Angiographic Coronary Artery Disease Research Articles

High-density lipoprotein (HDL) functionality and its relevance to atherosclerotic cardiovascular disease.

Several prospective epidemiological studies have shown that there is a clear inverse relationship between serum high-density lipoprotein-cholesterol (HDL-C) concentrations and risk for coronary heart disease (CHD), even at low-density lipoprotein-cholesterol (LDL-C) levels below 70 mg/dL. However, more recent evidence from genetic studies and clinical research has come to challenge the long-standing notion that higher HDL-C levels are always beneficial, while lower HDL-C levels are always detrimental. Thus, it becomes apparent that HDL functionality plays a much more important role in atheroprotection than circulating HDL-C levels. HDL cholesterol efflux capacity (CEC) from macrophages is a key metric of HDL functionality and exhibits a strong inverse association with both carotid intima-media thickness and the likelihood of angiographic coronary artery disease (CAD), independent of the HDL-C level. Thus, extensive research is being conducted to identify new agents with a favorable side effect profile, which would be able to enhance CEC, improve HDL functionality and potentially decrease cardiovascular risk. This review aims to present and discuss the current clinical and scientific evidence pertaining to the significance of HDL functionality over the actual HDL-C concentration in mediating the favorable effects on the cardiovascular system. Thus, we conducted a PubMed search until December 2017 through the English literature using the search terms ‘HDL function/functionality’, ‘HDL properties’, ‘cardiovascular risk’ and ‘cholesterol efflux capacity’. We also included references from the articles identified and publications available in the authors’ libraries.

Association of the waist-hip ratio with plasma adiponectin related to coronary artery disease

Objective: By enrolling a prospective study of 82 patients that underwent non-urgent coronary angiography for coronary artery disease (CAD), it is aimed to investigate the correlation between adiponectin and waist-hip-ratio with severity of CAD.Materials and methods: The results of the angiography, divided the patients into two groups, patients admitted with a diagnosis of CAD and non-CAD. In the conducted hospital based research, two groups were involved: the study group with documented angiographically CAD and control group without angiographic evidence of CAD. Some of the baseline adiponectin levels in stored serum samples of all patients, anthropometric and biochemical risk factors were assessed in both groups.Result and discussion: As the result, we have seen the presence of CAD that was associated with current smoking, male gender, waist–hip ratio (WHR).While, no significant difference between median adiponectin levels at baseline were observed between cases and controls.Conclusion: There is a significant positive correlation between waist - hip ratio and presence of severity of coronary artery disease.Bangladesh Journal of Medical Science Vol.17(2) 2018 p.290-295

The association of polymorphic variants, rs2267788, rs1333049 and rs2383207 with coronary artery disease, its severity and presentation in North Indian population

BackgroundThe polymorphic alleles of APOA5 (rs2266788 (C), rs3135506 (G)), LPA (rs10455872 (A), rs3798220 (G)) and 9p21.3 (rs1333049 (C), rs2383207(A)) have been reported in association with susceptibility of coronary artery disease (CAD) from genome wide association studies. We aimed to assess the association of genetic variants with coronary angiogram proven CAD, severity scored with modified Gensini score and association of risk for myocardial infraction (MI) in North Indian population. MethodsWe recruited 512 angiographic proven CAD patients (mean age 58.1±10.2years) and 272 controls (mean age 50.3±11.1years) with normal coronaries from North Indian population. The genotyping technique polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed for rs2266788, rs3135506 and rs10455872. Amplified refractory mutation system-PCR (ARMS-PCR) was used for genotyping of rs1333049, rs2383207 and rs3798220 genetic variants. ResultsThe polymorphic risk allele of variants rs2266788 (C), rs1333049 (C), rs2383207 (A) and heterozygous polymorphic alleles of rs2266788 (TC) were significantly associated with CAD. The homozygous alleles of rs22667788 (CC) and rs1333049 (CC) had also been significantly associated with CAD. The significance of association of rs2266788 (C, CC, TC) and rs1333049 (C, CC) increases with severity of CAD. The presence of mutant allele of rs2266788 (C) was associated with risk of MI and unstable angina (UA). Also, homozygous risk allele of rs2266788 (CC) significantly associated with risk of MI and UA in patients of chronic stable angina (CSA) patients. Whereas, the risk allele of rs1333049 (C) have shown the association with MI and UA compared to controls. The genetic variants of rs3135506 (G), rs10455872 (A) and rs3798220 (G) have low frequency in our population and reflected no association with CAD. ConclusionThe polymorphic variants of Apo-A5; rs2266788 (C), 9p21.3; rs1333049 (C) rs2383207 (A) are associated with CAD, its severity and exerts the risk of MI in North Indian population.

