Pre-Diabetes Tied To Increased Stroke Risk With Nonvalvular Atrial Fibrillation

Stroke risk in patients with nonvalvular atrial fibrillation may be further increased by pre-diabetes, a new study suggests.

Researchers examined data on 44,451 adults (median age 75 years) with a first diagnosis of nonvalvular atrial fibrillation between 2010 and 2016. This included 17,754 people with diabetes mellitus as well as 6,574 people with pre-diabetes.

After a median follow-up of 38 months, incident rates of stroke per 100 person-years were 1.14 among normoglycemic adults, 1.40 among individuals with pre-diabetes, and 2.15 among people with diabetes.

After accounting for age, sex, socioeconomic status, BMI, estimated glomerular filtration rate, hypertension, congestive heart failure, previous stroke, previous transient ischemic stroke, vascular disease, and oral anticoagulant use, both pre-diabetes (adjusted hazard ratio 1.19) and diabetes (aHR 1.56) were significantly associated with incident stroke.

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"We know that some of the metabolic changes that lead to diabetes mellitus, mainly insulin resistance in peripheral tissue, increased circulating insulin levels and hyperglycemia can be present long before the diagnostic criteria for diabetes mellitus are met," said lead study author Dr. Louise Kezerle of Soroka University Medical Center in Beer Sheva, Israel, and Ben Gurion University of the Negev.

"This metabolic disarray can promote inflammation and influence clot formation, which is probably what leads to the increase in stroke risk that we observed in our study, in the setting of atrial fibrillation," Dr. Kezerle said by email.

While diabetes was significantly associated with mortality (aHR 1.47), researchers didn't find a significant association between pre-diabetes and mortality (aHR 0.98).

One limitation of the study is that researchers used data on lab tests for diabetes mellitus and pre-diabetes at the time of nonvalvular atrial fibrillation diagnosis, instead of a coded diagnosis in medical records. In addition, 20% of participants had not been previously screened for diabetes, and they might differ in some way from those who did receive screening, the authors note in Journal of the American College of Cardiology.

Still, if these results are confirmed by additional research, the findings might help to identify patients at increased risk for stroke who might benefit from anticoagulation treatments, the study team concludes.

"The most effective therapy to lower stroke risk in patients with atrial fibrillation is with oral anticoagulation, preferably with a direct oral anticoagulant," said Dr. Gregg Fonarow, director of the Ahmanson Cardiomyopathy Center and co-director of the preventive cardiology program at the David Geffen School of Medicine at the University of California, Los Angeles.

Lowering blood sugar in patients with established diabetes through certain medications has not lowered stroke risk, whereas other medications that better target the underlying cardiometabolic risk have had greater impact, Dr. Fonarow, who wasn't involved in the study, said by email.

"Additional studies will be needed as to whether or not pre-diabetes should be considered for inclusion in risk scores that are used to help guide whether or not an atrial fibrillation patient is eligible for oral anticoagulation," Dr. Fonarow said.

—Lisa Rapaport

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