Risk Of Coronary Atherosclerosis Research Articles

Association of liver multi-parameter quantitative metrics determined by dual-layer spectral detector computed tomography (SDCT) with coronary plaque scores.

Hepatic steatosis is closely related to the occurrence and development of coronary plaques. Spectral detector computed tomography (SDCT) can provide more precise multiparameter quantitative parameters for hepatic steatosis. Hence, the purpose of this cross-sectional study was to explore the effect of quantitative liver metrics measured using SDCT on the extent and severity of coronary plaques. In patients who underwent upper abdomen unenhanced SDCT and coronary computed tomography angiography, plaque extent and severity were assessed using segmental involvement score (SIS) and segmental stenosis score (SSS). Liver fat quantification was evaluated by polychromatic and virtual mono-energetic images at 40 and 70 kev, spectral attenuation curve slope, and effective atomic number (CT40 keV, CT70 kev, λHU, and Zeff, respectively). A logistic regression model evaluated the factors influencing high SIS and SSS. Enrolled patients (n=644) were divided into groups: low SIS (<5) (n=451), high SIS (≥5) (n=193), low SSS (<5) (n=461), and high SSS (≥5) (n=183). Zeff was more closely correlated with SIS (standard partial regression coefficient =-0.422, P<0.001) and SSS (standard partial regression coefficient =-0.346, P<0.001). Zeff was divided into four groups using interquartile intervals. Compared with the patients in the lowest quartile, those in the second [odds ratio (OR) =2.116, 95% confidence interval (CI): 1.134-3.949, P=0.018], third (OR =2.832, 95% CI: 1.461-5.491, P=0.002), and fourth (OR =3.584, 95% CI: 1.857-6.918, P<0.001) quartiles showed higher risk for high SIS. And correspondingly, the second (OR =1.933, 95% CI: 1.040-3.592, P=0.037), third (OR =2.900, 95% CI: 1.499-5.609, P=0.002), and fourth (OR =3.368, 95% CI: 1.743-6.510, P<0.001) quartiles showed higher risk for high SSS, especially in those who were <60 years old, male and had visceral adipose tissue/subcutaneous adipose tissue <1.18. The SDCT-Zeff was an independent factor associated with high SIS and SSS. The quantification of liver fat may be useful for evaluating the risk and prognosis of coronary atherosclerosis.

Association of Angina, Myocardial Infarction and Atrial Fibrillation-A Bidirectional Mendelian Randomization Study.

Aims/Background Coronary heart disease (CHD) and atrial fibrillation (AF) exhibit a close relationship, yet the existing body of research predominantly relies on observational study methodologies, posing challenges in establishing causal relationships. The objective of our study is to investigate the causal linkages between coronary atherosclerosis (CAAs), angina pectoris, myocardial infarction (MI), and AF. Methods This study utilizes a two-sample Mendelian randomization (TSMR) methodology, leveraging genetic variation as a means of evaluating causality. Mendelian randomization is grounded in three primary assumptions: (1) the genetic variant is linked to the exposure, (2) the genetic variant is independent of confounding factors, and (3) the genetic variant influences the outcome solely through the exposure. Results The results of our study suggest a genetic predisposition in which CAAs, angina, and MI may enhance susceptibility to AF, while AF may reciprocally elevate the risk of CAAs. Conclusion In light of these findings, it is recommended that patients with CHD undergo regular cardiac rhythm monitoring, and that patients with AF receive anticoagulant and antiplatelet therapy whenever feasible. This study posits a practical implication for clinical practice.

