Significant Coronary Atherosclerosis Research Articles

Low Carotid Artery Wall Shear Stress is Associated with Significant Coronary Artery Disease in Patients with Chest Pain.

To investigate the relationships among carotid wall shear stress (WSS), carotid intima-media thickness (IMT), and total plaque area (TPA) using ultrasound (US) in the common carotid artery (CCA) in patients with suspected coronary artery disease (CAD). Carotid artery US was performed in 950 patients with suspected CAD, and mean IMT, TPA, and hemodynamic parameters of CCA, including peak and mean WSS, were measured. We analyzed the carotid parameters according to the presence of CAD and the predictive values of WSS and TPA for the presence of significant CAD. Compared with patients without CAD (n=667), patients with CAD (n=283) demonstrated significantly higher mean IMT (0.66 vs. 0.74 mm, p ＜ 0.001), TPA (0.13 vs. 0.20 cm(2), p=0.002), and beta stiffness index (5.12 vs. 5.60, p=0.045) and lower mean WSS (2.59 vs. 2.23 dyne/cm(2), p ＜ 0.001). Mean WSS revealed significant negative correlations with the beta stiffness index (r=-0.116, p ＜ 0.001), mean IMT (r=-0.193, p=0.007), and TPA (r =-0.296, p ＜ 0.001). Mean WSS, mean IMT and TPA revealed significant difference with respect to CAD severity (for all p ＜ 0.001). Age [OR, 1.038 (95% CI, 1.010-1.066), p=0.007], diabetes mellitus [1.606 (1.194-1.807), p= 0.011], smoking [1.758 (1.564-1.866), p ＜ 0.001], carotid TPA [2.615 (1.320-5.183), p=0.006], and mean WSS [0.554 (0.371-0.838), p=0.005] were significant CAD predictors. In patients with chest pain, low local shear stress and high plaque burden in the carotid arteries were significant CAD predictors. These findings indicate that carotid WSS has a role as an index of atherosclerosis and serves as a predictor of significant coronary atherosclerosis.

Left Main Coronary Spasm: an Extremely Rare Entity with Possible Life-Threatening Complications

Coronary artery spasm is a known cause of acute coronary syndrome. However, left main coronary spasm is an extremely rare entity and can present in different ways depending on the duration and severity of the spasm. We present a 44-year-old female patient who presented with transient ST elevation in the lead aVR and ST depression in the lateral and inferior leads. Coronary angiography showed mid left main and ostial right coronary artery spasm that significantly improved after intracoronary nitroglycerine administration. Intravascular ultrasound showed no significant left main coronary atherosclerosis. She was treated chronically with calcium channel blockers (CCB), nitrates, and arginine with significant improvement. In conclusion, left main coronary spasm is an extremely rare entity with wide spectrum of clinical manifestations. Definite etiology is still questionable, and special precaution is needed during coronary angiography in order not to be confused with significant fixed lesions. Intravascular ultrasound can be valuable in excluding underlying atherosclerosis. Medical management with nitrates acutely then CCB is the mainstay of chronic management with PCI preserved to refractory cases.

Morbid Obesity is Not a Risk Factor for the Development of Clinically Significant Coronary Artery Atherosclerosis

Morbid obesity represents a significant health problem to a large and growing segment of the industrialized world. The cardiovascular complications are numerous and include systemic and pulmonary hypertension, obesity cardiomyopathy, heart failure, left ventricular dilatation and hypertrophy, arrhythmias, and sudden cardiac death. Morbidly obese (MO) individuals who die suddenly and unexpectedly may not have significant coronary artery atherosclerosis or acutely lethal natural diseases at autopsy. In this way, forensic pathologists may be challenged to understand the mechanism of sudden death when the major anatomic finding is often limited to cardiomegaly with or without chamber dilatation and wall thickening. The death investigation files for a large metropolitan medical examiner department were the source of data in this case-control retrospective study. A total of 3863 cases met inclusion criteria. The following data were obtained: sex, age, cause of death, manner of death, weight in pounds, height in inches, body mass index, heart weight in grams, and coronary artery atherosclerosis (CAA) severity. A population of MO decedents (N = 1290) was identified, and sex- and age-matched case controls of non-obese decedents (N = 2573) were selected. The degree of CAA was recorded for all major vascular territories in both MO decedents and control cases, and there was no statistically significant difference in CAA between decedents in the MO group and the control group. These data illustrate that obesity is not a significant independent risk factor for CAA.