USVAH Study Demonstrates Statistically Significant Improvement in Diagnosis and Care of U.S Veterans Using FMTVDM – FHRWW©℗ “Quantitative” Nuclear Imaging. The Era of Truly Quantitative Stress- First, Stress-Only Imaging has begun!

Background: Myocardial perfusion imaging (MPI) has evolved over the last several decades with improvements in equipment and isotopes. Despite these limitations sensitivity and specificity of this study remains 65%-85% principally due to “qualitative” interpretation of the results. Numerous investigators have recommended changes in protocols and quantification of data to increase the diagnostic accuracy of this non-invasive physiologic test. Initial investigations have demonstrated the ability to “quantitatively” measure isotope redistribution with planar, SPECT and PET using FMTVDM©℗. This study was designed to compare the diagnostic and treatment outcomes of U.S. Veterans undergoing conventional “stress-rest” “qualitative” imaging using Technetium 99m isotopes (Sestamibi and Myoview) compared with FMTVDM©℗ “quantification” isotope redistribution using a single dose of the isotope.Methods: Forty-one U.S. Veterans were studied using pharmacologic and exercise stress approaches with either Sestamibi or Myoview following routine MPI Imaging protocols compared with FMTVDM©℗. The results were compared with coronary angiography.Result: Angiographic coronary artery disease (CAD) was defined using both 50% and 70% diameter narrowing/ stenosis (%DS). Accuracy of a “qualitative” (yes/no) test in the determination of the presence or absence of CAD is measured by the ability of the test to find CAD when present (sensitivity) and to show that CAD is not present (specificity) when absent, based upon the arbitrarily assigned value for %DS. The sensitivity, specificity and accuracy of “qualitative” MPI assessment of 50% DS CAD was 50.0%, 88.2% and 70.7% for the left coronary artery system and 29.2%, 64.7% and 43.9% respectively for the right coronary artery system. These values improved to 59.1%, 89.5% and 73.2% for the left coronary artery system and 64.3%, 85.2% and 78.0% respectively for the right coronary artery system when 70%DS was used as the cutoff for CAD. No differences noted between either of the technetium 99m isotopes or cameras used for either the “qualitative” or “quantitative” (FMTVDM©℗) methods. FMTVDM©℗ provides the First Ever “quantitative” Nuclear Cardiology MPI test, which consequently defines CAD not on a yes/no basis, but “quantitatively.” As such, the accuracy of FMTVDM©℗ must be compared first to a “quantitative” measure which is known; viz. isotope decay using TFM. Results of FMTVDM©℗ is then not simply a yes/no result, but rather a “quantitative” value which places the “extent” of CAD on a measured continuum much as a coronary angiogram would, specifically a quantitative coronary angiogram (QCA). FMTVDM©℗ demonstrated a statistically significant relationship between CAD and %DS (r=0.75, p < 0.001).Conclusion: Modern Nuclear Cameras have relied completely upon “quality” control methods, which do exactly that; they provide for “qualitative” control but not “quantitative” control. The accuracy of the cameras ability to correctly count the resulting scintillations from which “quantitative” analysis and even “qualitative” images are displayed for clinician interpretation are dependent, has never been established or used in either the experimental or clinical areas of Medicine. This study demonstrated the importance of first using TFM from the FMTVDM©℗ for “quantitative” camera calibration and correction prior to conducting MPI. Even with the correction of the “quantitative” errors in the Nuclear Cameras, errors in “qualitative” MPI resulted in a conservative estimate of misdiagnosis of CAD 35% of the time. These errors result in potential life threatening CAD being missed as demonstrated here. This same CAD is accurately measured using the new “quantitative” MPI test (FMTVDM©℗), which accurately “quantify” the extent of CAD. FMTVDM©℗ provides the first “quantitative” Nuclear Cardiology and Medicine test, ushering in the era of “machine learning” and “quantitative” Nuclear Cardiology and Medicine providing accurate, reproducible measurement of CAD in less time and with less radiation than the prior “qualitatively” applied method of “physician interpretation” of CAD, reducing healthcare costs and improving patient throughput and clinical management.

