The role of serum lipid in predicting coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease: a cohort study.

OBJECTIVE: To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis. RESULTS: A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients. CONCLUSION: KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.

Impact of coronary calcium morphology on intravascular lithotripsy.

BACKGROUND: Coronary calcification negatively impacts optimal stenting. Intravascular lithotripsy (IVL) is a new calcium modification technique. AIMS: We aimed to assess the impact of different calcium morphologies on IVL efficacy. METHODS: This was a prospective, multicentre study (13 tertiary referral centres). Optical coherence tomography (OCT) was performed before and after IVL, and after stenting. OCT-defined calcium morphologies were concentric (mean calcium arc >180°) and eccentric (mean calcium arc ≤180°). The primary outcomes were angiographic success (residual stenosis <20%) and the presence of fracture by OCT in concentric versus eccentric lesions. RESULTS: Ninety patients were included with a total of 95 lesions: 47 concentric and 48 eccentric. The median number of pulses was 60 (p=1.00). Following IVL, the presence of fracture was not statistically different between groups (79.0% vs 66.0% for concentric vs eccentric; p=0.165). The number of fractures/lesion (4.2±4.4 vs 2.3±2.8; p=0.018) and ≥3 fractures/lesion (57.1% vs 34.0%; p=0.029) were more common in concentric lesions. Angiographic success was numerically but not statistically higher in the concentric group (87.0% vs 76.6%; p=0.196). By OCT, no differences were noted in final minimum lumen area (5.9±2.2 mm2 vs 6.2±2.1 mm2; p=0.570), minimum stent area (5.9±2.2 mm² vs 6.25±2.4 mm2; p=0.483), minimum stent expansion (80.9±16.7% vs 78.2±19.8%), or stent expansion at the maximum calcium site (100.6±24.2% vs 95.8±27.3%) (p>0.05 for all comparisons of concentric vs eccentric, respectively). Calcified nodules were found in 29.5% of lesions; these were predominantly non-eruptive (57%). At the nodule site, dissection was more common than fracture with stent expansion of 103.6±27.2%. CONCLUSIONS: In this prospective, multicentre study, the effectiveness of IVL followed by stenting was not significantly affected by coronary calcium morphology.

Computed Tomography Angiography Characteristics of Thin-Cap Fibroatheroma in Patients With Diabetes.

BACKGROUND: It was recently reported that thin-cap fibroatheroma (TCFA) detected by optical coherence tomography was an independent predictor of future cardiac events in patients with diabetes. However, the clinical usefulness of this finding is limited by the invasive nature of optical coherence tomography. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied. The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes. METHODS AND RESULTS: Patients with diabetes who underwent preintervention CTA and optical coherence tomography were included. Qualitative and quantitative analyses were performed for plaques on CTA. TCFA was assessed by optical coherence tomography. Among 366 plaques in 145 patients with diabetes, 111 plaques had TCFA. The prevalence of positive remodeling (74.8% versus 50.6%, P<0.001), low attenuation plaque (63.1% versus 33.7%, P<0.001), napkin-ring sign (32.4% versus 11.0%, P<0.001), and spotty calcification (55.0% versus 34.9%, P<0.001) was significantly higher in TCFA than in non-TCFA. Low-density noncalcified plaque volume (25.4 versus 15.7 mm3, P<0.001) and remodeling index (1.30 versus 1.20, P=0.002) were higher in TCFA than in non-TCFA. The presence of napkin-ring sign, spotty calcification, high low-density noncalcified plaque volume, and high remodeling index were independent predictors of TCFA. When all 4 predictors were present, the probability of TCFA increased to 82.4%. CONCLUSIONS: The combined qualitative and quantitative plaque analysis of CTA may be helpful in identifying TCFA in patients with diabetes. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

Comparison of angiographic change in side-branch ostium after drug-coated balloon vs. drug-eluting stent vs. medication for the treatment of de novo coronary bifurcation lesions.

