Giovanna Gallo

Lipoprotein (a) is related to coronary atherosclerotic burden and a vulnerable plaque phenotype in angiographically obstructive coronary artery disease

BACKGROUND Lipoprotein Lp(a) has been shown to be an independent risk factor for coronary artery disease (CAD). However, its association with CAD burden in patients with ACS is largely unknown, as well as the association of Lp(a) with lipid rich plaques prone to rupture. AIM We aim at assessing CAD burden by coronary angiography and plaque features including thin cap fibroatheroma (TCFA) by optical coherence tomography (OCT) in consecutive patients presenting with acute coronary syndrome (ACS) and obstructive CAD along with serum Lp(a) levels. METHODS This study comprises an angiographic and an OCT cohort. A total of 500 ACS patients (370 men, average age 66 ± 11) were enrolled for the angiographic cohort and 51 ACS patients (29 males, average age 65 ± 11) were enrolled for the OCT cohort. Angiographic CAD severity was assessed by Sullivan score and by Bogaty score including stenosis score and extent index. OCT plaque features were evaluated at the site of the minimal lumen area and along the culprit segment. RESULTS In the angiographic cohort, at multivariate analysis, Lp(a) was a weak independent predictor of Sullivan score (p < 0.0001), stenosis score (p < 0.0001) and extent index (p < 0.0001). In the OCT cohort, patients with higher Lp(a) levels (≥ 30 md/dl) compared to patients with lower Lp(a) levels (<30 md/dl) exhibited a higher prevalence of lipidic plaque at the site of the culprit stenosis (67% vs. 27%; P = 0.02), a wider lipid arc (135 ± 114 vs 59 ± 111; P = 0.03) and a higher prevalence of TCFA (38% vs. 10%; P = 0.04). CONCLUSIONS Among patients with ACS, raised Lp(a) levels are associated with an increased atherosclerotic burden and it identifies a subset of patients with features of high risk coronary atherosclerosis.

2017 Position Paper of the Italian Society for Cardiovascular Prevention (SIPREC) for an Updated Clinical Management of Hypercholesterolemia and Cardiovascular Risk: Executive Document

The benefits achieved by implementing cardiovascular prevention strategies in terms of reduced incidence of atherosclerotic diseases and mortality are accepted, worldwide. In particular, the clinical management of hypercholesterolemia has a fundamental role for all preventive strategies, both in primary and secondary prevention, at each stage of cardiovascular risk. Since the net clinical benefit of lipid-lowering therapy largely depends on baseline individual cardiovascular risk profile, the assessment of individual risk is essential to establish type and intensity of both preventive and therapeutic strategies. Thus, the real challenge in a setting of clinical practice is not only to identify whom to treat among individuals at low-to-moderate risk, but mostly how much and how long to treat high or very-high risk patients. This manuscript, which reflects concepts and positions that have been published in a more extensive document of the Italian Society for Cardiovascular Prevention (SIPREC), deals with the diagnostic and therapeutic management of patients with dyslipidaemia, with an evidence-based approach adapted and updated from recent guidelines of the European Society of Cardiology and very recent results of randomized clinical trials. The purpose is to suggest a multidimensional and integrated actions aimed at eliminating or minimizing the impact of cardiovascular diseases and their related disabilities and mortality in patients with hypercholesterolemia.

Role of oxidative stress in the process of vascular remodeling following coronary revascularization

Percutaneous coronary interventions (PCI), including balloon angioplasty and implantation of both bare metal and drug eluting coronary stents, are associated with risk of restenosis and in-stent thrombosis. A better understanding of signals that regulate cellular proliferation, neointimal formation and vessel wall thickening following PCI may contribute to identify novel preventive and therapeutic strategies aimed to reduce the atherosclerosis progression and the consequent vascular sequelae. Among the possible mechanisms, an increased level of reactive oxygen species (ROS) is associated with endothelial dysfunction and vascular smooth muscle cells (VSMCs) proliferation and migration involved in the post-procedural remodeling process. This review article provides an overview of the current knowledge on the contribution of increased oxidative stress to the post-procedural pathological vascular changes. We discuss the role of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide synthase, and of proteins regulating the mitochondrial function and dynamics. We will also highlight new knowledge on the atypical Fat1 cadherin that appears to play a key role in VSMCs proliferation. In fact, its induction after vascular injury serves as a physiological regulator of VSMCs growth. Specific molecular mechanisms, including Pin1- and H2S-mediated pathways, have been identified in the vascular complications of type 2 diabetic patients. The identification of novel key players may expand our perspectives and promote the development of new tools for future preventive and therapeutic strategies in order to reduce the adverse vascular remodeling following PCI. The latter represents one of the major goals in the development of innovative technologies with relevance for clinical practice.

Is early and fast blood pressure control important in hypertension management

Control of blood pressure (BP) in hypertension is recognized as a key measure in the management of cardiovascular (CV) risk and is a cornerstone of preventive strategies. It is not defined, however, whether an initiation of the antihypertensive treatment in the early stages of hypertension (such as prehypertension or high-normal BP), may bring benefits for the long-term prevention of CV events. In addition, it has not been thoroughly addressed the issue whether achievement of a prompt BP reduction in hypertensive patients may contribute to reduce CV damage and events. The aim of this article is to critically examine data from studies exploring these important questions. Our conclusion is that the available evidence, though not very extensive, supports the prevailing benefits associated with early BP control. We also discuss the therapeutic strategies to achieve early control of BP. Finally, we believe that this aspect deserves to be more thoroughly addressed in upcoming international guidelines.

