Search Results (332)

Ischemia with non-obstructive coronary arteries (INOCA) and coronary microvascular dysfunction (CMD) are increasingly recognized causes of angina, reduced quality of life, and elevated cardiovascular risk, yet mechanistic heterogeneity complicates diagnosis and treatment. This narrative review synthesizes evidence from clinical guidelines, consensus documents, landmark trials, cohorts, mechanistic studies, and high-quality reviews identified through structured, non-exhaustive searches of PubMed/MEDLINE, Google Scholar, and major cardiovascular society documents. Current evidence indicates that endothelial mitochondria function primarily as signaling organelles, regulating reactive oxygen species, nitric oxide bioavailability, endothelium-dependent hyperpolarization, calcium signaling, inflammatory activation, mitophagy, and endothelial survival. Cardiometabolic risk factors, aging, chronic kidney disease, and postmenopausal hormonal changes may converge on mitochondrial quality-control and redox pathways, contributing to CMD susceptibility and sex-specific vulnerability. However, direct human evidence linking endothelial mitochondrial dysfunction causally to CMD defined by invasive coronary function testing remains limited. Coronary physiological testing and acetylcholine provocation are validated tools for CMD endotyping, whereas mitochondrial biomarkers remain investigational. Endotype-guided diagnosis and management remain central, while mitochondria-targeted strategies require prospective CMD-specific validation. Full article

Cardiac computed tomography (CT) has evolved into a pivotal tool in precision cardiology, enabling comprehensive, non-invasive evaluation of coronary anatomy, plaque composition, vascular function, and inflammation. From calcium scoring to advanced physiological imaging, CT now integrates multiple layers of cardiovascular information within a unified diagnostic framework. Coronary artery calcium (CAC) quantification provides a robust, reproducible measure of atherosclerotic burden and refines risk estimation beyond traditional algorithms, particularly in asymptomatic individuals with an intermediate likelihood. Building upon this anatomical foundation, coronary CT angiography (CCTA) extends evaluation to the anatomical and morphological characterization of coronary artery disease (CAD), identifying both obstructive and non-obstructive plaques with high prognostic accuracy. The addition of CT-derived fractional flow reserve (FFR-CT) and stress perfusion CT (CTP) bridges anatomy and physiology, improving identification of flow-limiting stenoses and guiding revascularization decisions while reducing unnecessary invasive procedures. Beyond luminal assessment, CT-derived biomarkers such as the perivascular fat attenuation index (pFAI) have introduced a new dimension of vascular inflammation imaging, revealing residual risk even in patients without significant stenosis and suggesting novel pathways for individualized therapeutic targeting. Driven by advances in artificial intelligence and photon-counting detector technology, cardiac CT is transitioning from a purely diagnostic modality to an integrative platform for cardiovascular phenotyping. Taken as a whole, this integration of structural, functional, and biological data provides a genuinely holistic view of coronary health. In practical terms, it shifts clinical decision-making from population-based risk models toward precision-guided patient-specific strategies. Full article

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants increasingly associated with cardiovascular disease. Identifying early manifestations of vascular aging before the onset of overt disease is essential for improving cardiovascular risk stratification and prevention. Emerging evidence suggests that PFAS exposure contributes to early vascular and atherosclerotic alterations detectable by imaging techniques, including increased carotid intima–media thickness (CIMT), arterial stiffness, and endothelial dysfunction. In contrast, evidence for associations with coronary artery calcium progression and coronary stenosis remains scarce. Mechanistically, PFAS exposure promotes endothelial dysfunction, oxidative stress, chronic inflammation, lipid dysregulation, and genetic and epigenetic modifications, all of which contribute to premature vascular aging and metabolic disturbances. The integration of imaging and molecular biomarkers may provide complementary insights into the structural, functional, and biological processes underlying PFAS-related vascular damage; however, to date, this field remains largely unexplored. This narrative review summarizes current evidence on imaging and molecular biomarkers of PFAS-induced vascular aging and discusses their potential role in cardiovascular risk assessment. It also highlights key knowledge gaps and the need for robust epidemiological and multi-omics studies to validate these biomarkers, clarify causal mechanisms, and support their application in cardiovascular and environmental health surveillance. Full article

