Genetic Mapping Predicts Risk of Cardiovascular Events in People With Type 2 Diabetes

Risk scores based on genetic mapping were found to correlate with hypertensive blood pressure (BP) traits and an increased likelihood of adverse cardiovascular events, such as stroke, myocardial infarction, and cardiovascular death, in individuals with type 2 diabetes (T2D), according to results of a study published in Hypertension. The risk of adverse cardiovascular events in those with higher genetic risk scores were unchanged by intensive glycemic therapy approaches.

Researchers conducted a post hoc analysis of the National Institutes of Health’s ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (ClinicalTrials.gov Identifier: NCT00000620) to assess whether genetic variants influenced BP traits and adverse cardiovascular outcomes in individuals with T2D. Out of the 10,251 participants with T2D in the ACCORD trial, 6335 individuals had genetic data that were needed to calculate polygenic risk scores.

During the ACCORD trial, BP data were calculated using an average of 3 BP measurements with 5 minutes rest in between measurements. Overall, the median systolic blood pressure was 147 mm Hg, the median diastolic blood pressure was 83 mm Hg, and the median HbA_1C was 8.1%.

For the post hoc assessment, the researchers collected participant genotype data and compared these data with the Trans-OMICs Precision Medicine (TOPMed) Freeze 8 gene map, which consists of more than 1000 genetic variants known to affect blood pressure. The researchers calculated polygenic risk scores based on the number of matches between each participant’s DNA and the genetic variants known to influence BP. The greater the number of matches, the higher the risk score. The median polygenic risk score was 168.4 (range, 166.6-170.6).

After analyzing BP polygenic risk scores in relation to adverse cardiovascular outcomes, each degree of increase in the risk score was found to correlate with a 12% increased risk of cardiovascular events. Glycemic control therapy did not influence the BP polygenic risk scores, nor did it influence the primary outcome of cardiovascular risk prevention.

Study limitations included the pre-existing nature of the subset of participants available for analysis, as well as a lack of power to evaluate possible interactions due to the study’s post hoc design.

“These results invigorate the potential implications of [using] BP polygenic risk score in the primordial prevention of microvascular and macrovascular complications in T2D through early intensification of life-style measures such as healthy diet, exercise, smoking cessation, weight management, and BP control among those with high genetic risk,” the authors said.

This genetic risk assessment may especially benefit those with newly diagnosed T2D and those with prediabetes to encourage earlier adoption of a healthier lifestyle.