OBJECTIVES: Data on side-branch (SB) ostial effect after drug-coated balloon (DCB) treatment in the context of de novo coronary bifurcation lesions are limited. We aimed to investigate the angiographic outcomes of SB ostium after DCB treatment compared with drug-eluting stents (DESs) implantation in the main vessel (MV) or optimal medical therapy (OMT) for the treatment of de novo coronary bifurcation lesions. METHODS: Serial angiographic changes in the SB ostium were compared between DCB, DES, and medication alone for MV treatment. Δ value was calculated by subtracting the follow-up value from the pre-procedure value. RESULTS: A total of 132 bifurcation lesions were included for analysis (44 lesions in DCB group; 38 lesions in DES group; 50 lesions in OMT group). The minimal lumen diameter (MLD) of SB ostium showed an increase at follow-up in the DCB group, whereas a decrease was observed in both the DES and OMT groups (ΔMLD: -0.16 ± 0.45 mm for DCB group vs. 0.50 ± 0.52 mm for DES group vs. 0.08 ± 0.38 mm for OMT group, p < 0.001). The diameter stenosis (DS) of SB ostium showed a marked decrease at follow-up in the DCB group, in contrast to an increase observed in both the DES and OMT groups (ΔDS: 8.01 ± 18.96% for DCB group vs. -18.68 ± 18.60% for DES group vs. -2.05 ± 14.58% for OMT group, p < 0.001). CONCLUSIONS: In de novo coronary bifurcation lesions, DCB treatment on the MV demonstrated favorable angiographic outcomes in the SB ostium at 6-9 month follow-up compared to DES implantation or OMT.

Renal Dysfunction Increases Risk of Adverse Cardiovascular Events in 5-Year Follow-Up Study of Intermediate Coronary Artery Lesions.

BACKGROUND Progression of chronic coronary syndrome (CCS) is influenced by chronic kidney disease (CKD). This 5-year follow-up study aimed to assess 100 patients with 118 intermediate coronary artery lesions evaluated by fractional flow reserve (FFR) and intravascular imaging stratified according to renal function. MATERIAL AND METHODS This prospective study enrolled patients with intermediate coronary stenosis identified by coronary angiogram. Patients with severe renal dysfunction (estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m²) were excluded from the study. The remaining were divided into 2 groups according to eGFR: 45-60 ml/min/1.73 m² for mild-to-moderate renal dysfunction and >60 ml/min/1.73 m² for no renal dysfunction. We analyzed intermediate-grade stenoses (40-80% as assessed in coronary angiography) with the use of optical coherence tomography (OCT), FFR, and intravascular ultrasound (IVUS). RESULTS Renal dysfunction patients were older (67.7±8.1 vs 63.6±9.7 years, P=0.044). Lesion characteristics, including plaque type and minimal lumen area in OCT, showed no significant differences between the renal dysfunction and no renal dysfunction groups. Thin-cap fibroatheroma, calcific plaques, lipidic plaques, and fibrous plaques had similar prevalence. FFR values and IVUS parameters did not significantly differ between the groups. Over a 5-year follow-up, individuals with mild-to-moderate renal dysfunction had an elevated risk of all-cause mortality and major adverse cardiovascular events in multivariate analyses adjusted for age and sex. CONCLUSIONS Mild-to-moderate renal dysfunction was not associated with significant differences in OCT- and IVUS-derived plaque morphology nor with functional indices characterizing intermediate-grade coronary stenoses. Renal dysfunction was related to a higher risk of all-cause mortality and major adverse cardiovascular events prevalence in 5-year follow-up.

CatLet score and clinical CatLet score as predictors of long-term outcomes in patients with acute myocardial infarction presenting later than 12 hours from symptom onset.

