Does glycated hemoglobin have clinical significance in ischemic stroke patients?

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Abstract

Objectives

It has been suggested that patients with an elevated hemoglobin A1c (HbA1c) level have an increased risk of cardiovascular disease regardless of the presence of diabetes. However, an association between HbA1c and stroke has not yet been determined. In this study, our purpose was to examine whether HbA1c was independently associated with various types of cerebral vascular lesions in stroke patients.

Methods

A consecutive series of acute ischemic stroke patients were included for this analysis from October, 2002, to March, 2006. HbA1c was examined on admission, and MR imaging was performed for analysis of large artery diseases (LADs) and small artery diseases (SADs). Symptomatic or asymptomatic LAD was diagnosed by MR angiography, and SAD was classified as leukoaraiosis, microbleeds, or old lacunar infarctions.

Results

A total of 639 stroke patients were analyzed (diabetics, n = 247; non-diabetics, n = 392). There was no relationship between the level of HbA1c and any type of cerebrovascular lesion in the non-diabetic patients. In contrast, HbA1c showed a significant negative association with symptomatic LAD and leukoaraiosis in the diabetic patients using univariate analysis (p = 0.01 and p < 0.05, respectively). These associations did not remain significant, however, after adjustment for age and hypertension. This was, in part, because the HbA1c level in our diabetic population decreased gradually with age (p = 0.03).

Conclusions

Our results indicate that HbA1c is not associated with risk for various types of cerebrovascular lesions in ischemic stroke patients. The negative association between age and HbA1c in diabetic patients should be further investigated.

Introduction

It is well known that diabetes may contribute to an increased risk for cardiovascular and cerebrovascular disease including stroke [1], [2]. However, the findings from meta-analyses of the effects of hyperglycemia on stroke are contradictory. While a meta-analysis focusing on prospective cohort studies found that people with chronic hyperglycemia had an increased risk of microvascular complications, such as retinopathy, as well as myocardial infarction and stroke [3], another two meta-analyses and recent randomized controlled trials such as ACCORD, ADVANCE, and VADT found that lowering blood glucose did not significantly reduce the pooled incidence of stroke [4], [5], [6], [7], [8].

The HbA1c level reflects long-term glycemic control and is a more accurate and stable measure than fasting blood glucose levels; therefore, it is widely used in clinical practice to assess control of diabetes [9]. Observational analyses of data from the United Kingdom Prospective Diabetes Study (UKPDS) suggested HbA1c is positively associated with stroke risk [10], and a cohort study revealed that elevated HbA1c could be an independent risk factor for ischemic stroke in people with and without diabetes [11]. Furthermore, it was reported that HbA1c was independently associated with cerebral microbleeds in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) [12]. The relationship between cerebral microbleeds and diabetes, however, has been unclear [13]. We wondered whether glycated hemoglobin might influence microbleeds in only a specific disease group, such as CADASIL, or if it might be related to general ischemic stroke.

In the present study, we examined whether HbA1c had any clinical significance associated with ischemic stroke and whether it could be an independent risk factor of vascular lesions in the brain.

Section snippets

Subjects

From October, 2002, to March, 2006, we first collected 849 consecutive ischemic stroke patients who visited the department in our hospital (less than 7 days after onset). We excluded patients whose stroke mechanism was cardioembolism (n = 170) or other determined etiologies (n = 10). HbA1c was examined on admission, and patients were excluded if they did not have laboratory data for HbA1c (n = 30). Therefore, the final study population consisted of a total of 639 patients.

This study was approved by

Results

Of the 639 subjects included in this study, 438 were male (68.5%) and the mean age of the patients was 64.9 ± 11.1 years. There were 448 patients with hypertension (70.1%), 247 with diabetes (38.7%), 300 with dyslipidemia (46.9%), and 259 with a smoking history (40.5%). We divided subjects into two groups depending on the presence of diabetes (Table 1). Previous stroke history, increased FG and HbA1c level, dyslipidemia, and reduced high density lipoprotein (HDL) level were more common in the

Discussion

We found that HbA1c was not independently associated with any of the examined types of cerebrovascular lesions in ischemic stroke patients with and without diabetes. In our study, age was the most important risk factor for LAD; while male gender, hypertension, and dyslipidemia showed tendencies towards a relationship with LAD. In addition, age and hypertension were significantly related with a risk of leukoaraiosis. These results were similar to previous studies demonstrating differences in

Competing interests

None.

Acknowledgements

This study was supported by grants of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (A060171).

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