Factor XIII B subunit polymorphisms and the risk of coronary artery disease.

The aim of the case-control study was to explore the effect of coagulation factor XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery disease, and on FXIII levels. In the study, 687 patients admitted for coronary angiography to investigate suspected coronary artery disease and 994 individuals representing the Hungarian population were enrolled. The patients were classified according to the presence of significant coronary atherosclerosis (CAS) and history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg and for intron K nt29756 C>G polymorphisms; the latter results in the replacement of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele provided significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII levels, and FXIII levels in the lower tertile provided significant protection against MI. It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.

Patient with ST-elevation myocardial infarction, coronary artery embolism and no signs of coronary atherosclerosis in angiography

1Faculty of Medical Sciences, University of Varmia and Masuria, Olsztyn, Poland 2Cardiac Catheterization Laboratory, Regional Specialist Hospital, Olsztyn, Poland 3Invasive Cardiology Department, Central Clinical Hospital of the Internal Affairs and Administration Ministry, Warsaw, Poland 4Institute of Experimental and Clinical Medicine, Polish Academy of Sciences, Warsaw, Poland 5Department of Cardiology, Regional Specialist Hospital, Olsztyn, Poland 6Department of Radiology and Medical Imaging, Regional Specialist Hospital, Olsztyn, Poland

Coronary microvascular spasm triggers transient ischemic left ventricular diastolic abnormalities in patients with chest pain and angiographically normal coronary arteries

AimsImpaired coronary microvascular dilatory function can lead to exercise induced myocardial ischemia and angina pectoris even in patients without significant (>50%) obstructive coronary atherosclerosis (APWOCA). Diffuse distal vessel epicardial spasm and microvascular spasm have been also proposed as a plausible explanation for angina at rest in these patients. However, objective systematic evidence for the latter i.e. echocardiographic wall motion abnormalities during angina, is lacking at present. Coronary epicardial and microvascular spasm can be triggered in susceptible patients by the administration of intracoronary acetylcholine (Ach). We sought to assess whether Ach induced diffuse distal epicardial coronary artery spasm (≥75% diameter reduction) and coronary microvascular spasm can cause transient ischemic left ventricular dysfunction, as assessed by echocardiography. Methods50 patients (19 men aged 60.5 ± 8.9 years) with stable APWOCA were assessed for coronary spasm and myocardial ischemia with intracoronary Ach infusion, 2D transthoracic echocardiography (before and during Ach testing), continuous 12-lead ECG monitoring, and ultrasensitive cardiac troponin (US-cTn) measurement before and within 4 h after Ach testing. Results14 patients (28%) had a “negative” Ach test, 14 (28%) developed coronary microvascular spasm and 17 (34%) had diffuse distal epicardial spasm. In 5 patients (10%) the test was inconclusive. Echocardiographic variables including deceleration time, EF slope and E/A, as well as ultrasensitive-cTn concentrations were abnormal during Ach induced ischemic ECG changes. Conclusions: We have, for the first time, demonstrated that Ach induced coronary microvascular spasm is associated with echocardiographic changes and ultrasensitive-cTn elevations, indicative of myocardial ischemia.

Tube potential can be lowered to 80 kVp in test bolus phase of CT coronary angiography (CTCA) and CT pulmonary angiography (CTPA) to save dose without compromising diagnostic quality.

