Each 6.5-cm decrease in adult height was linked to a 13.5% rise in the risk of coronary artery disease, investigators reported online in the New England Journal of Medicine.
An association between shorter height and lipid abnormalities could partially explain the finding, but the study also found overlapping biological pathways that contribute to both adult height and atherosclerosis, said Dr. Christopher Nelson at the University of Leicester in the United Kingdom and his associates. “Our study validates the epidemiologic observation of an inverse association between height and coronary artery disease,” they said.
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Past studies have linked shorter adult height with coronary artery disease (CAD) and relevant risk factors such as diabetes and high LDL cholesterol. To explore genetic reasons for the association, the investigators analyzed 180 single-nucleotide polymorphisms (SNPs) known to account for about 10% of the variation in adult height, using data from more than 18,000 individuals. They also modeled the link between CAD and final adult height among more than 128,300 controls and more than 650,000 individuals with a history of myocardial infarction, coronary revascularization, or angiographic coronary disease (N. Engl. J. Med. 2015 Apr. 8 [doi:10.1056/NEJMoa1404881]). Risk of CAD rose by 13.5% for each 6.5-cm (1 standard deviation) decrease in adult height, while having relatively more height-promoting SNPs was significantly protective against CAD, said the researchers. Among 12 risk factors for CAD, only LDL cholesterol and triglycerides achieved significance in the model, and these accounted for only about 30% of total CAD risk, they reported.
The analysis also revealed several genetic pathways that influenced adult height and atherosclerosis, including BMP- and TGF-beta-signaling pathways, axon-guidance pathways, and the STAT3 and IGF-I pathways, the investigators reported. “Taken together, these findings suggest that several overlapping and complex biologic pathways on the one hand influence development and height and on the other hand influence the risk of atherosclerosis through an effect on vascular biology and function,” they said.
Notably, the study found no significant inverse link between CAD and height among women. “Whether this represents a genuine difference in the effect of genetically determined height on the risk of CAD between men and women, or simply reflects the reduced power from the much smaller sample size available for analysis in women is unclear,” the investigators said.
The study was funded by the British Heart Foundation, the United Kingdom National Institute for Health Research, the European Union project CVgenes@target, and the Leducq Foundation. Several coauthors reported grant support from research foundations and/or receiving grants, lecture, consulting, or advisory board fees from pharmaceutical companies.