Regular endurance exercise is consistently associated with lower cardiovascular mortality, a favorable cardiometabolic profile, and superior cardiorespiratory fitness. However, coronary imaging studies in master endurance athletes have raised a clinically relevant paradox: despite a low burden of conventional risk factors, some athletes—particularly older men with high lifetime exercise exposure—show a greater prevalence of coronary artery calcium and subclinical coronary plaque than sedentary or less active controls. This observation has challenged the long-standing assumption that high-volume endurance exercise is uniformly protective against coronary artery disease. A binary interpretation of this literature is inadequate. Coronary flow reserve and ischemic threshold may remain adequate in some athletes, although this concept is supported by limited functional and outcome data. Based on experimental vascular biology and indirect human evidence, repetitive high-flow states during endurance exercise generate sustained laminar shear stress, cyclic wall strain, and marked increases in coronary blood flow, thereby activating endothelial mechanotransduction pathways and influencing vascular smooth muscle cell behavior, extracellular matrix remodeling, and calcification biology. These adaptations may culminate in positive arterial remodeling, luminal enlargement, and, in some individuals, a predominantly calcified plaque phenotype. Importantly, structural remodeling does not necessarily equate to functional impairment. In selected athletes, when outward remodeling and endothelial responsiveness are preserved, coronary flow reserve and ischemic threshold may remain adequate, although this concept remains supported by limited functional and outcome data. This narrative review integrates the clinical imaging literature with current concepts in vascular mechanobiology to propose that coronary remodeling in endurance athletes exists along an adaptive–maladaptive continuum shaped by cumulative exercise load, aging, sex, conventional risk factors, and biological susceptibility. This framework may help clinicians interpret CAC/CCTA findings in athletes more appropriately and avoid equating plaque burden with equivalent functional or prognostic significance. Full article

Background: Inflammation and lipid metabolism play critical roles in coronary artery calcium (CAC) progression. This study aimed to investigate the relationship between neutrophil-to-high-density lipoprotein-cholesterol ratio (NHR) and CAC score. Methods: This cross-sectional study included 2193 eligible participants from Sichuan Provincial People’s Hospital between November 2015 and July 2025. The correlation between NHR and CAC score was evaluated using multivariable logistic and multinomial logistic regression models. Restricted cubic splines (RCS) were employed to assess potential nonlinear relationships. Sensitivity analyses and subgroup analyses were performed to test the robustness of the findings. Results: Among 2193 eligible participants, 64.89% had detectable CAC. Higher NHR levels were significantly associated with increased CAC prevalence. After adjustment for multiple confounders, each 1-unit increase in NHR was associated with 9.0% higher odds of CAC (odds ratio (OR): 1.09, [95% confidence interval (CI) 1.03–1.16], p = 0.002). Compared with the lowest NHR quartile, the highest quartile was associated with modestly higher odds of CAC (OR: 1.43 [95% CI 1.05–1.95], p = 0.022). In multinomial analyses, NHR was modestly but significantly associated with CAC across mild, moderate, and severe calcification stages. The RCS analysis showed a linear relationship between NHR and CAC. Subgroup analyses and sensitivity analyses confirmed the robustness of the findings. Conclusions: Elevated NHR was associated with an increased likelihood of CAC. As a simple and readily available marker, NHR may reflect inflammatory and lipid metabolic status related to subclinical atherosclerosis, although its clinical utility requires further confirmation. Full article

