) with fewer co-morbidities and presented more often with STEMI (% presenting with STEMI: smokers 22.2%; former 18.9%; nonsmokers 19.4%, p=0.006). LDL was similar but CRP was higher in smokers (median µg/mL: smokers 4.0; former 3.1; nonsmokers 2.9, p=0.004). In multivariate models of nonculprit lesion morphology smoking history was not associated with maxPB or maxLCBI4mm but was associated with presence of calcified nodules (OR: 2.88 (95% CI 1.46–5.69) p=0.002 [smokers vs nonsmokers]). Calcified nodules were also associated with number of years smoked (OR: 1.02 (95% CI 1.01–1.03) p=0.004). Smoking was not associated with presence of ≥1 lesions with MaxLCBI4mm, ≥ 324.7, maxPB >=70% or the combination of both. Smoking was not associated with presence of plaque rupture or thrombus. Right coronary artery culprit lesions were more common in smokers and former smokers (smokers 29.9%; former 30.9%; nonsmokers 21.6%; OR: 1.12 (95% CI 1.04–1.21) p<0.001 [smokers vs nonsmokers]). Conclusion In this prospective intracoronary multimodality imaging study of patients with recent acute myocardial infarction, smoking was not associated with a higher rate of high-risk nonculprit plaques based on lipid content by NIRS or PB by IVUS when compared to former or nonsmokers. However, smoking was associated with higher presence of IVUS-detected calcified nodules, higher CRP-levels, and the right coronary artery as it angiographically was a more common site for culprit lesions. These results indicate that the elevated risk in smokers is unrelated to vulnerable plaque morphology defined by high PB and lipid content, and instead possibly related to inflammation, calcification, or hemodynamic changes.Table 1

Routine HbA1c screening identifies de novo (pre)diabetes mellitus in 37% of ACS patients which comes with an even higher ischemic risk compared to known diabetes mellitus

Abstract Background Diabetes is a prominent risk factor for coronary artery disease (CAD). By exacerbating the progression of CAD, it puts these patients at increased risk of acute coronary syndrome (ACS) and recurrent ischemic events. It is therefore important to identify hyperglycaemic individuals and to treat them accordingly. However, in daily practice it is seen that a subsequent proportion of people with diabetes is undiagnosed. Purpose The aim of this research is to gain insight in the prevalence of patients with de novo (pre)diabetes, the treatment, and the risk of major adverse cardiac and cerebrovascular events (MACCE) compared to patients with known diabetes in an ACS cohort treated by percutaneous coronary intervention (PCI). Methods The Southeast Netherlands Heart Registry (ZON-HR) is an ongoing, multicentre registry collecting data of patients who underwent a PCI procedure. Of this cohort, patients presenting with ACS and measured HbA1c concentrations (on admission) were selected (N=1507). Patients with diagnosed diabetes are considered well-regulated when HbA1c <53 mmol/mol. Patients undiagnosed with diabetes were divided into three groups: HbA1c concentration <42 mmol/mol (normal), HbA1c 42-47 mmol/mol (pre-diabetes) and HbA1c ≥48 mmol/mol (diabetes). The rates of 30-day repeated myocardial infarction (MI), unplanned revascularisation, ischemic CVA, stent thrombosis, and cardiovascular mortality were determined, separately and combined as MACCE in patients with known diabetes compared to prediabetes and diabetes de novo. Results In the selected population, 28.5% of the patients were previously diagnosed with diabetes, which was well-regulated in only 30.2% of these patients. Of the patients not previously diagnosed, 23.1% and 14.4% had pre-diabetic and diabetic HbA1c concentrations, respectively. In 56.1% of patients with de novo diabetes, no glucose-lowering medication was prescribed at discharge (Table 1). At 30-day follow-up, de novo diabetes patients had increased rates of MACCE compared to patients with known diabetes (HR: 3.51, 95%CI 1.48-8.52) after multivariate analysis which corrected for differences at baseline (Figure 1). In addition, a significant increase in unplanned revascularisation (p=.014) and MI (p=.037) was found between de novo diabetes and known diabetes patients. Conclusions Almost half of the ACS patients in this cohort had either poorly regulated diabetes (305 patients) or was undiagnosed with (pre)diabetes while having an increased HbA1c concentration on admission (401 patients). Despite routine HbA1c screening, a subsequent part of these patients is not adequately treated for (pre)diabetes, especially the de novo diabetes patients. By this group, an even larger rate of MACCE was found, compared to the already established risk of diabetes in ACS. Therefore, active screening and treatment (as recommended in the guidelines) should get more attention to improve outcomes in these high-risk patients.Table 1:ACS population based on HbA1cFigure 1:Survival curves of 30D MACCE

Long-term clinical implications of routine follow-up coronary angiography of asymptomatic patients with long-duration diabetes mellitus after percutaneous coronary intervention in drug-eluting stent e

Abstract Background Diabetes mellitus (DM) is a major risk factor for coronary artery disease (CAD), significantly contributing to mortality in affected patients. There are concerns about the adequacy of clinical follow-up for post-percutaneous coronary intervention (PCI) surveillance, especially in uncontrolled DM, due to potential asymptomatic CAD. This study assesses whether routine follow-up coronary angiography (FUCAG) offers a surveillance advantage over clinical follow-up in uncontrolled DM post-PCI. Methods From 2014 to 2020, a study was conducted on patients with DM who underwent PCI at our university medical. Poorly controlled DM was defined as a mean HbA1c of 9 or higher during the index PCI and follow-up period. Out of a total of 2,864 individuals, after excluding 538 individuals with a follow-up period of less than 4 years and 232 individuals who experienced an event within a year, a total of 2,094 was enrolled. Follow-up coronary angiography (FUCAG) was defined as angiography performed between 6- and 18-months post-index PCI for lesion evaluation. To adjust for any differences in baseline characteristics between the groups, propensity score matching (PSM) was implemented. The primary outcome was defined as Major Adverse Cardiac Events (MACE), comprising all-cause death, myocardial infarction, and target-lesion revascularization. Results PSM was conducted to correct the difference in baseline characteristics between the two groups. In the Kaplan-Meier analysis, there was no difference between FUCAG and clinical follow-up for MACE (Log-rank: P=0.770). Cox proportional regression analysis revealed a hazard ratio (HR) of 0.77 with a 95% confidence interval (CI) of 0.70-1.63, indicating no statistically significant difference. Conclusions Even in poorly controlled DM patients, there was no apparent clinical benefit of FUCAG compared to clinical follow-up. Particularly considering concerns such as renal function deterioration in DM patients, post-PCI surveillance through clinical follow-up may be advantageous.