Milena Leo

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.

Delayed neutrophil apoptosis in patients with unstable angina: relation to C-reactive protein and recurrence of instability

AIMS To investigate spontaneous polymorphonuclear neutrophils (PMNs) apoptosis in unstable angina (UA) and its association with recurrence of instability. METHODS AND RESULTS We compared PMNs apoptotic rate at 4 and 24 h in patients with UA, stable angina (SA), and controls (H) with two different protocols by flow cytometry. We measured apoptotic rate of isolated PMNs (Protocol 1) in 30 UA patients, 13 SA patients, and 34 H; and apoptosis of PMNs in whole blood culture (Protocol 2) in further 10 UA patients, 7 SA patients, and 6 H. Serum high-sensitivity C-reactive protein was also measured. Polymorphonuclear neutrophils of UA patients showed a decreased apoptotic rate compared with SA patients and H at 4 h in Protocol 1 (both P < 0.01), and at 24 h in Protocol 2 (P < 0.05 and <0.01, respectively). In overall population, a negative correlation was found between apoptotic rate at 4 h and high-sensitivity C-reactive protein levels (P < 0.01). Six among 40 patients with UA had early recurrence of symptoms and their apoptotic rate was significantly reduced compared with UA patients without recurrence of symptoms (P = 0.024). CONCLUSIONS Our study demonstrates delayed PMN apoptosis in UA. This alteration might be involved in the persistence of inflammatory activation and affects recurrence of instability.

Different Apparent Prognostic Value of hsCRP in Type 2 Diabetic and Nondiabetic Patients with Acute Coronary Syndromes

BACKGROUND C-reactive protein (CRP) is an established prognostic marker in acute coronary syndromes (ACS); however, no study has specifically addressed its prognostic role in type 2 diabetes with ACS. We evaluated the prognostic role of CRP separately in diabetic and nondiabetic patients with ACS. METHODS We enrolled 251 patients with unstable angina and measured serum concentrations of high sensitivity (hs)CRP. Ninety-seven patients underwent coronary angiography with evaluation of atherosclerotic disease severity and extent by Bogaty score. Assessed endpoint was the combined occurrence of myocardial infarction (MI) and death at 1 year. RESULTS No significant differences were found in hs-CRP between patients with and without diabetes. By Cox regression, hsCRP was not associated with 1-year follow-up events in diabetic patients but was strongly associated with events in nondiabetic patients (P = 0.0012). Coronary angiography exhibited a higher extent index in patients with diabetes than in those without (P = 0.04). hsCRP concentrations were not associated with angiographic atherosclerotic burden. By Cox analysis, hsCRP and extent score were associated with events in patients who underwent coronary angiography (P < 0.001 and P = 0.034, respectively). In nondiabetic patients, hsCRP was the only predictor of events at 1-year follow-up (P < 0.001), whereas in diabetic patients, hsCRP was not associated with events and a weak association was observed for extent score (P = 0.06). CONCLUSIONS Our study suggests that different pathophysiological mechanisms may be responsible for MI and death in unstable angina patients with or without diabetes and that severity of coronary artery disease plays a major role in diabetes (and inflammation in the absence of diabetes).

Local and Systemic Mechanisms of Plaque Rupture

Mechanisms at the basis of coronary plaque instability are still elusive. On the one hand, accumulating data, from clinical and postmortem studies, suggest the role of systemic factors, in particular inflammation, in plaque rupture. On the other hand, local factors, in particular plaque composition, such as a large lipid-rich core and a thin fibrous cap, presence of activated inflammatory cells, presence of plaque neovascularization, and specific apoptotic processes, may contribute to plaque susceptibility to rupture. In addition, other cofactors, such as platelet activation and clotting factors, are involved in the transition from stable to unstable plaque. The authors discuss the possibility that all these factors have a role in the development of acute coronary syndrome: a systemic inflammatory condition with an enhanced coagulation state may activate local hemodynamic, mechanical, and immune reactions leading to intraplaque cells activation, fibrous cap lysis, and thrombus formation.