Association of Insulin Resistance to Angiographic Coronary Artery Disease in Non-Diabetic Individuals Presenting for Cardiac Surgery

Association of Insulin Resistance to Angiographic Coronary Artery Disease in Non-Diabetic Individuals Presenting for Cardiac Surgery

Predictors of Coronary Artery Disease Progression among High-risk Patients with Recurrent Symptoms.

Background:Despite the availability of new potent medical therapies, the rate of progression of angiographic coronary artery disease (CAD) is not well described. The aim of this analysis is to describe the rate and predictors of progression of CAD among patients with recurrent symptoms.Materials and Methods:We reviewed 259 patients (mean age 61 ± 11 years, 70% males) who underwent two coronary angiograms between 2008 and 2013. Progressive CAD was defined as obstructive CAD in a previously disease-free segment or new obstruction in a previously nonobstructive segment. Patients who had coronary artery bypass surgery between these two angiograms were excluded from the analysis. Multivariate logistic regression was used to determine the independent predictors of progression of CAD.Results:The included cohort had a high prevalence of coronary risk factors; hypertension (71%), diabetes (69%), and dyslipidemia (75%). Despite adequate medical therapy, more than half of the patients (61%) had CAD progression. Using multivariate logistic regression, a drop in the left ventricular ejection fraction (LVEF) by more than 5% was the predictor of CAD progression (adjusted odds ratio 5.8, P = 0.042, 95% confidence interval 1.1–31.2).Conclusion:Among high-risk patients with recurrent symptoms, the short-term rate of progression of CAD is high. A drop in LVEF >5% is a predictor of CAD progression. Further studies are needed to determine the prognostic value of CAD progression in the era of potent medical therapy.

Elevated serum interleukin-6 is predictive of coronary artery disease in intermediate risk overweight patients referred for coronary angiography

BackgroundInterleukin-6 (IL-6) plays a central role in atherosclerosis and inflammation. It may improve risk prediction in patients at intermediate cardiovascular risk.ObjectiveTo analyze the impact of serum IL-6 in predicting early angiographic coronary artery disease in patients at intermediate cardiovascular risk with chest pain.MethodsIn a cross-sectional study, patients referred for coronary angiography due to suspected coronary artery disease (CAD) were included. Coronary artery disease was defined as the presence of at least 30% stenosis in one or more coronary artery. Severity of CAD was classified by the anatomic burden score. Performance of serum IL-6 assay was compared with ACC/AHA atherosclerotic cardiovascular disease (ASCVD) risk score and hs-CRP through receiver operating characteristic (ROC) curves.ResultsWe have included 48 patients with a mean 10-year ASCVD risk of 10.0 ± 6.8%. The prevalence of CAD was 72.9%. The presence of CAD was associated with higher mean levels of IL-6 (p = 0.025). Patients with CAD had significantly more overweight than subjects without CAD. In 27% of patients, IL-6 was >1.0 pg/mL and 100% of these patients had CAD, while only 64% in those with IL-6 <1.0 pg/mL, corresponding to a positive predictive value of 100% (p = 0.015). The area under the receiver operating characteristic (ROC) curve of IL-6, hs-CRP and ASCVD were respectively 0.72, 0.60 and 0.54. Intermediate risk patients with IL-6 >1.0 pg/mL were further reclassified into ASCVD high risk due to the presence of coronary lesions.ConclusionIn intermediate risk patients referred for coronary angiography, a serum IL-6 level above 1 pg/mL is predictive of significant CAD. IL-6 determination may be useful to reclassify ASCVD intermediate risk patients into higher risk categories.

P855Serum-amyloid-A/LDL complex and NT-proBNP independently correlated with severe angiographic coronary artery disease in patients with suspected, but no history of coronary heart disease: the ANOX study

P855Serum-amyloid-A/LDL complex and NT-proBNP independently correlated with severe angiographic coronary artery disease in patients with suspected, but no history of coronary heart disease: the ANOX study

Patients With Diabetes Without Significant Angiographic Coronary Artery Disease Have the Same Risk of Myocardial Infarction as Patients Without Diabetes in a Real-World Population Receiving Appropriate Prophylactic Treatment.

