Haptoglobin Gene Influences Blood Pressure Treatment Outcomes in Type 2 Diabetes

For individuals with type 2 diabetes, managing high blood pressure is critical in preventing serious cardiovascular diseases, including coronary artery disease and stroke. However, clinical trials evaluating intensive blood pressure control strategies have often presented conflicting results, leading to uncertainty about the optimal approach. Researchers hypothesized that an unmeasured biological factor might be at play, influencing how different individuals respond to treatment.

A recent re-analysis of data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial shed light on this mystery, pointing to the haptoglobin (Hp) phenotype as a key differentiator. By separating participants into groups based on their Hp phenotype – specifically Hp1 allele carriers versus those with the Hp2-2 phenotype – the study revealed a striking difference in treatment outcomes. Intensive blood pressure therapy was associated with a significantly lower risk of composite cardiovascular disease and stroke events, but crucially, this benefit was observed exclusively among Hp1 allele carriers.

This finding suggests that the varying responses to intensive blood pressure control seen in the original ACCORD trial and other studies could be largely attributed to an individual's haptoglobin genetics. As lead author Lavallée notes in the paper, "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." For patients with the Hp2-2 phenotype, intensive therapy did not show the same protective effect. This insight opens the door for a more personalized approach to treating hypertension in type 2 diabetes, where genetic screening could help identify which patients are most likely to benefit from aggressive blood pressure management. Further research is now needed to replicate these findings and explore their clinical applications.