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Haptoglobin Phenotype and Cardiovascular Risk: The ACCORD Blood Pressure RCT
Samantha K Lavallée1,2,3, Allie S Carew1,2,3, Rachel A Warren1,3
1Department of Medicine (S.K.L., A.S.C., R.A.W., J.L,S., L.E.C.), Dalhousie University, Halifax, Nova Scotia, Canada.
Insights
Intensive blood pressure control reduced cardiovascular events in type 2 diabetes patients with Hp1 alleles but not Hp2-2. Haptoglobin phenotype may explain differing treatment responses in cardiovascular risk reduction.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Endocrinology
Background:
- Hypertension is a known risk factor for cardiovascular disease (CVD), coronary artery disease (CAD), and stroke in type 2 diabetes.
- Previous trials on intensive blood pressure control have yielded conflicting results regarding cardiovascular event reduction.
- The haptoglobin (Hp) phenotype might be an unmeasured biological factor influencing these outcomes.
Purpose of the Study:
- To investigate the association between intensive blood pressure control and cardiovascular events stratified by haptoglobin (Hp) phenotype.
- To explore whether Hp phenotype influences the effectiveness of intensive blood pressure management in reducing cardiovascular risk in type 2 diabetes.
Main Methods:
- Analysis of data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial.
- Utilized multivariable-adjusted Cox proportional hazards regression models.
- Stratified analysis comparing intensive versus standard blood pressure control in participants with the Hp2-2 phenotype and Hp1 allele carriers.
Main Results:
- Intensive blood pressure therapy significantly lowered composite CVD risk in Hp1 allele carriers (HR, 0.76), but not in Hp2-2 phenotype participants (HR, 1.12).
- A significant reduction in stroke risk was observed with intensive therapy in Hp1 carriers (HR, 0.53), but not in Hp2-2 participants.
- No significant differences in CAD risk reduction were found between the groups with intensive versus standard therapy.
Conclusions:
- The variable response to intensive blood pressure control observed in the ACCORD trial may be partly explained by differences in haptoglobin phenotypes.
- Further research and replication are necessary to confirm the role of Hp phenotypes in modulating cardiovascular outcomes in type 2 diabetes.
Background:
A relationship between hypertension and risk of incident cardiovascular disease, coronary artery disease, and stroke is widely reported in type 2 diabetes. However, trials testing intensive blood pressure control therapy versus standard therapy to reduce cardiovascular events have reported conflicting results, which could potentially be due to an unmeasured biological factor such as the common Hp (haptoglobin) phenotype.
Methods:
Multivariable-adjusted Cox proportional hazards regression models assessed the relationship between intensive (versus standard) blood pressure control therapy and risk of composite cardiovascular disease, coronary artery disease, and stroke events in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial in participants with the Hp2-2 phenotype (n=1527) separately from Hp1 allele carriers (n=2748).
Results:
Intensive blood pressure therapy (versus standard therapy) was associated with a lower risk of composite cardiovascular disease among Hp1 allele carriers (hazard ratio, 0.76 [95% CI, 0.59-0.99]) but not among participants with the Hp2-2 phenotype (hazard ratio, 1.12 [95% CI, 0.80-1.55]; P-interaction=0.07). No significant hazard ratio was observed for intensive therapy versus standard therapy on risk of coronary artery disease (Hp1 allele carriers: hazard ratio, 0.85 [95% CI, 0.67-1.08]; Hp2-2 phenotype: hazard ratio, 1.12 [95% CI, 0.84-1.51]; P-interaction=0.11). Intensive therapy was associated with a lower risk of stroke among Hp1 allele carriers (hazard ratio, 0.53 [95% CI, 0.31-0.91]) but not among Hp2-2 participants (hazard ratio, 0.70 [95% CI, 0.33-1.46]; P-interaction=0.56).
Conclusions:
The lack of an effect of intensive blood pressure control on composite cardiovascular disease events in the original ACCORD blood pressure trial may be explained in part by variation in response among the Hp phenotypes. Further study and replication are required.
Registration:
URL: https://www.clinicaltrials.gov/study/NCT00000620?id=NCT00000620; Unique identifier: NCT00000620.
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