Expression Of Atherosclerosis Research Articles

Spontaneous Coronary Dissection as an Expression of Coronary Artery Disease: Correlation with Vasospasm

Background: Artificial coronary artery dissection is observed occasionally during percutaneous coronary intervention. However, “spontaneous” coronary artery dissection (SCAD) is not common and we tried to clarify its characteristics. Methods and Results: We reviewed the serial diagnostic coronary angiograms of 21,500 patients retrospectively. Sixty-two patients showed linear, longitudinal defects that were considered to be the angiographic expression of SCAD, in at least one major coronary artery. Vasospasm was shown in 38 patients. Among the remaining 24 subjects, 18 patients had chest pain even after all coronary narrowings of ≧50 %were treated with coronary intervention or bypass surgery. Chest pain was relieved promptly with sublingual administration of nitrate. Thus, 56 patients (90.3%) with SCAD were demonstrated or considered to have vasospasm. Fifty-two patients of these 56 individuals showed significant (≧50%) narrowing in at least one of the major coronary arteries. In the remaining 4 subjects, 3 patients subsequently developed significant coronary artery disease. Comparison of coronary risk factors was done in the 38 patients shown to have vasospasm and 144 patients with ordinary coronary artery disease. Smoking was more common in the group with vasospasm but there was no difference with regard to the other risk factors. Conclusion: SCAD seems to be an expression of coronary artery disease. However, vasospasm is a common factor in these patients.

Sex Differences in Aortic Valve Calcification

> “There is still need to think and plan, but on a different scale, and along different lines.”– C.S Forester1 Although sex differences in the pathophysiology and clinical expression of coronary artery disease are well appreciated, the impact of gender on valvular heart disease has not been extensively studied. Furthermore, the emphasis to date has been on understanding sex differences in the ventricular response to the pressure and volume overload posed by valvular disease rather than evaluating differences in the valves themselves. It is now known that women tend to respond differently than men to the increased afterload of worsening aortic stenosis (AS), with more concentric left ventricular (LV) hypertrophy, smaller LV cavities, and greater relative wall thicknesses.2–5 Recently, it has also been reported that although more women than men with severe AS have LV hypertrophy preoperatively, women more frequently experience reversal of hypertrophy shortly after aortic valve replacement.6 Lower collagen I and III, as well as matrix metalloproteinase 2 gene expression, in women versus men in the myocardial biopsy specimens performed at the time of surgery suggest that women have less fibrosis before surgery, leading to faster regression of LV hypertrophy postoperatively.6 On a molecular level, decreased extracellular fibrosis has been linked to the protective effect of estrogen in the setting of higher levels of estrogen receptors in women.6,7 Article see p 40 In this issue of Circulation: Cardiovascular Imaging , Aggarwal et al8 have directed their attention to the aortic valve itself, comparing the extent of aortic valve calcification (AVC) in men and women with comparable and at least mild degrees of AS. They prospectively examined AVC, measured in Agatston units (AU) by multidetector computed tomography (CT), and compared aortic valvular calcium load in 665 patients, 36% women, from …

