Enrica Golia

CRP and the risk of atherosclerotic events

A large body of literature supports the idea that inflammation plays a pivotal role in all phases of atherosclerosis, from the fatty streak lesion formation to the acute coronary event due to vulnerable plaque rupture. Indeed, vascular inflammation contributes to the pathogenesis of atherosclerosis, and later in the disease process, it is a major determinant for the acute coronary syndromes. There are various inflammatory markers that have been shown to predict cardiovascular events. These include high-sensitivity C-reactive protein (hs-CRP), a simple downstream marker of inflammation, recently emerged as a major cardiovascular risk factor. Elevated baseline concentrations of hs-CRP are associated with the risk of atherosclerotic events in general populations and show a predictive value even in terms of secondary prevention, both in patients with chronic stable angina and acute coronary syndromes. In recent year, a lot of concerns have emerged about the experimental models used to study the role of CRP in atherosclerosis; moreover, the results of trials evaluating the clinical association between this molecules and outcome are still controversial. In this paper, we attempt to review the pathophysiological evidences about the link between CRP and atherosclerosis and, most notably, about its utility as a marker and risk predictor in various clinical settings. The identification of specific triggers and mechanisms of underlying inflammation and a better understanding of each step involved in this complex process might lead to new ways to manage patients with atherosclerosis, both in terms of primary and secondary prevention, and CRP still appears to be a suitable candidate for this purpose.

Inflammation and Cardiovascular Disease: From Pathogenesis to Therapeutic Target

Atherosclerosis represents the most common pathological substrate of coronary heart disease (CHD), and the characterization of the disease as a chronic low-grade inflammatory condition is now largely accepted. A number of mediators of inflammation have been widely studied, both as surrogate biomarkers and as causal agents, in the pathophysiological network of atherogenesis and plaque vulnerability. The epidemiological observation that biomarkers of inflammation are associated with clinical cardiovascular risk supports the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk on the background of traditional medical therapy. A large number of randomized controlled trials have shown that drugs commonly used in cardiovascular disease (CVD), such as statins, may be effective in the primary and secondary prevention of cardiovascular events through an anti-inflammatory effect. Moreover, several anti-inflammatory drugs are being tested for their potential to reduce residual cardiovascular risk on the background of validated medical therapy for atherosclerotic disease. In this paper, we review relevant evidence with regard to the relationship between inflammation and CVD, from pathogenesis to therapeutic strategies.

Adipose tissue-mediated inflammation: the missing link between obesity and cardiovascular disease?

Until relatively recently, the role of adipose tissue in the development of obesity and its consequences was considered to be a passive one. Mounting evidence highlights the role of adipose tissue in the development of a systemic inflammatory state that contributes to obesity-associated vasculopathy and cardiovascular risk. It is now clear that, in addition to storing calories as triglycerides, adipocytes secrete a large variety of cytokines, chemokines and hormone-like factors, such as leptin, resistin, and acute-phase proteins. In addition, insulin resistance, both in nondiabetic and diabetic subjects, is frequently associated with obesity, particularly with an excess of intraabdominal fat. This production of pro-atherogenic substances is of particular interest since an increase in the plasma levels of these mediators may provide a novel mechanistic link between obesity and its vascular complications.

Right ventricular myocardial involvement in either physiological or pathological left ventricular hypertrophy: an ultrasound speckle-tracking two-dimensional strain analysis

AIMS To analyse right ventricular (RV) myocardial deformation in patients with left ventricular (LV) hypertrophy secondary to either hypertrophic cardiomyopathy (HCM) or athletes competitive endurance training. METHODS AND RESULTS Standard Doppler echo, exercise stress echo, and 2D speckle-tracking strain echocardiography (2DSE) of RV longitudinal deformation in RV septal and lateral walls were performed in 50 top-level endurance athletes and in 35 patients with HCM, all men, having evidence of LV hypertrophy. Right ventricular global longitudinal strain (GLS) was calculated by averaging local strains along the entire right ventricle. The two groups were comparable for age and blood pressure, whereas athletes showed lower heart rate and increased body surface area than HCM. Interventricular septal thickness was higher in HCM, whereas both LV and RV end-diastolic diameters (LVEDD and RVEDD) and LV stroke volume were increased in athletes. Right ventricular tricuspid annulus systolic excursion was comparable between the two groups. Conversely, RV GLS and regional peaks of RV myocardial strain were significantly impaired in patients with HCM (all P < 0.001). Multiple linear regression models detected an independent association between RV GLS and LVEDD (beta-coefficient = -0.68, P < 0.0001) in athletes, as well as an independent correlation of the same RV GLS with septal thickness (beta = 0.63, P < 0.0001) in HCM. An RV GLS cut-off value of -0.16% differentiated athletes and HCM with an 86% sensitivity and a 92% specificity. Furthermore, in the overall population, RV GLS (beta = 0.51, P < 0.0001) was a powerful independent predictor of maximal workload during exercise stress echo. CONCLUSION Right ventricular myocardial systolic deformation is positively influenced by preload increase in athletes and negatively associated with increased septal thickness in HCM. Therefore, 2DSE may represent a useful tool in the differential diagnosis between athletes heart and HCM, underlining the different involvement of RV myocardial function in either physiological or pathological LV hypertrophy.

