Review

Authors: Vincent L Aengevaeren, Arend Mosterd, Sanjay Sharma...

Physical activity and exercise training are effective strategies for reducing the risk of cardiovascular events, but multiple studies have reported an increased prevalence of coronary atherosclerosis, usually measured as coronary artery calcification, among athletes who are middle-aged and older. Our review of the medical literature demonstrates that the prevalence of coronary artery calcification and atherosclerotic plaques, which are strong predictors for future cardiovascular morbidity and mortality, was higher in athletes compared with controls, and was higher in the most active athletes compared with less active athletes. However, analysis of plaque morphology revealed fewer mixed plaques and more often only calcified plaques among athletes, suggesting a more benign composition of atherosclerotic plaques. This review describes the effects of physical activity and exercise training on coronary atherosclerosis in athletes who are middle-aged and older and aims to contribute to the understanding of the potential adverse effects of the highest doses of exercise training on the coronary arteries. For this purpose, we will review the association between exercise and coronary atherosclerosis measured using computed tomography, discuss the potential underlying mechanisms for exercise-induced coronary atherosclerosis, determine the clinical relevance of coronary atherosclerosis in middle-aged athletes and describe strategies for the clinical management of athletes with coronary atherosclerosis to guide physicians in clinical decision making and treatment of athletes with elevated coronary artery calcification scores.

Topics: Athletes; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Exercise; Female; Humans; Male; Plaque, Atherosclerotic; Prevalence; Risk Factors; Vascular Calcification

PubMed: 32310695
DOI: 10.1161/CIRCULATIONAHA.119.044467

Authors: Jianqi Zhao, Hongxuan Fan, Ting Wang...

BACKGROUND

Insulin resistance (IR), endothelial dysfunction, inflammation, glucose and lipid metabolism disorders, and thrombosis are believed involved in coronary heart disease (CHD) and non-alcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index, a new IR indicator, is correlated with NAFLD occurrence and severity, but its relationship with CHD risk remains unclear. This study investigated the correlation between TyG index and CHD risk among NAFLD patients.

METHODS

This cross-sectional study included 424 patients with NAFLD and chest pain in the Department of Cardiology, The Second Hospital of Shanxi Medical University, from January 2021 to December 2021. The TyG index was calculated and coronary angiography performed. All individuals were divided into NAFLD + CHD and NAFLD groups and then by TyG index level. The t-test, Mann-Whitney U-test, or one-way analysis of variance compared differences in continuous variables, while the chi-square test or Fisher's exact test compared differences in categorical variables. Logistic regression analysis determined the independent protective or hazardous factors of NAFLD with CHD. The receiver operating characteristic curve evaluated the ability of different TyG index rule-in thresholds to predict CHD. The relationship between Gensini score and TyG index was evaluated using linear correlation and multiple linear regression.

RESULTS

CHD was detected in 255 of 424 patients. Compared to NAFLD group, multivariate logistic regression showed that TyG index was a risk factor for CHD among NAFLD patients after adjustment for age, sex, hypertension, and diabetes mellitus with the highest odds ratio (OR, 2.519; 95% CI, 1.559-4.069; P < 0.001). TG, low-density lipoprotein cholesterol, FBG and TYG-body mass index were also risk factors for CHD among NAFLD patients. High-density lipoprotein cholesterol level was a protective factor for CHD events in patients with NAFLD. In an in-depth analysis, multivariate logistic regression analysis showed that each 1-unit increase in TyG index was associated with a 2.06-fold increased risk of CHD (OR, 2.06; 95% CI, 1.16-3.65; P = 0.013). The multifactor linear regression analysis showed each 0.1-unit increase in TyG in the NAFLD-CHD group was associated with a 2.44 increase in Gensini score (β = 2.44; 95% CI, 0.97-3.91; P = 0.002).

CONCLUSIONS

The TyG index was positively correlated with CHD risk in NAFLD patients and reflected coronary atherosclerosis severity.

Topics: Cholesterol, LDL; Coronary Artery Disease; Cross-Sectional Studies; Glucose; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Triglycerides

PubMed: 35778734
DOI: 10.1186/s12933-022-01548-y

Review

Authors: Marios Sagris, Panagiotis Theofilis, Alexios S Antonopoulos...

