Coronary Artery Disease Severity Score Research Articles

Liver Fibrosis Scores and Coronary Artery Disease: Novel Findings in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed term as a more appropriate definition for nonalcoholic fatty liver disease (NAFLD). Previous studies have shown an association between liver fibrosis scores and cardiovascular disease (CVD) in patients with NAFLD. In this study, we aimed to investigate the relationship between liver fibrosis scores and coronary artery disease (CAD) severity in patients with MAFLD. This study was conducted on 1346 patients with MAFLD at the Second Hospital of Dalian Medical University between January 2018 and December 2021. We calculated the liver fibrosis scores, including the fibrosis 4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase-to-platelet ratio index (APRI). We divided the participants into three groups based on the degree of coronary artery stenosis assessed using coronary computed tomography angiography (CCTA): CAD (≥50%), non-obstructive (1-49%), and normal (no stenosis). An increased FIB-4 score and NFS were significantly associated with CAD severity in patients with MAFLD. The percentage of patients with a high FIB-4 score was higher in the CAD group than in the other two groups (5.80%, 4.31%, and 2.24%, respectively; p<0.001), as was the percentage of patients with NFS (11.12%, 5.19%, and 0.93%, respectively; p<0.001). Carotid atherosclerosis, creatinine levels, and CAC scores were significant predictors of CAD. The FIB-4 score and NFS were independently associated with CAD even after adjusting for sex and well-known cardiovascular risk factors. The APRI was not a significant factor for CAD in any model. In the bivariate correlation analysis, the FIB-4 score and NFS were directly correlated with CAC scores. Non-invasive liver fibrosis scores (FIB-4 and NFS) were significantly associated with the CAD severity and CAC scores in patients with MAFLD. Screening for CAD may be beneficial for subjects with high liver fibrosis risk MAFLD.

Association of Angio-LncRNAs MIAT rs1061540/MALAT1 rs3200401 Molecular Variants with Gensini Score in Coronary Artery Disease Patients Undergoing Angiography.

Long non-coding RNAs (lncRNAs) have emerged as essential biomolecules with variable diagnostic and/or prognostic utility in several diseases, including coronary artery disease (CAD). We aimed for the first time to investigate the potential association of five angiogenesis-related lncRNAs (PUNISHER, SENCR, MIAT, MALAT1, and GATA6-AS) variants with CAD susceptibility and/or severity. TaqMan Real-Time genotyping for PUNISHER rs12318065A/C, SENCR rs12420823C/T, MIAT rs1061540C/T, MALAT1 rs3200401T/C, and GATA6-AS1 rs73390820A/G were run on the extracted genomic DNA from 100 unrelated patients with stable CAD undergoing diagnostic coronary angiography and from 100 controls. After adjusting covariates, the studied variants showed no association with disease susceptibility; however, MIAT*T/T genotype was associated with a more severe Gensini score. In contrast, MALAT1*T/C heterozygosity was associated with a lower score. The lipid profile, and to a lesser extent smoking status, male sex, weight, hypertension, and MALAT1 (T > C) (negative correlation), explained the variance between patients/control groups via a principal component analysis. Incorporating the principal components into a logistic regression model to predict CAD yielded a 0.92 AUC. In conclusion: MIAT rs1061540 and MALAT1 rs3200401 variants were associated with CAD severity and Gensini score in the present sample of the Egyptian population. Further large multi-center and functional analyses are needed to confirm the results and identify the underlying molecular mechanisms.

Aorta unfolding index as an indicator for coronary artery disease severity.

Aortic unfolding index (AUI) is an independent predictor of cardiovascular events, yet there is scarcity in the literature on its association with the severity of coronary artery disease (CAD). To investigate the correlation between aortic unfolding and coronary artery disease severity score. The study included 115 patients with various degrees of CAD who underwent invasive coronary angiography and were retrospectively studied. AUI derived from non-contrast computed tomography (CT) of the chest was correlated to the Gensini score describing the CAD severity. Its sensitivity and specificity in the detection of severe stenosis were examined at various cutoff points. CAD severity was significantly correlated with the patient age and AUI. On multivariate regression analysis, AUI was an independent predictor of severe CAD. The best cutoff value was ≥66, with 94.9% sensitivity and 81.6% specificity. AUI ≥66 was a predictor of severe CAD independent of the patient age.

Prior Oral Contraceptive Use and Longer Term Mortality Outcomes in Women with Suspected Ischemic Heart Disease.

