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CLINICAL STUDY: HYPERTENSION

Hyperinsulinemia and hemostatic abnormalities are associated with silent lacunar cerebral infarcts in elderly hypertensive subjects

Kazuomi Kario, MD, PhD, FACC^* , Takefumi Matsuo, MD, PhD, Hiroko Kobayashi, BA, Satoshi Hoshide, MD^* and Kazuyuki Shimada, MD, PhD^*

^* Department of Cardiology, Jichi Medical School, Tochigi, Japan
Department of Internal Medicine, Hyogo Prefectural Awaji Hospital, Hyogo, Japan
Integrative and Behavioral Cardiology Program, Zena and Michael A. Weiner Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York, USA

Manuscript received April 12, 2000; revised manuscript received September 28, 2000, accepted November 3, 2000.

Reprint requests and correspondence: Dr. Kazuomi Kario, Department of Cardiology, Jichi Medical School, 3311-159 Yakushiji, Minamikawachi, Kawachi, Tochigi 329-0431, Japan
tkario{at}kdd.net

OBJECTIVES

We sought to study the association of the silent cerebral infarct (SCI), a predisposing condition of stroke, with hyperinsulinemia and hemostatic abnormalities in older hypertensive subjects.

BACKGROUND

Hypertension is a powerful risk factor for stroke. However, the role of other risk factors for stroke in hypertensive subjects remains incompletely understood.

METHODS

We performed brain magnetic resonance imaging and measured cardiovascular risk factors, by administering the 75-g oral glucose tolerance test and measuring plasma insulin and hemostatic variables, in 123 asymptomatic hypertensive subjects (mean age 69 years).

RESULTS

At least one SCI was detected in 80 subjects (65%), and multiple SCIs were found in 48 subjects (39%). The presence of SCIs was associated with older age, higher levels of 24-h systolic blood pressure, 2-h insulin, thrombin-generation markers (prothrombin fragment 1+2 and thrombin-antithrombin complexes), plasminogen activator inhibitor-1 (PAI-1), D-dimer and von Willebrand factor (vWF), but not with plasmin-alpha₂-plasmin complex (PIC) levels. The 2-h insulin area under the curve (AUC) was positively correlated with PAI-1 and vWF levels (p < 0.01), and the PAI-1 level was negatively correlated with the PIC level (p < 0.02). Multiple logistic regression analysis revealed that age and the 2-h insulin AUC were significantly associated with SCIs, particularly those located in the subcortical white matter, and hemostatic abnormalities were significantly associated with the presence of multiple SCIs, particularly those located in the basal ganglia.

CONCLUSIONS

In older asymptomatic hypertensive subjects, hyperinsulinemia appears to be associated with lacunar-type SCIs, particularly those located in the subcortical white matter, and hemostatic abnormalities show an association with the presence of multiple SCIs, particularly those located in the basal ganglia.

Abbreviations and Acronyms   AUC = area under the curve   EC = endothelial cell   ELISA = enzyme-linked immunosorbent assay   F1+2 = prothrombin fragment 1+2   MRI = magnetic resonance imaging   OGTT = 75-g oral glucose tolerance test   PAI-1 = plasminogen activator inhibitor-1   PIC = plasmin-alpha2-plasmin inhibitor complex   SCI = silent cerebral infarct   TAT = thrombin-antithrombin complex   t-PA = tissue-type plasminogen activator   vWF = von Willebrand factor

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