Takotsubo syndrome (TTS) is an acute disorder characterized by transient left ventricular dysfunction with typical regional wall motion abnormalities, most commonly apical ballooning. It accounts for 1–3% of all suspected acute coronary syndromes and up to 5–6% in women presenting with ST-segment elevation myocardial infarction requiring coronary angiography to exclude obstructive coronary artery disease. The pathophysiology of TTS is complex and not fully elucidated, with sympathetic hyperactivation playing a central role through calcium dysregulation, oxidative stress, and metabolic alterations. Both clinical and experimental data demonstrate the importance of inflammation, with cell infiltration and persistent immune activation exceeding the acute phase. Increasing evidence highlights the impact of coronary microvascular disfunction (CMVD) as a secondary phenomenon, with some findings that support its role as a causative substrate. Beyond well-known predisposing conditions such as female sex, postmenopausal age, and neurological and psychiatric disorders with the trigger of a physical or psychological event, numerous case reports associate the syndrome with chronic autoimmune diseases, even if clear experimental evidence remains poor and worthy of further study. Echocardiography and advanced imaging techniques, including cardiac magnetic resonance and positron emission tomography, have provided insights into transient CMVD, reversible myocardial edema, and metabolic impairment, strengthening our knowledge of the syndrome as a dynamic process. It is also of growing interest to perform invasive hemodynamic assessment to explain the increase in microvascular resistance. This review offers a comprehensive and up-to-date overview of these techniques in the context of TTS. Since clinically, TTS may be associated with significant morbidity and mortality, with some unexplained cases of long-term myocardial disfunction or even recurrence, a deeper understanding of the interplay between catecholamines, inflammation, immune substrate, and CMVD may improve risk stratification and lead to the development of targeted therapeutic strategies. Full article

Background: Cardiovascular (CV) risk estimation is usually based on the assessment of classic risk factors and the extent of coronary artery stenosis. However, a substantial rate of acute coronary syndromes (ACS) and sudden cardiac deaths (SCD) is observed in patients with high-risk atherosclerotic plaques (HRP), even in the absence of significant stenosis. Therefore, this study aimed to evaluate the predictive value of traditional clinical risk factors for the presence of HRP in patients scheduled for coronary computed tomography (CCT). Methods: This single-center study included 123 patients undergoing CCT for suspected coronary artery disease (CAD). Atherosclerotic plaque morphology (HRP) and the degree of coronary artery stenosis (CAD-RADS categories) were assessed in all the patients. CV risk factors, including LDL serum levels and CT Calcium score (CS), were analyzed. Results: The study cohort was mostly males (54.5%), with an average age of 60.40 ± 12.45 years and typical risk factors: hypertension (70%), diabetes (22%), obesity (30%), and smoking (20%). Most patients (88%) were found to have coronary atherosclerosis with nonobstructive disease (CAD-RADS 1–2) in 39% of patients. HRP was confirmed in over one-fifth of the participants (22%), with half of the patients in the CAD-RADS 2 category. There were no differences in CV risk factors between patients with and without HRP in CCT. No significant clinical predictor of HRP in CCT was identified. Conclusions: CV risk factors do not predict HRP in CCT, which may underestimate the real risk of ACS and SCD. Full article

Background/Objectives: Coronary artery disease (CAD) is a leading cause of cardiovascular morbidity and mortality worldwide. Type 2 diabetes mellitus (T2DM) further increases CAD risk through metabolic disturbances and endothelial dysfunction. Adropin, S100A1, and SERCA2b are important regulators of endothelial function, energy metabolism, and calcium homeostasis. This study aimed to investigate the gene and protein expression levels of these biomarkers in CAD patients with and without T2DM. Methods: Gene and protein expression levels of adropin (ENHO), S100A1, and SERCA2b were evaluated in peripheral blood samples obtained from healthy controls (n = 50), CAD patients (n = 46), and CAD patients with T2DM (CAD+T2DM) (n = 40). Gene expression was determined using real-time PCR, while protein levels were measured with ELISA. Additionally, in silico bioinformatics analyses, such as protein–protein interaction networks and pathway enrichment analyses, were performed to explore potential molecular relationships among these biomarkers. Results: Adropin and ENHO gene expression levels were significantly lower in CAD patients and inversely related to the SYNTAX score. S100A1 levels were also reduced, and SERCA2b gene expression was significantly decreased, especially in the CAD+T2DM group. Bioinformatics analyses revealed that these molecules participate in interconnected pathways related to calcium signaling, cardiac muscle contraction, and metabolic regulation. Conclusions: These findings demonstrate links between altered levels of adropin, S100A1, and SERCA2b and CAD with or without T2DM. However, these observations are preliminary and need validation in larger prospective studies and mechanistic research before drawing definitive conclusions about their clinical utility, disease progression, or prognostic value. Full article