Left ventricular myocardial velocities and deformation indexes in top-level athletes.

BACKGROUND The aim of this study was to define the range of left ventricular (LV) velocities and deformation indexes in highly trained athletes, analyzing potential differences induced by different long-term training protocols. METHODS Standard echocardiography, pulsed-wave tissue Doppler echocardiography, and two-dimensional strain echocardiography of the interventricular septum and lateral wall were performed in 370 endurance athletes and 280 power athletes. Using pulsed-wave tissue Doppler, the following parameters of myocardial function were assessed: systolic peak velocities (S(m)), early (E(m)) and late (A(m)) diastolic velocities, and the E(m)/A(m) ratio. By two-dimensional strain echocardiography, peaks of regional systolic strain and LV global longitudinal strain were calculated. RESULTS LV mass index and ejection fraction did not significantly differ between the two groups. However, power athletes showed an increased sum of wall thicknesses (P < .01) and relative wall thickness, while LV stroke volume and LV end-diastolic diameter (P < .001) were greater in endurance athletes. By pulsed-wave tissue Doppler analysis, E(m) and E(m)/A(m) at both the septal and lateral wall levels were higher in endurance athletes. By two-dimensional strain echocardiography, myocardial deformation indexes were comparable between the two groups. E(m)/A(m) ratios ≥ 1 were found in the overall population, while 90 % of athletes had an E(m) ≥ 16 cm/sec, S(m) ≥ 10 cm/sec, and global longitudinal strain ≤ -16%. Multivariate analyses evidenced independent positive association between Em peak velocity and LV end-diastolic volume (P < .001) and an independent correlation of global longitudinal strain with the sum of LV wall thicknesses (P < .005). CONCLUSIONS This study describes the full spectrum of systolic and diastolic myocardial velocities and deformation indexes in a large population of competitive athletes.

Novel insights into the role of cardiotrophin-1 in cardiovascular diseases

Cardiotrophin-1 (CT-1), a member of interleukin (IL)-6 family, was originally isolated for its ability to induce a hypertrophic response in neonatal cardiac myocytes. This cytokine mediates a pleiotropic set of growth and differentiation activities through a unique receptor system, consisting of IL-6 receptor (IL-6R) and a common signal transducer, the glycoprotein 130 (gp130). Both in humans and in mice, CT-1 mRNA has been detected in several tissues, such as liver tissue, adipose tissue, and tissues in the respiratory and nervous systems; in each of these tissues it performs different functions. Predominant actions of CT-1 are on the heart, where it is synthesized and where it provides first myocardial protection by promoting cell survival and proliferation, it carries on its haemodynamic effects and endocrine properties, and finally, it predisposes the heart to pathological conditions. The aim of this review is to describe the pathophysiological mechanisms through which CT-1 carries out its activities, especially on the heart, and its potential contribution as a disease marker in clinical cardiology. Recent studies have confirmed its active role in promoting structural changes typical of most common cardiovascular disease, such as hypertension, valve diseases, congestive heart failure, and coronary artery disease. In fact, CT-1 induces myocyte hypertrophy and collagen synthesis, thereby participating in the progression of ventricular remodelling, which results in cardiac muscle failure at the latest stage. CT-1 plasma levels are elevated in patients with hypertension and coronary artery diseases, and they are also correlated with the severity of valve diseases and heart failure. Therefore, CT-1 may represent a diagnostic, staging, and prognostic biomarker of cardiovascular diseases.

