Healed Plaques in Patients With Stable Angina Pectoris.

OBJECTIVE: Healed plaques, signs of previous plaque destabilization, are frequently found in the coronary arteries. Healed plaques can now be diagnosed in living patients. We investigated the prevalence, angiographic, and optical coherence tomography features of healed plaques in patients with stable angina pectoris. Approach and Results: Patients with stable angina pectoris who had undergone optical coherence tomography imaging were included. Healed plaques were defined as plaques with one or more signal-rich layers of different optical density. Patients were divided into 2 groups based on layered or nonlayered phenotype at the culprit lesion. Among 163 patients, 87 (53.4%) had layered culprit plaque. Patients with layered culprit plaque had more multivessel disease (62.1% versus 44.7%, P=0.027) and more angiographically complex culprit lesions (64.4% versus 35.5%, P<0.001). Layered culprit plaques had higher prevalence of lipid plaque (83.9% versus 64.5%, P=0.004), macrophage infiltration (58.6% versus 35.5%, P=0.003), calcifications (78.2% versus 63.2%, P=0.035), and thrombus (28.7% versus 14.5%, P=0.029). Lipid index (P=0.001) and percent area stenosis (P=0.015) were greater in the layered group. The number of nonculprit plaques, evaluated using coronary angiograms, tended to be greater in patients with layered culprit plaque (4.2±2.5 versus 3.5±2.1, P=0.053). Nonculprit plaques in patients with layered culprit lesion had higher prevalence of layered pattern (P=0.002) and lipid phenotype (P=0.005). Lipid index (P=0.013) and percent area stenosis (P=0.002) were also greater in this group. CONCLUSIONS: In patients with stable angina pectoris, healed culprit plaques are common and have more features of vulnerability and advanced atherosclerosis both at culprit and nonculprit lesions.

Inflammasome, T Lymphocytes and Innate-Adaptive Immunity Crosstalk: Role in Cardiovascular Disease and Therapeutic Perspectives.

Over the past few decades, lot of evidences have shown atherosclerosis as a chronic progressive disease with an exquisite inflammatory feature. More recently, the role of innate immune response in the onset and progression of coronary artery disease (CAD) and an adaptive immunity imbalance, mostly involving T cell sub-sets, have been documented. Therefore, like in many other inflammatory and autoimmune disorders, an altered innate-adaptive immunity crosstalk could represent the key of the inflammatory burden leading to atherosclerotic plaque formation and progression and to the breakdown of plaque stability. In this review, we will address the role of inflammasome in innate immunity and in the imbalance of adaptive immunity. We will discuss how this altered immune crosstalk is related to CAD onset and progression. We will also discuss how unravelling the key molecular mechanisms is of paramount importance in the development of therapeutic tools to delay the chronic progression and prevent the acute destabilization of atherosclerotic plaque.

Endothelial progenitor cells in morbid obesity.

BACKGROUND: The aim of this study was to assess the relationship among anthropometric indexes of adiposity (body mass index [BMI], waist circumference [WC]), endothelial progenitor cells (EPC) and carotid intima-media thickness (IMT) in patients with morbid obesity, and the effect of diabetes and weight loss. METHODS AND RESULTS: BMI, WC, IMT and circulating EPC (defined as CD34+/KDR+/CD45- cells) were assessed in 100 patients (37 with diabetes). Fifty patients underwent bariatric surgery, and in 48 of them a complete re-assessment after an average follow-up of 252±108 days was carried out. In 29 of them subcutaneous and visceral adipose tissue samples were obtained at the time of intervention and analyzed for the presence and number of EPC. EPC were directly correlated with weight, BMI, WC and insulin level, and inversely with mean IMT. All correlations were confined to non-diabetic patients. EPC were found in both subcutaneous and visceral adipose tissue specimens. Circulating EPC significantly decreased after weight loss (P=0.002). CONCLUSIONS: EPC are positively related to markers of adiposity in severe obesity, when not complicated by diabetes. Weight loss is associated with decrease in EPC level. EPC are inversely correlated with IMT, confirming their protective role also in severe obesity. Diabetes has a negative modulating action.