Chronic low-grade inflammation is involved in coronary atherosclerosis, presenting multiple clinical manifestations ranging from asymptomatic to stable angina, acute coronary syndrome, heart failure and sudden cardiac death. Coronary microvasculature consists of vessels with a diameter less than 500 μm, whose potential structural and functional abnormalities can lead to inappropriate dilatation and an inability to meet the required myocardium oxygen demands. This review focuses on the pathogenesis of coronary microvascular dysfunction and the capability of non-invasive screening methods to detect the phenomenon. Anti-inflammatory agents, such as statins and immunomodulators, including anakinra, tocilizumab, and tumor necrosis factor-alpha inhibitors, have been assessed recently and may constitute additional or alternative treatment approaches to reduce cardiovascular events in atherosclerotic heart disease characterized by coronary microvascular dysfunction.

Topics: Acute Coronary Syndrome; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Death, Sudden, Cardiac; Heart Failure; Humans; Inflammation; Microcirculation; Microvessels; Myocardial Infarction; Myocardial Ischemia; Risk Factors

PubMed: 34948272
DOI: 10.3390/ijms222413471

Review

Authors: Heyu Meng, Jianjun Ruan, Zhaohan Yan...

Coronary atherosclerosis is a potentially chronic circulatory condition that endangers human health. The biological cause underpinning cardiovascular disease is coronary atherosclerosis, and acute cardiovascular events can develop due to thrombosis, platelet aggregation, and unstable atherosclerotic plaque rupture. Coronary atherosclerosis is progressive, and three specific changes appear, with fat spots and stripes, atherosclerosis and thin-walled fiber atherosclerosis, and then complex changes in arteries. The progression and severity of cardiovascular disease are correlated with various levels of calcium accumulation in the coronary artery. The therapy and diagnosis of coronary atherosclerosis benefit from the initial assessment of the size and degree of calcification. This article will discuss the new progress in the early diagnosis of coronary atherosclerosis in terms of three aspects: imaging, gene and protein markers, and trace elements. This study intends to present the latest methods for diagnosing patients with early atherosclerosis through a literature review.

Topics: Atherosclerosis; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Early Diagnosis; Humans; Plaque, Atherosclerotic; Risk Factors

PubMed: 36012202
DOI: 10.3390/ijms23168939

Authors: Zirui Liu, Haocheng Wang, Zhengkai Yang...

BACKGROUND

The presence of type 1 diabetes mellitus (T1DM) has been demonstrated to pose an increased risk for developing cardiovascular diseases (CVDs). However, the causal relationships between T1DM and CVDs remain unclear due to the uncontrolled confounding factors and reverse causation bias of the observational studies.

METHODS

Summary statistics of T1DM and seven CVDs from the largest available genome-wide association studies (GWAS) of European ancestry and FinnGen biobank were extracted for the primary MR analysis, and the analysis was replicated using UK biobank (UKBB) for validation. Three complementary methods: inverse variance weighted (IVW), weighted median, and MR-Egger were used for the MR estimates. The potential pleiotropic effects were assessed by MR-Egger intercept and MR-PRESSO global test. Additionally, multivariable MR (MVMR) analysis was performed to examine whether T1DM has independent effects on CVDs with adjustment of potential confounding factors. Moreover, a two-step MR approach was used to assess the potential mediating effects of these factors on the causal effects between T1DM and CVDs.

RESULTS

Causal effects of T1DM on peripheral atherosclerosis (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.02-1.10; p = 0.002)] and coronary atherosclerosis (OR = 1.03, 95% CI: 1.01-1.05; p = 0.001) were found. The results were less likely to be biased by the horizontal pleiotropic effects (both p values of MR-Egger intercept and MR-PRESSO Global test > 0.05). In the following MVMR analysis, we found the causal effects of T1DM on peripheral atherosclerosis and coronary atherosclerosis remain significant after adjusting for a series of potential confounding factors. Moreover, we found that hypertension partly mediated the causal effects of T1DM on peripheral atherosclerosis (proportion of mediation effect in total effect: 11.47%, 95% CI: 3.23-19.71%) and coronary atherosclerosis (16.84%, 95% CI: 5.35-28.33%). We didn't find significant causal relationships between T1DM and other CVDs, including heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF), myocardial infarction (MI) and stroke. For the reverse MR from CVD to T1DM, no significant causal relationships were identified.

