Clinical research
Patients with diabetes mellitus with ischemic stroke have a higher hemoglobin A1c level and a higher serum low-density lipoprotein cholesterol level than diabetics without ischemic stroke

Introduction
Diabetes mellitus is a major risk factor for ischemic stroke [1, 2]. The hemoglobin A1c level in patients with diabetes mellitus should be reduced to < 7.0% to reduce the incidence of ischemic stroke [3, 4]. Patients with diabetes mellitus should also be treated with statins to reduce the serum low-density lipoprotein (LDL) cholesterol level to < 70 mg/dl to reduce the incidence of ischemic stroke [3, 5-9]. The present study reports the prevalence of risk factors for ischemic stroke in 408 patients with diabetes mellitus and ischemic stroke and in 404 age-matched and gender-matched patients with diabetes mellitus without ischemic stroke. The present study also investigated whether diabetics with a hemoglobin A1c level < 7.0% and a serum LDL cholesterol < 70 mg/dl had a lower prevalence of ischemic stroke than diabetics with a hemoglobin A1c level > 7.0% and a serum LDL cholesterol > 70 and > 100 mg/dl.

Material and methods
The patients included 408 consecutive patients (218 men and 190 women), mean age 66 ±8 years, with diabetes mellitus and ischemic stroke and 404 consecutive age-matched and gender-matched patients with diabetes mellitus without ischemic stroke. There were no exclusion criteria. Ischemic stroke was diagnosed in all patients by a neurologist and confirmed by magnetic resonance imaging or brain computed tomography in all patients. Obstructive coronary artery disease was diagnosed in all patients if there was greater than 50% obstruction of at least 1 major coronary artery [10-12]. Blood samples for hemoglobin A1c levels and serum LDL cholesterol levels were drawn within 1 month prior to the ischemic stroke. The study duration was 2 years. The prevalence of whites and nonwhites, hypertension, current smoking, use of statins, body mass index ł 30 kg/m², carotid arterial disease, obstructive coronary artery disease, prosthetic valve, atrial fibrillation, hemoglobin A1c < 7.0%, serum LDL cholesterol < 100 mg/dl, and serum LDL cholesterol < 70 mg/dl was investigated in the patients with diabetes mellitus with ischemic stroke and without ischemic stroke.
Student’s t tests were used to analyze continuous variables. Chi-square tests were used to analyze dichotomous variables. Multivariate analysis was also performed.
This study was approved by the Institutional Review Board of New York Medical College.

Results
Table I shows the baseline characteristics of the patients with diabetes mellitus with and without ischemic stroke. No significant differences are present. Table II shows the prevalence of carotid arterial disease, obstructive coronary artery disease, prosthetic valve, and atrial fibrillation in the patients with diabetes mellitus with and without ischemic stroke. No significant differences are found.
Table III shows the prevalence of a hemoglobin A1c level < 7.0%, of a serum LDL cholesterol level < 100 mg/dl, and of a serum LDL cholesterol level < 70 mg/dl in the patients with diabetes mellitus with and without ischemic stroke. Table III also lists levels of statistical significance between the 2 groups. Multivariate analysis showed that a hemoglobin A1c level < 7.0%, of a serum LDL cholesterol level < 100 mg/dl, and of a serum LDL cholesterol level < 70 mg/dl were significant independent predictors of a reduced prevalence of ischemic stroke in the patients with diabetes mellitus (p < 0.001). These results were not affected by the use of cardiovascular drugs other than statins.

Discussion
An elevated hemoglobin A1c level is a risk factor for ischemic stroke [3, 4] and for coronary artery disease [3, 13]. The American Diabetes Association recommends reducing the hemoglobin A1c level in patients with diabetes mellitus to < 7.0% to reduce ischemic stroke and coronary events [3].
In the Atherosclerosis Risk in Communities (ARIC) Study, compared with adult diabetics in the lowest tertile of hemoglobin A1c, adult diabetics in the highest tertile of hemoglobin A1c had a 4.7 times significant increase in adjusted risk of stroke [4]. In the present study, the prevalence of a hemoglobin A1c level < 7.0% was significantly higher in patients with diabetes mellitus without ischemic stroke (55%) than in diabetics with ischemic stroke (35%) (p < 0.001).
Statins have been demonstrated to reduce ischemic stroke in patients with diabetes mellitus [6-9] and are recommended for the treatment of patients with diabetes mellitus [3, 5]. The lower the serum LDL cholesterol level achieved by statins, the greater the reduction in ischemic stroke [6-9].
In the present study, the prevalence of use of statins was similar in patients with diabetes mellitus with ischemic stroke (91%) and without ischemic stroke (93%). However, the prevalence of a serum LDL cholesterol < 100 mg/dl was 67% in the patients with diabetes mellitus without ischemic stroke and 40% in the diabetics with ischemic stroke (p < 0.001). The prevalence of a serum LDL cholesterol < 70 mg/dl was 31% in the patients with diabetes mellitus without ischemic stroke and 8% in the diabetics with ischemic stroke (p < 0.001). These data support reducing the serum LDL cholesterol with statins to < 70 mg/dl to decrease the incidence of ischemic stroke. The weakness of this study is that it was an observational study and not a randomized double-blind, placebo-controlled study.
In conclusion, the data from this observational study support reducing the hemoglobin A1c level in patients with diabetes mellitus to < 7.0% to reduce the incidence of ischemic stroke [3, 4] and support reducing the serum LDL cholesterol level to < 70 mg/dl to reduce the incidence of ischemic stroke [3, 5-9].

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