Haptoglobin Phenotype, Intensive Blood Pressure Control, and Risk of Incident Cardiovascular Disease, Coronary Artery Disease, and Stroke within the Action to Control Cardiovascular Risk in Diabetes Randomized Control Trial

Abstract

Background: A relationship between hypertension and risk of CVD is widely reported in T2DM. However, clinical studies of intensive blood pressure control therapy (targeting a systolic pressure of less than 120mm Hg) or standard therapy (less than 140mm Hg) in patients with T2DM have reported conflicting results.

Objectives: To determine whether the effect of intensive versus standard blood pressure control therapy on risk of total CVD, CAD, and stroke events in the ACCORD blood pressure study depends on Hp phenotype. This study aims to determine these results in sex and race-based groups separately.

Methods: Multivariable-adjusted Cox proportional hazards regression models assessed the relationship between blood pressure control therapy and risk of total CVD, CAD, and stroke events in the ACCORD blood pressure trial in participants with the Hp2-2 phenotype (n=1,527) separately from Hp1 allele carriers (n=2,748). Analyses were then further stratified by sex and race-based groups.

Results: Intensive therapy was associated with a lower risk of total CVD among Hp1 allele carriers (aHR: 0.76; 95% CI: 0.59-0.99) but not among participants with the Hp2-2 phenotype (1.12; 0.80-1.55, p interaction=0.07). No reduced risk was observed for intensive therapy versus standard therapy and risk of CAD. Compared to standard, intensive therapy was associated with a lower risk of stroke among Hp1 allele carriers (0.53; 0.31-0.91) but not among Hp2-2 (0.70; 0.33-1.46; p-interaction=0.56). Phenotype frequencies were only in HWE in White and Hispanic race-based groups, indicating that our findings need to be interpreted with caution.

Conclusions: Haptoglobin phenotype influence may help explain the lack of a significant effect of intensive blood pressure control in the original ACCORD blood pressure trial. Hp phenotype characterization could allow personalized recommendations for blood pressure control to improve cardiovascular outcomes. Further study and replication are required.