Background: Previous Women's Ischemia Syndrome Evaluation (WISE) work demonstrated prior oral contraceptive (OC) use was associated with lower coronary artery disease (CAD) in women with suspected ischemia. The association of prior OC use with longer term all-cause and cardiovascular disease (CVD) mortality is unclear. Materials and Methods: WISE women undergoing coronary angiography for suspected ischemia (enrolled 1996-2001) with prior OC use history and 10-year follow-up data were analyzed. A blinded core laboratory assessed atherosclerotic CAD severity. Kaplan-Meier analyses evaluated prior OC use relative to all-cause and CVD mortality. Cox regression analyses adjusted for baseline differences. Mediation, interaction, and multicollinearity were analyzed. Results: Our 686 women had a mean age 62.5 ± 9.6 years, multiple cardiac risk factors, and 39% previously used OC. Prior OC users were younger, with less lipid-lowering medication use and lower atherosclerotic CAD severity scores (all p < 0.05). Prior OC use was associated with lower 10-year all-cause (p = 0.007) and CVD mortality (p = 0.019). After adjustment, this was no longer significant (p = 0.77 and p = 0.90, respectively). Atherosclerotic CAD severity score mediated one-third of the observed association. Prior OC use was associated with increased CVD mortality among women with very elevated menopausal systolic blood pressure (SBP). Conclusions: Unadjusted prior OC use was associated with lower longer-term all-cause and CVD mortality. One-third of this observed effect appears mediated by the atherosclerotic CAD severity score. Prior OC was adversely associated with CVD mortality in women with very elevated menopausal SBP. Additional investigation is needed to understand the potential benefits and harms of prior OC use. Clinical Trial Number: NCT00000554, or https://www.clinicaltrials.gov/ct2/show/NCT00000554.

To Assess Relationship of Lipoprotein (a) with Severity of Coronary Artery Disease in Patients with Acute Myocardial Infarction: A Hospital based Cross-sectional Study

Introduction: Elevated plasma concentrations of lipoprotein {Lp(a)} have been consistently shown to be a risk factor for the development of a spectrum of thrombotic and atherosclerotic disorders including Coronary Artery Disease (CAD). Aim: To assess relationship of Lp(a) with severity of CAD in patients of Acute Myocardial Infarction (AMI). Materials and Methods: A hospital based, cross-sectional study was conducted at Topiwala National Medical College and B.Y.L. Nair Charitable Hospital, Mumbai, Maharashtra, India, between November 2016 to April 2018 (18 months). A total of 200 diagnosed cases of AMI who were willing to undergo coronary angiography were enrolled for this study. Prior to coronary angiography, a fasting blood sample was assessed for lipids and Lp(a) levels. The Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) score was calculated according to the coronary angiography results. Patients were divided into two groups based on Lp(a) levels: &lt;25 mg/dL and &gt;25 mg/dL and categorised based on CAD severity and SYNTAX scores as low (&lt;22), intermediate (23-32) and high (&gt;32). Lp(a) levels were categorised as low (&lt;25 mg/dL) and high (&gt;25 mg/dL). A p-value of &lt;0.05 was considered as statistically significant. The statistical evaluation of data was done using the Statistical Package for Social Sciences (SPSS; Chicago, IL, USA) program, version 20.0. Results: Majority of the patients belonged to the age group 41- 60 years. Males comprised 161 (80.5%) patients of the study population. Hypertension was the most prevalent risk factor, observed in 101 (50.5%) patients. Left ventricular ejection fraction &lt;40% was observed in 85 (42.5%) patients. Majority had low SYNTAX score {92 (46%)}. There was a significant difference in patients with Lp(a) &lt;25 mg/dL compared to patients with Lp(a) &gt;25 mg/dL with low (45.7% vs. 54.3%, p-value=0.0001), intermediate (9.9% vs. 90.1%, p-value=0.0001) and high SYNTAX scores (10.8% vs. 89.2%, p-value=0.0001), respectively. Conclusion: The Lp(a) was significantly associated with severity of CAD and it also displays prognostic significance.

