Current Pharmaceutical Design - Volume 15, Issue 10, 2009

Nowadays, there is no doubt that cardiovascular risk factors, how ever they may be identified - and there is considerable evidence that permits to assess their role to cause, maintain and potentiate cardiovascular events - are continuously increasing in number and new pathogenetic mechanisms of damage are continuously recognised. The degree of cardiovascular damage caused by risk factors depends on isolated or combined action of how these factors determine clinical, biochemical, metabolic and pharmacologic alterations which could be strongly related with cardiovascular pathology. The reviews in this issue set a goal to analyse newer insights that link some features of the main cardiovascular risk factors with cardiac and vascular pathology. Among the major cardiovascular risk factors, there is always more and more evidence that genetic mechanisms adversely influence heart and blood vessels of active smokers or individuals exposed passively to cigarette smoke. Armani et al. [1] analyse molecular and biochemical changes of cardiac myocytes as well as the mechanisms involved in cigarette smoking-related cardiovascular dysfunction.

Cigarette smoking (CS) is a major health hazard particularly for the cardiovascular system and cancer. The mechanisms involved in CS-related cardiovascular dysfunction have been largely debated. CS increases inflammation, thrombosis, and oxidation of low-density lipoproteins. Recent experimental and clinical data support the hypothesis that cigarette smoke exposure increases oxidative stress as a potential mechanism for initiating cardiovascular dysfunction. Cardiac myocytes, as well as and other long-lived postmitotic cells show dramatic smoke-related alterations that mainly affect the mitochondria and lysosomal compartment. Mitochondria are primary sites of reactive oxygen species formation that cause progressive damage to mitochondrial DNA and proteins in parallel to intralysosomal lipofuscin accumulation. There is amassing evidence that various mechanisms may contribute to accumulation of damaged mitochondria following initial oxidative injury. Such mechanisms may include clonal expansion of defective mitochondria, decreased propensity of altered mitochondria to become autophagocytosed, suppressed autophagy because of heavy lipofuscin loading of lysosomes and decreased efficiency of specific proteases involved into mitochondrial degradation. A possible interplay between microtubule plasticity and oxidative stress also exists in cardiomyocytes, so this could represent another potential mechanism by which smoking induces/accelerates atherosclerosis.

Coronary heart disease (CHD) is the leading cause of death in the developed world in both men and women. Elevated low-density lipoprotein cholesterol (LDL-C) levels are strong and independent vascular risk factors in both genders. Statins effectively decrease LDL-C levels, reduce vascular morbidity and mortality and are an essential component of CHD preventive strategies. However, women are less likely to be prescribed statins than men in both primary and secondary prevention settings. It was argued that there is no conclusive evidence showing that statins are beneficial for the prevention of vascular disease in women, particularly in those without established CHD. This review summarizes the evidence regarding the effects of statins in the prevention of CHD in women. Accumulating data suggest that statins are equally effective in both men and women. The lack of significant effects in some studies appears to be primarily due to the under-representation of women and the ensuing lack of statistical power. Current guidelines for the prevention of vascular disease also recommend a similar management of dyslipidemia in both men and women. Therefore, statin treatment should be implemented with the same criteria and with the same goals in both genders.

The rapid increasing prevalence of obesity worldwide represents a serious health hazard. Obesity predisposes to increased risk for diabetes, hypertension, renal failure. Direct mechanisms link visceral adiposity and the atherosclerosis process through the action of adipose-derived proinflammatory cytokines. In particular, hypertension can be considered the most important cardiovascular risk factor linking obesity to the development of cardiovascular disease. Obesity among children and adolescents has also reaching epidemic proportions in the industrialized world. Childhood obesity strongly predisposes to cardiovascular adult mortality. Recent reports documented a tracking of blood pressure from childhood to adulthood and obesity occurring in young age plays a crucial pathogenic role. Indeed, fighting overweight and obesity in the pediatric and adolescent age may prevent the occurrence of adults with hypertension and cardiovascular disease. The main strategies for prevention and treatment of overweight and obesity in childhood, which need to involve community, school and family, are the promotion of lifestyle interventions, including as a correct dietary approach, rich in fruit and vegetables and low-fat dairy products, and physical activity.

A large body of evidence supports that the dietary intake of polyphenols - particularly of flavonoids and the specific class of flavonoids named flavanols - might be able to exert some beneficial vascular effects and reduce the risk for cardiovascular morbidity and mortality. The review of epidemiological and mechanistic studies supports the role of flavonoids, particularly cocoa and tea flavanols, in protecting the cardiovascular system against cardiovascular disease. Nevertheless, flavonoids are an heterogeneous group of natural molecules differently represented in fruit and vegetables and definitive data on cardiovascular benefits are lacking. The weakness of the available data include few and very small studies, no crossover designed studies and a wide range of dose and type of flavonoids tested. Thus, although flavonoidrich foods and beverages are likely to protect cardiovascular system, further research is needed to characterize the mechanism of action on flavanol-rich foods. Long-term clinical trials are also needed to definitively clarify the benefits deriving from long-term consumption of flavanol-rich foods, particularly focussing on the lowest effective levels as well as synergism or antagonistic actions between different classes of flavonoids commonly found in foods.