Psychological factors and outcomes of coronary surgery

IntroductionRecent studies provide clear andconvincing evidence that such psychological factors as depression, anxiety,personality factors, social isolation, and chronic life stress contribute greatlyto the pathogenesis and expression of coronary artery disease (CAD) (Rosancki,Blumenthal, Kaplan, 1999, Sokolova, Nikolaeva, 1995). The pathophysiologicalmechanism by which these factors promote CAD includes 1) behavioral and 2)direct pathophysiological effects (Rosancki, Blumenthal, Kaplan, 1999). Sincethere is plenty of information on this part of the problem, we will turn ourattention straight to the situation of open heart surgery.By and large, there are severaltreatment choices to consider in a patient with significant CAD disease:medication, bypass surgery, angioplasty, or combination of these (Laurence,2002). If the treatment were simple and without potentially adverse effects,the decision on treatment would be simple. But the reality is more complicated.Bypass surgery is by far the most traumatic, as it involves surgery andanesthesia, a long recovery period, and potential complications (Bokeria, 2010,Laurence, 2002). It can fail, prove ineffective, or even result in death. Uncertaintyis the hardest part of experiencing illness.Although the cardiologist decides onthe best treatment in every situation, the patient takes his share ofresponsibility in agreeing to the surgery. Even when the best treatment choiceis obvious for the physician, it can be unacceptable to the patient, who fearshospitalization, pain, or has a friend whose outcome from similar treatment waspoor. In such a situation, the biopsychosocial view of illness and the role ofthe psychologist who can help identify the problem is very important.The situation of open heart surgeryconsists of a patient's subjective perception of what medics do and say, aprognosis of the surgery outcome, and many other factors which take on asecondary psychosemantic meaning. Inadequate implicit concepts of forthcomingsurgery can produce respective somatic sensations and, on the contrary, realsomatic sensations can be wrongly identified by the patient (Thostov, 2002).Models of negative surgery outcomes can cause a negative placebo affect (noceboeffect). A nocebo effect is an ill effect caused by the suggestion or beliefthat something is harmful.When a patient faces the necessity ofopen heart surgery (coronary artery by- pass for CAD patients) he finds himselfin a terrifying situation with an unknown outcome. The threat for his bodyimage, life risk, pain, and helplessness stir up many feelings.Recent studies show that depressionand anxiety symptoms common for CAD patients worsen the outcomes of cardiacsurgery (Allen, Becker, 1990; Appels, Mulder, 1988; Atrinian, 1991; Berron,1986; Blumental, 1988, 2003; Connerney, 2010; Contrada, 2008; Cserep, 2010,Gallagher, 2007; Hoyer, 2008; Pigney-Demaria, 2003; Rozancki, 1999;Rymaszewska, 2003; Viars, 2009, Zaitsev, 1997). In such a situation,psychological support is very necessary.Patients stay in hospital for only afew days before the surgery, so there is not much time for deep psychologicalintervention. This means that identifying the main targets for psychologicalhelp is very important.We suggest that the negative attitudeof patients towards forthcoming open heart surgery is associated with theadverse postsurgical period. The type of attitude towards forthcoming openheart surgery determines illness behavior, compliance, and coping strategies.Assistance in modeling adequate expectations from surgical treatment should beone of the targets of psychological maintenance in the perioperative period.Method120 patients (44% female) with CAD,scheduled for open heart surgery, volunteered for the study (the study group).The mean age was 48±13. NYHA class -- II-III.The control group consisted of 35people (45% females) without somatic and mental disorders.Patients from the study group wereinterviewed and asked to fill in questionnaires the day before heart surgery,and one week afterwards. …

Comparison of Family History of Sudden Cardiac Death in Nonischemic and Ischemic Heart Disease

Recent studies have identified the presence of familial clustering of ischemic sudden cardiac death (SCD) as a clinical expression of coronary artery disease. The purpose of this study was to determine whether nonischemic SCD has a similar familial background, which would be evidence of a genetic predisposition. The retrospective case-control study included (1) consecutive victims of nonischemic SCD (n=223), (2) consecutive victims of ischemic SCD (n=596), whose deaths and diagnosis were verified at medicolegal autopsy, and (3) control subjects without heart disease (n=475). In each study group, the family history of SCD among the first-degree relatives was determined and verified from death certificates. The prevalence of SCD in ≥1 first-degree relative was significantly higher in victims of ischemic (34.2%) than nonischemic SCD (13.4%; P<0.001) or controls (17.6%; P<0.001). The history of SCD in first-degree relatives did not differ from controls in nonischemic SCD victims (P=0.155). In a subgroup analysis of victims of ischemic SCD, the prevalence of family history of SCD in first-degree relatives did not differ between those with or without a prior infarct scar at autopsy (33.1% versus 29.9%, respectively; P=0.222). Ischemic SCD has a strong familial background both in cases with and without a prior myocardial infarction. The family history of SCD is not significantly increased in victims of nonischemic SCD, suggesting a larger role of sporadic occurrence than inherited traits as the cause of nonischemic SCD.

Does endothelial dysfunction contribute to the clinical status of patients with peripheral arterial disease?

Peripheral arterial disease leads to lower extremity ischemia and limb loss, and is linked to cardiovascular events. The anatomical extent of lower extremity atherosclerosis fails to fully explain ischemic symptoms or predict the development of critical limb ischemia. Endothelial dysfunction is known to contributed to the pathogenesis and clinical expression of coronary artery disease, but the importance of endothelial dysfunction in peripheral arterial disease remains incompletely understood. Endothelial dysfunction could contribute to lower extremity ischemia by impairing blood flow responses to ischemia, collateral formation and arterial remodelling, and by promoting vasospasm, thrombosis, plaque rupture and lesion progression. There is a need for additional studies examining the contribution of endothelial dysfunction to the pathogenesis of peripheral arterial disease, and the potential role of endothelial dysfunction as a surrogate marker with utility in the management of patients.