BACKGROUND: Our recently developed Coronary Artery Tree description and Lesion EvaluaTion (CatLet) angiographic scoring system is unique in its description of the variability in the coronary anatomy, the degree of stenosis of a diseased coronary artery, and its subtended myocardial territory, and can be utilized to predict clinical outcomes for patients with acute myocardial infarction (AMI) presenting ≤12 h after symptom onset. The current study aimed to assess whether the Clinical CatLet score (CCS), as compared with CatLet score (CS), better predicted clinical outcomes for AMI patients presenting >12 h after symptom onset. METHODS: CS was calculated in 1018 consecutive AMI patients enrolled in a retrospective registry. CCS was calculated by multiplying CS by the ACEF I score (age, creatinine, and left ventricular ejection fraction). Primary endpoint was major adverse cardiac events (MACEs) at 4-year-follow-up, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. RESULTS: Over a 4-year follow-up period, both scores were independent predictors of clinical outcomes after adjustment for a broad spectrum of risk factors. Areas-under-the-curve (AUCs) for CS and CCS were 0.72(0.68-0.75) and 0.75(0.71-0.78) for MACEs; 0.68(0.63-0.73) and 0.78(0.74-0.83) for all-cause death; 0.73(0.68-0.79) and 0.83(0.79-0.88) for cardiac death; and 0.69(0.64-0.73) and 0.75(0.7-0.79) for myocardial infarction; and 0.66(0.61-0.7) and 0.63(0.58-0.68) for revascularization, respectively. CCS performed better than CS in terms of the above-mentioned outcome predictions, as confirmed by the net reclassification and integrated discrimination indices. CONCLUSIONS: CCS was better than CS to be able to risk-stratify long-term outcomes in AMI patients presenting >12 h after symptom onset. These findings have indicated that both anatomic and clinical variables should be considered in decision-making on management of patients with AMI presenting later.

Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans-Brief Report.

BACKGROUND: Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS. METHODS: We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis. RESULTS: CD4+ T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells. CONCLUSIONS: For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier: UMIN000040747.

Receptor for advanced glycation end products polymorphisms in coronary artery ectasia.

BACKGROUND: Although the implication of receptor of advanced glycation endproducts (RAGE) has been reported in coronary artery disease, its roles in coronary artery ectasia (CAE) have remained undetermined. Furthermore, the effect of RAGE polymorfisms were not well-defined in scope of soluble RAGE (sRAGE) levels. Thus, we aimed to investigate the influence of the functional polymorphisms of RAGE -374T > A (rs1800624) and G82S (rs2070600) in CAE development. METHODS: This prospective observational study was conducted in 2 groups selected of 2452 patients who underwent elective coronary angiography (CAG) for evaluation after positive noninvasive heart tests. Group-I included 98 patients with non-obstructive coronary artery disease and CAE, and Group-II (control) included 100 patients with normal coronary arteries. SNPs were genotyped by real-time PCR using Taqman® genotyping assay. Serum sRAGE and soluble lectin-like oxidized receptor-1 (sOLR1) were assayed by ELISA and serum lipids were measured enzymatically. RESULTS: The frequencies of the RAGE -374A allele and -374AA genotype were significantly higher in CAE patients compared to controls (p < 0.001). sRAGE levels were not different between study groups, while sOLR1 levels were elevated in CAE (p = 0.004). In controls without systemic disease, -374A allele was associated with low sRAGE levels (p < 0.05), but this association was not significant in controls with HT. Similarly, sRAGE levels of CAE patients with both HT and T2DM were higher than those no systemic disease (p = 0.02). The -374A allele was also associated with younger patient age and higher platelet count in the CAE group in both total and subgroup analyses. In the correlation analyses, the -374A allele was also negatively correlated with age and positively correlated with Plt in all of these CAE groups. In the total CAE group, sRAGE levels also showed a positive correlation with age and a negative correlation with HDL-cholesterol levels. On the other hand, a negative correlation was observed between sRAGE and Plt in the total, hypertensive and no systemic disease control subgroups. Multivariate logistic regression analysis confirmed that the -374A allele (p < 0.001), hyperlipidemia (p < 0.05), and high sOLR1 level (p < 0.05) are risk factors for CAE. ROC curve analysis shows that RAGE -374A allele has AUC of 0.713 (sensitivity: 83.7 %, specificity: 59.0 %), which is higher than HLD (sensitivity: 59.2 %, specificity: 69.0 %), HT (sensitivity: 62.4 %, specificity: 61.1 %) and high sOLR1 level (≥0.67 ng/ml)) (sensitivity: 59.8 %, specificity: 58.5 %). CONCLUSION: Beside the demonstration of the relationship between -374A allele and increased risk of CAE for the first time, our results indicate that antihypertensive and antidiabetic treatment in CAE patients causes an increase in sRAGE levels. The lack of an association between the expected -374A allele and low sRAGE levels in total CAE group was attributed to the high proportion of hypertensive patients and hence to antihypertensive treatment. Moreover, the RAGE -374A allele is associated with younger age at CAE and higher Plt, suggesting that -374A may also be associated with platelet activation, which plays a role in the pathogenesis of CAE. However, our data need to be confirmed in a large study for definitive conclusions.