Global longitudinal speckle-tracking strain is predictive of left ventricular remodeling after coronary angioplasty in patients with recent non-st elevation myocardial infarction

AIMS To test whether two-dimensional longitudinal strain (2DSE) performed after revascularization by percutaneous coronary intervention (PCI) could predict left ventricular (LV) remodeling in patients with recent non-ST elevation myocardial infarction (NSTEMI). METHODS In 70 patients (62.7 ± 8.7 years) with recent NSTEMI (between 72 hours and 14 days), undergoing coronary angiography for recurrent angina, myocardial deformation parameters were measured by 2DSE before and 24 hours after reperfusion therapy. Strain in all LV segments was averaged to obtain a global value (Global longitudinal Strain--GLS). Infarct size was estimated by clinical parameters and cardiac markers. After 6 months from intervention, LV negative remodeling was defined as lack of improvement of LV function, with increase in LV end-diastolic volume of greater than or equal than 15%. RESULTS At follow-up, patients were subdivided into remodeled (n=32) and non-remodeled (n = 38) groups. Patients with negative LV remodeling had significantly lower baseline LV ejection fraction (44.8±6.9 vs. 48.7 ± 5.5 %; p < 0.05), higher peak troponin I (p < 0.001) and reduced GLS (- 10.6±6.1 vs - 17.6 ± 6.7 % p < 0.001) than those without LV remodeling. GLS showed a close correlation with peak troponin I after PCI (r = 0.64, P < 0.0001) and LV WMSI (r = 0.42, p < 0.01). By multivariable analysis, diabetes mellitus (P < 0.005), peak of Troponin I after PCI (P < 0.0005), GLS at baseline (OR: 4.3; p < 0.0001), and lack of improvement of GLS soon after PCI (OR: 1.45, P < 0.01) were powerful independent predictors of negative LV remodelling at follow-up. In particular, a GLS ≤ 12 % showed a sensitivity and a specificity respectively of 84.8% and 87.8% to predict negative LV remodelling at follow-up. CONCLUSIONS in patients with recent NSTEMI, longitudinal LV global and regional speckle-tracking strain measurements are powerful independent predictors of LV remodeling after reperfusion therapy.

Platelet function and long-term antiplatelet therapy in women: is there a gender-specificity? A ‘state-of-the-art’ paper

Although the female gender is generally less represented in cardiovascular studies, observational and randomized investigations suggest that-compared with men-women may obtain different benefits from antiplatelet therapy. Multiple factors, including hormonal mechanisms and differences in platelet biology, might contribute to such apparent gender peculiarities. The thrombotic and bleeding risks, as well as outcomes after a cardiovascular event, appear to differ between genders, partly in relation to differences in age, comorbidities and body size. Equally, the benefits of antiplatelet therapy may differ in women compared with men in different vascular beds, during primary or secondary prevention and according to the type of an antiplatelet agent used. This document is an attempt to bring together current evidence, clinical practices and gaps of knowledge on gender-specific platelet function and antiplatelet therapy. On the basis of the available data, we provide suggestions on current indications of antiplatelet therapy for cardiovascular prevention in women with different clinical features; no strong recommendation may be given because the available data derive from observational studies or post hoc/subgroup analyses of randomized studies without systematic adjustments for baseline risk profiles.

Role of C-reactive protein in acute myocardial infarction and stroke: Possible therapeutic approaches

Myocardial infarction (MI) and stroke are relevant clinical issues in Western Countries for morbidity and mortality. In the last decades, great interest has been paid to the identification of non-traditional risk factors for a better stratification of patients and to recognize those at higher risk, who might particularly benefit from a more aggressive approach. In this field, C-reactive protein (CRP) is the most extensively studied novel marker, since it seems related to several stages of atherogenesis, from its beginning to clinical events (i.e. acute coronary syndromes - ACS). Among its possible pathogenetic role both in coronary artery disease (CAD) and ischemic stroke, several studies have shown that CRP could be used to predict first ever MI and stroke in healthy subjects, as well as outcome in acute settings. Moreover, a decrease of CRP levels can be achieved by several therapies, first of all statins, and this seems to be associated with a better outcome. Then a possible role for CRP to guide treatment of patient with ACS and stroke has been claimed and need to be specifically addressed by large randomized controlled trials.

The left atrial appendage: from embryology to prevention of thromboembolism

The left atrial appendage (LAA) is the main source of thromboembolism in patients with non-valvular atrial fibrillation (AF). As such, the LAA can be the target of specific occluding device therapies. Optimal management of patients with AF includes a comprehensive knowledge of the many aspects related to LAA structure and thrombosis. Here we provide baseline notions on the anatomy and function of the LAA, and then focus on current imaging tools for the identification of anatomical varieties. We also describe pathogenetic mechanisms of LAA thrombosis in AF patients, and examine the available evidence on treatment strategies for LAA thrombosis, including the use of non-vitamin K antagonist oral anticoagulants and interventional approaches.