Determinación del índice tobillo-brazo en pacientes con dolor torácico agudo de posible origen coronario

Background and objective Acute chest pain (ACP) is a non-specific symptom that may be the expression of coronary artery disease (CAD). Atherosclerosis is usually present in more than one vascular territory. Ankle-brachial index (ABI) is a useful tool for the diagnosis of peripheral arterial disease (PAD). Our aim was to evaluate the value of ABI in patients with ACP when CAD is suspected. Patients and methods We performed a cross-sectional study of 94 patients, mean age: 57.4 (12.2), admitted consecutively due to ACP with suspicion of CAD. ABI and presence of CAD were determined. Results CAD was present in 22 patients (23.4%) and absent in 72 (76.6%). Asymptomatic PAD (ABI≤0.9) was present in 6 patients (27.2%) of CAD group and in 7 patients (9.7%) of the non-CAD group. Significant difference was found in ABI based on the presence or not of CAD [0.95 (0.23) vs 1.17 (0.15), p<0.001]. The diagnostic value of ABI for CAD detection was evaluated: area under the ROC curve was 0.8 (IC 95%: 0.70–0.87) and optimal cut-off point was 0.8 (sensitivity=22.7% and specificity=98.6%). In the multivariate analysis, ABI was the best independent predictor of CAD (p<0.001). Conclusion ABI is a simple, cheap and efficient method, which complements other conventional diagnostic methods in the recognition of patients with ACP due to CAD.

Polyphenols and cardiovascular disease: effects on endothelial and platelet function2–3

Epidemiologic studies suggest that higher polyphenol intake from fruits and vegetables is associated with decreased risk for cardiovascular disease. The mechanisms explaining this observation remain unclear. This review summarizes data suggesting that flavonoids improve endothelial function and inhibit platelet aggregation in humans. The vascular endothelium is a critical regulator of vascular homeostasis, and endothelial dysfunction contributes to the pathogenesis and clinical expression of coronary artery disease. Platelet aggregation is a central mechanism in the pathogenesis of acute coronary syndromes, including myocardial infarction and unstable angina. For these reasons, the observed effects of flavonoids on endothelial and platelet function might explain, in part, the observed beneficial effects of flavonoids on cardiovascular disease risk.

The human G-protein beta3 subunit C825T polymorphism is associated with coronary artery vasoconstriction.

Abnormal coronary vasomotion plays a role in the clinical expression of coronary artery disease. We hypothesized that the functional C825T polymorphism located in the ubiquitous G-protein beta3 subunit, implicated in the cellular signal transduction of many receptors, could modify artery coronary vasomotion. We assessed the potential association of the pertussis toxin-sensitive G protein beta3 subunit (GNB3) gene C825T polymorphism on coronary vasomotion in humans. We examined the response of angiographically normal human coronary arteries (n=131) after intravenous injection of methylergonovine maleate, a vasoconstrictor, followed by injection of isosorbide dinitrate, a vasodilator, according to GNB3 genotypes. Coronary vasomotion was assessed with quantitative coronary angiography. Subjects bearing at least one T allele had greater susceptibility to vasoconstriction in response to methylergonovine maleate than CC subjects, whereas vasodilation in response to isosorbide dinitrate did not differ among the different genotypes. The C825T polymorphism of the G-protein beta3 subunit may be a genetic determinant of coronary artery vasomotion in humans.

Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.

Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.

Animal studies on antioxidants.

The wealth of existing epidemiologic evidence suggests that antioxidant intake limits the clinical expression of coronary artery disease. Because the oxidative modification of low-density lipoprotein is an important event in atherogenesis, it has been attractive to speculate that antioxidants act by limiting low-density lipoprotein orientation and, as a consequence, atherosclerotic lesion development. Early studies on animals also suggested that a number of structurally distinct antioxidant compounds could limit the extent of lesion development in animal models of atherosclerosis. More recently, however, secure evidence linking the antioxidant protection of low-density lipoprotein with a reduction in atherosclerosis has been elusive. This discrepancy may be explained by emerging evidence demonstrating that antioxidants may prove beneficial through tissue-specific effects that are not strictly related to the antioxidant protection of low-density lipoprotein.