A stratified study of human blood metabolites and coronary artery diseases—A Mendelian randomization study

Background and aimsMetabolic dysregulation is closely associated with coronary artery diseases (CAD). Exploring the relationship between metabolites and CAD is helpful in identifying changes in energy metabolism during disease progression. Methods and resultsWe use Mendelian Randomization (MR) analysis to assess the relationships between 275 serum metabolites and CAD such as angina pectoris, post-myocardial infarction complications, coronary atherosclerosis, myocardial infarction (MI), and unstable angina pectoris (UA). The inverse variance-weighted method (IVW) served as the primary approach for causal analysis, with MR-Egger and weighted median (WM) as supplementary methods. Sensitivity analyses were conducted to assess heterogeneity and multiple effects. We also analyzed potentially related metabolic pathways.We identified causal relationships between 42 known metabolites and CAD. Among them, the genetic susceptibility to elevated levels of amino acid Isobutyrylcarnitine is associated with an increased risk of coronary artery atherosclerosis; but it provides protection against the development of MI. Genetic susceptibility to elevated levels of fatty acids Stearate, Caprylate is associated with higher risk of angina pectoris, while Threonate has a protective effect in the development of angina; Stearate is associated with an increased risk of UA, whereas higher levels of the lipids Choline, 1−arachidonoylglycerophosphoinositol∗, Hexadecanedioate, Tetradecanedioate play a protective role in UA.Metabolic pathway analysis identified 6 pathways that may be associated with CAD. ConclusionWe identified causal relationships between 42 serum metabolites and CAD. Specifically, changes in metabolites such as Isobutyrylcarnitine, Caprylate, and Stearate were associated with risks of CAD. These findings provide new insights into the metabolic mechanisms of CAD.

Apolipoprotein E E3/E4 genotype is associated with an increased risk of coronary atherosclerosis in patients with hypertension

ObjectiveApolipoprotein E (APOE) gene polymorphisms were associated with coronary atherosclerosis and hypertension. However, the relationship between APOE polymorphisms and coronary atherosclerosis susceptibility in hypertensive patients is unclear. The aim of this study was to assess the relationship.MethodsA total of 1713 patients with hypertension who were admitted to Meizhou People’s Hospital from November 2019 to August 2023 were retrospectively analyzed, including 848 patients with coronary atherosclerosis and 865 patients without coronary atherosclerosis. The rs429358 and rs7412 polymorphisms of APOE were genotyped, and relationship between APOE polymorphisms and the risk of coronary atherosclerosis in hypertensive patients were analyzed.ResultsThere were 10 (0.6%), 193 (11.3%), 30 (1.8%), 1234 (72.0%), 233 (13.6%), and 13 (0.8%) individuals with APOE ɛ2/ɛ2, ɛ2/ɛ3, ɛ2/ɛ4, ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4 genotype, respectively. The frequency of APOE ɛ3/ɛ4 was higher (16.4% vs. 10.9%, p = 0.001) in the patients with coronary atherosclerosis than controls. Logistic 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): 1.361, 95% confidence interval (CI): 1.112–1.666, p = 0.003), advanced age (≥ 65/<65, OR:1.303, 95% CI: 1.060–1.602, p = 0.012), history of smoking (OR: 1.830, 95% CI: 1.379–2.428, p < 0.001), diabetes mellitus (OR: 1.380, 95% CI: 1.119–1.702, p = 0.003), hyperlipidemia (OR: 1.773, 95% CI: 1.392–2.258, p < 0.001), and APOE ɛ3/ɛ4 genotype (ɛ3/ɛ4 vs. ɛ3/ɛ3, OR: 1.514, 95% CI: 1.133–2.024, p = 0.005) were associated with coronary atherosclerosis in hypertensive patients.ConclusionsOverweight (BMI ≥ 24.0 kg/m2), advanced age, history of smoking, diabetes mellitus, and APOE ɛ3/ɛ4 genotype were independent risk factors for coronary atherosclerosis in hypertensive patients.

Diagnostic utility of sortilin & other biomarkers in the diagnosis of carotid & coronary atherosclerosis in individuals with arterial hypertension.

