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Cardiovascular Risk Factors and Ischemic Heart Disease: Is the Confluence of Risk Factors Greater Than the Parts? A Genetic Approach

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dc.contributor.author Elosua Llanos, Roberto
dc.contributor.author Lluís Ganella, Carla, 1984-
dc.contributor.author Subirana Cachinero, Isaac
dc.contributor.author Havulinna, Aki
dc.contributor.author Läll, Kristi
dc.contributor.author Lucas, Gavin, 1977-
dc.contributor.author Sayols, Sergi
dc.contributor.author Pietilä, Arto
dc.contributor.author Alver, Maris
dc.contributor.author Cabrera de León, Antonio
dc.contributor.author Sentí Clapés, Mariano
dc.contributor.author Siscovick, David
dc.contributor.author Mellander, Olle
dc.contributor.author Fischer, Krista
dc.contributor.author Salomaa, Veikko
dc.contributor.author Marrugat de la Iglesia, Jaume
dc.date.accessioned 2016-07-08T08:34:53Z
dc.date.issued 2016
dc.identifier.citation Elosua R, Lluís-Ganella C, Subirana I, Havulinna A, Läll K, Lucas G. et al. Cardiovascular Risk Factors and Ischemic Heart Disease: Is the Confluence of Risk Factors Greater Than the Parts? A Genetic Approach. Circ Cardiovasc Genet. 2016 Jun;9(3):279-86. DOI: 10.1161/CIRCGENETICS.115.001255
dc.identifier.issn 1942-3268
dc.identifier.uri http://hdl.handle.net/10230/27014
dc.description.abstract BACKGROUND: Cardiovascular risk factors tend to aggregate. The biological and predictive value of this aggregation is questioned and genetics could shed light on this debate. Our aims were to reappraise the impact of risk factor confluence on ischemic heart disease (IHD) risk by testing whether genetic risk scores (GRSs) associated with these factors interact on an additive or multiplicative scale, and to determine whether these interactions provide additional value for predicting IHD risk. METHODS AND RESULTS: We selected genetic variants associated with blood pressure, body mass index, waist circumference, triglycerides, type-2 diabetes mellitus, high-density lipoprotein and low-density lipoprotein cholesterol, and IHD to create GRSs for each factor. We tested and meta-analyzed the impact of additive (synergy index) and multiplicative (βinteraction) interactions between each GRS pair in 1 case-control (n=6042) and 4 cohort studies (n=17 794) and evaluated the predictive value of these interactions. We observed 2 multiplicative interactions: GRSLDL·GRSTriglycerides (βinteraction=-0.096; SE=0.028) and nonpleiotropic GRSIHD·GRSLDL (βinteraction=0.091; SE=0.028). Inclusion of these interaction terms did not improve predictive capacity. CONCLUSIONS: The confluence of low-density lipoprotein cholesterol and triglycerides genetic risk load has an additive effect on IHD risk. The interaction between low-density lipoprotein cholesterol and IHD genetic load is more than multiplicative, supporting the hazardous impact on atherosclerosis progression of the combination of inflammation and increased lipid levels. The capacity of risk factor confluence to improve IHD risk prediction is questionable. Further studies in larger samples are warranted to confirm and expand our results.
dc.description.sponsorship The MIGen Consortium was funded by grant R01 HL087676 (NIH, USA). The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195). This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Lippincott Williams & Wilkins
dc.relation.ispartof Circ Cardiovasc Genet. 2016 Jun;9(3):279-86
dc.rights © Lippincott Williams & Wilkins "This is a non-final version of an article published in final form inElosua R, Lluís-Ganella C, Subirana I, Havulinna A, Läll K, Lucas G. et al. Cardiovascular Risk Factors and Ischemic Heart Disease: Is the Confluence of Risk Factors Greater Than the Parts? A Genetic Approach. Circ Cardiovasc Genet. 2016 Jun;9(3):279-86. http://dx.doi.org/10.1161/CIRCGENETICS.115.001255
dc.subject.other Infart de miocardi
dc.subject.other Malalties -- Factors de risc
dc.subject.other Cor -- Malalties -- Aspectes genètics
dc.title Cardiovascular Risk Factors and Ischemic Heart Disease: Is the Confluence of Risk Factors Greater Than the Parts? A Genetic Approach
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1161/CIRCGENETICS.115.001255
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

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