Genetic predisposition to high blood pressure associates with cardiovascular complications among patients with type 2 diabetes: two independent studies

Abstract

Hypertension and type 2 diabetes (T2D) commonly coexist, and both conditions are major risk factors for cardiovascular disease (CVD). We aimed to examine the association between genetic predisposition to high blood pressure and risk of CVD in individuals with T2D. The current study included 1,005 men and 1,299 women with T2D from the Health Professionals Follow-up Study and Nurses' Health Study, of whom 732 developed CVD. A genetic predisposition score was calculated on the basis of 29 established blood pressure-associated variants. The genetic predisposition score showed consistent associations with risk of CVD in men and women. In the combined results, each additional blood pressure-increasing allele was associated with a 6% increased risk of CVD (odds ratio [OR] 1.06 [95% CI 1.03-1.10]). The OR was 1.62 (1.22-2.14) for risk of CVD comparing the extreme quartiles of the genetic predisposition score. The genetic association for CVD risk was significantly stronger in patients with T2D than that estimated in the general populations by a meta-analysis (OR per SD of genetic score 1.22 [95% CI 1.10-1.35] vs. 1.10 [1.08-1.12]; I² = 71%). Our data indicate that genetic predisposition to high blood pressure is associated with an increased risk of CVD in individuals with T2D.

FIG. 1.

Linear relationship between blood pressure genetic predisposition score and risk of CVD. Data are OR (solid lines) and 95% CI (dashed lines), adjusted for age, BMI, family history of myocardial infarction, smoking, menopausal status (women only), physical activity, alcohol intake, DASH diet score, nonnarcotic analgesics use, and supplemental folic acid use.

FIG. 2.

CVD risk per SD of the genetic predisposition score in patients with T2D and general populations. Risk ratios (RRs) per SD of the genetic predisposition score are given as hazard ratio in the NEURO-CHARGE study and ORs in other studies. The cardiovascular outcomes were stroke in the NEURO-CHARGE and SCG; CHD in the HPFS-NHS_CHD, CARDIoGRAM, C4D ProCARDIS, and C4D HPS; and CHD and stroke in patients with T2D from the HPFS and NHS. The RRs in the general populations (participant groups not restricted to patients with diabetes) were derived from a previous study (5), except for in the case of HPFS-NHS_CHD.