Microparticles in health and disease: small mediators, large role?

Microparticles are circulating fragments derived from blebbing and shedding of cell membranes through several mechanisms that include activation, apoptosis and cell damage. In the past they were largely considered as unimportant cell "dust", but more refined detection techniques have revealed large variations in their relative proportion and concentration in numerous disease states. Importantly, these conditions include the most prevalent causes of death and disability in our societies, namely cardiovascular, neoplastic, and inflammatory diseases. Microparticles carry procoagulant, proapoptotic and neoangiogenetic materials in the blood stream, and can also be viewed as a technique cells may adopt to rapidly modify their phenotype, independently from genetic signals. In this review, we focus on the role of these very small ( 1 micron) particles, not only as mere markers of an underlying pathologic state, but also as primordial intercellular messengers and defense mechanism that every viable cell can exploit in distress conditions. In this view, we suggest that this old communication system could be the target of future high-tech interventions, with potential broad consequences.

Role of tissue C-reactive protein in atrial cardiomyocytes of patients undergoing catheter ablation of atrial fibrillation: pathogenetic implications.

AIMS: Histological studies support the important role of inflammation in the initiation and maintenance of atrial fibrillation (AF). We describe a novel and safe technique of atrial biopsy during AF radiofrequency catheter ablation (RFCA) to investigate the role of atrial tissue inflammation. METHODS AND RESULTS: We enrolled 70 consecutive patients (age 60 ± 12 years, 49 males) undergoing RFCA for AF. The control group was represented by 10 patients with Wolff-Parkinson-White syndrome undergoing trans-septal puncture. Atrial biopsies were obtained by washing the dilator and needle used for trans-septal puncture with 20 mL sterile phosphate-buffered saline. The presence of intracytoplasmic C-reactive protein was assessed in formalin-fixed atrial specimens by immunohistochemistry. A sufficient amount of atrial tissue was obtained in 23/70 (32%) patients with AF and in 4/10 (40%) of the control group. Intracytoplasmic localization of C-reactive protein was found in isolated atrial cardiomyocytes in 11 (73%) of 15 patients with paroxysmal AF as compared with 2 (25%) of eight patients with persistent AF (P= 0.02). CONCLUSION: In this study, we demonstrate the safety and feasibility of a novel technique to obtain atrial specimens during routine trans-septal puncture. Local inflammation assessed by atrial tissue localization of C-reactive protein is more likely involved in paroxysmal rather than in persistent AF.

Inflammatory biomarkers and coronary heart disease: from bench to bedside and back.

Inflammation plays a pivotal role in all stages of atherosclerosis from endothelial dysfunction and plaque formation to plaque destabilization and disruption. Inflammatory biomarkers, originally studied to better understand the pathophysiology of atherosclerosis, have generated increasing interest among clinicians, because of their utility in the challenging problems of diagnosis and risk assessment of patients with suspected or proved coronary heart disease. Moreover, in fascinating perspective, they could be used as therapeutic target, counteracting initiation, progression, and development of complications of atherosclerosis. In this review, we will provide an overview of the more promising inflammatory biomarkers, focusing on their utility and limitations in the clinical setting.

Comparison of the effects of ramipril versus telmisartan on high-sensitivity C-reactive protein and endothelial progenitor cells after acute coronary syndrome.

To compare the anti-inflammatory and endothelial progenitor cell mobilizing effects of ramipril and telmisartan in patients presenting with acute coronary syndrome (ACS), 42 patients with ACS were randomized after successful percutaneous coronary intervention to ramipril 5 mg/day (22 patients) or telmisartan 80 mg/day (20 patients). Peripheral blood samples were drawn at baseline and at 20 days to measure high-sensitivity C-reactive protein and to assess 4 populations of progenitor cells by flow cytometry, namely CD34+/KDR+, CD34+/CD133+, CD34+/CD133+/CD45-, and CD34+/KDR+/CD45- cells. High-sensitivity C-reactive protein levels, similar in the 2 groups at baseline, were significantly more decreased by telmisartan than by ramipril at follow up (p = 0.013 for time-by-drug interaction). The main effect for time was also significant (p <0.001). CD34+/KDR+ and CD34+/CD133+ cells were similar at baseline and did not change over time (p = 0.2 and p = 0.1, respectively). In contrast, for CD34+/KDR+/CD45- and CD34+/CD133+/CD45- cells, a significant increase with time was seen (p = 0.02 and p = 0.002, respectively) and no differential effect of either drug was seen. In conclusion, telmisartan shows a more potent anti-inflammatory effect than ramipril after an ACS. The 2 drugs do not show a differential effect on endothelial progenitor cell mobilization.

