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

Elosua Llanos, Roberto; Lluís Ganella, Carla, 1984-; Subirana Cachinero, Isaac; Havulinna, Aki; Läll, Kristi; Lucas, Gavin, 1977-; Sayols, Sergi; Pietilä, Arto; Alver, Maris; Cabrera de León, Antonio; Sentí Clapés, Mariano; Siscovick, David; Mellander, Olle; Fischer, Krista; Salomaa, Veikko; Marrugat de la Iglesia, Jaume

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, Robertoca
dc.contributor.author Lluís Ganella, Carla, 1984-ca
dc.contributor.author Subirana Cachinero, Isaacca
dc.contributor.author Havulinna, Akica
dc.contributor.author Läll, Kristica
dc.contributor.author Lucas, Gavin, 1977-ca
dc.contributor.author Sayols, Sergica
dc.contributor.author Pietilä, Artoca
dc.contributor.author Alver, Marisca
dc.contributor.author Cabrera de León, Antonioca
dc.contributor.author Sentí Clapés, Marianoca
dc.contributor.author Siscovick, Davidca
dc.contributor.author Mellander, Olleca
dc.contributor.author Fischer, Kristaca
dc.contributor.author Salomaa, Veikkoca
dc.contributor.author Marrugat de la Iglesia, Jaumeca
dc.date.accessioned 2016-07-08T08:34:53Z
dc.date.issued 2016
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.ca
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/pdfca
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.115.001255ca
dc.identifier.doi http://dx.doi.org/10.1161/CIRCGENETICS.115.001255
dc.identifier.issn 1942-3268
dc.identifier.uri http://hdl.handle.net/10230/27014
dc.language.iso engca
dc.publisher Lippincott Williams & Wilkinsca
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.115.001255ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.other Infart de miocardica
dc.subject.other Malalties -- Factors de riscca
dc.subject.other Cor -- Malalties -- Aspectes genèticsca
dc.title Cardiovascular Risk Factors and Ischemic Heart Disease: Is the Confluence of Risk Factors Greater Than the Parts? A Genetic Approachca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/acceptedVersionca

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