The purpose of this study was to determine whether performing the test bolus (TB) of computed tomography coronary angiography (CTCA) and computed tomography pulmonary angiography (CTPA) at 80kVp reduces dose without compromising diagnostic quality. An 80kVp TB protocol for CTCA and CTPA was retrospectively compared to standard TB protocol (non-obese: 100kVp, obese: 120kVp). CT angiogram parameters were unchanged between cohorts. Thirty-seven consecutive 80kVp TB CTCA images were compared to 53 standard CTCA images. Fifty consecutive CTPAs from each protocol were analysed. Diagnostic quality of the CT angiogram was assessed by: mean attenuation, signal-to-noise ratio (SNR) in the ascending aorta (AA) in CTCA and in the main pulmonary artery (MPA) in CTPA, diagnostic rate, and number of repeated monitoring scans. Mean effective dose was estimated using the dose-length product. Mean TB effective doses were significantly lower (P < 0.0001) for 80kVp scans compared to the standard in non-obese CTCA (0.15 ± 0.04mSv Vs 0.33 ± 0.09mSv), obese CTCA (0.17 ± 0.06mSv Vs 0.57 ± 0.12mSv), and CTPA patients (0.07 ± 0.03mSv Vs 0.15 ± 0.06mSv). No difference was demonstrated in mean attenuation, SNR (AA), SNR (MPA), diagnostic rates, or number of repeated monitoring scans between protocols. Routinely performing TB at 80kVp, regardless of body habitus, in CTCA and CTPA results in a small but significant dose reduction, without compromising CT angiogram diagnostic quality. • CT coronary angiography is performed to exclude the presence of significant coronary atherosclerosis. • CT pulmonary angiography is performed to diagnose pulmonary thromboembolism. • This retrospective study showed dose reduction by performing test bolus at 80kVp. • Diagnosis can be made with reduced exposure to ionising radiation.

Abstract 218: Contributions of Microangiopathy to the Pathogenesis of Coronary Macroangiopathy of Nonobese Diabetes

Background: Visceral obesity and metabolic syndrome have been proposed as major coronary risk factors, however non-obese diabetes patients have also significant coronary atherosclerosis. Purpose: To elucidate the difference of prognosis between obese diabetes and non-obese diabetes. Methods: Up to December 2003, 606 patients who were initially treated with PCI, were recruited as cohort, and followed up for mean 10.3 years. Patients were divided into four groups according to diabetes and obesity. Endpoints are occurrence of new coronary lesions. Results: Non-obese diabetes had more frequently new coronary lesions than obese diabetic patients, indicating the incidence rate at 10 years was 56% and 31%, respectively (p=0.0017). At baseline, frequency of chronic kidney disease (CKD) was almost equal in these two groups, however, during follow-up, percentage of death associated with renal failure significantly increased up to 21.4% in non-obese diabetes, whereas 4.4% in obese diabetes. This increase is coincidence with occurrence of new coronary lesions, indicating diabetic microangiopathy is strong promoting factor in pathogenesis of coronary atherosclerosis in non-obese diabetes. Conclusion: In lean diabetes, microangiopathy especially nephropathy are frequently occurred, and this may contribute to progression of coronary atherosclerosis via the same mechanisms such as oxidative stress and glycation endproducts, or indirectly via secondary hypertension. these intriguing interaction of microangiopathy and macroangiopathy make unique coronary anatomy observed in diabetes.

Abstract 455: The Effects of Diet on Occlusive Coronary Artery Atherosclerosis, Thrombosis and Myocardial Infarction in SR-BI/LDL Receptor Double KO Mice

Objective: Deficiency of the HDL receptor, SR-BI, in apolipoprotein E knockout or hypomorphic mice respectively results in spontaneous or diet-inducible occlusive coronary artery atherosclerosis, myocardial infarction, and early death. Here, we examine the effects of SR-BI deficiency on cardiovascular phenotypes in LDLR knockout mice fed different atherogenic diets. Approach and Results SR-BI/LDLR double knockout and control LDLR knockout mice were fed diets containing different amounts of fat and cholesterol and which either lacked or contained 0.5% sodium cholate. Double knockout mice fed diets high in cholesterol exhibited significantly reduced survival compared to LDLR knockout mice fed the same diets. In addition to increased aortic sinus atherosclerosis, we observed significant coronary artery atherosclerosis in double knockout mice, and diet dependent accumulation of platelets in coronary artery atherosclerotic plaques. This was accompanied by substantial myocardial fibrosis in double knockout mice fed high cholesterol diets. Double knockout mice also exhibited higher circulating cytokine levels, monocytosis with increased proportions of monocytes expressing high levels of Ly6C, and higher adhesion molecule expression in coronary artery endothelial cells compared to control LDLR knockout mice. Conclusions: Diet accelerated atherosclerosis and occlusive, platelet rich coronary artery disease in SR-BI/LDLR dKO mice is affected by amounts of cholesterol and cholate in atherogenic diets, and is accompanied by increased expression of VCAM-1 and ICAM-1 in coronary arteries and increased Ly6C+ monocytes in circulation. The increased VCAM-1 and ICAM-1 in coronary artery endothelial cells in SR-BI-deficient mice likely explains their increased susceptibility to atherosclerosis in coronary arteries.

