Genetic hyperglycemia increases risk for CAD

A genetic predisposition for hyperglycemia increases the odds of developing coronary artery disease independent of type 2 diabetes and other risk factors for coronary artery disease, according to data published in Diabetes Care.

“Epidemiologic studies have demonstrated that the relation between glycemia and CAD risk starts within the normal blood glucose range,” Jordi Merino, PhD, of the diabetes unit and Center for Genomic Medicine at Massachusetts General Hospital, Boston, and colleagues wrote. “Yet, randomized clinical trials that successfully lowered glucose levels and delayed the onset of type 2 diabetes in participants with prediabetes have had mixed effects on cardiovascular protection.”

The researchers performed a Mendelian randomization analysis using data from meta-analyses of genome-wide association studies on CAD (63,746 case subjects; 130,681 control subjects) and fasting glucose (133,010 participants without diabetes). Patients were described as having predominantly European ancestry. Merino and colleagues excluded glucose-increasing variants related to type 2 diabetes, as well as variants with pleiotropic effects on other CAD risk factors.

The researchers reported finding 12 fasting glucose-raising genetic variants that were not associated with type 2 diabetes. A fasting glucose increase of 1 mmol/L increased a patient’s odds of CAD by 43% (OR = 1.43; 95% CI, 1.14-1.79), Merino and colleagues wrote. This association remained even after the researchers excluded variants for heterogeneity and pleiotropic effects on other risk factors for CAD (OR = 1.33; 95% CI, 1.02-1.73). Researchers reported no association between the 12 fasting glucose-raising genetic variants and risk for type 2 diabetes (OR = 1.05; 95% CI, 0.91-1.23).

“Our findings quantify the causal relationship between increased [fasting glucose] and CAD risk beyond the genetic effect of type 2 diabetes and other major CAD risk factors,” the researchers wrote. “Our results provide additional evidence for the design and interpretation of clinical trials of interventions specifically designed to lower glycemia on CAD outcomes.” – by Andy Polhamus

Disclosure: The researchers report no relevant financial disclosures.