Coronary artery vasospasm (CAV) is a transient, reversible constriction of the epicardial coronary arteries that reduces coronary blood flow and may cause myocardial ischemia. Despite its clinical significance, CAV remains underdiagnosed and can present as chest pain, acute coronary syndrome, malignant arrhythmias or sudden cardiac death. Vasospasm may occur in both angiographically normal coronary arteries and at sites of pre-existing atherosclerotic stenosis. The pathophysiology of CAV is multifactorial and involves vascular smooth muscle cells (VSMCs) hyperreactivity, endothelial dysfunction, chronic inflammation and autonomic dysregulation. VSMCs contraction is mediated by phosphorylation of the myosin light chain (MLC) through calcium (Ca²⁺)/calmodulin-dependent myosin light chain kinase (MLCK), while relaxation is regulated by myosin light chain phosphatase (MLCP). Increased intracellular Ca²⁺ levels and enhanced Ca²⁺ sensitivity contribute to excessive vasoconstriction. Rho-kinase (ROCK) plays a pivotal role in sustained vasospasm by inhibiting MLCP, thereby promoting prolonged smooth muscle contraction. Endothelial dysfunction contributes to CAV by disrupting normal vascular tone regulation, largely as a result of decreased nitric oxide (NO) mediated vasodilation. Chronic low-grade inflammation and oxidative stress exacerbate both endothelial dysfunction and VSMCs contraction. Understanding these molecular mechanisms is essential for identifying novel therapeutic targets. Emerging treatment strategies, including ROCK inhibitors, endothelin receptor antagonists and anti-inflammatory agents, may improve outcomes in patients with refractory CAV. Full article

Background: The deep learning-derived retinal cardiovascular risk index (Reti-CVD) is a deep learning-derived retinal biomarker calculated from non-mydriatic fundus photographs for cardiovascular risk assessment. This study examined whether obesity phenotype, particularly central adiposity, modifies the association between Reti-CVD and coronary artery calcium score (CACS) in asymptomatic adults undergoing routine health screening. Methods: We retrospectively analyzed 237 Korean adults who underwent fundus photography for Reti-CVD assessment and cardiac computed tomography for CACS measurement. Abdominal obesity was defined as waist circumference (WC) ≥ 90 cm in men and ≥85 cm in women, and general obesity as body mass index (BMI) ≥ 25 kg/m². Multivariable linear regression models with sequential adjustment were used to evaluate the association between Reti-CVD and CACS. Effect modification was assessed using interaction terms for Reti-CVD×WC and Reti-CVD×BMI. Discriminatory performance for coronary calcification, defined as CACS > 0, was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Abdominal obesity was present in 78 participants (32.9%), and general obesity in 102 (43.0%). Participants with CACS > 0 had significantly higher Reti-CVD scores than those with CACS = 0 (0.15 ± 0.09 vs. 0.09 ± 0.05; p < 0.001). Reti-CVD remained positively associated with CACS after adjustment for metabolic and lifestyle factors. In fully adjusted models, WC significantly moderated this association (interaction p = 0.0288), whereas BMI did not (interaction p = 0.5381). Overall discrimination for CACS > 0 was moderate (AUC = 0.735) and numerically higher in participants with abdominal obesity than in those with normal WC (0.787 vs. 0.695). Conclusions: Reti-CVD is independently associated with coronary calcification, and WC-based central adiposity modifies this relationship. Incorporating obesity phenotype may improve personalized interpretation of retinal biomarker-based cardiovascular risk assessment. Full article