Background & objectives Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. The aim of this investigation was to study the role of biological markers in predicting the risk of carotid and coronary artery atherosclerosis. Methods A total of 161 males in the age group of 30-65 yr were included in this study. All participants underwent biochemical analyses [cholesterol, low density lipoprotein cholesterol (LDL-C), triglycerides, glucose, (interleukin) IL-8, IL-10, (proprotein convertase inhibitors subtilisin/kexin type 9) PCSK9, sortilin, creatinine]; ECG; echocardiography; coronary angiography; ultrasound doppler of brachiocephalic arteries. Based on PCSK9 levels, participants were divided into four groups: group 1, n=41 individuals with PCSK9 level of 100-250 ng/ml; group 2, n=37 individuals with PCSK9 level of 251-400 ng/ml; group 3, n=51 individuals with PCSK9 level of 401-600 ng/ml and group 4, n=32 individuals with PCSK9 level of 601-900 ng/ml. Results Sortilin level was the highest in group 2. Group 3 individuals had the highest level of IL-8. Correlation analysis of the entire data set revealed the relationship of relative left ventricular thickness index with age, cardiovascular risk, body mass index, intima-media thickness and left ventricular mass index; sortilin had a negative relationship of weak strength with age and smoking, a direct relationship between the risk of cardiovascular complications and with IL-10. Interpretation & conclusions Sortilin is the innovative marker of CVDs. In the present investigation, we demonstrated the clear increase in the inflammatory markers (IL-8) in individuals with subclinical atherosclerosis. This fact can be explained by the oxygen stress activation. In individuals with coronary artery stenosis (50% and more), the increase in IL-10 levels demonstrates, to our opinion, the activation of antioxidant protection activation.

A phenome-wide association and factorial Mendelian randomization study on the repurposing of uric acid-lowering drugs for cardiovascular outcomes

Uric acid has been linked to various disease outcomes. However, it remains unclear whether uric acid-lowering therapy could be repurposed as a treatment for conditions other than gout. We first performed both observational phenome-wide association study (Obs-PheWAS) and polygenic risk score PheWAS (PRS-PheWAS) to identify associations of uric acid levels with a wide range of disease outcomes. Then, trajectory analysis was conducted to explore temporal progression patterns of the observed disease outcomes. Finally, we investigated whether uric acid-lowering drugs could be repurposed using a factorial Mendelian randomization (MR) study design. A total of 41 overlapping phenotypes associated with uric acid levels were identified by both Obs- and PRS- PheWASs, primarily cardiometabolic diseases. The trajectory analysis illustrated how elevated uric acid levels contribute to cardiometabolic diseases, and finally death. Meanwhile, we found that uric acid-lowering drugs exerted a protective role in reducing the risk of coronary atherosclerosis (OR = 0.96, 95%CI: 0.93, 1.00, P = 0.049), congestive heart failure (OR = 0.64, 95%CI: 0.42, 0.99, P = 0.043), occlusion of cerebral arteries (OR = 0.93, 95%CI: 0.87, 1.00, P = 0.044) and peripheral vascular disease (OR = 0.60, 95%CI: 0.38, 0.94, P = 0.025). Furthermore, the combination of uric acid-lowering therapy (e.g. xanthine oxidase inhibitors) with antihypertensive treatment (e.g. calcium channel blockers) exerted additive effects and was associated with a 6%, 8%, 8%, 10% reduction in risk of coronary atherosclerosis, heart failure, occlusion of cerebral arteries and peripheral vascular disease, respectively. Our findings support a role of elevated uric acid levels in advancing cardiovascular dysfunction and identify potential repurposing opportunities for uric acid-lowering drugs in cardiovascular treatment.

Association of Autoimmune Diseases With Coronary Atherosclerosis Severity and Ischemic Events

BackgroundSome autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear. ObjectivesThis study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk. MethodsThe study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated. ResultsDuring 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81). ConclusionsAutoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases.

Frailty and risk of systemic atherosclerosis: A bidirectional Mendelian randomization study.

