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      Data in support of a central role of plasminogen activator inhibitor-2 polymorphism in recurrent cardiovascular disease risk in the setting of high HDL cholesterol and C-reactive protein using Bayesian network modeling

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          Abstract

          Data is presented that was utilized as the basis for Bayesian network modeling of influence pathways focusing on the central role of a polymorphism of plasminogen activator inhibitor-2 (PAI-2) on recurrent cardiovascular disease risk in patients with high levels of HDL cholesterol and C-reactive protein (CRP) as a marker of inflammation, “Influences on Plasminogen Activator Inhibitor-2 Polymorphism-Associated Recurrent Cardiovascular Disease Risk in Patients with High HDL Cholesterol and Inflammation” (Corsetti et al., 2016; [1]). The data consist of occurrence of recurrent coronary events in 166 post myocardial infarction patients along with 1. clinical data on gender, race, age, and body mass index; 2. blood level data on 17 biomarkers; and 3. genotype data on 53 presumptive CVD-related single nucleotide polymorphisms. Additionally, a flow diagram of the Bayesian modeling procedure is presented along with Bayesian network subgraphs (root nodes to outcome events) utilized as the data from which PAI-2 associated influence pathways were derived (Corsetti et al., 2016; [1]).

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          Thrombogenic factors and recurrent coronary events.

          Thrombosis is a pivotal event in the pathogenesis of coronary disease. We hypothesized that the presence of blood factors that reflect enhanced thrombogenic activity would be associated with an increased risk of recurrent coronary events during long-term follow-up of patients who have recovered from myocardial infarction. We prospectively enrolled 1045 patients 2 months after an index myocardial infarction. Baseline thrombogenic blood tests included 6 hemostatic variables (D-dimer, fibrinogen, factor VII, factor VIIa, von Willebrand factor, and plasminogen activator inhibitor-1), 7 lipid factors [cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, lipoprotein(a), apolipoprotein (apo)A-I, and apoB], and insulin. Patients were followed up for an average of 26 months, with the primary end point being coronary death or nonfatal myocardial infarction, whichever occurred first. The hemostatic, lipid, and insulin parameters were dichotomized into their top and the lower 3 risk quartiles and evaluated for entry into a Cox survivorship model. High levels of D-dimer (hazard ratio, 2.43; 95% CI, 1.49, 3.97) and apoB (hazard ratio, 1.82; 95% CI, 1.10, 3.00) and low levels of apoA-I (hazard ratio, 1.84; 95% CI, 1.10, 3.08) were independently associated with recurrent coronary events in the Cox model after adjustment for 6 relevant clinical covariates. Our findings indicate that a procoagulant state, as reflected in elevated levels of D-dimer, and disordered lipid transport, as indicated by low apoA-1 and high apoB levels, contribute independently to recurrent coronary events in postinfarction patients.
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            Cholesteryl ester transfer protein polymorphism (TaqIB) associates with risk in postinfarction patients with high C-reactive protein and high-density lipoprotein cholesterol levels.

            To investigate the roles of inflammation and a cholesteryl ester transfer protein (CETP) polymorphism potentially related to recent findings demonstrating coronary risk with increasing high-density lipoprotein cholesterol (HDL-C) level. A novel graphical exploratory data analysis tool allowed the examination of coronary risk in postinfarction patients relating to HDL-C and C-reactive protein levels. Results demonstrated a high-risk subgroup, defined by high HDL-C and C-reactive protein levels, exhibiting larger HDL particles and lower lipoprotein-associated phospholipaseA(2) levels than lower-risk patients. Subgroup CETP-associated risk was probed using a functional CETP polymorphism (TaqIB, rs708272). In the high-risk subgroup, multivariable modeling revealed greater risk for B2 allele carriers (less CETP activity) versus B1 homozygotes (hazard ratio, 2.41; 95% CI, 1.04 to 5.60; P=0.04). Within the high-risk subgroup, B2 allele carriers had higher serum amyloid A levels than B1 homozygotes. Evidence also demonstrates that CETP genotypic differences in HDL subfraction distributions regarding non-HDL-C and lipoprotein-associated phospholipaseA(2) may potentially relate to impaired HDL remodeling. Postinfarction patients with high HDL-C and C-reactive protein levels demonstrate increased risk for recurrent events. Future studies should aim at characterizing altered HDL particles from such patients and at elucidating the mechanistic details related to inflammation and HDL particle remodeling. Such patients should be considered in drug trials involving an increase in HDL-C level.
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              Serum glucose and triglyceride determine high-risk subgroups in non-diabetic postinfarction patients.

              A strategy was developed to identify subgroups at high risk for recurrent coronary events in non-diabetic postinfarction patients as a function of metabolic, inflammatory, and thrombogenic blood markers. A graphical screening technique for presumptively identifying high-risk subgroups from outcome prevalence maps was devised that was equally sensitive for all values of risk factors in contrast to traditional approaches where risk is presumed for the highest or the lowest values. Traditional statistical analysis confirms high risk in identified subgroups. Serum glucose and triglyceride served as bivariate search domain. Results demonstrated three high-risk subgroups. One was characterized as pre-diabetic; another as metabolic syndrome-enriched; and the third, with unexpectedly high risk, as normoglycemic and modestly hypertriglyceridemic. Within-subgroup risk as determined by Cox proportional hazards model gave for odds ratios and 95 percentile confidence intervals: glucose, 2.49 (1.17-5.33) in pre-diabetic; PAI-1, 3.95 (1.81-8.61) in metabolic syndrome-enriched; and BMI, 2.79 (1.17-6.63) and fibrinogen, 2.79 (1.29-6.04) in normoglycemic, modestly hypertriglyceridemic patients. We conclude that the graphical approach holds promise in screening for high-risk patient subgroups. Finding different within-subgroup predictors of risk underscores the notion of context-dependent risk, an observation that may be relevant for determining optimal use of emerging risk factors.
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                Author and article information

                Contributors
                Journal
                Data Brief
                Data Brief
                Data in Brief
                Elsevier
                2352-3409
                21 May 2016
                September 2016
                21 May 2016
                : 8
                : 98-104
                Affiliations
                [a ]Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
                [b ]Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
                [c ]Department of Medicine – Cardiology Unit, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
                Author notes
                [* ]Correspondence to: Department of Pathology and Laboratory Medicine University of Rochester Medical Center 601 Elmwood Avenue Rochester, NY 14642, USA. Tel.: +1 585 275 4907; fax: +1 585 273 3003. james_corsetti@ 123456urmc.rochester.edu
                Article
                S2352-3409(16)30314-6
                10.1016/j.dib.2016.05.026
                4887557
                27284570
                45a440c0-4bb9-48d8-b6e1-af47699338cf
                © 2016 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 April 2016
                : 5 May 2016
                : 14 May 2016
                Categories
                Data Article

                recurrent cardiovascular disease risk,pathophysiology,plasminogen activator inhibitor-2,bayesian network

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