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      Nontraditional Cardiovascular Biomarkers and Risk Factors: Rationale and Future Perspectives

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          Abstract

          The primary prevention of cardiovascular (CV) disease depends on the capacity to identify subjects at higher risk long before the occurrence of CV clinical manifestations. Traditional risk factors do not cover fully prediction of individual risk. Moreover, there is an area of gray for patients at intermediate CV risk, which offers wide margins of improvement. These observations highlight the need for new additive tools for a more accurate risk stratification. An increasing number of candidate biomarkers have been identified to predict CV risk and events, although they generally give only a moderate increase when added to currently available predictive scores. The approach utilizing a relative small number of biomarkers in multiple combinations, but only weakly related to each other or unrelated, thus belonging to independent-pathways, and so able to catch the multidimensional characteristic of atherosclerosis, appears promising. We discuss vitamin D and bone turnover biomarkers, hepatitis C virus, and psycho-emotional factors that may reflect alternative pathways over those generally considered for atherosclerosis (e.g., aspects directly related to inflammation and thrombosis). These new biomarkers could facilitate a more accurate assessment of CV risk stratification if incorporated in the current risk assessment algorithms.

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          Most cited references82

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          Impact of Psychological Factors on the Pathogenesis of Cardiovascular Disease and Implications for Therapy

          Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.
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            The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology.

            Observational studies indicate that psychologic factors strongly influence the course of coronary artery disease (CAD). In this review, we examine new epidemiologic evidence for the association between psychosocial risk factors and CAD, identify pathologic mechanisms that may be responsible for this association, and describe a paradigm for studying positive psychologic factors that may act as a buffer. Because psychosocial risk factors are highly prevalent and are associated with unhealthy lifestyles, we describe the potential role of cardiologists in managing such factors. Management approaches include routinely screening for psychosocial risk factors, referring patients with severe psychologic distress to behavioral specialists, and directly treating patients with milder forms of psychologic distress with brief targeted interventions. A number of behavioral interventions have been evaluated for their ability to reduce adverse cardiac events among patients presenting with psychosocial risk factors. Although the efficacy of stand-alone psychosocial interventions remains unclear, both exercise and multifactorial cardiac rehabilitation with psychosocial interventions have demonstrated a reduction in cardiac events. Furthermore, recent data suggest that psychopharmacologic interventions may also be effective. Despite these promising findings, clinical practice guidelines for managing psychosocial risk factors in cardiac practice are lacking. Thus, we review new approaches to improve the delivery of behavioral services and patient adherence to behavioral recommendations. These efforts are part of an emerging field of behavioral cardiology, which is based on the understanding that psychosocial and behavioral risk factors for CAD are not only highly interrelated, but also require a sophisticated health care delivery system to optimize their effectiveness.
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              Worldwide vitamin D status.

              The aim of the present study is to summarize existing literature on vitamin D levels in adults in different continents and different countries worldwide. The best determinant of vitamin D status is the serum concentration of 25-hydroxyvitamin D (25(OH)D). Most investigators agree that serum 25(OH)D should be higher than 50 nmol/l, but some recommend higher serum levels. Traditional risk groups for vitamin D deficiency include pregnant women, children, older persons, the institutionalized, and non-western immigrants. This chapter shows that serum 25(OH)D levels are not only suboptimal in specific risk groups, but also in adults in many countries. Especially, in the Middle-East and Asia, vitamin D deficiency in adults is highly prevalent. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Biomolecules
                Biomolecules
                biomolecules
                Biomolecules
                MDPI
                2218-273X
                15 June 2018
                June 2018
                : 8
                : 2
                : 40
                Affiliations
                [1 ]Fondazione G. Monasterio CNR-Regione Toscana and Institute of Clinical Physiology, CNR San Cataldo Research Area, via Moruzzi, 1, 56124 Pisa, Italy; itraghella@ 123456ftgm.it (I.T.); alessia.pepe@ 123456ftgm.it (P.A.)
                [2 ]Institute of Clinical Physiology, CNR San Cataldo Research Area, via Moruzzi, 1, 56124 Pisa, Italy; mastorcif@ 123456ifc.cnr.it (F.M.); pingi@ 123456ifc.cnr.it (A.P.)
                Author notes
                [* ]Correspondence: cristina.vassalle@ 123456ftgm.it ; Tel.: +39-050-3153525; Fax: +39-050-3152166
                Article
                biomolecules-08-00040
                10.3390/biom8020040
                6023023
                29914099
                ed4abe63-8210-4b22-b20a-29a587a3a40a
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 May 2018
                : 13 June 2018
                Categories
                Review

                cardiovascular risk,biomarker,vitamin d,hepatitis c virus,bone turnover biomarkers,psycho-emotional factors

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