The risk of myocardial infarction (MI) in patients with diabetes is greater than for patients without diabetes. Consequently, prophylactic treatment is recommended for patients with diabetes and risk factors for ischemic heart disease. We aimed to estimate the risk of adverse cardiac events in patients with and without diabetes with and without coronary artery disease (CAD) after coronary angiography (CAG). A population-based cohort of patients registered in the Western Denmark Heart Registry who underwent CAG between 1 January 2003 and 31 December 2012 was stratified according to the presence or absence of obstructive CAD and diabetes. End points were death, cardiac death, and MI. Unadjusted and adjusted rate ratios (RRs) were calculated by using patients without diabetes and without CAD as the reference group. We included 93,866 patients of whom 12,544 (13.4%) had diabetes at the time of CAG. Median follow-up was 4.1 years. Patients with and without diabetes without obstructive CAD had the same adjusted risk of death (RR 1.03 [95% CI 0.92-1.15]), cardiac death (RR 1.21 [95% CI 0.90-1.64]), and MI (RR 0.88 [95% CI 0.65-1.17]). Patients with diabetes without CAD were more often treated with statins (75.3% vs. 46.0%) and aspirin (65.7% vs. 52.7%) than patients without diabetes and CAD. In a real-world population, patients with diabetes with high rates of statin and aspirin treatment had the same risk of cardiovascular events as patients without diabetes in the absence of angiographically significant CAD.

Genetic risk score and cardiovascular mortality in a southern european population with coronary artery disease.

The objective of this study was to evaluate long-term cardiovascular mortality according to the genetic risk score in a Southern European population with CAD. A cohort of 1464 CAD patients with angiographic proven CAD were followed up prospectively for up to 58.3 (interquartile range: 25.8-88.1) months. Genotyping of 32 single-nucleotide polymorphisms previously associated with CAD was performed using oligonucleotides probes marked with fluorescence for each allele. GRS was constructed according to the additive model assuming codominance and categorised using the median (=26). Cox Regression analysis was performed to determine independent multivariate predictors of cardiovascular mortality. Kaplan-Meier survival curves compared high vs low GRS using log-rank test. C-index was done for our population, as a measure of discrimination in survival analysis model. During a mean follow-up of 58.3months, 156 patients (10.7%) died, 107 (7.3%) of CV causes. High GRS (≥26) was associated with reduced cardiovascular survival. Survival analysis with Cox regression model adjusted for 8 variables showed that high GRS, dyslipidemia, diabetes and 3-vessel disease were independent risk factors for cardiovascular mortality (HR=1.53, P=.037; HR=3.64, P=.012; HR=1.75, P=.004; HR=2.97, P<.0001, respectively). At the end of follow-up, the estimated survival probability was 70.8% for high GRS and 80.8% for low GRS (Log-rank test 5.6; P=.018). C-Index of 0.71 was found when GRS was added to a multivariate survival model of diabetes, dyslipidemia, smoking, hypertension and 3 vessel disease, stable angina and dual antiplatelet therapy. Besides the classical risk factors management, this work highlights the relevance of the genetic profile in survival from CAD. It is expected that new therapies will be dirsected to gene targets with proven value in cardiovascular survival.

Ranolazine in Symptomatic Diabetic Patients Without Obstructive Coronary Artery Disease: Impact on Microvascular and Diastolic Function.

BackgroundTreatments for patients with myocardial ischemia in the absence of angiographic obstructive coronary artery disease are limited. In these patients, particularly those with diabetes mellitus, diffuse coronary atherosclerosis and microvascular dysfunction is a common phenotype and may be accompanied by diastolic dysfunction. Our primary aim was to determine whether ranolazine would quantitatively improve exercise‐stimulated myocardial blood flow and cardiac function in symptomatic diabetic patients without obstructive coronary artery disease.Methods and ResultsWe conducted a double‐blinded crossover trial with 1:1 random allocation to the order of ranolazine and placebo. At baseline and after each 4‐week treatment arm, left ventricular myocardial blood flow and coronary flow reserve (CFR; primary end point) were measured at rest and after supine bicycle exercise using 13N‐ammonia myocardial perfusion positron emission tomography. Resting echocardiography was also performed. Multilevel mixed‐effects linear regression was used to determine treatment effects. Thirty‐five patients met criteria for inclusion. Ranolazine did not significantly alter rest or postexercise left ventricular myocardial blood flow or CFR. However, patients with lower baseline CFR were more likely to experience improvement in CFR with ranolazine (r=−0.401, P=0.02) than with placebo (r=−0.188, P=0.28). In addition, ranolazine was associated with an improvement in E/septal e′ (P=0.001) and E/lateral e′ (P=0.01).ConclusionsIn symptomatic diabetic patients without obstructive coronary artery disease, ranolazine did not change exercise‐stimulated myocardial blood flow or CFR but did modestly improve diastolic function. Patients with more severe baseline impairment in CFR may derive more benefit from ranolazine.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01754259.