Asymptomatic coronary artery disease in a Norwegian cohort with type 2 diabetes: a prospective angiographic study with intravascular ultrasound evaluation

AimsThe prevalence of asymptomatic coronary artery disease (CAD) in type 2 diabetes (T2D) is unclear. We investigated the extent and prevalence of asymptomatic CAD in T2D patients by utilizing invasive coronary angiography (ICA) and intravascular ultrasound (IVUS), and whether CAD progression, evaluated by ICA, could be modulated with a multi-intervention to reduce cardiovascular (CV) risk.MethodsFifty-six T2D patients with ≥ 1 additional CV risk factor participated in a 2 year randomized controlled study comparing hospital-based multi-intervention (multi, n = 30) versus standard care (stand, n = 26), with a pre-planned follow-up at year seven. They underwent ICA at baseline and both ICA and IVUS at year seven. ICA was described by conventional CAD severity and extent scores. IVUS was described by maximal intimal thickness (MIT), percent and total atheroma volume and compared with individuals without T2D and CAD (heart transplant donors who had IVUS performed 7–11 weeks post-transplant, n = 147).ResultsDespite CV risk reduction in multi after 2 years intervention, there was no between-group difference in the progression of CAD at year seven. Overall, the prevalence of CAD defined by MIT ≥ 0.5 mm in the T2DM subjects was 84%, and as compared to the non-T2DM controls there was a significantly higher atheroma burden (mean MIT, PAV and TAV in the T2D population were 0.75 ± 0.27 mm, 33.8 ± 9.8% and 277.0 ± 137.3 mm3 as compared to 0.41 ± 0.19 mm, 17.8 ± 7.3% and 134.9 ± 100.6 mm3 in the reference population).ConclusionWe demonstrated that a 2 year multi-intervention, despite improvement in CV risk factors, did not influence angiographic progression of CAD. Further, IVUS revealed that the prevalence of asymptomatic CAD in T2D patients is high, suggesting a need for a broader residual CV risk management using alternative approaches.Trial registration Clinical trials.gov id: NCT00133718 (https://clinicaltrials.gov/ct2/show/NCT00133718)

The Relationship Between the Prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) with the Severity of Coronary Artery Disease (CAD) in Patients Undergoing Coronary Artery Angiography: A Cross- Sectional Study

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent liver diseases worldwide. There are several common risk factors between NAFLD and coronary artery disease (CAD). Objectives: This study aims to evaluate the relationship between the prevalence of Non-alcoholic fatty liver disease (NAFLD) with severity of Coronary Artery Disease (CAD) in patients undergoing coronary artery angiography. Methods: This study was a cross-sectional, descriptive-analysis research that included 514 patients who underwent angiography. The severity of CAD was assessed by the number of vessels involved (vessel score: vd). An ultrasound was performed for all the patients also, intensity of fatty liver involvement was graded from zero (absence of steatosis) to three (severe steatosis). Results: Ultrasonographic examination proven NAFLD in 59.1% of patients with different grades. Patients with NAFLD had significantly higher body mass index (P < 0.001), waist circumference (P = 0.03), and age (P < 0.001). In addition, there were significant differences between ALT and AST within the normal group and NAFLD patients (P < 0.001). Moreover, coronary angiographic data indicated that the presence of NAFLD significantly correlated with the CAD severity score as so: 64% of people with 2vd and 60.5% of people with three-vessle lisense had fatty liver that was statistically significant (df = 4; P = 0.014). Conclusions: This study showed a high prevalence of NAFLD in patients with documented CAD. It is extremely important since knowing risk factors, designing screening programs, and early treatment of fatty liver could lead to reducing the risk of cardiovascular diseases.

Epicardial adipose tissue volume as a marker of coronary artery disease severity in patients with diabetes independent of coronary artery calcium: Findings from the CTRAD study

AimsThe association between epicardial adipose tissue (EAT) volume and coronary artery disease (CAD) severity was evaluated, independent of traditional risk factors and coronary artery calcium (CAC) scores, in patients with diabetes type 2 (DM-2) using cardiac computed tomography angiography (CTA). MethodsA multivariate analysis was utilized to assess for an independent association after calculating EAT volume, CAD severity, and calcium scores in 92 patients with DM-II from the CTRAD study. We graded CAD severity as none (normal coronaries), mild-moderate (<70% stenosis), and severe (70% or greater stenosis). ResultsA total of 39 (42.3%) asymptomatic patients with diabetes did not have CAD; 30.4% had mild/moderate CAD; and 27.1% had severe CAD. Mean EAT volume was highest in patients with severe CAD (143.14cm3) as compared to mild/moderate CAD (112.7cm3), and no CAD (107.5cm3) (p=0.003). After adjustment of clinical risk factors, notably, CAC score, multivariate regression analysis showed EAT volume was an independent predictor of CAD severity in this sample (odds ratio 11.2, 95% confidence interval 1.7–73.8, p=0.01). ConclusionsIncreasing EAT volume in asymptomatic patients with DM-II is associated with presence of severe CAD, independent of BMI and CAC, as well as traditional risk factors.