Numerous observational studies have reported an association between frailty and atherosclerosis. However, the causal relationship between frailty and the occurrence of atherosclerosis in different anatomical sites remains unclear. we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causal relationship between the frailty index (FI), and both systemic atherosclerosis and lipids. We obtained summary statistics from large-scale genome-wide association studies (GWAS) of various phenotypes, including frailty (n = 175,226), coronary atherosclerosis (n = 56,685), cerebral atherosclerosis (n = 150,765), peripheral arterial disease (PAD) (n = 361,194), atherosclerosis at other sites (n = 17,832), LDL-C (n = 201,678), HDL-C (n = 77,409), and triglycerides (n = 78,700). The primary MR analysis employed the inverse variance weighted (IVW) method. Furthermore, to assess reverse causality, we employed inverse MR and multivariate MR analysis. Genetically predicted FI showed positive associations with the risk of coronary atherosclerosis (OR = 1.47, 95% CI 1.12-1.93) and cerebral atherosclerosis (OR = 1.99, 95% CI 1.05-3.78), with no significant association (p >0.05) applied to peripheral arterial disease and atherosclerosis at other sites. Genetically predicted FI was positively associated with the risk of triglycerides (OR = 1.31, 95% CI 1.08-1.59), negatively associated with the risk of LDL-C (OR = 0.87, 95% CI 0.78-0.97), and showed no significant association with the risk of HDL-C (p >0.05). Furthermore, both reverse MR and multivariate MR analyses demonstrated a correlation between systemic atherosclerosis, lipids, and increased FI. Our study elucidated that genetically predicted FI is associated with the risk of coronary atherosclerosis and cerebral atherosclerosis by the MR analysis method, and they have a bidirectional causal relationship. Moreover, genetically predicted FI was causally associated with triglyceride and LDL-C levels. Further understanding of this association is crucial for optimizing medical practice and care models specifically tailored to frail populations.

Predicting coronary artery severity in patients undergoing coronary computed tomographic angiography: Insights from pan-immune inflammation value and atherogenic index of plasma

Background and aimsCoronary computed tomographic angiography (CCTA) is pivotal in diagnosing coronary artery disease (CAD). We explored the link between CAD severity and two biomarkers, Pan-Immune Inflammation Value (PIV) and Atherogenic Index of Plasma (AIP), in stable CAD patients. Methods and resultsA retrospective observational study of 409 CCTA patients with stable angina pectoris. Logistic regression identified predictors of severe CAD, stratified by CAD-RADS score. Receiver Operating Characteristic (ROC) curves evaluated predictive performance. PIV and AIP were significant predictors of severe CAD (PIV: OR 1.002, 95% CI: 1.000–1.004, p < 0.021; AIP: OR 0.963, 95% CI: 0.934–0.993, p < 0.04). AUC values for predicting severe CAD were 0.563 (p < 0.001) for PIV and 0.625 (p < 0.05) for AIP. Combined with age, AUC improved to 0.662 (p < 0.02). ConclusionsPIV and AIP were associated with severe CAD, with AIP demonstrating superior predictive capability. Incorporating AIP into risk assessment could enhance CAD prediction, offering a cost-effective and accessible method for identifying individuals at high risk of coronary atherosclerosis.

Genetic insights into the role of cathepsins in cardiovascular diseases: a Mendelian randomization study.

This study aimed to explore the causal relationships between cathepsins and cardiovascular diseases (CVDs) by Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) associated with nine cathepsin types (cathepsins B, E, F, G, H, O, S, L2, and Z) were obtained from the INTERVAL study (3301 individuals). CVDs data were acquired from the UK Biobank (coronary atherosclerosis: 14334 cases, 346860 controls) and a genome-wide association study (GWAS) (myocardial infarction: 20917 cases, 440906 controls; myocarditis: 633 cases, 427278 controls; chronic heart failure: 14262 cases, 471898 controls; angina pectoris: 30025 cases, 440906 controls; stable angina pectoris: 17894 cases, 325132 controls; unstable angina pectoris: 9481 cases, 446987 controls; pericarditis: 1795 cases, 453370 controls). Inverse variance weighted (IVW), MR-Egger, weighted median methods were adopted to conduct univariable MR (UVMR), reverse MR, multivariable MR (MVMR) analyses to estimate causality. The UVMR analyses demonstrated significant causal relationships between higher cathepsin E levels and increased risk of coronary atherosclerosis [IVW: P=0.0051, odds ratio (OR)=1.0033, 95% confidence interval (CI)=1.0010-1.0056] and myocardial infarction (IVW: P=0.0097, OR=1.0553, 95% CI=1.0131-1.0993), while elevated cathepsin L2 levels were causally related to reduced risk of myocarditis (IVW: P=0.0120, OR=0.6895, 95% CI=0.5158-0.9216) and chronic heart failure (IVW: P=0.0134, OR=0.9316, 95% CI=0.8807-0.9854). Reverse MR analyses revealed that myocardial infarction increased cathepsin O levels (IVW: P=0.0400, OR=1.0708, 95% CI=1.0031-1.1431). MVMR analyses treating nine cathepsins together revealed that the positive causality between cathepsin E levels and coronary atherosclerosis risk (IVW: P=0.0390, OR=1.0030, 95% CI=1.0000-1.0060), and the protective effect of cathepsin L2 levels on myocarditis (IVW: P=0.0030, OR=0.6610, 95% CI=0.5031-0.8676) and chronic heart failure (IVW: P=0.0090, OR=0.9259, 95% CI=0.8737-0.9812) remained, as higher cathepsin O levels were found to be causally related to increased risks of myocarditis (IVW: P=0.0030, OR=1.6145, 95% CI=1.1829-2.2034) and chronic heart failure (IVW: P=0.0300, OR=1.0779, 95% CI=1.0070-1.1537). The study highlights the causalities of cathepsin E, L2, and O on CVDs, offering insights into their roles in cardiovascular biomarkers and therapeutic targets development. Further research is required to apply these genetic findings clinically.