Background/Objectives: The prognostic value of serial coronary artery calcium (CAC) progression remains uncertain in Asian populations and statin-treated patients. We evaluated the association between CAC progression and subsequent major adverse cardiovascular events (MACE) in a Taiwanese cohort. Methods: We retrospectively studied 1791 individuals undergoing two CAC-scoring cardiac CT scans at a tertiary center in Taiwan from 2006 to 2021, excluding those with MACE before the second scan. CAC progression was defined as an annualized Agatston score increase of ≥20 units/year. Time-to-event analyses used landmark Cox models beginning at the second scan, with inverse probability weighting (IPW), balance diagnostics, multivariable Cox regression, and multiple-imputation sensitivity analyses. Results: CAC progression occurred in 365 participants (20.4%). Progressors were older and had greater cardiometabolic risk and baseline CAC burden. In a landmark IPW analysis, CAC progression was associated with higher subsequent MACE risk (HR 2.02, 95% CI 1.49–2.74), with a graded association across annualized CAC change categories: HR 1.72 (95% CI 1.17–2.74) for 21–49 units/year and HR 2.86 (95% CI 2.29–3.57) for ≥50 units/year. The association remained consistent in multiple-imputation analysis (HR 1.90, 95% CI 1.36–2.66) and across major clinical subgroups. Discrimination for 10-year MACE was stronger among statin users than non-statin users (AUC 0.774 vs. 0.571), although statin-stratified analyses were exploratory. Conclusions: CAC progression was independently associated with subsequent MACE and showed a graded risk relationship. Serial CAC assessment may serve as a useful dynamic marker for refining longitudinal cardiovascular risk stratification, while prospective studies are needed to validate progression-guided management. Full article

Coronary artery calcification (CAC) represents a clear sign of advanced atherosclerosis and a strong indicator of coronary artery disease burden and cardiovascular risk. Beyond its established prognostic value, CAC significantly influences plaque biology, lesion morphology, and the technical complexity of percutaneous coronary intervention (PCI). This review summarizes current knowledge on the mechanisms of vascular calcification, its clinical determinants, diagnostic assessment, and therapeutic implications. Vascular calcification is now understood as an active, regulated process involving osteogenic transdifferentiation of vascular smooth muscle cells, inflammatory signaling pathways, extracellular vesicle release, and disturbances in mineral metabolism. Distinct calcification phenotypes exert different effects on plaque stability: micro- and spotty calcifications are frequently linked to plaque vulnerability, whereas dense, sheet-like calcification is more typical of stable fibrocalcific lesions. The prevalence of CAC increases with age and differs between sexes, while cardiometabolic risk factors, chronic kidney disease, systemic inflammation, and genetic predisposition further contribute to its development. Noninvasive computed tomography remains the cornerstone for CAC detection and quantification, enabling reliable cardiovascular risk stratification. Intravascular imaging techniques, particularly intravascular ultrasound and optical coherence tomography, provide detailed characterization of calcified plaque morphology and support optimal procedural planning. In patients with heavily calcified lesions, intravascular imaging-guided lesion preparation and stent optimization represent the most effective strategy for improving PCI outcomes. Full article

Background: In patients with type 2 diabetes mellitus (T2DM), angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are first-line antihypertensive treatments with important cardiovascular benefits, but their impacts on coronary-specific inflammation are unknown. Pericoronary adipose tissue (PCAT) attenuation, as assessed by coronary computed tomography angiography (CCTA), serves as a specific biomarker for coronary inflammation. Here, we aim to assess whether treatment with ACE-I or ARB is correlated with lower PCAT attenuation. Methods: In this retrospective observational study, we analyzed 223 patients with T2DM and coronary atherosclerosis who underwent CCTA from 1 January 2017 to 1 September 2024 at our institution. PCAT attenuation was measured in the proximal right coronary artery. Propensity score matching and multivariate linear regression analyses were performed for comparisons. Results: Of the 223 patients (mean age of 64.9 ± 8.8 years, 69.1% male), 122 patients were on ACE-I or ARB (ACE-I/ARB). ACE-I/ARB users had similar PCAT attenuation as their counterparts after propensity score matching (−72.1 ± 7.5 and −71.7 ± 8.1 HU, respectively; p = 0.722). Subgroup analysis in patients with glomerular filtration rate (GFR) < 90 mL/min revealed lower PCAT attenuation in ACE-I/ARB users (−74.8 ± 6.6 vs. −71.4 ± 7.1 HU; p = 0.038), with a significant interaction between these two factors in the multivariate analysis (p = 0.047). Other antihypertensive treatments (beta blockers, dihydropyridine calcium channel blockers, and thiazides) were not linked with lower coronary inflammation. Conclusions: In T2DM patients with coronary atherosclerosis, we did not find an association between ACE-I/ARB treatment and lower coronary inflammation as defined by PCAT attenuation, although such a relationship may exist in those with reduced GFRs. Full article