Clinical Utility of Serum Cystatin C in Predicting Coronary Artery Disease in Patients Without Chronic Kidney Disease

BackgroundCystatin C has been proposed as a novel marker of renal function and predictor of cardiovascular risk. The aim of this study was to investigate the role of cystatin C level as a predictor of cardiovascular events in patients with coronary artery disease (CAD).MethodsThree hundred and five coronary artery patients were included in this study. Serum cystatin C levels, high‐sensitive C‐reactive protein (hs‐CRP), and oxidative stress were measured. Estimated glomerular filtration rate (eGFR) and the CAD severity score were calculated.ResultsCystatin C was correlated with the CAD severity score (r = 0.631, P < 0.0001) and was significantly elevated in the CAD severity score >50. Every 0.1 mg/l increase in cystatin C, 2 mg/l increase in hs‐CRP, 0.2 mmol/l decrease in high‐density lipoprotein cholesterol, 13.7 ml/min decrease in eGFR, and 1.51 μmol/l increase in homocysteine caused a 34, 12, 5, and 22% increase in the risk of having CAD, respectively.ConclusionCystatin C could be a useful laboratory biochemical marker in predicting the severity of CAD. Cystatin C is associated with biochemical atherosclerosis markers such as CRP and homocysteine.

Myocardial washout rate of resting 99mTc-Sestamibi (MIBI) uptake to differentiate between normal perfusion and severe three-vessel coronary artery disease documented with invasive coronary angiography

Patients with severe coronary artery disease (CAD) may present impaired mitochondrial function to enhance (99m)Tc-sestamibi (MIBI) washout from ischemic myocardium. In this study, we aimed to study the MIBI washout rate (WR) between patients with three-vessel CAD (3V-CAD) confirmed by invasive coronary angiography and healthy normal volunteers (HNV) to evaluate the potential utility of MIBI WR to differentiate between these two populations and to stratify the CAD severity. Ten HNV (male = 5, age = 56 ± 10 years) and eight 3V-CAD patients (male = 4, age = 62 ± 8 years) with 3V lumen stenosis ≥50% were enrolled for this study. Each study subject had a resting MIBI perfusion scan at 90 min and a repeated scan at 4 h post the MIBI injection. Global WR (GWR) and regional WR (RWR) were quantified with the percentage difference of decay-corrected polar maps obtained from the two scans and compared between the HNV and 3V-CAD groups. For the 3V-CAD group, the severity of CAD was assessed with CAD severity scores (CADSS) utilizing degree and location of obstructive lesions (stenosis ≥50%) for quantification and compared with WR to evaluate the correlation between these two variables. Significantly higher GWR was observed in the 3V-CAD (21.1 ± 4.6 %) group than the HNV group (9.5 ± 4.9%) (p < 0.001). RWR values in left anterior descending (LAD), right coronary artery (RCA) and left circumflex (LCX) in the 3V-CAD group were also higher than those of the HNV group (LAD 20.7 ± 5.9 vs 9.4 ± 5.6, p < 0.001; RCA 21.3 ± 4.8 vs 9.2 ± 5.8, p < 0.001; LCX 20.5 ± 7.2 vs 10.1 ± 4.4, p = 0.002). Additionally, the linear correlation of GWR and total CADSS for the whole myocardium was strong and statistically significant (y = 0.86x - 1.12, r (2) = 0.73, p = 0.006). Patients with impaired mitochondrial function due to 3V-CAD had consistently higher global and regional rest (99m)Tc-sestamibi washout rates than those of healthy normal volunteers. The global rest (99m)Tc-sestamibi washout rate is a sensitive indicator to stratify the severity of 3V-CAD and to differentiate between severe 3V-CAD and normal perfusion populations.

Relationship of health-related quality of life with fatigue and exercise capacity in patients with coronary artery disease

The study objective was to evaluate the relationship of health-related quality of life (HRQoL) with fatigue and exercise capacity in coronary artery disease (CAD) patients. A total of 1072 consecutive CAD patients on admission to a cardiac rehabilitation program were evaluated for HRQoL (36-item Short Form Medical Outcome Questionnaire; SF-36), body mass index, clinical characteristics (New York Heart Association (NYHA) class, angina pectoris class, coronary interventions, treatment with beta blockers, hypertension and diabetes), symptoms of depression and anxiety (Hospital Anxiety and Depression Scale), fatigue (Multidimensional Fatigue Inventory-20; MFI-20), and exercise capacity (bicycle ergometer test). In univariate regression analyses lower scores on all SF-36 domains were associated with greater scores on all MFI-20 subscales. Exercise capacity was associated with all SF-36 domains, except for social functioning and mental health domains. In multivariate regression analyses, after adjusting for age, gender, body mass index, NYHA class, angina pectoris class, hypertension, diabetes, coronary interventions, treatment with betablockers, and symptoms of depression and anxiety, greater limitation due to physical and due to emotional problems, poor social functioning, decreased energy/vitality, worse general health perception, reduced mental component summary and lower global SF-36 score were independently associated with higher MFI-20 general fatigue score. Reduced physical functioning, greater pain, and reduced physical component summary SF-36 scores were associated with greater MFI-20 physical fatigue score. Lower SF-36 mental health score was associated, with greater MFI-20 mental fatigue score. In CAD patients undergoing rehabilitation, poor HRQoL is associated with greater fatigue and decreased exercise capacity independently from mental distress and CAD severity score.