Risk factor profiling and study of atherosclerotic coronary plaque burden and morphology with coronary computed tomography angiography in coronary artery disease among young Indians

BackgroundWith a decade earlier manifestation of coronary artery disease (CAD) and paucity of data characterizing coronary plaque with coronary computed tomography angiography (CTA) among CAD patients in India, the study aimed to analyze patient characteristics and coronary plaque burden and morphology in young Indian patients with CAD. MethodsSerial coronary CTA was performed in 96 CAD patients. Among 60 patients ≤40years, risk factor and coronary plaque analysis done using a 256- slice CT in 33 patients with acute coronary syndrome (ACS) was compared with 27 patients with chronic stable angina (CSA). Univariate and multivariate analysis was performed, for factors predicting ACS as an outcome among young CAD patients. In addition, quantitative and morphologic plaque characteristics were compared among those ≤40years and >40years. ResultsAmong 60 subjects ≤40years of age, 77% had dyslipidemia, 70% high lipoprotein(a), 53.33% elevated hs-CRP and 73.33% raised homocysteine. hs-CRP (9.33 vs. 3.33, p value=0.01) and serum triglycerides (178.67 vs. 141.42, p value=0.03) were markedly raised in patients with ACS. Statistically significant number of patients in the ACS group had positive remodelling (ACS, 69.7% vs. CSA, 14.8%; p value<0.001), low attenuation plaque (ACS, 63.6% vs. CSA, 11.1%; p value<0.001), spotty calcification (ACS, 36.4% vs. CSA, 3.7%; p=0.002) and non-calcified plaque (ACS, 69.7% vs. CSA, 11.1%; p<0.001). On multivariate analysis, only lipoprotein (a) >30mg/dL and composite vulnerability score maintained a predictive value for ACS in patients ≤40years. Statistically significant number of patients in the younger age group had higher mean total plaque volume (66.17±41.31mm3 vs. 44.94±49.07mm3; p=0.03), remodelling index (1.5±0.27 vs. 1.08±0.38; p=0.0001). Comparing culprit lesion characteristics of ACS patients in the two age groups, positive remodelling (95.8% vs. 70.5%, p=0.02), spotty calcification (50% vs. 11.7%, p=0.01) and non-calcified plaque (95.8% vs. 70.5%, p=0.02) were significantly more frequent in patients ≤40years. ConclusionACS in young Indians is characterized by a higher prevalence of both conventional and newer risk factors. In addition, culprit lesions in young ACS patients are more frequently characterized by coronary plaques with high risk morphological features. This may have implications in terms of preventive strategies to identify this high-risk group.

Effect of Metabolic Syndrome Score, Metabolic Syndrome, and Its Individual Components on the Prevalence and Severity of Angiographic Coronary Artery Disease.

Background:The clinical significance of metabolic syndrome (MS) score, MS, and its individual components with respect to risk prediction of coronary artery disease (CAD) remains unclear. The objective of this study was to investigate whether and to what extent MS score, MS, and its individual components were related to the risk of CAD.Methods:Among 1191 participants who underwent coronary angiography for the confirmation of suspected myocardial ischemia, 858 were included in this study according to the inclusion criteria from September 2010 to June 2013. MS was diagnosed with the 2005 National Cholesterol Education Program Adult Treatment Panel III criteria. The severity of coronary atherosclerosis was assessed by Gensini score.Results:The results showed that the age- and sex-adjusted odds ratios (ORs) for CAD were as follows: MS score, 1.327; MS, 2.013; elevated waist circumference, 1.447; reduced high-density lipoprotein cholesterol, 1.654; and elevated fasting glucose, 1.782; all P < 0.05; whereas for elevated triglycerides, 1.324, and elevated blood pressure, 1.342, both P > 0.05. After multivariate adjustment, results showed that only MS and elevated fasting glucose were significantly associated with CAD (OR, 1.628, 95% confidence interval [CI], 1.151–2.305, P = 0.006 for elevated fasting glucose, and OR, 1.631, 95% CI, 1.208–2.203, P = 0.001 for MS). The study showed that only MS score and elevated fasting glucose were significantly associated with Gensini score (standardized coefficient, 0.101, P = 0.031 for elevated fasting glucose and standardized coefficient, 0.103, P = 0.009 for MS score).Conclusions:The present study demonstrated that MS score, MS, and its individual components might have different contributions to CAD prevalence and severity. MS and elevated fasting glucose were independent risk factors for the prevalence of angiographic CAD whereas MS score and elevated fasting glucose were significantly associated with the severity of CAD.