Aspirin is the cornerstone of treatment in patients with coronary artery disease. However, several studies investigating the in vitro response of platelets to the administration of aspirin showed this response to be variable, with some patients exhibiting non-responsiveness or resistance. Aspirin resistance may be categorised as either ‘laboratory’ or ‘clinical’. Laboratory aspirin resistance is defined as the failure of aspirin to inhibit the production of thromboxane A2 (TxA2) by platelets or to inhibit platelet activation that depends on TxA2 production. Clinical aspirin resistance is defined as the failure to prevent the occurrence of atherothrombotic ischaemic episodes in patients to whom it is administered. So far, there is no generally accepted method for the ex vivo evaluation of platelet activation or for assessing the degree of platelet activation following aspirin administration and data concerning the clinical impact of aspirin resistance are conflicting. For these reasons it is not possible to suggest specific guidelines for the treatment of patients who show high levels of platelet activation or a low level of platelet inhibition after treatment with aspirin. The aim of this review is to present data from laboratory and clinical studies that are related to resistance to aspirin, and to discuss the possible causes, the clinical significance, and the ways of managing such resistance at a clinical level.

Atherosclerosis is now generally accepted as an inflammatory disease, characterized by degenerative changes and extracellular accumulation of lipid and cholesterol. The evolving inflammatory reaction plays an important role in the initiation of atherosclerotic plaques and their destabilization, converting a chronic process into an acute disorder with an ensuing thrombo-embolism. Neovascularization has been, also, recognized as an important process for the progression of atherosclerotic plaques. In fact, vulnerable atherosclerotic plaque prone to rupture are characterized by an enlarged necrotic core containing an increased number of vasa vasorum, apoptotic macrophages, and more frequent intraplaque haemorrhage. Various functional roles have been assigned to intimal microvessels. This network of immature blood vessels is a viable source of intraplaque haemorrhage providing erythrocyte-derived phospholipids and free cholesterol. However, it is still challenging and controversial the relationship between the very process of angiogenesis and its causal association with the progression and complication of atherosclerosis. The selective targeting of neoangiogenesis poses a possible approach for the elimination of pre-existing and new growth of microvessels. The identification of target lesions is a critical issue, because current technologies have yet to achieve the goal of characterizing plaque morphology to the degree necessary to correctly identify rupture-prone lesions according to pathologic criteria. However, few imaging techniques can be used to detect the neovascularization within the atherosclerotic plaque in vivo. This review discusses the potential role of intraplaque angiogenesis as risk factor for plaque vulnerability.

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived cells, contributing to endothelial cell regeneration of injured vessels as well as neovascularization of ischemic lesions. EPC levels and function are inversely correlated with cardiovascular risk factors, can predict the occurrence of adverse events and atherosclerotic disease progression. Ischemia and inflammation are the primary triggers for EPC mobilization and homing, however, vascular trauma, as it occurs during surgical procedures, has been demonstrated to stimulate EPC mobilization even in absence of tissue ischemia. The effect of angioplasty on EPCs is not well defined, mainly because of the different and sometimes contrasting clinical results, due to low numbers of patients enrolled and to lack of standardization in evaluating EPCs. Aim of this review is to report recent results on the effect of EPC mobilization and homing after angioplasty, attempting to summarize them in a comprehensive model. The effect on EPCs of different kind of stents and the potential use of new stents able to attract EPCs will be also described. Results obtained in patients undergoing angioplasty in different vascular districts (coronary, peripheral and carotid) will be shown, together with the correlation between circulating progenitor cells and restenosis.

In this paper the authors deal with the main imaging techniques available to clinical cardiologists, with a brief overview of biophysical and biological aspects which are of relevance for the assessment of health effects related to the exposure of patients to both ionizing and non ionizing radiation. A main contribute is the reviewing published evidence on biological effects of radiation, trying to compose a balanced issue in order to increase awareness and knowledge about radiation exposure from cardiac imaging and implications for health risk.

Imaging and laboratory biomarkers are an essential support to modern practice of medicine, allowing a better identification, severity titration, staging and follow-up of atherosclerosis and heart failure disease. This review provides an overview of imaging, biochemical and genetic biomarkers used in clinical practice and for research purposes in order to evaluate the 4 different aspect of patient vulnerability to cardiovascular disease: arterial; blood; myocardial; metabolic vulnerability. Yet, no single perfect biomarker exists and there is wide room for optimization and integration between clinical evaluation and biomarker evaluation. In general, a targeted approach tailored on the individual patient should be preferred to a carpet diagnostic bombing, which will lead to an exorbitant multiplier of costs, risks and inappropriate testing.

Cardiovascular diseases represent a relevant problem worldwide. Data from World Health Organization (W.H.O.) demonstrate that they are one of the principle causes of death: 30% of all losses of human life throughout the world are due to heart diseases. Such data buries a substantial economic cost considering both the direct component, first of all the national health expense, and the indirect part, such as absenteeism rate, productivity loss, quality of life and, more generally, social costs. The future scenario pictured by the W.H.O. reveals a negative trend due to an increasing in the rate of morbidity and mortality especially in Emerging Countries. One of the solution to stem the costs - economic and not - connected to cardiovascular diseases is to empower the prevention activities overall the actions of primary prevention. This require a change in the traditional patient-physician relationship management model to get to an organizational model centred on patient and based on a proactive approach. In this perspective in the paper will be analysed the principal changes that occurred in the Italian national healthcare system and in particular the strategic plans and actions in theme of cardiovascular prevention.