Adverse outcomes among women presenting with signs and symptoms of ischemia and no obstructive coronary artery disease: Findings from the National Heart, Lung, and Blood Institute–sponsored Women's Ischemia Syndrome Evaluation (WISE) angiographic core laboratory

Women presenting with signs and symptoms of myocardial ischemia frequently have no or nonobstructive coronary artery disease (CAD). This study aimed to investigate the associations between angiographic measures and longer-term clinical outcomes among women with signs and symptoms of ischemia referred for coronary angiography. A prospective cohort analysis of women referred for coronary angiography and enrolled in the National Heart, Lung, and Blood Institute-sponsored WISE was performed. An angiographic severity score was prospectively developed, assigning points for any stenosis weighted by stenosis severity, location, and collaterals and was then tested for prediction for adverse outcome in 917 women, over a median of 9.3 years. The study was conducted in referral centers. Women with signs and/or symptoms of myocardial ischemia referred for coronary angiography were consecutively consented and enrolled in a prospective study. Main outcomes included first occurrence of cardiovascular death or nonfatal myocardial infarction. Hospitalization for angina was a secondary outcome. Cardiovascular death or myocardial infarction at 10 years occurred in 6.7%, 12.8%, and 25.9% of women with no, nonobstructive, and obstructive CAD (P < .0001), respectively. Cumulative 10-year cardiovascular death or myocardial infarction rates showed progressive, near-linear increases for each WISE CAD severity score range of 5, 5.1 to 10, 10.1 to 20, 20.1 to 50, and >50. The optimal threshold in the WISE severity score classifications for predicting cardiovascular mortality was >10 (eg, 5.0-10 vs 10.1-89), with both a sensitivity and specificity of 0.64 and an area under the curve of 0.64 (P = .02, 95% CI 0.59-0.68). Among women with signs and symptoms of ischemia, nonobstructive CAD is common and associated with adverse outcomes over the longer term. The new WISE angiographic score appears to be useful for risk prediction in this population.

Abstract 18685: Global Myocardial Blood Flow Measurements Correlate with Angiographic Severity of Coronary Artery Disease

Background. The correct identification of multivessel coronary artery disease (CAD) is a potential limitation of routine stress-rest using positron emission tomography (PET) myocardial perfusion imaging .We examined whether PET-based myocardial blood flow (MBF) and flow reserve (MFR) can be used to enhance the identification of extensive CAD. Methods. We identified 115 consecutive patients (pts; 65±11 yrs, 75% men) who underwent Regadenoson stress 82 Rb PET and coronary angiography within 6 months. MBF during hyperemia and rest and their ratio (MFR) were quantified. PET metrics included summed rest, stress and difference scores (SRS, SSS and SDS, respectively), transient ischemic dilatation (TID) and changes in ejection fraction (ΔEF). PET results were stratified based on angiographic severity grade from 0 (no stenosis&gt;70% or left main&gt;50%) to 5 (significant 3 vessel and left main CAD) and were analyzed using one way analysis of variance. Results. In total, 26 pts had no significant CAD (severity score=0); 27, 30, 22 and 10 patients had severity scores of 1, 2, 3 and 4, respectively. Resting global MBF did not vary as a function of CAD severity (ANOVA F-statistic = 1.63, p = 0.17), where as there was a strong correlation between CAD severity and global MBF during stress (F=13.5, p&lt;0.0001, figure), SSS (F=12.8, P&lt;0.0001) and global MFR (F=10.8, p&lt;0.0001). Weaker correlations were observed between coronary severity and SDS, Delta EF, and TID, respectively (F=8.2, 3.1, and 0.6). In the 35 pts (30% of total) with left main stenosis or 3-vessel CAD, 31 (89%) pts had abnormal stress MBF and MFR (using cut-offs of 1.80 ml/min/g and ratio of 2.0, respectively); whereas 54% had negative [[Unable to Display Character: ▵]]EF and only 20% had abnormal TID. Conclusion. Absolute stress MBF and MFR enhance the diagnostic accuracy of cardiac PET over conventional parameters for the identification of high-risk, severe and extensive CAD. This approach may reduce the incidence of CAD underestimation by PET.