Effect of intensive vs standard statin therapy on endothelial progenitor cells and left ventricular function in patients with acute myocardial infarction: Statins for regeneration after acute myocardial infarction and PCI (STRAP) trial.

BACKGROUND: Intensive statin therapy can lower the risk of recurrence of major cardiac events in patients with acute coronary syndromes. This could be related to the ability of statins to increase levels of Endothelial Progenitor Cells (EPCs), which were demonstrated to be favorably associated with a better prognosis and post-infarction left ventricular remodeling in patients with ischemic heart disease. AIM OF THE STUDY: First, to evaluate, in a randomized clinical trial, the effect of an intensive vs a standard treatment with statins on EPC mobilization in patients undergoing a successful primary or rescue percutaneous coronary intervention; secondary, to evaluate whether left ventricular remodeling could be influenced by statin therapy through EPC mobilization. METHODS: Forty ST-segment elevation myocardial infarction (STEMI) patients undergoing a successful primary or rescue PCI were randomized to receive atorvastatin 80 mg immediately after the admission (Intensive Treatment, IT) or atorvastatin 20 mg from the day of the discharge (Standard Treatment, ST). CD34+/KDR+ EPC count by flow cytometry and left ventricular function by 2-D Echo were measured on admission, at discharge and at 4 months follow up. RESULTS: We found that EPC count was similar in the two groups of patients both on admission and at discharge. At follow up, however, EPC count was higher in patients randomized to IT compared to patients randomized to ST (7.59+/-7.30 vs 3.04+/-3.93, p=0.04). However, LV volumes, ejection fraction and wall motion score index were similar in both groups. CONCLUSIONS: An intensive statin treatment after primary or rescue PCI is associated with a higher EPC count at follow up as compared to standard treatment. This beneficial effect did not translate in an improvement of LV function.

Inflammation as a possible link between coronary and carotid plaque instability.

BACKGROUND: Multiple complex stenoses, plaque fissures, and widespread coronary inflammation are common in acute coronary syndromes. A systemic cause of atherosclerotic plaque instability is also suggested by studies of ischemic cerebrovascular disease. We investigated the association between coronary and carotid plaque instability and the potential common causal role of inflammation. METHODS AND RESULTS: The ultrasound characteristics of carotid plaques were evaluated retrospectively in patients scheduled for coronary bypass surgery, 181 with unstable and 92 with stable angina, and prospectively in a similar group of patients, 67 with unstable and 25 with stable angina, in whom serum C-reactive protein levels were also measured. The prevalence of carotid plaques was similar in the retrospective and prospective studies and >64% in both unstable and stable coronary patients. The prevalence of complex, presumably unstable carotid plaques was 23.2% in unstable versus 3.2% in stable patients (P<0.001) in the retrospective study and 41.8% versus 8.0% (P=0.002) in the prospective study. C-reactive protein levels were higher in patients with complex (7.55 mg/L) than in those with simple (3.94 mg/L; P<0.05) plaques or without plaques (2.45 mg/L; P<0.05). On multivariate analysis, unstable angina and C-reactive protein levels >3 mg/L were independently associated with complex carotid plaques (OR, 6.09; 95% CI, 1.01 to 33.72; P=0.039, and OR, 5.80; 95% CI, 1.55 to 21.69; P=0.009, respectively). CONCLUSIONS: In unstable angina, plaque instability may not be confined to coronary arteries, and inflammation may be the common link with carotid plaque instability. These observations may have relevant implications for understanding the mechanisms of acute widespread atherothrombotic plaque inflammation.