Non-Invasive Imaging for Subclinical Coronary Atherosclerosis in Patients with Peripheral Artery Disease

Patients with peripheral artery disease are at high risk of coronary artery disease. An increasing number of studies show that a large proportion of patients with peripheral artery disease have significant coronary atherosclerosis, even in the absence of symptoms. Although the reported prevalence of subclinical coronary artery disease varies widely in patients with peripheral artery disease, it could include more than half of patients. No consensus exists to date on either the rationale for screening patients with peripheral artery disease for coronary atherosclerosis or the optimal algorithm and method for screening. An increasing number of imaging modalities are emerging that allow improved in vivo non-invasive characterization of atherosclerotic plaques. These novel imaging methods may lead to early detection of high-risk vulnerable plaques, enabling clinicians to improve risk stratification of patients with peripheral artery disease, and thus paving the way for individualized therapy.

PARAMETERS ASSOCIATED WITH ABSENCE OF SIGNIFICANT CORONARY ATHEROSCLEROSIS BY DATA OF REGISTER OF PROVIDED CORONARY ANGIOGRAPHY

The study aimed to reveal the sign of coronary atherosclerosis absence using the factor analysis in patients referred for the coronary angiography. 9409 patients suspected stable coronary artery disease (CAD) or with confirmed diagnosis of CAD from the "Registry of provided coronary angiography" were included in the study. Principal factor described about 59% of the variation and included the burdens of 4 parameters (gender, smoking, significant coronary atherosclerosis and hypothyroidism) and was interpreted as factor of coronary atherosclerosis. It was found that the absence of coronary stenosis was associated with female gender, non-smoking status and hypothyroidism.

Sudden coronary death due to IgG4-related disease

A 54-year-old male entered the emergency room in cardiorespiratory arrest after syncope at home. Resuscitation was attempted, but the patient died a few hours later. At necropsy, aneurysms were found at the right and left anterior descending coronary arteries. At microscopic examination, there was no significant coronary atherosclerosis, and a dense inflammatory infiltrate was detected, with a high number of igG4-positive cells (94.0 positive cells/hpf). The case illustrates that IgG4-related disease can cause coronary disease and sudden cardiac death.

Can hypothyroidism manifest as ischemic heart disease in elderly patients with the absence of significant coronary atherosclerosis?

Can hypothyroidism manifest as ischemic heart disease in elderly patients with the absence of significant coronary atherosclerosis?

Comparison of diagnostic utilities of ankle–brachial index and Carotid intima-media thickness as surrogate markers of significant coronary atherosclerosis in Indians

We aimed to compare Ankle-brachial index (ABI) and Carotid intima-media thickness (CIMT) as surrogate markers of significant coronary atherosclerosis in South Indians with coronary artery disease (CAD). There were two groups: CAD group (n = 59) and Control group (n = 55). Mean ABI (0.82 ± 0.06 vs. 1.16 ± 0.11, p < 0.0001) and mean CIMT (0.74 ± 0.22 mm vs. 0.45 ± 0.09 mm, p < 0.0001) were statistically different between two groups. ABI < 0.9 (sensitivity: 91.53%, specificity: 100%) and CIMT > 0.63 mm (sensitivity: 61.02%, specificity: 98.18%) implied significant CAD. ABI and CIMT were negatively correlated to one another. With increasing severity of CAD, ABI decreased but CIMT increased. ABI and CIMT are simple noninvasive tools providing insight into coronary atherosclerosis. They can be done at bedside and easily repeated than coronary angiography. ABI < 0.9 is a better surrogate marker of significant coronary atherosclerosis than CIMT > 0.63 mm in South Indians with CAD.