Association of serum calcitonin with coronary artery disease in individuals with and without chronic kidney disease

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Recent data implicate disordered bone and mineral metabolism, including changes in serum levels of calcium, phosphate, parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), and fetuin A, as novel risk factors for arterial calcification. The potential role of calcitonin, another hormonal regulator of mineral and bone metabolism, has not been studied in detail. We investigated the link between serum calcitonin and the total burden of coronary artery disease (CAD) using the validated Gensini score, in a cross-sectional study of 88 patients with estimated GFR (eGFR) between 46 and 87 ml/min/1.73 m² who underwent coronary angiography. We evaluated the associations between serum calcitonin, minerals (calcium, phosphate), calcium × phosphate product, and other factors that regulate mineral metabolism (intact PTH, 25-OH-vitamin D, FGF-23, and fetuin A) and the severity of CAD. The mean serum calcitonin was 11.5 ± 7.8 pg/ml. In univariate analysis, the Gensini CAD severity score correlated significantly with male gender, eGFR, and serum levels of 25-OH-vitamin D, iPTH, FGF-23, fetuin A, and calcitonin (R = 0.474, P = 0.001 for the latter). In multivariate analysis adjusted for calcium, phosphate, 25-OH-vitamin D, iPTH, FGF 23, fetuin A, and calcitonin, only calcitonin (β = 0.20; P = 0.03), FGF-23, fetuin A, and 25-OH-vitamin D emerged as independent predictors of Gensini score. In the second step, we adjusted for the presence of traditional risk factors, proteinuria, and GFR. After these adjustments, the FGF-23 and fetuin A remained statistically significant predictors of the Gensini score, while calcitonin did not. Our study suggests that, in addition to other well-known components of mineral metabolism, increased calcitonin levels are associated with greater severity of CAD. However, this relation was not independent of traditional and nontraditional cardiovascular risk factors. Longitudinal studies in larger populations including patients with more advanced CKD are needed.

Prognostic Value of 64-Slice Cardiac Computed Tomography: Severity of Coronary Artery Disease, Coronary Atherosclerosis, and Left Ventricular Ejection Fraction

We sought to determine the prognostic and incremental value of coronary artery disease (CAD) severity, coronary atherosclerosis, and left ventricular ejection fraction (LVEF) measured with cardiac computed tomography angiography (CTA). CTA is an emerging tool used for the detection of obstructive CAD. However, there are limited data supporting the prognostic value of 64-slice CTA and its ability to predict all-cause mortality and major adverse cardiac events such as cardiac death and nonfatal myocardial infarction. Consecutive patients (without history of revascularization, heart transplantation, and congenital heart disease) were prospectively enrolled. Each CTA was evaluated for CAD severity, total plaque score, and LVEF. Patients were followed, and all events were confirmed with death certificates or hospital or physician records and reviewed by a clinical events committee. Between February 2006 and February 2008, 2,076 consecutive patients were prospectively enrolled and followed for a mean of 16 +/- 8 months. At follow-up, a total of 31 (1.5%) patients had cardiac death or nonfatal myocardial infarction and 47 (2.3%) had all-cause mortality or nonfatal myocardial infarction. Multivariate analysis showed that CAD severity (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.89 to 4.83) was a predictor of major adverse cardiac events and that LVEF (HR: 1.47; 95% CI: 1.17 to 1.86) had incremental value over CAD severity. Total plaque score had incremental value over CAD severity and LVEF for all-cause mortality and nonfatal myocardial infarction (HR: 1.17; 95% CI: 1.06 to 1.29). Using CTA, CAD severity, LVEF, and total plaque score seems to have prognostic and incremental value over routine clinical predictors. Cardiac CTA seems to be a promising noninvasive modality with prognostic value.

