Optimum A1c to Prevent Events in Stroke Patients With Diabetes?

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For patients with diabetes who have had a stroke, glycated hemoglobin (A1c) level at the time of admission to the hospital was significantly associated with the risk for future vascular events in a new study.

The optimum range of admission A1c associated with a minimum risk for vascular events and stroke recurrence was estimated to be between 6.8% and 7.0%. The risk significantly increased above this level.

But the study also suggested that the optimum range of A1c associated with the lowest risk for future vascular events differed in accordance with the ischemic stroke subtype. The lowest range was with the small-vessel occlusion subtype.

“The result from the current study is in agreement with the previous reports that lowering the target level of HbA1c from 7% to 6% confers an additional benefit for preventing microvascular complications of diabetes, provided that the target can be safely achieved without hypoglycemia. Thus, a more intense glycemic control may be warranted to reduce the risk of recurrent small vessel occlusion,” the authors comment.

The study was published online in Neurology on September 29.

The authors, led by Moon-Ku Han, MD, Seoul National University College of Medicine, Seoul, Korea, note that guidelines recommend maintaining a target level of A1c <7.0%. A less stringent A1c target is recommended for elderly patients as well as those with established vascular disease, long-standing diabetes, or limited life expectancy.

They add that intensive glucose control with a target A1c level of <6.5% was shown to reduce the risk for microvascular events and that the risk for macrovascular complications was significantly increased when A1c >7.0% was used as a threshold.

“Current guidelines focus on identifying the characteristics of patients who may benefit more from intensive glucose control, but studies regarding the beneficial effects of intensive glucose control according to specific disease entities are lacking,” they state.

Although higher levels of A1c are associated with an increased risk for first-ever stroke, there is a lack of evidence regarding the optimum target level of A1c that minimizes the risk for cardiovascular events among patients with acute ischemic stroke. Moreover, there are several subtypes of ischemic stroke, and these have different pathogenic mechanisms. The effect of pre-stroke glucose control on cardiovascular events may differ in accordance with the ischemic stroke subtype, they suggest.

The current retrospective cohort study involved patients with diabetes who had had a transient ischemic attack or an acute ischemic stroke. The patients, who were included in the stroke registry of the Clinical Research Center for Stroke in Korea, were enrolled within 7 days of symptom onset,. The association between admission A1c and composite vascular events (stroke, myocardial infarction [MI], vascular death) during 1-year follow-up was estimated.

Of the 18,567 patients in the study, 1437 experienced composite vascular events during follow-up. Results of multivariable analysis showed that the risk for a vascular event significantly increased at an A1c threshold of 6.8% to 7.0%.

The risk for a future vascular event was 27% greater among patients whose pre-stroke A1c level was >7.0%, compared to those whose level on admission was <6.5%. The risk for recurrent stroke was 28% greater with baseline A1c levels >7.0% than with levels <6.5%.

The optimum range of A1c associated with minimal risks for vascular events was lower for the small-vessel occlusion subtype (6.6%) compared to the large-artery atherosclerosis (7.3%) or the cardioembolic subtype (7.4%).

“Ischemic stroke with small vessel occlusion subtype was more likely to benefit from intensive pre-stroke glucose control,” the authors state.

They point out that pathologically, the small-vessel occlusion stroke subtype “may be considered as a disease entity that is partway between the micro and macrovascular complications of diabetes.” They say that the results from the current study are in line with previous reports that lowering the target level of A1c from 7% to 6% confers an additional benefit for preventing microvascular complications of diabetes, provided that the target can be safely achieved without hypoglycemia.

“Thus, a more intense glycemic control may be warranted to reduce the risk of recurrent small vessel occlusion,” they add.

Commenting on the study for Medscape Medical News, Adam Kelly, MD, associate professor of neurology at the University of Rochester Medical Center, Rochester, New York, said the study’s strengths included use of a large national registry. Weaknesses included a relatively short follow-up period of 1 year.

“We have known that diabetes is associated with risk of stroke and other vascular complications, though this is an important study that focuses on the risk of recurrent stroke and other events, such as MI within patients who have already experienced a stroke,” he said. “The degree to which an elevated A1c and elevated fasting glucose at the time of an initial stroke influence the risk of future stroke at 1 year is more effectively quantified in this study and may lead to more effective treatment approaches and patient counseling on the importance of glycemic control.”

The study also provides “some justification for our usual recommendation of targeting an A1c of 7% or less for stroke prevention,” he said.

Kelly pointed out that it is still not well established that improvements in glycemic control after a first stroke result in a lower stroke risk.

“This study looked at initial A1c levels and subsequent stroke risk, but it did not definitively investigate whether, for example, going from an A1c of 7.5% to 6.5% over the course of 1 year after stroke translates to a lower risk of stroke and MI,” he said.

He added that the study underscores the fact that stroke patients who have diabetes, especially those with elevated A1c and/or fasting glucose levels at the time of presentation, represent a population that is at high risk for recurrent stroke and other vascular events.

“Because of this, these patients should also have intensive management of other risk factors that will hopefully lower the likelihood of another stroke, such as blood pressure control, lipid-lowering therapy, and smoking cessation,” he noted.

The authors have disclosed no relevant financial relationships.

Neurology. Published online September 29, 2021. Abstract

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