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      Current Therapies Focused on High-Density Lipoproteins Associated with Cardiovascular Disease

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          Abstract

          High-density lipoproteins (HDL) comprise a heterogeneous family of lipoprotein particles divided into subclasses that are determined by density, size and surface charge as well as protein composition. Epidemiological studies have suggested an inverse correlation between High-density lipoprotein-cholesterol (HDL-C) levels and the risk of cardiovascular diseases and atherosclerosis. HDLs promote reverse cholesterol transport (RCT) and have several atheroprotective functions such as anti-inflammation, anti-thrombosis, and anti-oxidation. HDLs are considered to be atheroprotective because they are associated in serum with paraoxonases (PONs) which protect HDL from oxidation. Polyphenol consumption reduces the risk of chronic diseases in humans. Polyphenols increase the binding of HDL to PON1, increasing the catalytic activity of PON1. This review summarizes the evidence currently available regarding pharmacological and alternative treatments aimed at improving the functionality of HDL-C. Information on the effectiveness of the treatments has contributed to the understanding of the molecular mechanisms that regulate plasma levels of HDL-C, thereby promoting the development of more effective treatment of cardiovascular diseases. For that purpose, Scopus and Medline databases were searched to identify the publications investigating the impact of current therapies focused on high-density lipoproteins.

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          Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies.

          J Hokanson, M. Austin (1996)
          Despite nearly 40 years of research, the role of plasma triglyceride as a risk factor for cardiovascular disease remains elusive. The objectives of the present study were to quantify the magnitude of the association between triglyceride and cardiovascular disease in the general population, and to determine whether this relationship is independent of high-density lipoprotein (HDL) cholesterol, using the semi-quantitative techniques of metaanalysis. Seventeen studies were selected for the analysis based on published reports of population-based, prospective studies, including 46413 men and 10864 women. To insure comparability, only studies reporting the association between fasting triglyceride levels and incident cardiovascular endpoints were included. Using standard meta-analysis calculations, relative risks (RR) and 95% confidence intervals (CI) were calculated and standardized with respect to a 1 mmol/l increase in triglyceride. Multivariable-adjusted RRs were determined for the six studies in men and two studies in women that reported adjustments for HDL cholesterol. For men and women, the univariate RRs for triglyceride were 1.32 (95% Cl 1.26-1.39) and 1.76 (95% Cl 1.50-2.07), respectively, indicating an approximately 30% increased risk in men and a 75% increase in women. Adjustment of HDL cholesterol and other risk factors attenuated these RRs to 1.14 (95% Cl 1.05-1.28) and 1.37 (95% Cl 1.13-1.66), respectively, which were still statistically significant values. Based on combined data from prospective studies, triglyceride is a risk factor for cardiovascular disease for both men and women in the general population, independent of HDL cholesterol. These finding demonstrate the necessity for clinical trials to evaluate whether lowering plasma triglyceride decreases the risk of cardiovascular disease.
          Article 0 comments Cited 328 times – based on 0 reviews     Review now
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            Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies.

            Juan Aviña-Zubieta, Jamie Thomas, Mohsen Sadatsafavi … (2012)
            To determine the magnitude of the risk of incident cardiovascular disease (CVD; fatal and non-fatal), including acute myocardial infarction (MI), cerebrovascular accidents (CVA) and congestive heart failure (CHF), in patients with rheumatoid arthritis (RA) compared to the general population through a meta-analysis of controlled observational studies. The authors searched the Medline, Embase, LILACS and Cochrane databases from their inception to June 2011. Observational studies meeting the following criteria were included: (1) prespecified RA criteria; (2) predefined CVD criteria for incident CVD (MI, CVA or CHF); (3) a comparison group; and (4) RR estimates, 95% CI or data for calculating them. The authors calculated the pooled RR using the random-effects model and tested for heterogeneity using the bootstrap version of the Q statistic. Fourteen studies comprising 41 490 patients met the inclusion criteria. Overall, there was a 48% increased risk of incident CVD in patients with RA (pooled RR 1.48 (95% CI 1.36 to 1.62)). The risks of MI and CVA were increased by 68% (pooled RR 1.68 (95% CI 1.40 to 2.03)) and 41% (pooled RR 1.41 (95% CI 1.14 to 1.74)). The risk of CHF was assessed in only one study (RR 1.87 (95% CI 1.47 to 2.39)). Significant heterogeneity existed in all main analyses. Subgroup analyses showed that inception cohort studies were the only group that did not show a significantly increased risk of CVD (pooled RR 1.12 (95% CI 0.97 to 1.65)). Published data indicate that the risk of incident CVD is increased by 48% in patients with RA compared to the general population. Sample and cohort type influenced the estimates of RR.
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              Dysfunctional HDL and atherosclerotic cardiovascular disease.