Abstract MP076: Angiographic Coronary Artery Disease Severity and Risk of Mental and Conventional Stress Induced Myocardial Ischemia

Background: Mental stress induced myocardial ischemia (MSIMI) is linked to increased risk of adverse cardiovascular outcomes, but its mechanisms are thought to be different from those of conventional stress-induced ischemia (CSIMI). Specifically, whether MSIMI is associated with more severe underlying obstructive coronary artery disease (CAD) is unclear. We investigated the association between angiographically-defined CAD severity and both MSIMI and CSIMI with a hypothesis that, CAD severity will be linked to CSIMI, but not MSIMI. Methods: A total of 273 patients with stable CAD, aged 51±7 years, 49% female, who survived a myocardial infarction (MI) within the past 8 months (median 167±52 days) were enrolled in the Myocardial Infarction and Mental Stress 2 (MIMS-2) study. The coronary angiogram performed during the index MI hospitalization was used to assess CAD severity. Coronary artery obstruction was assessed by counting the number of diseased vessels with 70% stenosis (DV70%) and using the Gensini Score (GS) after correcting for revascularized vessels. Patients underwent 99mTc sestamibi myocardial perfusion imaging during mental stress, using a public speaking task, and during conventional stress test, using exercise or pharmacological stress. MSIMI and CSIMI were defined as a new or worsening impairment in myocardial perfusion using a 17-segment model. Results: A total of 68 (26%) patients developed CSIMI, while 46 (17%) developed MSIMI. Median DV70% and GS were 0 (0-1), and 3 (0-12), respectively. Using logistic regression models, and after adjustment for age, gender, hypertension, hyperlipidemia and diabetes, obstructive CAD was associated with increased risk of CSIMI [OR(95%CI) of 1.54 (1.02 - 2.31) for DV70% and 1.25 (1.03-1.53), for GS], but not MSIMI [OR(95%CI) of 0.93 (0.56 - 1.53) for DV70%, and 0.94 (0.75-1.18) for GS]. Conclusion: Although CSIMI is linked to underlying coronary obstruction, MSIMI is independent of CAD severity among post- MI patients. Other mechanisms are likely responsible for MSIMI post MI.

Prevalence and Prognosis of Nonobstructive Coronary Artery Disease in Patients Undergoing Coronary Angiography or Coronary Computed Tomography Angiography: A Meta-Analysis

ObjectiveTo evaluate the prevalence, clinical characteristics, and risk of cardiac events in patients with nonobstructive coronary artery disease (CAD). Patients and MethodsWe searched PubMed, EMBASE, and the Cochrane Library from January 1, 1990, to November 31, 2015. Studies were included if they reported prevalence or prognosis of patients with nonobstructive CAD (≤50% stenosis) among patients with known or suspected CAD. Patients with nonobstructive CAD were further grouped as those with no angiographic CAD (0% or ≤20%) and those with mild CAD (>0% or >20% to ≤50%). Data were pooled using random effects modeling, and annualized event rates were assessed. ResultsFifty-four studies with 1,395,190 participants were included. The prevalence of patients with nonobstructive CAD was 67% (95% CI, 63%-71%) among patients with stable angina and 13% (95% CI, 11%-16%) among patients with non–ST-segment elevation acute coronary syndrome. The prevalence varied depending on sex, clinical setting, and risk profile of the population investigated. The risk of hard cardiac events (cardiac death or myocardial infarction) in patients with mild CAD was lower than that in patients with obstructive CAD (risk ratio, 0.28; 95% CI, 0.20-0.38) but higher than that in those with no angiographic CAD (risk ratio, 1.85; 95% CI, 1.52-2.26). The annualized event rates of hard cardiac events in patients with no angiographic CAD, mild CAD, and obstructive CAD were 0.3% (95% CI, 0.1%-0.4%), 0.7% (95% CI, 0.5%-1.0%), and 2.7% (95% CI, 1.7%-3.7%), respectively, among patients with stable angina and 1.2% (95% CI, 0.02%-2.3%), 4.1% (95% CI, 3.3%-4.9%), and 17.0% (95% CI, 8.4%-25.7%) among patients with non–ST-segment elevation acute coronary syndrome. The correlation between CAD severity and prognosis is consistent regardless of clinical presentation of all-cause death, myocardial infarction, total cardiovascular events, and revascularization. ConclusionNonobstructive CAD is associated with a favorable prognosis compared with obstructive CAD, but it is not benign. The high prevalence and impaired prognosis of this population warrants further efforts to improve the risk stratification and management of patients with nonobstructive CAD.