Atherosclerosis, oxidative stress, and antioxidant protection in endothelium-derived relaxing factor action

The vascular endothelium plays a central role in the regulation of vascular function. In particular, the local release of endothelium-derived relaxing factor (EDRF) regulates vascular tone and prevents platelet adhesion to the vascular wall. Impairment of EDRF action develops early in atherosclerosis and, in part, contributes to platelet deposition and vasospasm involved in the clinical expression of coronary artery disease. Recent evidence suggests that an imbalance between vascular oxidative stress and antioxidant protection is involved in the development of this vascular dysfunction. In this report, the relation between oxidative stress, atherosclerosis, and abnormal EDRF action is reviewed with particular attention to the effects of antioxidant supplementation in animal models of atherosclerosis and hypercholesterolemia.

Lp(a) concentration and apo(a) isoform size. Relation to the presence of coronary artery disease in familial hypercholesterolemia.

We studied the relation between the concentration of lipoprotein(a) [Lp(a)] in plasma, apolipoprotein (a) [apo(a)] phenotype, and the clinical expression of coronary artery disease (CAD) in a previously described cohort of patients with familial hypercholesterolemia (FH) and an appropriate population of control subjects. The plasma concentration of Lp(a) was markedly skewed in both the FH and control populations; however, the distribution was less skewed in FH (50% greater than 300 mg/L) compared with control subjects (27% greater than 300 mg/L). Patients with FH had significantly higher median and mean log Lp(a) levels compared with control subjects. There was no difference in the level of Lp(a) between men and women in both the control and FH groups. Frequency distribution analysis of the major apo(a) isoform size for each subject showed that, in contrast to the near-normal distribution seen in control subjects, two major subpopulations were apparent in the FH cohort, based on apo(a) isoform size > 700 kD or < or = 700 kD. There was no correlation between Lp(a) plasma concentration and apo(a) isoform size in either population. FH subjects with smaller apo(a) isoforms were more likely to have a history of signs of, or symptoms of CAD than those with larger isoforms. These data illustrate that on the basis of Lp(a) plasma concentration alone, there is no significant difference between FH patients with and without signs or symptoms of CAD. In the control population the smaller apo(a) isoforms were associated with higher Lp(a) levels, whereas in the FH population both small and large apo(a) isoforms were associated with higher Lp(a) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathophysiology of ischemia in patients with coronary artery disease

C ORONARY atherosclerosis is characterized by subintimal thickening that leads to plaque formation and stenosis.’ During the progression of this pathology in the large epicardial arteries, episodes of transient myocardial ischemia occur and each event is characterized by a reversible decrease in regional myocardial oxygen concentration that characteristically effects a segment of the left ventricle.2 This leads to the failure of systolic and diastolic muscle function, varying degrees of left ventricular failure, and profound metabolic disturbances. This functional expression of coronary artery disease can be induced by provoking disturbances in coronary blood supply and/or increases in myocardial demand for oxygen (ie, during exercise); ischemia also occurs during the activities of everyday life and it can precede damaging clinical events such as acute myocardial infarction, pulmonary edema, and sudden death.?,’ Transient myocardial ischemia in patients with obstructive coronary artery disease occurs in many different clinical syndromes (eg, chronic stable angina, unstable angina, and after myocardial infarction) and its presence always indicates the increased risk of adverse coronary events.2-7 In the majority of patients with ischemia and proven coronary artery disease, there are atherosclerotic stenoses that severely reduce crosssectional area in a segment of at least one epicardial artery. In these circumstances, standardized exercise protocols can provoke and reproduce ischemia and angina at a reproducible level of exercise. These clinical features have nurtured the belief that coronary blood supply is fixed and myocardial demand increases to cause ischemia. Although this concept is useful when considering the benefits of beta-adrenoreceptor blocking drugs, coronary angioplasty and by-pass graft surgery, these therapies probably do not address the disturbed biology of developing atherosclerotic lesions. Clinical studies of transient myocardial ischemia during daily life,8*9 studies of regional myocardial blood flow before and during ischemia”‘-I5 and studies of coronary vasomotion during cardiac catheterization all highlight the active role of the diseased epicardial arteries in causing transient ischemia.16-r9 An enhanced understanding of the biology of atherosclerotic stenoses has clarified pathophysiological mechanisms of myocardial ischemia and has suggested new directions in the development of therapies aimed at physical regression of coronary atherosclerosis and the control of constriction and thrombosis.20.2i This article will focus on transient myocardial ischemia by examining new clinical characteristics and pathogenic mechanisms rather than simply evaluating diagnostic techniques. It will discuss new clinical information about the biology of atherosclerosis and stenoses in relation to the occurrence of ischemia and adverse clinical outcomes. New insights from basic research will only be discussed as they provide fresh directions for clinical research. This paper will focus on transient ischemia rather than myocardial infarction or sudden death and will try to explore the relationship between coronary atherosclerosis, coronary vasoconstriction, and thrombosis as these problems occur in patients.

