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Cardiovascular risk factors and ischemic heart disease

Elosua, Roberto; Lluís-Ganella, Carla; Subirana, Isaac; Havulinna, Aki; Läll, Kristi; Lucas, Gavin; Sayols-Baixeras, Sergi; Pietilä, Arto; Alver, Maris and De León, Antonio Cabrera, et al. (2016) In Circulation: Cardiovascular Genetics 9(3). p.279-286
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... (More)

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 (β interaction) 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: GRS LDL ·GRS Triglycerides (β interaction =-0.096; SE=0.028) and nonpleiotropic GRS IHD ·GRS LDL (β interaction =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.

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publication status
published
subject
keywords
genetic association studies, genetic variation, regression analysis, risk assessment, risk factors
in
Circulation: Cardiovascular Genetics
volume
9
issue
3
pages
8 pages
publisher
American Heart Association
external identifiers
  • Scopus:84975722533
ISSN
1942-325X
DOI
10.1161/CIRCGENETICS.115.001255
language
English
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yes
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f37e6900-c7df-4f52-9cd2-304eb3614e78
date added to LUP
2016-07-20 13:32:12
date last changed
2016-10-27 13:08:44
@misc{f37e6900-c7df-4f52-9cd2-304eb3614e78,
  abstract     = {<p>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 (β interaction) 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: GRS LDL ·GRS Triglycerides (β interaction =-0.096; SE=0.028) and nonpleiotropic GRS IHD ·GRS LDL (β interaction =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.</p>},
  author       = {Elosua, Roberto and Lluís-Ganella, Carla and Subirana, Isaac and Havulinna, Aki and Läll, Kristi and Lucas, Gavin and Sayols-Baixeras, Sergi and Pietilä, Arto and Alver, Maris and De León, Antonio Cabrera and Sentí, Mariano and Siscovick, David and Melander, Olle and Fischer, Krista and Salomaa, Veikko and Marrugat, Jaume},
  issn         = {1942-325X},
  keyword      = {genetic association studies,genetic variation,regression analysis,risk assessment,risk factors},
  language     = {eng},
  month        = {06},
  number       = {3},
  pages        = {279--286},
  publisher    = {ARRAY(0xc5f0260)},
  series       = {Circulation: Cardiovascular Genetics},
  title        = {Cardiovascular risk factors and ischemic heart disease},
  url          = {http://dx.doi.org/10.1161/CIRCGENETICS.115.001255},
  volume       = {9},
  year         = {2016},
}