              Robert S. Rosenson, H Brewer, Benjamin Ansell … (2016)
              High-density lipoproteins (HDLs) protect against atherosclerosis by removing excess cholesterol from macrophages through the ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) pathways involved in reverse cholesterol transport. Factors that impair the availability of functional apolipoproteins or the activities of ABCA1 and ABCG1 could, therefore, strongly influence atherogenesis. HDL also inhibits lipid oxidation, restores endothelial function, exerts anti-inflammatory and antiapoptotic actions, and exerts anti-inflammatory actions in animal models. Such properties could contribute considerably to the capacity of HDL to inhibit atherosclerosis. Systemic and vascular inflammation has been proposed to convert HDL to a dysfunctional form that has impaired antiatherogenic effects. A loss of anti-inflammatory and antioxidative proteins, perhaps in combination with a gain of proinflammatory proteins, might be another important component in rendering HDL dysfunctional. The proinflammatory enzyme myeloperoxidase induces both oxidative modification and nitrosylation of specific residues on plasma and arterial apolipoprotein A-I to render HDL dysfunctional, which results in impaired ABCA1 macrophage transport, the activation of inflammatory pathways, and an increased risk of coronary artery disease. Understanding the features of dysfunctional HDL or apolipoprotein A-I in clinical practice might lead to new diagnostic and therapeutic approaches to atherosclerosis.
              Article 0 comments Cited 250 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 23 October 2018
                Publication date Collection: November 2018
                Volume: 23
                Issue: 11
                Electronic Location Identifier: 2730
                Affiliations
                [1 ]Instituto Nacional de Cardiología “Ignacio Chávez” Juan Badiano No. 1, Belisario Domínguez Sección 16, 14080 Tlalpan, Mexico City, Mexico; diego.estrada.luna@ 123456gmail.com (D.E.-L.); qfbelizabethcm@ 123456yahoo.es (E.C.-T.); opmendez@ 123456yahoo.com (O.P.-M.)
                [2 ]Facultad de Nutrición, Universidad Autónoma del Estado de Morelos, UAEM, Calle Río Iztaccihuatl S/N, Vista Hermosa, 62350 Cuernavaca, Morelos, Mexico; araceli.ortiz@ 123456gmail.com
                [3 ]Universidad de la Sierra Sur, UNSIS, Miahuatlán de Porfirio Díaz, 70800 Oaxaca, Mexico; lizmedinab@ 123456gmail.com
                [4 ]Área Académica de Medicina, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Carretera Actopan-Tilcuautla, Ex-Hacienda La Concepción S/N, San Agustín Tlaxiaca, 42160 Hidalgo, Mexico; jizquierdovega@ 123456gmail.com
                [5 ]Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Epigmenio Gonzalez 500, 76130 Queretaro, Mexico; asharma@ 123456itesm.mx
                [6 ]Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, 11340 Ciudad de México, Mexico; jccancinodiaz@ 123456hotmail.com
                [7 ]Dale Bumpers National Rice Research Center, Stuttgart, AR 72160, USA; drhelenmiller@ 123456gmail.com
                Author notes
                [* ]Correspondence: gbetanzo@ 123456uaeh.edu.mx ; Tel.: +52-771-7172000 (ext. 4312); Fax: +52-771-7172000 (ext. 5114)
                Author information
                https://orcid.org/0000-0003-0847-0261
                https://orcid.org/0000-0003-3600-249X
                https://orcid.org/0000-0002-9847-8824
                Article
                Publisher ID: molecules-23-02730
                DOI: 10.3390/molecules23112730
                PMC ID: 6278283
                PubMed ID: 30360466
                SO-VID: 7398d1d2-40e2-4880-a92b-003eff4d7fcc
                Copyright © © 2018 by the authors.
                License:

                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
                Date received : 12 September 2018
                Date accepted : 21 October 2018
                Categories
                Subject: Review

                Keywords: lipoproteins,hdl-c,paraoxonase,polyphenols
                Data availability:
                Keywords: lipoproteins, hdl-c, paraoxonase, polyphenols

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