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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
The relationship between risk factor levels and presence of coronary artery calcification is dependent on
S L Kardia1, M B Haviland, R E Ferrell
1Department of Human Genetics, University of Michigan, Ann Arbor 48109- 0618, USA. skardia@umich.edu
Insights
Genetic variations in Apolipoprotein E (ApoE) do not directly predict coronary artery calcification (CAC) in asymptomatic adults. However, ApoE genotype influences how traditional risk factors affect CAC development.
Area of Science:
- Genetics
- Cardiovascular Disease
- Biochemistry
Background:
- Coronary artery disease (CAD) genetics research aims to improve risk prediction.
- Identifying young, asymptomatic individuals with coronary atherosclerosis is crucial for early intervention.
- Coronary artery calcification (CAC) via electron-beam computed tomography is a sensitive marker for coronary atherosclerosis in asymptomatic individuals.
Purpose of the Study:
- To investigate if Apolipoprotein E (ApoE) genotypes improve the prediction of CAC beyond established risk factors.
- To determine if ApoE genotype modifies the association between traditional risk factors and CAC presence.
Main Methods:
- Logistic regression analysis was employed.
- A study population of 329 asymptomatic adults (169 women, 160 men) aged 20-59 was analyzed.
- The association between common ApoE genotypes (epsilon3/2, epsilon3/3, epsilon4/3) and CAC presence was assessed.
Main Results:
- ApoE genotypes did not significantly improve CAC prediction when added to models with individual risk factors (P>0.10).
- Significant genotype-dependent associations were observed: ApoE genotype influenced the relationship between body mass index, plasma lipids (total cholesterol, ApoB, triglycerides, ApoA1), and CAC in men and women.
- Specifically, ApoE genotype modulated the impact of body mass index, plasma total cholesterol, and ApoB in men, and body mass index, plasma triglycerides, ApoA1, and ApoE in women on CAC risk.
Conclusions:
- Apolipoprotein E genotype alone does not enhance the prediction of coronary artery calcification.
- ApoE genotype plays a role in modulating the influence of established cardiovascular risk factors on the development of CAC.
- Understanding these gene-environment interactions is key to refining CAD risk assessment.
Abstract:
An important research question in the study of the genetics of coronary artery disease (CAD) is whether information about genetic variation will improve our ability to predict CAD beyond established risk factors. This question is especially relevant to the goal of identifying young, asymptomatic adults with coronary atherosclerosis who would benefit most from interventions to reduce risk. Coronary artery calcification (CAC) detected by electron-beam computed tomography is a relatively new method for detecting coronary atherosclerosis in asymptomatic individuals that has been shown to be a more accurate indicator of coronary atherosclerosis in asymptomatic individuals than other noninvasive techniques. In a study of asymptomatic women (n=169) and men (n=160) between the ages of 20 and 59 representative of the Rochester, Minnesota population, we used logistic regression to ask whether the most common Apolipoprotein (Apo) E genotypes (epsilon3/2, epsilon3/3, and epsilon4/3) predict the presence of CAC. The addition of information about ApoE genotypes to logistic models containing each separate risk factor did not improve prediction of CAC (P>0.10 in both women and men). However, there was significant evidence (P<0.10) that associations between variation in the probability of having CAC and variation in body mass index, plasma total cholesterol, and plasma ApoB in men and body mass index, plasma triglycerides, plasma ApoA1, and plasma ApoE in women were dependent on ApoE genotype. Thus, variation in the gene coding for ApoE may play a role in determining the contribution of established risk factors to risk of CAC.
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