LDL-C and TC mediate the risk of PNPLA3 inhibition on cardiovascular diseases.

PNPLA3 is a promising target for the treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. ARO-PNPLA3 is a drug that efficiently lowers PNPLA3 expression in hepatocytes at the mRNA level, resulting in a significant reduction in liver fat in Phase I clinical trials. However, the long-term effects and potential side effects of ARO-PNPLA3 are not well understood. We conducted a two-sample, two-step Mendelian randomization (MR) analysis to investigate the association between PNPLA3 inhibition and 10 cardiovascular diseases (CVDs), as well as the role of lipid traits as mediators. We identified genetic variants near the PNPLA3 gene, which are linked to liver fat percentage, as instrumental variables for inhibiting PNPLA3. Additionally, positive control analyses on liver diseases were conducted to validate the selection of the genetic instruments. Genetically predicted PNPLA3 inhibition significantly increased the risk of coronary atherosclerosis (1.14, 95% CI 1.06, 1.23), coronary heart disease (1.14, 95% CI 1.08, 1.21), and myocardial infarction (1.16, 95% CI 1.08, 1.26). Suggestive associations were observed for increased risk of heart failure (1.09, 95% CI 1.02, 1.17, P = 0.0143) and atrial fibrillation (1.17, 95% CI 1.00, 1.36, P = 0.0468). Blood low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) mediated approximately 16-25%, 16-30%, and 14-22% of the associations between PNPLA3 inhibition and coronary atherosclerosis, myocardial infarction, and coronary heart disease, respectively. This study suggests that PNPLA3 inhibition increases the risk of major CVDs. Moreover, blood LDL-C and TC may mediate a significant proportion of the associations between PNPLA3 inhibition and coronary atherosclerosis, coronary heart disease, or myocardial infarction.

Early-onset vs late-onset preeclampsia and risk of coronary atherosclerosis later in life: a clinical follow-up study

