Association between future events of brain infarction and soluble levels of intercellular adhesion molecule-1 and C-reactive protein in patients with type 2 diabetes mellitus
Introduction
It is widely recognized that diabetic patients have a higher incidence of stroke [1], [2], [3]. In Japan, the incidence of cerebral infarctions in middle-aged and elderly people is higher than in Western countries and that of cardiovascular complications is increasing [3], [4]. A serious problem is that the complication of cerebrovascular disease is associated with a less favorable functional prognosis and not only increases mortality but also greatly reduces quality of life [5], [6]. As the elderly population gradually increases, it is predicted that the number of elderly diabetic patients will also increase. Strategies to prevent complications in diabetic patients will therefore become more important than they are now, since aging itself is a risk factor for vascular breakdown.
It has been reported that atherosclerosis is the result of inflammatory changes [7] and increased levels of inflammatory markers such as C-reactive protein (CRP) may reflect vascular complications and predict future events [8], [9], [10]. It is well known that adhesion molecules are expressed at the initial stage of atherosclerosis and play an important role in its progression [11]. Also, an association between increased levels of adhesion molecules and atherosclerotic disease has been reported, although their pathophysiological role and metabolism remain unclear [12], [13]. Furthermore, recent studies have found high rates of cardiovascular [14], [15] and cerebrovascular disease [16] in subjects who had increased levels of soluble adhesion molecules beforehand. Therefore, it is likely that hs-CRP and sICAM-1 are predictive markers of future events and they may possibly be used to assess the effectiveness of treatment.
In a previous study, we noted that levels of soluble adhesion molecules were higher in elderly diabetic patients with silent brain infarction (SBI) than those without SBI [17]. In addition, it was found that SBI had progressed in diabetic patients with high levels of sICAM-1, but not in those with high hs-CRP levels after 3 years follow-up. We also found that patients who developed symptomatic stroke had higher levels of sICAM-1 and hs-CRP at baseline [18]. Therefore, in this study we investigated the influence of the reciprocal association between hs-CRP and sICAM-1 on the risk of symptomatic brain infarction and monitored the changes in their levels during an average 8 years of follow-up.
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Patients
For this study, which were from 1995 to 2003, we recruited 179 consecutive patients with type 2 diabetes mellitus who were older than 45 years of age and had no history or clinical symptoms of cerebrovascular diseases (mean, 62.7 ± 8.2 years; range 46–81 years at baseline; 83 males, 61.4 ± 7.6 years; 96 females, 63.9 ± 8.6 years), from a group of outpatients at Chubu Rosai Hospital's Diabetic Center. The exclusion criteria at the time of registration were as follows: malignancy, chronic inflammatory
Comparisons of clinical and biochemical characteristics at baseline between type 2 diabetic patients with and without onset of brain infarction during follow-up (Table 1)
Significant differences were observed in duration of diabetes, systolic blood pressure, presence of SBI, treatment modality, microvascular complications and their severity, serum creatinine concentrations and levels of sICAM-1 and hs-CRP at baseline between diabetic patients with and without onset of brain infarction during follow-up. Also, a trend toward development of brain infarction was found for sex (male), diastolic blood pressure, and HbA1c levels at baseline. SBI was observed in 51 of
Discussion
It is well established that hypertension and aging are powerful risk factors for the development of stroke and this is irrespective of diabetes [20], [21]. Hypertension and diabetes mellitus often occur concomitantly and it is clear that when they are both present the risk of stroke increases dramatically [22]. In this study, hypertensive patients were the most likely to have a brain infarction and no patients with an average systolic pressure of less than 130 mmHg had one.
Diabetes mellitus has
Conflicts of interest
There are no conflicts of interest.
Acknowledgments
This research was supported by research funds to promote the hospital function of Japan Labor Health and Welfare Organization. We are grateful to N. Kajita for her excellent technical assistance.
References (39)
- et al.
Cellular adhesion molecules and atherogenesis
Am. J. Med.
(1999) - et al.
Adhesion molecules and atherosclerosis
Atherosclerosis
(2003) - et al.
Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy
Lancet
(1998) - et al.
Soluble adhesion molecules and C-reactive protein in the progression of silent cerebral infarction in patients with type 2 diabetes mellitus
Metabolism
(2006) - et al.
Glycaemia (haemoglobinA1c) and incident ischaemic stroke: the Atherosclerosis Risk in Communities (ARIC) study
Lancet Neurol.
(2005) - et al.
Circulating adhesion molecules ICAM-1 and VCAM-1 and incident coronary heart disease: the PRIME study
Atherosclerosis
(2003) - et al.
Relation between soluble intercellular adhesion molecule-1, statin therapy, and long-term risk of clinical cardiovascular events in patients with previous acute coronary syndrome (from PROVE IT-TIMI 22)
Am. J. Cardiol.
(2006) - et al.
Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity–mortality study
Lancet
(2007) - et al.
Diabetes and the risk of stroke: the Honolulu Heart Program
J. Am. Med. Assoc.
(1987) - et al.
Stroke in patients with diabetes mellitus
Diabetes Metab. Res. Rev.
(2004)
Incidence and risk factors for subtype of cerebral infarction in general population: the Hisayama study
Stroke
Type 2 diabetes and risk of non-embolic ischaemic stroke in Japanese men and women
Diabetologia
Medical complication after stroke: a multicenter study
Stroke
Prospective study of single and multiple lacunar infarcts using magnetic resonance imaging: risk factors, recurrence, and outcome in 175 consecutive cases
Stroke
The pathogenesis of atherosclerosis—an update
N. Engl. J. Med.
C-reactive protein and others of inflammation in the prediction of cardiovascular disease in women
N. Engl. J. Med.
C-reactive protein and future risk of thromboembolic stroke in healthy men
Circulation
C-reactive protein and risk of first-ever ischemic and hemorrhagic stroke in general Japanese population: the Hisayama study
Stroke
Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the atherosclerosis risk in communities (ARIC) study
Circulation
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