Background: Interventional cardiology is increasingly being reshaped by rapid progress in non-invasive cardiovascular imaging. Coronary computed tomography angiography (CTCA), once used mainly to exclude obstructive coronary artery disease (CAD), is now being adopted as a broader planning instrument before percutaneous coronary intervention (PCI). Its ability to generate high-resolution three-dimensional visualization of the coronary tree, together with functional assessment through CT-derived fractional flow reserve (FFR-CT) and more advanced plaque analysis supported by artificial intelligence (AI), has expanded its relevance from diagnosis alone to strategic procedural preparation. In this setting, CTCA can help refine lesion assessment, anticipate technical complexity, and support better procedural and clinical outcomes. Technological Advancements: The value of CTCA for both diagnosis and risk stratification has increased substantially with recent technical innovation. Among the most important developments is the maturation of FFR-CT, which enables non-invasive physiological interrogation of coronary stenoses using computational modeling. At the same time, artificial intelligence and deep learning tools are reshaping the CTCA workflow by improving automation, facilitating plaque analysis, and highlighting adverse plaque characteristics such as positive remodeling, spotty calcification, and the napkin-ring sign. Clinical Applications: In modern catheterization practice, CTCA is increasingly used to address anatomically demanding scenarios. Its role is particularly valuable in chronic total occlusion (CTO) intervention, where it can delineate occlusion length, stump characteristics, vessel course, and collateral anatomy before the procedure. Its usefulness also extends beyond CTO PCI by supporting vessel sizing, stent planning, and anticipation of lesion preparation requirements in complex coronary disease. Challenges: Despite these advantages, several barriers continue to limit wider implementation, including blooming from heavy calcification, radiation burden, contrast-related renal concerns, and the practical difficulty of embedding CTCA-based planning into routine workflows. Conclusions: CTCA is becoming an increasingly important adjunct in PCI planning because it can combine anatomical definition, physiological interpretation, and plaque-level information before invasive treatment is undertaken. Overall, this review emphasizes CTCA not only as a diagnostic modality, but also as a practical pre-procedural roadmap that can guide lesion selection, stent planning, calcium modification strategies, and overall PCI strategy. Full article

A substantial proportion of cardiovascular (CV) events occurs in individuals without previously diagnosed CV disease, underscoring the need for improved primary prevention strategies. Traditional risk scores provide probabilistic estimates but fail to directly identify the presence and heterogeneity of subclinical atherosclerosis. This review summarizes current evidence on advanced multimodality imaging approaches for identifying high-risk individuals without prior CV events. Evidence from cohort studies, randomized trials, and meta-analyses was examined to evaluate the role of coronary artery calcium (CAC) scoring, coronary computed tomography angiography (CCTA), perivascular fat attenuation index (FAI), and vascular ultrasound in risk stratification. CAC scoring remains the most validated and widely recommended tool, offering robust prognostic value and significant risk reclassification, particularly in intermediate-risk individuals. CCTA provides additional insights into plaque burden and high-risk phenotypes, while FAI enables noninvasive assessment of coronary inflammation, improving risk prediction beyond anatomical measures. Vascular ultrasound offers a radiation-free, accessible method for detecting systemic plaque burden and refining risk estimation. Overall, multimodality imaging enhances the identification of subclinical disease and supports more individualized, disease-based risk assessment. Future research should clarify cost effectiveness, optimize patient selection, and determine whether imaging-guided strategies improve long-term clinical outcomes. Full article