Diabetes Mellitus, Hypothalamic Hypoestrogenemia, and Coronary Artery Disease in Premenopausal Women (from the National Heart, Lung, and Blood Institute Sponsored WISE Study)

Diabetes mellitus (DM) portends a higher risk of coronary heart disease mortality in women compared with men. This relationship appears to be independent of traditional cardiac risk factors, and the role of reproductive hormones has been postulated. We assessed the relationship between DM, hypothalamic hypoestrogenemia (HHE), angiographic coronary artery disease (CAD), and major adverse cardiovascular events (MACE) during a median of 5.9 years in premenopausal women enrolled in the WISE Study. We evaluated 95 premenopausal women from WISE who underwent coronary angiography for suspected ischemia and were not using exogenous reproductive hormones. Results showed no difference in age between women with (n = 30) and without (n = 65) DM (43 +/- 6 years). DM was associated with hypertension, HHE, angiographic CAD, and coronary artery severity score (all p <0.05). Women with DM were twice as likely to have HHE (50% vs 26%; p = 0.02) compared with women without DM. The presence of both DM and HHE was associated with increased prevalence (40% vs 12% or 13%; p = 0.006) and severity of angiographic CAD (coronary artery severity score 19.9 +/- 19.2 vs 7.7 +/- 4.6 or 12.3 +/- 18.8; p = 0.008) compared with either HHE or DM alone, respectively. DM was moderately predictive of MACE. In conclusion, in premenopausal women undergoing coronary angiography for suspected myocardial ischemia, DM was associated with HHE. The presence of both DM and HHE predicted a greater burden of angiographic CAD. Prospective research is warranted to better understand causal relations between DM, endogenous hormones, and MACE in premenopausal women.

P1-76 INTERLEUKIN-18: A STRONG PREDICTOR OF THE EXTENT OF CORONARY ARTERY DISEASE IN PATIENTS WITH UNSTABLE ANGINA

The aim of this study was to confirm that plasma interleukin (IL)-18 level is associated with the extent of coronary artery disease in unstable angina patients. Previous studies have shown that patients with unstable angina have significantly higher plasma IL-18 levels than healthy volunteers. However, the association between IL-18 and the extent of coronary artery atherosclerosis in patients with unstable angina remains unclear. Plasma concentrations of IL-18 and high-sensitivity C-reactive protein (hs-CRP) were measured in 166 consecutive patients admitted for coronary arteriography. One hundred and eighteen patients with unstable angina had coronary artery disease (coronary artery disease group; severity score: 2.32 ± 1.47; Gensini score: 31.3 ± 25.9), and 48 patients with coronary risk factors and without coronary artery lesions served as the risk control group. Plasma levels of IL-18 were higher in the coronary artery disease group than in the risk control group (P = 0.062). Additionally, plasma levels of IL-18 were significantly higher in 77 coronary artery disease patients with severity score ≥2 than in the risk control group (242.3 ± 110.6 vs 209.8 ± 120.3 pg/ml, P = 0.016). By univariate analysis, log-transformed plasma IL-18 concentration was positively correlated with coronary artery disease severity score (r = 0.244, P = 0.009). By multiple regression analyses, the association between coronary artery disease severity score and IL-18 remained significant (β = 0.733, P = 0.017) when controlling for age, diabetes mellitus and left ventricular ejection fraction. Additionally, coronary artery disease severity score was greater in the highest tertile (>246 pg/ml) of plasma IL-18 levels than in the middle (176–246 pg/ml) and the lowest (<176 pg/ml) tertiles (2.79 ± 1.52 vs 2.05 ± 1.08 vs 2.13 ± 1.66, P = 0.028). Of note, plasma hs-CRP level had no significant correlation with coronary artery severity. Plasma IL-18 level is associated with the extent of coronary artery disease in unstable angina patients, suggesting the link between IL-18 and coronary artery atherosclerosis in these patients.

Interleukin-18: a strong predictor of the extent of coronary artery disease in patients with unstable angina

The aim of this study was to confirm that plasma interleukin (IL)-18 level is associated with the extent of coronary artery disease in unstable angina patients. Previous studies have shown that patients with unstable angina have significantly higher plasma IL-18 levels than healthy volunteers. However, the association between IL-18 and the extent of coronary artery atherosclerosis in patients with unstable angina remains unclear. Plasma concentrations of IL-18 and high-sensitivity C-reactive protein (hs-CRP) were measured in 166 consecutive patients admitted for coronary arteriography. One hundred and eighteen patients with unstable angina had coronary artery disease (coronary artery disease group; severity score: 2.32 +/- 1.47; Gensini score: 31.3 +/- 25.9), and 48 patients with coronary risk factors and without coronary artery lesions served as the risk control group. Plasma levels of IL-18 were higher in the coronary artery disease group than in the risk control group (P = 0.062). Additionally, plasma levels of IL-18 were significantly higher in 77 coronary artery disease patients with severity score > or =2 than in the risk control group (242.3 +/- 110.6 vs 209.8 +/- 120.3 pg/ml, P = 0.016). By univariate analysis, log-transformed plasma IL-18 concentration was positively correlated with coronary artery disease severity score (r = 0.244, P = 0.009). By multiple regression analyses, the association between coronary artery disease severity score and IL-18 remained significant (beta = 0.733, P = 0.017) when controlling for age, diabetes mellitus and left ventricular ejection fraction. Additionally, coronary artery disease severity score was greater in the highest tertile (>246 pg/ml) of plasma IL-18 levels than in the middle (176-246 pg/ml) and the lowest (<176 pg/ml) tertiles (2.79 +/- 1.52 vs 2.05 +/- 1.08 vs 2.13 +/- 1.66, P = 0.028). Of note, plasma hs-CRP level had no significant correlation with coronary artery severity. Plasma IL-18 level is associated with the extent of coronary artery disease in unstable angina patients, suggesting the link between IL-18 and coronary artery atherosclerosis in these patients.