Biomarkers in Acute Coronary Syndrome

Background Evaluation of patients who present to the hospital with acute undifferentiated chest pain or other symptoms and signs suggestive of Acute Coronary Syndrome (ACS) is often a clinical challenge. The initial assessment, requiring a focused history (including risk factors analysis), a physical examination, an electrocardiogram (EKG) and serum cardiac marker determination, is time-consuming and troublesome. Recent investigations have indicated that increases in biomarkers of necrosis, inflammation, ischemia and myocardial stretch may provide earlier assessment of overall patient risk, help in identifying the adequate diagnostic and therapeutic management for each patient and allow for prevention of substantial numbers of new events. Approach and Content The purpose of this review is to provide an overview of the characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. Patho-physiology, analytical and clinical characteristics have been evaluated for each marker, underlying the properties for potential routine clinical use. Summary The biomarkers discussed in this review are promising and might lead to improved diagnosis and risk stratification of patients with ACS, however their clinical application requires further studies. It is important to define their clinical role as diagnostic markers, their predictive value and the specificity, standardization and detection limits of the assays.

Statins Reduce Incidence of Early Perioperative Complications and Length of in-Hospital Stay after Coronary Artery Bypass Graft Surgery

Background: Coronary artery bypass grafting (CABG) is associated with several perioperative complications that may significantly prolong length of in-hospital stay, increase costs and provide worse long term outcome. The 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, or statins, exert anti-inflammatory and vascular protective effects. We hypothesized that pre-operatory statin therapy may reduce incidence of early perioperative complications and length of in-hospital stay following CABG.Methods: We retrospectively enrolled 103 patients (age 67±3; 18 females), who underwent CABG. Patients were allocated into 2 groups: 57 patients on statin therapy prior to CABG (St Group) and 46 patients not on statin therapy (n-St group). Demographic and clinical features, pre-operative medications use and the incidence of early adverse postoperative events were collected. Pre-operative risk of death using the European System for Cardiac Operative Risk Evaluation (EuroSCORE) was also calculated. The primary end-point was the composite of early complications occurring after surgery, including infections, bleedings, sustained ventricular and supra-ventricular tachyarrhythmias, cardiogenic shock, myocardial infarction and mortality. As secondary end-points single perioperative complications were considered. In-hospital stay length was also evaluated.Results: Clinical features, cholesterol levels and EuroSCORE were similar between two groups. Statin therapy and EuroSCORE emerged as predictors of the composite adverse outcome. n-St patients had a significant higher rate of early complications if compared with St patients: the primary endpoint occurred in 18 St patients (31%) versus 25 (54%) non-St patients (p=0.019). Multivariate analysis confirmed pre-operative statin therapy and EuroSCORE as independent predictors of the primary endpoint (OR=0.307, 95% CI=0.123-0.766, p=0.011 and OR= 2.114, 95% CI= 1.213- 4.407, p= 0.002 respectively) showing a protective role of the statin therapy.The incidence of secondary end-points did not differ significantly between the groups, while in-hospital stay was longer in n-St group if compared with St group (7.7±3,9 days vs 5,6±1,8 days; p=0,001).Conclusion: Our data suggest that statin therapy may reduce early perioperative complications after coronary artery bypass grafting. This effect is independent from cholesterol basal levels, thus supporting pre-operative statin use in patients undergoing CABG.

Epidemiology, Classification and Description of Cardiac Arrhythmias

The term arrhythmia is used to indicate an alteration of the normal rate or regularity of the heart-beat, as well as an alteration of the physiological conduction sequence of electrical impulse from the sinus node to the His-Purkinje system and the ventricles. The term bradycardia refers to a heart rate (HR) of less than 60 beats per minute (bpm), while the term tachycardia identifies a sequence of 3 or more beats with HR above 100 bpm.

Medical History and Physical Examination in Sports Medicine

Medical history and physical examination are recognized worldwide as the milestone of athletes’ preparticipation cardiovascular screening. They are defined as the systematic medical practice of evaluating large populations of athletes before sports participation in order to identify (or raise suspicion of) those abnormalities that might undergo disease progression or sudden cardiac death.