CONCLUSION

This MR study provided evidence supporting the causal effect of T1DM on peripheral atherosclerosis and coronary atherosclerosis, with hypertension partly mediating this effect.

Topics: Humans; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus, Type 1; Genome-Wide Association Study; Mendelian Randomization Analysis; Hypertension; Atherosclerosis; Nonoxynol

PubMed: 37659996
DOI: 10.1186/s12933-023-01974-6

The triglyceride-glucose index is associated with atherosclerosis in patients with symptomatic coronary artery disease, regardless of diabetes mellitus and hyperlipidaemia.

Authors: Jiao Li, Zixian Dong, Hao Wu...

BACKGROUND

Diabetes and hyperlipidaemia are both risk factors for coronary artery disease, and both are associated with a high triglyceride-glucose index (TyG index). The TyG index has been presented as a marker of insulin resistance (IR). Its utility in predicting and detecting cardiovascular disease has been reported. However, few studies have found it to be a helpful marker of atherosclerosis in patients with symptomatic coronary artery disease (CAD). The purpose of this study was to demonstrate that the TyG index can serve as a valuable marker for predicting coronary and carotid atherosclerosis in symptomatic CAD patients, regardless of diabetes mellitus and hyperlipidaemia.

METHODS

This study included 1516 patients with symptomatic CAD who underwent both coronary artery angiography and carotid Doppler ultrasound in the Department of Cardiology at Tianjin Union Medical Center from January 2016 to December 2022. The TyG index was determined using the Ln formula. The population was further grouped and analysed according to the presence or absence of diabetes and hyperlipidaemia. The Gensini score and carotid intima-media thickness were calculated or measured, and the patients were divided into four groups according to TyG index quartile to examine the relationship between the TyG index and coronary or carotid artery lesions in symptomatic CAD patients.

RESULTS

In symptomatic CAD patients, the TyG index showed a significant positive correlation with both coronary lesions and carotid plaques. After adjusting for sex, age, smoking, BMI, hypertension, diabetes, and the use of antilipemic and antidiabetic agents, the risk of developing coronary lesions and carotid plaques increased across the baseline TyG index. Compared with the lowest quartile of the TyG index, the highest quartile (quartile 4) was associated with a greater incidence of coronary heart disease [OR = 2.55 (95% CI 1.61, 4.03)] and carotid atherosclerotic plaque [OR = 2.31 (95% CI 1.27, 4.20)] (P < 0.05). Furthermore, when compared to the fasting blood glucose (FBG) or triglyceride (TG) level, the TyG index had a greater area under the ROC curve for predicting coronary lesions and carotid plaques. The subgroup analysis demonstrated the TyG index to be an equally effective predictor of coronary and carotid artery disease, regardless of diabetes and hyperlipidaemia.

CONCLUSION

The TyG index is a useful marker for predicting coronary and carotid atherosclerosis in patients with symptomatic CAD, regardless of diabetes mellitus and hyperlipidaemia. The TyG index is of higher value for the identification of both coronary and carotid atherosclerotic plaques than the FBG or TG level alone.

Topics: Humans; Coronary Artery Disease; Hyperlipidemias; Carotid Intima-Media Thickness; Diabetes Mellitus; Atherosclerosis; Plaque, Atherosclerotic; Carotid Artery Diseases

PubMed: 37620954
DOI: 10.1186/s12933-023-01919-z

Randomized Controlled Trial

Authors: Matthew J Budoff, Deepak L Bhatt, April Kinninger...

AIMS

Despite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients.

METHODS AND RESULTS

A total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P < 0.01 for all). When further adjusted for age, sex, diabetes status, hypertension, and baseline TG, plaque volume changes between groups remained significantly different, P < 0.01. Only dense calcium did not show a significant difference between groups in multivariable modelling (P = 0.053).

CONCLUSIONS

Icosapent ethyl demonstrated significant regression of LAP volume on MDCT compared with placebo over 18 months. EVAPORATE provides important mechanistic data on plaque characteristics that may have relevance to the REDUCE-IT results and clinical use of IPE.