Drug-coated balloon in the treatment of coronary artery de-novo large lesions angiography.

The superiority of drug-coated balloon (DCB) in treating small vessels, branching lesions, and high-risk bleeding lesions in coronary heart disease patients has been confirmed. However, its safety and efficacy in large vessels are still unclear. We aimed to investigate whether the efficacy of DCB in large vessels is not inferior to that of drug-eluting stent (DES). From November 2019 to April 2022, a total of 88 patients in our hospital who underwent coronary angiography for the first time and decided to receive DCB or DES treatment were selected. Indicators including late lumen loss (LLL), major adverse cardiovascular event (MACE) rate, major bleeding and all-cause mortality were evaluated at 9 months and 1-year post percutaneous coronary intervention (PCI) therapy. The primary endpoint of 9-month LLL was -0.07 in the DCB group and 0.19 mm in the DES group (p value＜0.001). 1-year cumulative MACE rates were similar in the DCB and DES groups (3.03% vs. 7.23%, P=0.519), TLR rates were similar (3.03% vs. 7.23%, P=0.519), Major bleeding was similar (3.03% vs. 5.45%, P=0.580), and 1 case of Cardiac death in DES group. For LLL, the DCB-only strategy was non-inferior to DES in treating de novo large lesions in the coronary arteries. Furthermore, the efficacy of DCB was comparable to DES at 1 year of follow-up for secondary clinical endpoints.

Doses to the right coronary artery and the left anterior descending coronary artery and death from ischemic heart disease after breast cancer radiotherapy: a case-control study in a population-based cohort.

BACKGROUND AND PURPOSE: Doses to the coronary arteries in breast cancer (BC) radiotherapy (RT) have been suggested to be a risk predictor of long-term cardiac toxicity after BC treatment. We investigated the dose-risk relationships between near maximum doses (Dmax) to the right coronary artery (RCA) and left anterior descending coronary artery (LAD) and ischemic heart disease (IHD) mortality after BC RT. PATIENTS AND METHODS: In a cohort of 2,813 women diagnosed with BC between 1958 and 1992 with a follow-up of at least 10 years, we identified 134 cases of death due to IHD 10-19 years after BC diagnosis. For each case, one control was selected within the cohort matched for age at diagnosis. 3D-volume and 3D-dose reconstructions were obtained from individual RT charts. We estimated the Dmax to the RCA and the LAD and the mean heart dose (MHD). We performed conditional logistic regression analysis comparing piecewise spline transformation and simple linear modeling for best fit. RESULTS: There was a linear dose-risk relationship for both the Dmax to the RCA (odds ratio [OR]/Gray [Gy] 1.03 [1.01-1.05]) and the LAD (OR/Gy 1.04 [1.02-1.06]) in a multivariable model. For MHD there was a linear dose-risk relationship (1,14 OR/Gy [1.08-1.19]. For all relationships, simple linear modelling was superior to spline transformations. INTERPRETATION: Doses to both the RCA and LAD are independent risk predictors of long-term cardiotoxicity after RT for BC In addition to the LAD, the RCA should be regarded as an organ at risk in RT planning.

Swine Model of Coronary Artery Dissection.

Coronary artery dissection (CAD) is the intimal tearing of the coronary arterial wall and can be iatrogenic, spontaneous, or traumatic in origin. CAD is a rare but challenging condition that can cause significant hemodynamic compromise. Management strategies for CAD, such as the use of mechanical circulatory support devices, are available in the clinical setting. However, the incidence, etiology, and optimal management of CAD are not well-defined, emphasizing the need for adequate animal models in preclinical studies. Large animal models provide the human-like conditions necessary for testing and development of potential treatment strategies. In this chapter, we describe a method for the creation of a CAD swine model.

Matrix metallopeptidase 9 contributes to the beginning of plaque and is a potential biomarker for the early identification of atherosclerosis in asymptomatic patients with diabetes.

