Research Article: Glycated Hemoglobin Independently Predicts Stroke Recurrence within One Year after Acute First-Ever Non-Cardioembolic Strokes Onset in A Chinese Cohort Study

Date Published: November 13, 2013

Publisher: Public Library of Science

Author(s): Shuolin Wu, Yuzhi Shi, Chunxue Wang, Qian Jia, Ning Zhang, Xingquan Zhao, Gaifen Liu, Yilong Wang, Liping Liu, Yongjun Wang, Yan Gong.

http://doi.org/10.1371/journal.pone.0080690

Abstract

Hyperglycemia is related to stroke. Glycated hemoglobin (HbA1c) can reflect pre-stroke glycaemia status. However, the information on the direct association between HbA1c and recurrence after non-cardioembolic acute ischemic strokes is rare and there is no consistent conclusion.

The ACROSS-China database comprised of 2186 consecutive first-ever acute ischemic stroke patients with baseline HbA1c values. After excluding patients who died from non-stroke recurrence and patients lost to follow up, 1817 and 1540 were eligible for 3-month and 1-year analyses, respectively. Multivariate Cox regression was performed to evaluate the associations between HbA1c and 3-month and 1-year stroke recurrence.

The HbA1c values at admission were divided into 4 levels by quartiles: Q1 (<5.5%); Q2 (5.5 to <6.1%); Q3 (6.1% to <7.2%); and Q4 (≥7.2%). The cumulative recurrence rates were 8.3% and 11.0% for 3 months and 1 year, respectively. In multivariate analyses, when compared with Q1, the adjusted hazard ratios (AHRs) were 2.83 (95% confidence interval (CI) 1.28-6.26) in Q3 and 3.71(95% CI 1.68-8.21) in Q4 for 3-month stroke recurrence; 3.30 (95% CI 1.31-8.34) in Q3 and 3.35 (95% CI 1.36-8.21) in Q4 for 1-year stroke recurrence. Adding fasting plasma glucose in the multivariate analyses did not modify the association: AHRs were 2.75 (95% CI 1.24-6.11) in Q3 and 3.67 (95% CI 1.59-8.53) in Q4 for 3-month analysis; AHRs were 3.08 (95% CI 1.10-8.64) in Q3 and 3.31(95% CI 1.35-8.14) in Q4 for 1-year analysis. A higher “normal” HbA1c level reflecting pre-stroke glycaemia status independently predicts stroke recurrence within one year after non-cardioembolic acute ischemic stroke onset. HbA1c is recommended as a routine test in acute ischemic stroke patients.

Partial Text

Stroke has surpassed heart disease and become the leading cause of mortality and adult disability in China. The cumulative rate of stroke is 11.2% [1], and the most recent data show that the cumulative acute ischemic stroke (AIS) recurrence rate within 1 year is 17.7% [2] in China, which is apparently higher than that in the Western countries [3]. Hyperglycemia or diabetes mellitus is a known risk factor for stroke recurrence [4,5]. Prediabetes has also widely been considered as a risk predictor for initial stroke [6,7] and impaired fasting glucose is associated with recurrent cardiovascular disease (CVD) [8]. An HbA1c level of ≥6.5% is one of the criteria for diagnosing diabetes mellitus [9], and a range of HbA1c from 5.7% to ≤6.4% was also recommended as the diagnostic criterion for prediabetes by American Diabetes Association in 2012 [10]. Moreover, the baseline HbA1c value at admission to hospital presents the mean plasma glucose level of the 2-3 months preceding acute stroke onset, which reflects pre-stroke glycaemia status (PSGS) [11]. Although HbA1c has been identified to directly associate with CVD incidence [12], the investigation on the relation between the PSGS (measured as HbA1c) and stroke recurrence is rare [13]. Whether the HbA1c level of lower than the HbA1c cutoff point for diabetes diagnosis (6.5%) is independently associated with stroke recurrence still remains unclear. The present study aimed to determine such an association among patients with first-ever non-cardioembolic acute ischemic strokes (AIS) within 1 year after stroke onset.

Of all 2186 patients with first-ever AIS, 1817 patients with non-cardioembolic AIS were available for 3-month follow-up, among which 2 patients died from recurrent stroke and 180 live patients experienced stroke recurrence. For 3-month stroke recurrence, there were 155 ischemic strokes, 21 intracerebral hemorrhages, 4 subarachnoid hemorrhage and 2 other vascular events. For 1-year stroke recurrence, there were 178 ischemic strokes, 31 intracerebral hemorrhages, 6 subarachnoid hemorrhages and 5 other vascular events. The cumulative rate was 8.3% for 3-month stroke recurrence. One thousand five hundred and forty patients with non-cardioembolic AIS were contacted at 1-year follow-up, of which there were 240 patients who experienced stroke recurrence, including 8 patients who died from recurrent stroke. The cumulative rate was 11.0% for 1-year stroke recurrence.

In the present study, an HbA1c level of ≥6.1% but not 6.5% independently increased risk for stroke recurrence within 1 year in patients with initial non-cardioembolic AIS. This is somewhat different with the traditional notion about the HbA1c threshold of risk. Usually the HbA1c value would be noticed until it reaches a level of ≥6.5% that is one of the criteria for diagnosing diabetes [9]. Diabetes has been acknowledged as one of the most essential risk predictors for stroke recurrence [5]. However, we found that a high “normal” HbA1c level was also related to stroke recurrence. Our findings indicated that when the HbA1c level achieved 6.1 to ≤7.2%, the risk for stroke recurrence in patients with first-ever non-cardioembolic AIS were significantly increased by 0.54 to 2.30 times higher than that in patients with the HbA1c level of <5.5%; when the HbA1c level reached 7.2% or higher, the risk was increased by 1.56 to 3.18 times higher than those with the HbA1c level of <5.5%. A higher “normal” HbA1c level of ≥6.1% at admission is an independent predictor for risk of stroke recurrence within 1 year after initial non-cardioembolic AIS onset. When the HbA1c value increases, the risk of stroke recurrence is increased compared with the patients with the HbA1c level of <5.5%. PSGS expressed as baseline HbA1c is a much more significant factor for stroke recurrence than post-stroke glycemic level. The HbA1c level should be recommended as a routine examination in all acute stroke patients for better predicting stroke prognosis. However, our findings cannot deduce that lowering the baseline HbA1c level can benefit decreasing the risk of stroke recurrence.   Source: http://doi.org/10.1371/journal.pone.0080690