Genetic determinants of blood pressure traits are associated with carotid arterial thickening and plaque formation in patients with type 2 diabetes

Abstract

Objectives: The aim of this study is to explore the contribution of genetically driven cardiometabolic risk factors for development of carotid arterial thickening in patients with type 2 diabetes. Methods: In total, 12 genetic risk scores for blood pressure, blood lipids and glycaemic traits were constructed. The genetic risk scores were tested for association with carotid intima-media thickness and plaques in patients with type 2 diabetes (n = 401) and in non-diabetic individuals (n = 648) and for association with glucose levels in two population-based cohorts (n = 1328 and n = 6161). Results: In patients with type 2 diabetes, the genetic risk scores for pulse pressure were positively associated with plaque formation (β = 0.036 ± 0.01 standard deviation/allele, p = 0.003). The genetic risk score for diastolic blood pressure was negatively associated with carotid intima-media thickness (β = –0.037 ± 0.01 standard deviation/allele, p = 0.005), although not significant after correction for multiple testing (p < 0.0042). In a meta-analysis of individuals with and without type 2 diabetes, the high-density lipoprotein genetic risk scores showed a trend towards an inverse association with carotid intima-media thickness and plaques, while the low-density lipoprotein genetic risk scores showed a trend towards a positive association with plaque formation but did reach the statistical threshold. Conclusion: Genetic loci for pulse pressure are associated with plaque formation among patients with type 2 diabetes, suggesting an underlying genetic contribution to arterial stiffening and atherosclerosis.