Aims: To determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) in vitro, early beginning of atherosclerosis in vivo in diabetic mice, and drug naïve patients with diabetes. Methods: Active human MMP9 (act-hMMP9) was added to HCASMCs and the expressions of MCP-1, ICAM-1, and VCAM-1 were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to diabetic KK.Cg-Ay/J (KK) mice. Carotid artery inflammation and atherosclerosis measurements were made at 2 and 10 weeks after treatment. An observational study of newly diagnosed drug naïve patients with type 2 diabetes mellitus (T2DM n=234) and healthy matched controls (n=41) was performed and patients had ultrasound of carotid arteries and some had coronary computed tomography angiogram for the assessment of atherosclerosis. Serum MMP9 was measured and its correlation with carotid artery or coronary artery plaques was determined. Results: In vitro, act-hMMP9 increased gene and protein expressions of MCP-1, ICAM-1, VCAM-1, and enhanced macrophage adhesion. Exogenous act-hMMP9 increased inflammation and initiated atherosclerosis in KK mice at 2 and 10 weeks: increased vessel wall thickness, lipid accumulation, and Galectin-3+ macrophage infiltration into the carotid arteries. In newly diagnosed T2DM patients, serum MMP9 correlated with carotid artery plaque size with a possible threshold cutoff point. In addition, serum MMP9 correlated with number of mixed plaques and grade of lumen stenosis in coronary arteries of patients with drug naïve T2DM. Conclusion: MMP9 may contribute to the initiation of atherosclerosis and may be a potential biomarker for the early identification of atherosclerosis in patients with diabetes. Clinical trial registration: https://clinicaltrials.gov, identifier NCT04424706.

Evaluation of fractional flow reserve and atherosclerotic plaque characteristics on coronary non-contrast T1-weighted magnetic resonance imaging.

BACKGROUND AND AIMS: The relationship between high-risk coronary plaque characteristics regardless of the severity of lesion stenosis and myocardial ischemia remains unsettled. High-intensity plaques (HIPs) on non-contrast T1-weighted magnetic resonance imaging (T1WI) have been characterized as high-risk coronary plaques. We sought to elucidate whether the presence of coronary HIPs on T1WI influences fractional flow reserve (FFR) in the distal segment of the vessel. METHODS: We retrospectively analyzed 281 vessels in 231 patients with chronic coronary syndrome who underwent invasive FFR measurement and coronary T1WI using a multicenter registry. The plaque-to-myocardial signal intensity ratio (PMR) of the most stenotic lesion was evaluated; a coronary plaque with PMR ≥1.4 was defined as a HIP. RESULTS: The median PMR of coronary plaques on T1WI in vessels with FFR ≤0.80 was significantly higher than that of plaques with FFR >0.80 (1.17 [interquartile range (IQR): 0.99-1.44] vs. 0.97 [IQR: 0.85-1.09]; p < 0.001). Multivariable analysis showed that an increase in PMR of the most stenotic segment was associated with lower FFR (beta-coefficient, -0.050; p < 0.001). The presence of coronary HIPs was an independent predictor of FFR ≤0.80 (odds ratio (OR), 6.18; 95% confidence interval (CI), 1.93-19.77; p = 0.002). Even after adjusting for plaque composition characteristics based on computed tomography angiography, the presence of coronary HIPs was an independent predictor of FFR ≤0.80 (OR, 4.48; 95% CI, 1.19-16.80; p = 0.026). CONCLUSIONS: Coronary plaques with high PMR are associated with low FFR in the corresponding vessel, indicating that plaque morphology might influence myocardial ischemia severity.

SLAMF1-derived peptide exhibits cardio protection after permanent left anterior descending artery ligation in mice.

Acute myocardial infarction (MI) results in tissue damage to affected areas of the myocardium. The initial inflammatory response is the most damaging for residual cardiac function, while at later stages inflammation is a prerequisite for proper healing and scar formation. Balancing the extent and duration of inflammation during various stages after MI is thus pivotal for preserving cardiac function. Recently, a signaling lymphocytic activation molecule 1 (SLAMF1)-derived peptide (P7) was shown to reduce the secretion of inflammatory cytokines and protected against acute lipopolysaccharide-induced death in mice. In the present study, we experimentally induced MI by permanent ligation of the left anterior descending artery (LAD) in mice and explored the beneficial effect of immediately administering P7, with the aim of dampening the initial inflammatory phase without compromising the healing and remodeling phase. Blood samples taken 9 h post-LAD surgery and P7 administration dampened the secretion of inflammatory cytokines, but this dampening effect of P7 was diminished after 3 days. Echocardiography revealed less deterioration of cardiac contraction in mice receiving P7. In line with this, less myocardial damage was observed histologically in P7-treated mice. In conclusion, the administration of a SLAMF1-derived peptide (P7) immediately after induction of MI reduces the initial myocardial inflammation, reduces infarct expansion, and leads to less deterioration of cardiac contraction.