BackgroundYounger women with previous preeclampsia have an increased risk of coronary atherosclerosis. It is unknown if this risk is associated with the time of onset of preeclampsia. ObjectivesThe aim of the study was to investigate if women with early-onset preeclampsia have a higher risk of coronary atherosclerosis compared to women with late-onset preeclampsia, independent of other perinatal risk factors. Study DesignA total of 911 women with previous preeclampsia aged 35-55 years participated in a clinical follow-up study, including clinical examination, comprehensive questionnaires, and cardiac computed tomography scan 13 years (range 0-28) after index pregnancy. Early-onset preeclampsia versus late-onset preeclampsia was defined as gestational age at delivery < versus ≥ 34+0 gestational weeks, respectively. The primary outcome of the study was the presence of coronary atherosclerosis on the cardiac computed tomography. A logistic regression analysis was performed to investigate the association between time of onset of preeclampsia, perinatal risk factors and the primary outcome. ResultsWomen with early-onset preeclampsia (N=139) were older (46.2±5.7 vs. 44.4±5.5 years, P<0.001), more likely to have hypertension (51.1% vs. 35.1%, P=<0.001), and had a higher body mass index (27.9±6.3 vs. 26.9±5.5 kg/m2, P=0.051) compared to women with late-onset preeclampsia (N=772) at follow-up. The prevalence of the primary outcome coronary atherosclerosis on the cardiac computed tomography was 28.8% vs. 22.2% (P=0.088) with an adjusted OR=1.74, 95% CI (1.01-3.01), P=0.045 after adjustment for maternal age at index pregnancy, pre-pregnancy body mass index, parity, diabetes in pregnancy, smoking in pregnancy, offspring birth weight and sex, and follow-up length. ConclusionsWomen with early-onset preeclampsia had a slightly higher risk of coronary atherosclerosis compared to women with late-onset preeclampsia. However, based on the current evidence it does not seem indicated to limit screening, diagnostic and preventive measures for cardiovascular disease only to women with early-onset preeclampsia.

Steatotic liver disease and its newly proposed sub-classifications correlate with progression of the coronary artery calcium score.

A new nomenclature, Steatotic Liver Disease (SLD), has been proposed by consensus with sub-classifications and requires evidence-based validation. We assessed whether the presence and severity of SLD, as well as its sub-classifications, are associated with the progression of coronary atherosclerosis. This longitudinal cohort study included 13,811 adults who participated in repeated regular health screening examinations between January 1, 2004 and December 31, 2021 that included assessments of their coronary artery calcium (CAC) scores. SLD was defined using abdominal ultrasonography and classified as metabolic dysfunction associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and cryptogenic SLD. SLD severity was assessed using fibrosis-4 (FIB-4) scores. The progression of CAC scores was measured using multidetector CT scans. The average duration of follow-up was 5.8 years. During follow-up, the annual rate of CAC progression in participants with and without SLD was 18% (95% CI 17%-19%) and 14% (95% CI 13%-14%) (p < 0.01), respectively. The multivariable ratios of progression rates when we compared participants with cryptogenic SLD, MASLD, or MetALD with those without SLD were 0.98 (95% CI 0.95-1.01), 1.03 (95% CI 1.03-1.04), and 1.07 (95% CI 1.04-1.09), respectively. The multivariable ratios of progression rates when we compared participants with SLD with FIB-4 score <1.3 and SLD with FIB-4 score ≥1.3 with those without SLD were 1.03 (95% CI 1.02-1.04), and 1.05 (95% CI 1.04-1.06), respectively. SLD was associated with a higher risk of coronary atherosclerosis, and the risk differed by sub-classifications and severity. These findings suggest that the newly proposed definition has clinical relevance in terms of stratifying cardiovascular disease risk.

Marathon Running: Blowing the Whistle on Race-Related Cardiac Arrest

Sudden cardiac death in marathon runners is not a new problem. At increased risk are middle-aged men who are unaware of the risk of sub-clinical coronary atherosclerosis. For over a decade, Dr Arthur J Siegel at Harvard Medical School, USA has researched and published extensively on this topic in a bid to raise awareness of the risks of race-related cardiac arrest. He calls on healthcare providers to consider coronary artery calcium scoring to assess the anticipated benefit of pre-race aspirin for enhanced primary prevention. Humans have been partaking in long-distance running for thousands of years.

Depression and Subclinical Coronary Atherosclerosis in Adults Without Clinical Coronary Artery Disease.

