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Genetically Determined Height and Coronary Artery Disease | Journal Scan
Study Questions:
What are the underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD)?
Methods:
A genetic approach was used to investigate the association between height and CAD, using 180 height-associated genetic variants. The association between a change in genetically determined height of 1 standard deviation (SD) (6.5 cm) with the risk of CAD was tested in 65,066 cases (history of myocardial infarction [MI], coronary revascularization, or angiographic CAD) and 128,383 controls. Using individual-level genotype data from 18,249 persons, the authors also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, they analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes.
Results:
Average age was 57 years and 65% of cases had a history of an MI. There was a relative increase of 13.5% (p < 0.001) in the risk of CAD per 1-SD decrease in genetically determined heights. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 vs. quartile 1, 0.74 [p < 0.001]). Of the 12 risk factors that were studied, a significant association was only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). There were several overlapping pathways involving genes associated with both development and atherosclerosis.
Conclusions:
There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association.
Perspective:
Short stature has been known to be associated with an increase in clinical CAD and risk factors, as well as small coronary arteries, which may impact the significance of the volume of plaque. Among the associated variables include socioeconomic status, smoking during pregnancy, and birth weight. The degree to which these variables interact with the genes that are associated with height is not known.
Keywords: Coronary Artery Disease, Atherosclerosis, Biological Products, Cholesterol, Cholesterol, LDL, Coronary Angiography, Genotype, Lipoproteins, LDL, Myocardial Infarction, Risk Factors, Secondary Prevention, Triglycerides
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