Extent of coronary artery disease in patients undergoing angiography for stable or acute coronary syndromes

BackgroundWe aimed to investigate whether the angiographic extent of coronary artery disease (CAD) differs in patients undergoing coronary angiography for stable CAD or acute coronary syndrome (ACS) and identify predictors of CAD extent in these patients. MethodsWe enrolled 584 consecutive patients (463 with stable CAD, 121 with ACS) with angiographically established CAD (≥1 stenosis >25%). The Gensini score was used to assess the extent of coronary atherosclerosis. ResultsStable CAD patients had greater Framingham risk score and greater prevalence of hypertension, hypercholesterolemia, and diabetes (p<0.05 for all). Fasting glucose and systolic and diastolic blood pressure were higher, while high-sensitivity C-reactive protein (hsCRP) levels were lower in patients with stable CAD than in those with ACS (p<0.05 for all). No difference in Gensini score was observed between the two groups (p=0.118), but patients with ACS were more likely to have at least one significant epicardial angiographic lesion (>50% stenosis) (OR 2.0, p=0.022). Higher Gensini score was independently associated with (i) higher hsCRP and glucose levels, hypercholesterolemia, and increased age in stable CAD patients (R2 0.15, p<0001) and (ii) increased age and higher glucose and hsCRP levels in patients with ACS (R2 0.17, p<0001). ConclusionsPatients undergoing coronary angiography for ACS or stable CAD presented with a similar extent of angiographic CAD, although patients with ACS had a higher prevalence of significant lesions in the presence of a better cardiovascular risk profile and higher inflammation levels. The extent of angiographic CAD in both the groups shared common determinants such as hsCRP, age, and hyperglycemia, but these appeared to explain only a small part of the variation of coronary atherosclerosis.

Genetic variation at ADAMTS7 and severity of coronary artery disease

BackgroundGenome-wide association studies have identified ADAMTS7 as a risk locus for coronary artery disease and myocardial infarction. Functional studies suggest that ADAMTS7 might promote cellular processes in atherosclerosis. We sought to examine whether carriers of a loss-of-function genetic variant exhibit favourable characteristics on plaque histology, angiographic coronary artery disease severity, and cardiovascular outcomes. MethodsThe single-nucleotide polymorphism rs3825807 was used as a marker for ADAMTS7. Human coronary atherosclerotic plaques (n=50) were genotyped, and characterised with immunohistochemical analysis. Burden of angiographic coronary artery disease was assessed by angiographic severity scores in two independent population-based cohorts—the Southampton Atherosclerosis Study (SAS, n=1359) in the UK, and the prospective Emory Genebank study (Emory GB, n=2684) in the USA. Follow-up data were collected in Emory GB over a median of 7 years. FindingsHuman coronary atherosclerotic plaques with the loss-of-function G allele exhibited thinner fibrous cap (p=0·017) and lower percentage area of α-actin (smooth muscle cell marker) in the intima (p=0·029). After adjustment for age and sex, the G allele was associated with less coronary artery disease in both SAS (odds ratio 0·82, 95% CI 0·67–0·99), and Emory GB (0·84, 0·74–0·95). Angiographic burden was further characterised with the Gensini Score (GS) and Sullivan Extent Score (SES). ADAMTS genotypes were associated with all of the angiographic severity scores in both SAS (GS p=0·026, SES p=0·029) and Emory GB (GS p<0·0001, SES p<0·0001). Outcome analysis showed lower incidence of revascularisation for G allele carriers (hazard ratio 0·77, 95% CI 0·60–0·98), but not all cause mortality (1·12, 0·92–1·35). InterpretationCarriers of the ADAMTS7 loss-of-function allele G had reduced atherosclerotic plaque progression, as demonstrated by thinner cap and smooth muscle migration. In addition there was less severe angiographic coronary artery disease in the SAS and Emory GB cohorts, as well as lower incidence of revascularisation procedure, further supporting the role of this protease in promoting atherosclerosis. FundingNone.

Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive Disease.

Cardiovascular disease (CVD) fatality rates are higher for women than for men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Coronary flow reserve (CFR), an integrated measure of large- and small-vessel CAD and myocardial ischemia, identifies patients at risk for CVD death, but is not routinely measured in clinical practice. We sought to investigate the impact of sex, CFR, and angiographic CAD severity on adverse cardiovascular events. Consecutive patients (n=329, 43% women) referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography and with left ventricular ejection fraction >40% were followed (median, 3.0 years) for a composite end point of major adverse cardiovascular events, including cardiovascular death and hospitalization for nonfatal myocardial infarction or heart failure. The extent and severity of angiographic CAD were estimated by using the CAD prognostic index, and CFR was quantified by using positron emission tomography. Although women in comparison with men had lower pretest clinical scores, rates of prior myocardial infarction, and burden of angiographic CAD (P<0.001), they demonstrated greater risk of CVD events, even after adjustment for traditional risk factors, imaging findings, and early revascularization (adjusted hazard ratio, 2.05; 95% confidence interval, 1.05-4.02; P=0.03). Impaired CFR was similarly present among women and men, but in patients with low CFR (<1.6, n=163), women showed a higher frequency of nonobstructive CAD, whereas men showed a higher frequency of severely obstructive CAD (P=0.002). After also adjusting for CFR, the effect of sex on outcomes was no longer significant. When stratified by sex and CFR, only women with severely impaired CFR demonstrated significantly increased adjusted risk of CVD events (P<0.0001, P for interaction=0.04). Women referred for coronary angiography had a significantly lower burden of obstructive CAD in comparison with men but were not protected from CVD events. Excess cardiovascular risk in women was independently associated with impaired CFR, representing a hidden biological risk, and a phenotype less amenable to revascularization. Impaired CFR, particularly absent severely obstructive CAD, may represent a novel target for CVD risk reduction.

Abstract 12650: Genetic Risk Score and Cardiovascular Mortality in a Portuguese Population

Several genetic risk scores (GRS) have been associated with cardiovascular disease; however, their role in survival from proven coronary artery disease (CAD) have yield conflicting results. Objective: To evaluate long-term cardiovascular mortality according to the genetic risk score. Methods: A study was performed with a cohort of 1464 CAD patients with angiographic proven CAD who were followed-up prospectively for up to 58.3 (interquartile range 25.8 - 88.1) months. Genotyping of 33 SNP associated with CAD was performed using oligonucleotides probes marked with fluorescence for each allele. GRS was constructed according to the additive model assuming co-dominance and was categorized using the median. Cox Regression analysis was performed to determine independent multivariate predictors of cardiovascular mortality. Kaplan Meier Survival curves compared higher than median GRS vs lower than median GRS and log rank test was calculated. Results: During a mean follow-up of 58.3 months (interquartile range 25.8 - 88.1), 156 patients (10.7%) died, 107 (7.3%) of CV causes. Higher than median GRS (≥26) was associated with reduced cardiovascular survival. Survival analysis with COX regression model adjusted for 5 variables showed that high GRS and diabetes were independent risk factors for cardiovascular mortality (HR=1.58, CI: 1.06 - 2.35, p=0.025; HR=1.80, CI: 1.23-2.63, p=0.003, respectively). At the end of follow-up, the estimated survival probability was 70.8% for high GRS, 80.8% for low GRS (Log rank test 5.6; p=0.018). Conclusions: Besides the classical risk factors control, this work highlights the relevance of the genetic profile in survival from CAD. It is expected that new therapies will be directed to gene targets with proven value in cardiovascular survival.

TCT-344 Impact of Body Mass Index on the Clinical outcomes of patients with Angiographic High-risk Coronary Artery Disease underwent Percutaneous Coronary Intervention: data from the Asan multi-vessel registry and IRISMAIN registry

TCT-344 Impact of Body Mass Index on the Clinical outcomes of patients with Angiographic High-risk Coronary Artery Disease underwent Percutaneous Coronary Intervention: data from the Asan multi-vessel registry and IRISMAIN registry