Ambulatory systolic–diastolic pressure regression index predicts acute coronary syndromes

Objectives. Ambulatory systolic–diastolic pressure regression index (ASDPRI) is a composite marker of cardiovascular properties. The study was conducted to investigate the relationship between ASDPRI and cardiovascular events in patients with significant coronary atherosclerosis confirmed in angiography. Methods. Associations between ASDPRI and cardiovascular events were examined in 891 subjects referred for diagnostic coronary angiography. ASDPRI was calculated as 1 minus the slope of the linear relation between 24-h DBP and 24-h SBP. Results. During follow-up (median 6.7 years), 135 acute coronary syndromes (ACS), including five deaths and 55 strokes occurred in the studied group. There was a higher 24-h ASDPRI in patients with ACS than in patients with no ACS (0.35 ± 01 vs 0.30 ± 0.1, p < 0.01); 24-h ASDPRI was the independent predictor for ACS (OR = 4.0; 95% CI 1.3–12.0). Conclusions. ASDPRI has an important role as a risk factor of ACS in patients with coronary atherosclerosis.

Prognostic Impact of Coronary Endothelial Dysfunction on Long-Term Adverse Outcome in Patients with Chest Pain and Non-Obstructive Coronary Artery Disease

Coronary endothelial dysfunction is known to be related with adverse cardiovascular outcome. We obtained a long-term follow-up of patients without significant coronary atherosclerosis, complaining of chest pain, in whom intra-coronary acetylene testing was performed in order to assess endothelial function. The study included 41 patient (35 with endothelial dysfunction, 6 with preserved endothelial function). Events considered as adverse outcome were cardiovascular death, acute myocardium-dial infarction, unstable angina pectoris, percutaneous coronary intervention, coronary-aortic by-pass grafting, ischemic stroke and peripheral artery re-vascularization. A high cardiovascular event rate was observed in patients with and without endothelial dysfunction, 34,3% and 50% respectively. Adverse outcome was related not only to endothelial dysfunction but also to traditional cardiovascular risk factors. Thus, evaluation of endothelial function or its determinants seems to be helpful in identifying a subgroup of patients at high risk.

Biventricular Failure due to Stress Cardiomyopathy after Pericardiectomy for Constrictive Pericarditis

Importance. Constrictive pericarditis is a rare clinical entity that frequently necessitates surgical intervention. Here we present a case of biventricular failure due to stress cardiomyopathy after pericardiectomy. This is an extremely rare complication that is not well described and does not have a definitive mechanism. Observations. A 40-year-old Ecuadorian woman who was found to have constrictive pericarditis due to Mycobacterium tuberculosis infection was referred to our institution. The presence of constrictive pericarditis was confirmed by echocardiography, computed tomography, magnetic resonance imaging, and cardiac catheterization. Following pericardiectomy, the patient developed biventricular failure consistent with stress cardiomyopathy (Takotsubo cardiomyopathy), based on the echocardiographic assessment of the ventricles, which demonstrated an akinetic apex and hyperactive base in both ventricles, the absence of significant epicardial coronary atherosclerosis, and prompt normalization of the cardiac function after intensive medical therapy. Conclusions and Relevance. Biventricular failure in the form of stress cardiomyopathy after pericardiectomy in the manner presented here has not been previously described in the literature. While postulations as to the cause of single ventricle dysfunction have been described, the exact mechanism is unclear and current theories do not explain the clinical features in this case of stress cardiomyopathy after pericardiectomy.

Rage Gene Polymorphism in Heart Failure Patients with and without Angiographic Evidence of Significant Coronary Atherosclerosis