Topics: Aged; Coronary Artery Disease; Eicosapentaenoic Acid; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Triglycerides

PubMed: 32860032
DOI: 10.1093/eurheartj/ehaa652

Authors: Shenghan Lai

Topics: Coronary Angiography; Coronary Artery Disease; HIV Infections; Humans; Plaque, Atherosclerotic

PubMed: 33881374
DOI: 10.1148/radiol.2021210373

Authors: Soe Hee Ann, Hyeji Lee, Kyung Sun Park...

Background Data are limited on the association between marital status and subclinical coronary atherosclerosis. This study investigated the influence of marital status on subclinical coronary atherosclerosis detected by coronary computed tomographic angiography in an asymptomatic population. Methods and Results This retrospective study analyzed 9288 asymptomatic individuals (mean age, 53.7±8.0 years; 6041 [65%] men) with no history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography during a general health examination. Marital categories were married (n=8481) versus unmarried (n=807), comprising never married (n=195), divorced (n=183), separated (n=119), and widowed (n=310) individuals. The degree and extent of subclinical coronary atherosclerosis were evaluated by coronary computed tomographic angiography; ≥50% diameter stenosis was defined as significant. Logistic regression and propensity score matching analyses were used to determine the association between marital status and subclinical coronary atherosclerosis. After adjustment for cardiovascular risk factors, no significant differences were observed in the adjusted odds ratio (OR) of unmarried status for any coronary plaque (OR, 1.077; 95% CI, 0.899-1.291), calcified plaque (OR, 1.058; 95% CI, 0.881-1.271), noncalcified plaque (OR, 0.966; 95% CI, 0.691-1.351), mixed plaque (OR, 1.301; 95% CI, 0.884-1.917), and significant coronary artery stenosis (OR, 1.066; 95% CI, 0.771-1.474). Similarly, in the 2:1 propensity-score matched population (n=2398), no statistically significant differences were observed for the OR of marital status for any subclinical coronary atherosclerosis (>0.05 for all). Conclusions In this large cross-sectional study, marital status was not associated with an increased risk of subclinical coronary atherosclerosis.

Topics: Asymptomatic Diseases; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Male; Marital Status; Middle Aged; Plaque, Atherosclerotic; Retrospective Studies; Risk Factors

PubMed: 35621225
DOI: 10.1161/JAHA.121.024942

Authors: Ji Hyun Song, Young Sun Kim, Su-Yeon Choi...

BACKGROUND AND AIM

Gastroesophageal reflux disease (GERD) typically presents with symptoms of heartburn and acid regurgitation but occasionally manifests as atypical chest pain. Coronary artery disease (CAD) and GERD share some risk factors, such as smoking and obesity. The aims of this study were to evaluate the association between GERD and coronary atherosclerosis and to assess the risk factors for coronary atherosclerosis in GERD patients.

METHODS

A total of 16616 subjects who underwent upper gastrointestinal endoscopy from 2003 to 2017 and a cardiac computed tomography (CT) scan within one year were included in this study. Coronary atherosclerosis was evaluated by the coronary artery calcium score (CACS). The severity of GERD was evaluated based on endoscopic findings using the Los Angeles classification.

RESULTS

The proportion of high CACSs (≥100) increased significantly in subjects with severe GERD (p = 0.008). However, the presence of a high CACS did not increase the risk of GERD (OR = 1.007, 95% CI 0.857-1.182), nor did that of GERD increase the risk of a high CACS (OR = 1.018, 95% CI 0.865-1.198). The risk factors for a high CACS in GERD patients included age (OR = 1.087, 95% CI 1.066-1.109), male sex (OR = 5.645, 95% CI 2.561-12.446), hypertension (OR = 1.800, 95% CI 1.325-2.446), and hypercholesterolemia (OR = 1.684, 95% CI 1.213-2.338).

CONCLUSIONS

Although the presence of a high CACS did not increase the risk of GERD or vice versa, the proportion of high CACSs was significantly higher in subjects with severe GERD. Therefore, it might be helpful to assess the CACS in GERD patients with multiple risk factors.

Topics: Chest Pain; Coronary Artery Disease; Endoscopy, Gastrointestinal; Gastroesophageal Reflux; Heartburn; Humans; Male; Risk Factors

PubMed: 35594317
DOI: 10.1371/journal.pone.0267053