The accuracy of detailed analysis of optical coherence tomography in detection of plaque lipid content: dual-imaging study with optical coherence tomography and near-infrared spectroscopy.

BACKGROUND: Lipid-rich plaque covered by a thin fibrous cap (FC) has been identified as a frequent morphological substrate for the development of acute coronary syndrome. Optical coherence tomography (OCT) permits the identification and measurement of the FC. Near-infrared spectroscopy (NIRS) has been approved for detection of coronary lipids. AIMS: We aimed to assess the ability of detailed OCT analysis to identify coronary lipids, using NIRS as the reference method. METHODS: In total, 40 patients with acute coronary syndrome underwent imaging of a non-culprit lesion by both NIRS and OCT. For each segment, the NIRS-derived 4 mm segment with maximal lipid core burden index (maxLCBI4mm) was assessed. OCT analysis was performed using a semi-automated method including measurement of the fibrous cap thickness (FCT) of all detected fibroatheromas. Subsequent quantitative volumetric evaluation furnished FCT, FC surface area (FC SA), lipid arc, and FC (fibrous cap) volume data. OCT features of lipid plaques were compared with maxLCBI4mm. Predictors of maxLCBI4mm >400 was assessed by using univariable and multivariable analysis. RESULTS: OCT features (mean FCT, total FC SA, FC volume, maximal, mean, and total lipid arcs) strongly correlated with the maxLCBI4mm (p = 0.012 for the mean FCT, respectively p < 0.001 for all other aforementioned features). The strongest predictors of maxLCBI4mm >400 were the maximal (p = 0.002) and mean (p = 0.002) lipid arc, and total FC SA (p = 0.012). CONCLUSIONS: We found a strong correlation between the OCT-derived features and NIRS findings. Detailed OCT analysis may be reliably used for detection of the presence of coronary lipids.

Association between BMD and coronary artery calcification: an observational and Mendelian randomization study.

Observational studies have reported inconsistent associations between bone mineral density (BMD) and coronary artery calcification (CAC). We examined the observational association of BMD with CAC in 2 large population-based studies and evaluated the evidence for a potential causal relation between BMD and CAC using polygenic risk scores (PRS), 1- and 2-sample Mendelian randomization (MR) approaches. Our study populations comprised 1414 individuals (mean age 69.9 yr, 52.0% women) from the Rotterdam Study and 2233 individuals (mean age 56.5 yr, 50.9% women) from the Framingham Heart Study with complete information on CAC and BMD measurements at the total body (TB-), lumbar spine (LS-), and femoral neck (FN-). We used linear regression models to evaluate the observational association between BMD and CAC. Subsequently, we compared the mean CAC across PRSBMD quintile groups at different skeletal sites. In addition, we used the 2-stage least squares regression and the inverse variance weighted (IVW) model as primary methods for 1- and 2-sample MR to test evidence for a potentially causal association. We did not observe robust associations between measured BMD levels and CAC. These results were consistent with a uniform random distribution of mean CAC across PRSBMD quintile groups (P-value > .05). Moreover, neither 1- nor 2-sample MR supported the possible causal association between BMD and CAC. Our results do not support the contention that lower BMD is (causally) associated with an increased CAC risk. These findings suggest that previously reported epidemiological associations of BMD with CAC are likely explained by unmeasured confounders or shared etiology, rather than by causal pathways underlying both osteoporosis and vascular calcification processes.

