Evidence map›Paper›PMID 27103211›Full record

SynthesisCirculation. Cardiovascular genetics2016

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

Roberto Elosua, Carla Lluís-Ganella, Isaac Subirana, Aki Havulinna, Kristi Läll, Gavin Lucas, Sergi Sayols-Baixeras, Arto Pietilä, Maris Alver, Antonio Cabrera de León and 6 more

Open access · diamondAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Circulation. Cardiovascular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.0field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 7 institutions in 4 countries.

Roberto ElosuaFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.). relosua@imim.es.
Carla Lluís-GanellaFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Isaac SubiranaFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Aki HavulinnaFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Kristi LällFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Gavin LucasFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Sergi Sayols-BaixerasFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Arto PietiläFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Maris AlverFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Antonio Cabrera de LeónFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Mariano SentíFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
David SiscovickFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Olle MellanderFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Krista FischerFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Veikko SalomaaFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
Jaume MarrugatFrom the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna, Spain (A.C.d.L.); Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain (M.S.); The New York Academy of Medicine (D.S.); and Skåne University Hospital Clinical Research Center, Malmö, Sweden (O.M.).
New York Academy of Medicine · USCentre for Biomedical Network Research on Rare Diseases · ESUniversidad de La Laguna · ESUniversity of Tartu · EECentro de Investigación Biomédica en Red de Epidemiología y Salud Pública · ESFinnish Institute for Health and Welfare · FIPompeu Fabra University · ES

Funding

A Genome-wide Association Study for Early-Onset Myocardial InfarctionR01HL087676 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ALTSHULER, DAVID · 2007 to 2009
$4.7M
SLEEP AND ENTRAINMENT OF SCN FUNCTIONR01HL064278 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI STROHL, KINGMAN PERKINS · 1999 to 2002
$871k
THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–
NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N02 HL064278NHLBI NIH HHS R01 HL087676
6 · The paper itself

Abstract

backgroundCardiovascular 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

resultsWe 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.

conclusionsThe 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.

Indexed as

Polymorphism, Single NucleotideBlood PressureBody Mass IndexCase-Control StudiesDiabetes Mellitus, Type 2DyslipidemiasGenetic Association StudiesGenetic MarkersGenetic Predisposition to DiseaseHumansHypertensionLipidsMyocardial IschemiaObesityPhenotypeRisk AssessmentGenetic MarkersLipidsgenetic association studiesgenetic variationregression analysisrisk assessmentrisk factors

Identifiers

PMID27103211
PMCPMC4917423
OpenAlexW2338165790

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.