Heart failure (HF) is a multifactorial disorder in which clinical, environmental and genetic components take part. For this reason it is possible that common gene variants could affect development, progression and response to pharmacological therapy. In recent years the role of AGEs in the pathogenesis of cardiovascular diseases has become recognized but little is known about the role of the AGE–RAGE system in heart failure. The aim of the present study was to identify possible relationship between -374 T/A RAGE gene polymorphism with heart failure. The population in this study consists of 386 subjects with HF, selected according to the presence of depressed Left Ventricular Ejection Fraction (LVEF) less than45 percent, and 639 patients with CAD documented at coronary angiography. Within the population with HF there are 228 patients with disease secondary to not ischemic cause and 158 with post-ischemic condition. The sample of AA genotype was significantly lower in patients with post-ischemic HF in respect to HF secondary to non-ischemic causes (pless than0.001). A significant difference between the two groups was also observed regarding the allele frequency. In addition, differences in the allelic and the genotypic frequencies of homozygous genotypes were found between the HF patients free from evidence of coronary significant lesions and patients with at least one hemodynamically significant coronary lesion, both HF and CAD. In patients with at least one vessel compromised the presence of A allele and the homozygous AA genotype were significantly lower than in patients with lesion-free coronary. In conclusion, our research reveals that the -374 T/A polymorphism is related to the genesis of atherosclerotic coronary artery disease but not to its evolution. The protective role of AA genotype in respect to atheromatous disease is therefore confirmed also in the HF population with non-ischemic origin.

1068 Relationship between ambulatory artery stiffness index and coronary atherosclerosis in hypertensive women

Introduction: The ambulatory arterial stiffness index (AASI) derived from ambulatory blood pressure (BP) monitoring recordings is an indirect marker of arterial stiffness. We evaluated relationship between AASI and coronary artery disease (CAD) in hypertensive women. Methods: To the study group of 529 female was included (mean age 65.0 ± 8.6 years). In all patients 24-hour blood pressure monitoring and coronary angiography was performed (significant coronary atherosclerosis was recognized as at least 70% lumen stenosis of at least one coronary artery). AASI was defined as 1 minus the regression slope of 24-hour DBP on 24-hour SBP, and was calculated by standard and symmetric regression. Results: Study population was divided into two groups: with CAD (n = 276, mean age 66.4 ± 8.4 y.) and without CAD (n = 253, mean age 63.4 ± 8.4 y.). Higher value of AASI was found in CAD group than without CAD (0.33 ± 0.05 vs. 0.31 ± 0.05, p < 0.01). There was significant relationship between AASI and age in CAD group (r = 0.49, p < 0.01) and without CAD (r = 0.35, p < 0.01) as well. In CAD group in comparison to no CAD group, the stepwise multiple linear regression model reveled that AASI was independently related with age (β=0.44, p < 0.001), BMI (β=0.21, p < 0.001) and number of significant coronary atherosclerotic lesions (β=0.1, p < 0.01). Conclusion: AASI is strongly dependent on age, BMI and number of coronary atherosclerosis lesions in hypertensive women with significant coronary atherosclerosis.

Prediction of Coronary Artery Disease in Patients Undergoing Operations for Rheumatic Aortic Valve Disease

We sought to develop and validate a logistic model and a simple score system for prediction of significant coronary artery disease (CAD) in patients undergoing operations for rheumatic aortic valve disease. The simple score model we established based on the logistic model was efficient and practical. A total of 669 rheumatic patients (mean age 51 ± 9 years), who underwent routine coronary angiography (CAG) before aortic valve surgery between 1998 and 2010, were analyzed. A bootstrap-validated logistic regression model on the basis of clinical risk factors was developed to identify low-risk (≤5%) patients, from which an additive model was derived. Receiver operating characteristic (ROC) curves were used to compare discrimination, and precision was quantified by the Hosmer-Lemeshow statistic. Significant coronary atherosclerosis was defined as 50% or more luminal narrowing in 1 or more major epicardial vessels determined by means of coronary angiography. Eighty-eight (13.2%) patients had significant coronary atherosclerosis. Independent predictors of CAD include age, angina, diabetes mellitus, and hypertension. A total of 325 patients were designated as low risk according to the bootstrap logistic regression and additive models. Of these patients, only 4 (1.2%) had single-vessel disease, and none had high-risk CAD (ie, left main trunk, proximal left anterior descending, or multivessel disease). The bootstrap logistic regression and additive models show good discrimination, with an area under the ROC curve of 0.948 and 0.942, respectively. Our logistic regression model can reliably estimate the prevalence of significant CAD in rheumatic patients undergoing aortic valve operation, while the additive simple score system could reliably identify the low-risk patients in whom routine preoperative angiography might be safely avoided.