The relationship between depression and subclinical coronary atherosclerosis in asymptomatic individuals is not clear. We evaluated this relationship in a Korean population. We analyzed 3920 individuals (mean age 54.7±7.9 years and 2603 men [66.4%]) with no history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography and screening for depression using the Beck Depression Inventory as part of a general health examination. The degree and extent of subclinical coronary atherosclerosis were evaluated by coronary computed tomographic angiography, and ≥50% diameter stenosis was defined as significant. Participants were categorized into groups of those with or without depression using the Beck Depression Inventory scores ≥16 as a cutoff value. Of the study participants, 272 (6.9%) had a Beck Depression Inventory score of 16 or higher. After adjustment for cardiovascular risk factors, depression was not significantly associated with any coronary plaque (adjusted odds ratio [OR], 1.05 [95% CI, 0.78-1.41]; P=0.746), calcified plaque (OR, 0.95 [95% CI, 0.71-1.29]; P=0.758), noncalcified plaque (OR, 1.31 [95% CI, 0.79-2.17]; P=0.305), mixed plaque (OR, 1.16 [95% CI, 0.60-2.23]; P=0.659), or significant coronary artery stenosis (OR, 1.22 [95% CI, 0.73-2.03]; P=0.450). In the propensity score-matched population (n=1318) as well, none of the coronary artery disease measures of subclinical coronary atherosclerosis were statistically significantly associated with depression (all P>0.05). In this large cross-sectional study with asymptomatic individuals undergoing coronary computed tomographic angiography and Beck Depression Inventory evaluation, depression was not associated with an increased risk of subclinical coronary atherosclerosis.

Relationship Between Genetic Prediction of Diabetes and Coronary Atherosclerosis: A Two-Sample Bidirectional Mendelian Randomization Study

Background: To explore the relationship between diabetes and coronary atherosclerosis at the genetic level by using two-sample Mendelian randomization (MR). Methods: Diabetes and coronary atherosclerosis are the exposure factors and outcomes respectively. The study employed the inverse-variance weighted method (IVW), MR-Egger regression, weighted median method (WM), simple mode, and weighted mode for bidirectional Mendelian randomization analysis, using the odds ratio (OR) to assess the causal relationship between diabetes and coronary atherosclerosis. Results: MR heterogeneity demonstrated heterogeneity in single nucleotide polymorphisms (SNPs) for each nucleotide (all P values &lt; 0.001). Therefore, the IVW random effects model was selected. The results showed that at the gene level, there was a correlation between an increased risk of diabetes and coronary atherosclerosis (OR=1.103). Additionally, there was a correlation between an increased risk of coronary atherosclerosis and diabetes (OR=1.108). No horizontal pleiotropy of instrumental variables was found (P=0.419, 0.808). The MR analysis results remained robust after sequentially excluding SNPs. Conclusion: Diabetes and coronary atherosclerosis are mutually predisposing risk factors for each other at the gene level in the European population.

Unraveling the role of VLDL in the relationship between type 2 diabetes and coronary atherosclerosis: a Mendelian randomization analysis.

The causal link between Type 2 diabetes (T2D) and coronary atherosclerosis has been established through wet lab experiments; however, its analysis with Genome-wide association studies (GWAS) data remains unexplored. This study aims to validate this relationship using Mendelian randomization analysis and explore the potential mediation of VLDL in this mechanism. Employing Mendelian randomization analysis, we investigated the causal connection between T2D and coronary atherosclerosis. We utilized GWAS summary statistics from European ancestry cohorts, comprising 23,363 coronary atherosclerosis patients and 195,429 controls, along with 32,469 T2D patients and 183,185 controls. VLDL levels, linked to SNPs, were considered as a potential mediating causal factor that might contribute to coronary atherosclerosis in the presence of T2D. We employed the inverse variance weighted (IVW), Egger regression (MR-Egger), weighted median, and weighted model methods for causal effect estimation. A leave-one-out sensitivity analysis was conducted to ensure robustness. Our Mendelian randomization analysis demonstrated a genetic association between T2D and an increased coronary atherosclerosis risk, with the IVW estimate at 1.13 [95% confidence interval (CI): 1.07-1.20]. Additionally, we observed a suggestive causal link between T2D and VLDL levels, as evidenced by the IVW estimate of 1.02 (95% CI: 0.98-1.07). Further supporting lipid involvement in coronary atherosclerosis pathogenesis, the IVW-Egger estimate was 1.30 (95% CI: 1.06-1.58). In conclusion, this study highlights the autonomous contributions of T2D and VLDL levels to coronary atherosclerosis development. T2D is linked to a 13.35% elevated risk of coronary atherosclerosis, and within T2D patients, VLDL concentration rises by 2.49%. Notably, each standard deviation increase in VLDL raises the likelihood of heart disease by 29.6%. This underscores the significant role of lipid regulation, particularly VLDL, as a mediating pathway in coronary atherosclerosis progression.