Gender and Lipids in Coronary Artery Disease

To the Editor.— The article by Reinhart et al 1 deserves special attention because of the inclusion of women (31%) into the study. Indeed, the authors found differences between men and women in the predictive power of certain lipoprotein and apolipoprotein (apo) measurements. In men, coronary artery disease was associated with elevated levels of apo B, total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol in serum and depressed apo A-I/B ratio. In women, coronary artery disease was associated with elevated apo B and triglyceride levels and depressed apo A-I/B ratio. These differences are worthy of note, because the expression of coronary artery disease in men is different from that in women and these differences are at least partially due to the sex-steroid milieu. 2 The contribution of menopause to the lipid profile may, in fact, be small, 3 but that of replacement sex hormones appears definite, albeit complex. 4

Current technology in assessing painless and painful ischemia

Recent technologic advances have yielded diverse techniques for studying myocardial ischemia, a useful functional expression of coronary artery disease. These techniques have revealed new characteristics and expanded our understanding of myocardial ischemia. In turn this has led to the establishment of more realistic and discriminating criteria on which to base diagnostic and management decisions. Many of the techniques are noninvasive and can be performed in the cardiologist's office. These include treadmill exercise testing; radioisotope techniques, including ejection fraction studies, stress thallium scintigraphy, and tomographic imaging; and ambulatory monitoring. Other, newer techniques include provocative tests that induce ischemia in patients who cannot exercise. These new noninvasive tests should be used to detect transient ischemia, estimate its severity, and thus record a measure of the patient's risk for adverse coronary events.

Drug therapy and the prevention of atherosclerosis in humans

The results of the World Health Organization Cooperative Trial, the Coronary Drug Project, the Coronary Primary Prevention Trial and the Helsinki Heart Study indicate that clinical expression of coronary artery disease can be delayed with pharmacologic modification of plasma lipoproteins. Change in coronary artery disease can be semiquantitated by repeat arteriograms. Three randomized clinical trials indicate that rate of progression of atherosclerosis, as defined by arteriography, can be reduced, and existing lumen obstruction decreased. Tendon xanthomas occur in hypercholesterolemia, and reduction in xanthoma size with drug therapy suggests an improved atherosclerotic disease state. The clinician has a variety of pharmacologic therapies available. The role of bile acid-binding resins, fibric acid derivatives, hydroxymethylglutaryl coenzyme A reductase inhibitors, nicotinic acid and antioxidants is each unique. Understanding the role of lipoproteins in atherosclerosis will help in selecting the most appropriate therapy for each individual patient. Medications not designed for their lipoprotein effects can significantly alter lipoproteins. Medications, such as nonselective β blockers, can alter low-density lipoprotein (LDL) subclass distribution with no change in LDL cholesterol content. Such changes may eradicate part of the beneficial cardiovascular effect of β blockade therapy. In the future, therapeutic choices may depend in part on lipoprotein abnormalities such as lipoprotein (a), apolipoprotein E isoforms, hyperapobetalipoproteinemia, or small, large and modified LDL.

Analysis of cardiac symptoms preceding cardiac arrest

Prodromal symptoms and cardiac history were examined in 227 patients with coronary artery disease who were successfully resuscitated after out-of-hospital cardiac arrest. Cardiac arrest was sudden—with either no symptoms or symptoms for less than 1 hour—in 71% of the patients. Nonsudden death—death occurring after more than 1 hour of symptoms—occurred in 29% of the patients. A history of cardiovascular disease was present in 85% of patients with sudden cardiac arrest and in 83% with nonsudden arrest. Cardiac arrest occurred without symptoms in 38% of the patients with sudden cardiac arrest and was the first expression of coronary artery disease in 4% of the entire study group. This study indicates that cardiac arrest usually occurs with symptoms and almost always in the setting of a history of cardiovascular disease.