Searching for biomarker patterns characterizing carotid atherosclerotic burden in patients with reduced renal function

Evidence linking chronic kidney disease (CKD) with the increased risk of cardiovascular (CV) complications is firm. It is becoming clear that testing functions of the vascular endothelium in conjunction with various biomarkers may better the definition of CV risk profile in CKD patients. Using Multiplexed analysis of 16 markers reflecting pro-inflammatory, anti-inflammatory, angiogenic, metabolic and anti-fibrinolytic factors in a series of 75 patients with CKD, who underwent echo-coloured Doppler study of carotid arteries, we analysed the contribution of each parameter to the characterization of atherosclerotic burden. As control group we enrolled 33 healthy individuals. On univariate analysis, intima-media thickness, number of atherosclerotic plaques and internal diameter of carotid arteries were strongly interrelated. Starting with these indicators of carotid atherosclerosis, we extracted by principal component analysis a single composite atherosclerosis severity score that accounted for 68% of the total variance of original variables. Biomarkers significantly related to severity of carotid atherosclerosis were MMP9, t-PAI-1, IL-6, NT-proBNP, IL-8 and VEGF. In multiple linear regression models adjusting for clinical variables the gain in prediction power was achieved when we added MMP9 and t-PAI-1 to the basic model. IL-6 produced the highest increase in the multiple R2 of the basic model. The combination of MMP9, t-PAI-1, IL-6, NT-proBNP, IL-8 and VEGF added to the basic model achieved gain in prediction power of + 7.5%. In this expanded model, IL-6 was the only biomarker that significantly predicted the severity of atherosclerosis. Multiplexed screening revealed that IL-6, MMP-9, tPAI-1 and VEGF showed a tight correlation with carotid atherosclerotic burden in patients with CKD.

The effect of acetylsalicylic acid resistance on prognosis of patients who have developed acute coronary syndrome during acetylsalicylic acid therapy

The relationships between clinical events and acetylsalicylic acid resistance (AR), as well as its frequency, have been established in stable patients with coronary artery disease (CAD). Although acute coronary syndrome (ACS) patients taking acetylsalicylic acid have been accepted as a high-risk population, the role of AR has not been investigated in these patient groups. Thus, in the present study, the impact of AR was investigated in patients with ACS who were taking acetylsalicylic acid. Between January 2001 and February 2003, 140 ACS patients were included in the present prospective study. All patients had ACS while taking acetylsalicylic acid. Coronary angiographic scores for severity and extent of CAD were determined for all patients. The effect of acetylsalicylic acid on platelet function was assessed by the platelet function analyzer PFA-100 (Dade Behring, USA). The primary end point was the composite of death, myocardial infarction, cerebrovascular accident and revascularization. The mean follow-up period was 20 months. Patients with AR were older than patients without AR (63.8+/-10.8 years versus 58.3+/-11.2 years; P=0.005). Moreover, myocardial damage was higher in patients with AR according to cardiac troponin T values (1.11+/-1.3 mug/L versus 0.41+/-0.5 mug/L; P=0.01). The composite end point of death, myocardial infarction, cerebrovascular accident or revascularization was present in 16 of 45 patients (35%) with AR and in 13 of 79 patients (16%) without AR (hazard ratio 2.46, 95% CI 1.18 to 5.13; P=0.016). After adjustment for age, platelet count, cardiac troponin T value and CAD severity score, AR remained an independent predictor for long-term adverse events (hazard ratio 3.03, 95% CI 1.06 to 8.62; P=0.038). The clinical event rate was found to be higher in ACS patients with AR than in those without AR. Thus, it may be concluded that there is a strong correlation between a worse prognosis and AR in these patients.