Association of serum cystatin C level with coronary atherosclerotic plaque burden: a comprehensive analysis of observational studies and genetic study

Background and AimsEpidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden.MethodsThis study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk.ResultsA total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59–3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21–2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002–1.006, P < 0.001) .ConclusionElevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.What is already known on this topic?Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear.What this study adds?Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.How this study might affect research, practice or policy?Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD.

Number of blood neutrophil granulocytes is associated with diffuse coronary involvement in patients with increased lipoprotein (a)

Aim. To assess the level of lipoprotein (a) (Lp(a)) and other lipid profile parameters, the composition of blood leukocytes in patients with focal and diffuse coronary atherosclerosis who underwent coronary artery bypass surgery (CABG), as well as to study the effect of Lp(a) on the activation of leukocytes in vitro.Material and methods. The study included 120 male patients (mean age, 67±5 years) with multivessel coronary artery disease after elective CABG surgery. According to the type of coronary artery involvement, patients were divided into groups of diffuse (n=77) and focal (n=43) atherosclerosis. In peripheral blood samples, the content of the main fractions of lipoproteins, including Lp(a), was determined. Activation of neutrophil granulocytes upon addition of Lp(a) was assessed in whole blood and in primary cell culture.Results. In patients with diffuse coronary stenosis, there was a tendency to higher Lp(a) levels; no changes in other lipid profile parameters were detected. In this group of patients, an increase in the absolute leukocyte count was noted due to neutrophilic granulocytes. An absolute neutrophil count &gt;2,9 million/mL was associated with diffuse disease (AUC, 0,69 (95% confidence interval (CI) 0,600,77), p=0,0002, sensitivity 85%, specificity 42%). In patients with Lp(a) ³30 mg/dL, the diagnostic value of a neutrophil count &gt;2,9 million/mL for diffuse stenosis was higher (AUC, 0,74 (95% CI 0,60-0,86), p= 0,005, sensitivity 90%, specificity 48%). According to logistic regression analysis with the introduction of neutrophils and conventional risk factors (age, body mass index, hypertension and smoking) into the model, only the number of neutrophils above the threshold level remained an independent factor in diffuse coronary stenosis. Lp(a) can induce neutrophil activation, detected by increased CD66b overexpression in whole blood, as well as the formation of neutrophil extracellular traps in primary cell culture.Conclusion. Neutrophil granulocytes can participate in the formation of diffuse atherosclerotic coronary lesions. One of the neutrophil activators may be Lp(a). The combination of high neutrophil count and Lp(a) level in the blood increases the risk of diffuse coronary atherosclerosis.

Transient ischemic attack and coronary artery disease: a two-sample Mendelian randomization analysis.

Although observational studies have shown that patients who experienced transient ischemic attacks (TIAs) had a higher risk of coronary artery disease (CAD), the causal relationship is ambiguous. We conducted a two-sample Mendelian randomization (MR) study to analyze the causal relationship between TIA and CAD using data from the FinnGen genome-wide association study. Analysis was performed using the inverse-variance weighted (IVW) method. The robustness of the results was evaluated using MR-Egger regression, the weighted median, MR pleiotropy residual sum, and outlier (MR-PRESSO) and multivariable MR analysis. Results from IVW random-effect model showed that TIA was associated with an increased risk of coronary artery atherosclerosis (OR 1.17, 95% CI 1.06-1.28, P = 0.002), ischemic heart disease (OR 1.15, 95% CI 1.04-1.27, P = 0.007), and myocardial infarction (OR1.15, 95% CI 1.02-1.29, P = 0.025). In addition, heterogeneity and horizontal pleiotropy were observed in the ischemic heart disease results, while the sensitivity analysis revealed no evidence of horizontal pleiotropy in other outcomes. This MR study demonstrated a potential causal relationship between TIA and CAD. Further research should be conducted to investigate the mechanism underlying the association.