Aspirin and the Primary Prevention of Cardiovascular Diseases: An Approach Based on Individualized, Integrated Estimation of Risk

While the use of aspirin in the secondary prevention of cardiovascular (CVD) is well established, aspirin in primary prevention is not systematically recommended because the absolute CV event reduction is similar to the absolute excess in major bleedings. Recently, emerging evidence suggests the possibility that the assumption of aspirin, may also be effective in the prevention of cancer. By adding to the CV prevention benefits the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in the primary prevention in favour of the latter and broaden the indication for treatment with in populations at average risk. While prospective and randomized study are currently investigating the effect of aspirin in prevention of both cancer and CVD, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention could be already based on a balanced evaluation of the benefit/risk ratio.

Data on the lipoprotein (a), coronary atherosclerotic burden and vulnerable plaque phenotype in angiographic obstructive coronary artery disease

Lipoprotein Lp(a) represents an independent risk factor for coronary artery disease (CAD). However, its association with CAD burden and lipid rich plaques prone to rupture in patients with acute coronary syndrome (ACS) still remains unknown. These data aim to investigate the association among serum Lipoprotein(a) (Lpa) levels, coronary atherosclerotic burden and features of culprit plaque in patients with ACS and obstructive CAD. For his reason, a total of 500 ACS patients were enrolled for the angiographic cohort and 51 ACS patients were enrolled for the optical coherence tomography (OCT) cohort. Angiographic CAD severity was assessed by Sullivan score and by Bogaty score including stenosis score and extent index, whereas OCT plaque features were evaluated at the site of the minimal lumen area and along the culprit segment. In the angiographic cohort, Lp(a) was a weak independent predictor of Sullivan score (p<0.0001), stenosis score (p<0.0001) and extent index (p<0.0001). In the OCT cohort, patients with higher Lp(a) levels (>30 md/dl) compared to patients with lower Lp(a) levels (<30 md/dl) exhibited a higher prevalence of lipidic plaque at the site of the culprit stenosis (P=0.02), a wider lipid arc (p=0.003) and a higher prevalence of thin-cap fibroatheroma (p=0.004)

Chronic heart failure is characterized by altered mitochondrial function and structure in circulating leucocytes

Oxidative stress is currently viewed as a key factor in the genesis and progression of Heart Failure (HF). The aim of this study was to characterize the mitochondrial changes linked to oxidative stress generation in circulating peripheral blood mononuclear cells isolated from chronic HF patients (HF_PBMCs) in order to highlight the involvement of mitochondrial dysfunction in the pathophysiology of HF. To assess the production of reactive oxygen species (ROS), mitochondrial function and ultrastructure and the mitophagic flux in circulating PBMCs we enrolled 15 patients with HF and a control group of ten healthy subjects. The HF_PBMCs showed a mitochondrial population consisting of damaged and less functional organelles responsible of higher superoxide anion production both at baseline and under in vitro stress conditions, with evidence of cellular apoptosis. Although the mitophagic flux at baseline was enhanced in HF_PBMCs at level similar to those that could be achieved in control PBMCs only under inflammatory stress conditions, the activation of mitophagy was unable to preserve a proper mitochondrial dynamics upon stress stimuli in HF. In summary, circulating HF_PBMCs show structural and functional derangements of mitochondria with overproduction of reactive oxidant species. This mitochondrial failure sustains a leucocyte dysfunctional status in the blood that may contribute to development and persistence of stress conditions within the cardiovascular system in HF.

Use of Fixed-Dose Combinations in Hypertension and Cardiovascular Disease Prevention

In spite of the wide availability of effective and well-tolerated antihypertensive drugs, the proportions of treated hypertensive patients achieving the recommended BP targets are persistently low, worldwide. Among the various factors that can be advocated for explaining the so-called “hypertension paradox”, low adherence to prescribed medications probably represents the most relevant. During the long-term treatment of hypertension, in fact, drug discontinuations due to therapeutic failure or occurrence of drug-related side effects and adverse reactions are very common.

Executive Summary of the 2018 Joint Consensus Document on Cardiovascular Disease Prevention in Italy

Cardiovascular diseases (CVDs) are the leading cause of death, disability and hospitalization in Italy. Primary prevention strategies are able to prevent clinically evident CVDs, mostly by early identifying asymptomatic, otherwise healthy individuals at risk of developing CVDs. A more modern approach recommended for effective CVD prevention is based on “4P”, that is: Predictive, Preventive, Personalized and Participative. This executive document reflects the key points of a consensus paper on CV prevention in Italy, realized though the contribution of different Italian Scientific Societies and the National Research Council, and coordinated by the Italian Society of Cardiovascular Prevention (SIPREC), published in 2018. The need for such document relies on the difficulty to apply “sic et simpliciter” European guidelines, to which this document is largely inspired, to national, regional and local realities, in this Mediterranean country, namely Italy. Indeed, our Country has specific features in terms of demography, socio-cultural habits, distribution and prevalence of risk factors, organization, policy and access to National Health Service compared to other European countries.