Decreased bone mineral density, the determinant of osteoporosis, and increased coronary artery calcification are common in people at an advanced age and share some common risk factors. Some studies have reported a higher risk for coronary artery calcification in people with osteoporosis than in people without, whereas others failed to find evidence for this relationship. Recently, Mendelian randomization has emerged as an important epidemiological tool that offers a simple way to distinguish causation, minimizing the confounding present in observational studies, leveraging individual genetic data and the findings from robust genome-wide association studies. We combined data from the participants of both the Rotterdam Study and the Framingham Heart Study, and did not observe sufficient evidence for the association between bone mineral density at different skeletal sites and coronary artery calcification. Also, when using Mendelian randomization, we concluded there was no causal relation between bone deterioration and the build-up of calcium in the coronary arteries. Although more research is needed, we conclude that the associations between decreased bone mineral density and increased coronary artery calcification reported in previous studies are likely attributed to other confounders rather than a causal relationship between these traits.

Circulating miR-6821-5p levels and coronary calcification in asymptomatic familial hypercholesterolemia patients.

BACKGROUND AND AIMS: Premature atherosclerotic cardiovascular disease (CVD) is a clinic characteristic of familial hypercholesterolemia (FH). Coronary calcium score (CCS) is a highly used imaging modality to evidence atherosclerotic plaque burden. microRNAs (miRNAs) are non-coding RNAs that epigenetically regulate gene expression. Here, we investigated whether CCS associates with a specific miRNA-signature in FH-patients. METHODS: Patients with genetic diagnosis of FH (N = 86) from the nationwide SAFEHEART-cohort were investigated by computed tomography angiography imaging and classified depending on the presence of coronary calcification in FH-CCS (+) and FH-CCS (-) groups by the Agatston score. Differential miRNA profiling was performed in two stages: first by Affymetrix microarray technology (high-throughput differential profiling-studies) and second by RT-PCR using TaqMan-technology (analytical RT-qPCR study) in plasma of the two patient groups. RESULTS: miR-193a-5p, miR-30e-5p and miR-6821-5p levels were significantly higher in FH-CCS (+) compared to FH-CCS (-). miR-6821-5p was the best miRNA to discriminate FH-patients CCS(+), according to receiver operating characteristic (ROC) analysis (AUC: 0.70 ± 0.06, p = 0.006). High miR-6821-5p levels were associated with older age (p = 0.03) and high LDL-burden (p = 0.014) using a ROC-derived cut-off value. However, miR-6821-5p did not correlate with age in either the CCS- or CCS + group. Genes involved in calcification processes were identified by in silico analysis. The relation of cell-calcification and expression levels of miR-6821-5p, BMP2 and SPP1 was validated experimentally in human vascular smooth muscle cell cultures. CONCLUSIONS: Up-regulated levels of miR-6821-5p are found in the plasma of asymptomatic FH-patients with coronary calcified atherosclerotic plaques, as well as in isolated human vascular smooth muscle cells expressing the pro-calcification genes BMP2 and SPP1. These findings highlight the impact of epigenetic regulation on the development of subclinical atherosclerosis.

Predictive value of the serum uric acid to high-density lipoprotein cholesterol ratio for culprit plaques in patients with acute coronary syndrome.

BACKGROUND: Hyperuricemia and low level of high-density lipoprotein cholesterol (HDL-C) are both risk factors for coronary artery disease (CAD). The uric acid to HDL-C ratio (UHR) has recently been identified as a new inflammatory and metabolic biomarker. However, the relationship between the UHR and coronary culprit plaques has not been fully investigated in patients with acute coronary syndrome (ACS). METHODS: A total of 346 patients with ACS were enrolled in this study. Culprit lesion characteristics were assessed by optical coherence tomography (OCT). Logistic regression and linear correlation analyses were performed to assess the association between the UHR and culprit plaques. The predictive value of the UHR was investigated by receiver operating characteristic (ROC) curve analysis. RESULTS: The percentages of typical culprit plaques, including ruptures, erosions and thrombi, were greater in the high-UHR subgroup than those in the low-UHR subgroup. A positive relationship was also found between the UHR and diameter stenosis (r = 0.160, P = 0.003) and between the UHR and area stenosis (r = 0.145, P = 0.007). The UHR was found to be independently associated with plaque rupture, erosion and thrombus. Furthermore, ROC analysis suggested that the UHR had a better predictive value than low-density lipoprotein cholesterol. CONCLUSIONS: An elevated UHR level was independently related to the occurrence rate of culprit plaques. The UHR is a simple and easily acquired parameter for detecting culprit plaques in patients with ACS.