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Biomedical subjects

Takami Miki

Publications and source records attributed to Takami Miki.

At least 55 records · Page 3Linked to original sources

Platelet P-selectin expression is associated with atherosclerotic wall thickness in carotid artery in humans.

BACKGROUND: Recent genetic animal models reveal important roles of platelet P-selectin on progression of atherosclerosis. In the present study, we examine the relation between platelet P-selectin expression and atherosclerotic parameters in 517 subjects. METHODS AND RESULTS: Unrelated subjects (n=517; 235 male and 282 female), including 187 with type 2 diabetes, 184 with hypertension, and 366 with hyperlipidemia, were enrolled in the study. P-selectin expression was determined by whole-blood flow cytometry. Arterial stiffness (stiffness index beta) and arterial wall thickness (intima-media thickness [IMT]) were determined by carotid ultrasound. P-selectin expression was significantly and positively correlated with carotid IMT and stiffness index beta. Multiple regression analyses showed that the association of the percentage of P-selectin-positive platelets with carotid IMT was independent of other clinical factors. Moreover, the percentage of P-selectin-positive platelets was higher in subjects with carotid plaque and was an independent factor associated with occurrence of carotid plaque analyzed by multiple logistic regression analysis. Finally, the percentage of P-selectin-positive platelets was positively associated with age, body mass index, systolic and diastolic blood pressure, and HbA1c and inversely associated with HDL cholesterol. CONCLUSIONS: Platelet P-selectin is independently associated with atherosclerotic arterial wall changes in human subjects.

Age Factors↗

Clinical usefulness of measurements of urinary deoxypyridinoline (DPD) in patients with postmenopausal osteoporosis receiving intermittent cyclical etidronate: advantage of free form of DPD over total DPD in predicting treatment efficacy.

Deoxypyridinoline (DPD) in urine, which reflects systemic bone resorption, is considered useful for assessing the effects of osteoporosis treatment. However, there are various methods of measuring DPD in urine but have been few comparative studies of the effectiveness of these methods. In this study, we investigated 94 postmenopausal women (63 patients administered with intermittent cyclical etidronate (ICE), and 31 control patients) focusing on total DPD and free DPD, measured by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA), respectively. For other metabolic bone markers, i.e., tartrate-resistant acid phosphatase (TRAP), bone-specific alkaline phosphatase (BAP), and osteocalcin (OC), we also investigated the ability of these markers to predict increases in bone mineral density (BMD), by employing receiver operating characteristic (ROC) analysis in relation to increasing BMD following ICE therapy, and we determined the usefulness of the different metabolic bone markers, using the signal-noise ratio derived from the mean significant change (MSC), which is double the day-to-day coefficient of variation in healthy volunteers. In the same way, we defined a significant change in BMD as double the mean change in BMD for 6 months after the initiation of observation in the control group, and we used this value as the cutoff value for ROC analysis. It was found that the assessment of urinary DPD was useful for assessing the treatment efficacy of ICE, and the assessment of changes at week 12 of therapy was most effective. In order to recognize changes in metabolic bone markers when the MSC is considered as the cutoff value, it is useful to assess the change in total DPD by HPLC. However, in order to predict increases in BMD 6 months or more after the initiation of ICE, it seems more effective to measure free DPD by ELISA. We conclude, therefore, that the measurement of free DPD by ELISA is more useful, especially when treatment efficacy of ICE is clinically predicted in individual patients with osteoporosis.

Aged↗

Risk factors for osteoporosis in men.

We evaluated the risk factors for osteoporosis in men. The subjects of this study consisted of 686 healthy middle-aged (40-59 years) men who had undergone bone mineral density (BMD) measurement and medical examination, including physical strength. BMD of L2-4 was measured at the anterior-posterior position, using dual X-ray absorptiometry. Physical investigations, such as height, weight, and physical strength, were carried out on the examination day. Details of tobacco and alcohol consumption, exercise, and food intake were described on a questionnaire completed by the subjects. Sixty-five (9.5%) of the 686 subjects had a BMD less than 2.5 SD below the peak bone mass (PBM), 182 (26.5%) had a BMD between 1 SD and 2.5 SD below the PBM; and 439 (64.0%) had a BMD no less than 1 SD below the PBM. Body mass index (BMI) and leg strength were significant positive determinants of BMD, and smoking was a significant negative determinant on multiple regression analysis, with a coefficient of determination of 9.5%. Calcium intake, exercise, and alcohol consumption were not significant determinants of BMD. These results suggest that poor lifestyle behaviors (i.e., smoking) accelerate the reduction of bone density.

Absorptiometry, Photon↗

Vitamin K(2) (menaquinone 4) reduces serum undercarboxylated osteocalcin level as early as 2 weeks in elderly women with established osteoporosis.

Twenty elderly osteoporotic women with vertebral fracture(s) were randomly allocated to two groups; women in the MK(4) group received calcium with menaquinone 4 (MK(4)) at a dose of 45 mg/day for 2 weeks, and women in the control group received calcium alone for the same period. Serum intact osteocalcin (OC) and undercarboxylated osteocalcin (uc-OC) levels were measured by immunoradiometric assay and enzyme immunoassay, respectively, at baseline and on the 7th and 14th days following the start of the treatment. There were no differences in the baseline data including age, weight, phylloquinone, menaquinone 4, menaquinone 7, OC, and uc-OC levels between the MK(4) group and the control group. Administration of MK(4) significantly raised the MK(4) level from 0.20 +/- 0.10 (mean +/- SE) pg/ml to 15.09 +/- 5.62 pg/ml ( P < 0.04), and reduced serum uc-OC levels from 2.80 +/- 0.93 ng/ml to 1.76 +/- 0.56 ng/ml ( P < 0.05) at the end of the study, respectively. No significant changes in these levels were observed in the control group. Serum OC levels were stable during the period in both groups. In this randomized prospective study, the MK(4) group shows a reduction in the serum uc-OC level within 2 weeks without any significant change in OC, suggesting that the uc-OC is changed to carboxylated OC. This early effect of MK(4) on bone metabolism may be estimated by the measurement of serum uc-OC in elderly osteoporotic women with vertebral fractures.

Aged↗

Arterial wall stiffness is associated with peripheral circulation in patients with type 2 diabetes.

The prevalence of peripheral vascular disease (PVD) in diabetic patients is manyfold higher than that of age- and sex-matched nondiabetic subjects. This study was designed to evaluate the relationship between quantitatively determined peripheral circulation in the lower extremities and arterial wall thickness or stiffness in 68 patients with type 2 diabetes. Peripheral circulation during treadmill-exercise was monitored by transcutaneous oxygen tension (TcPO2) and was expressed as percentage of post-exercise TcPO2 adjusted by that of pre-exercise (TcPO2 index). Arterial wall thickness (intima-media thickness; IMT) and stiffness (stiffness beta) were measured by ultrasonography. TcPO2 index was negatively (r=-0.350, P=0.0007) correlated with stiffness beta, not with IMT, of the femoral artery. In patients without insulin therapy (n=52), both fasting plasma insulin concentration (r=-0.323, P=0.0023) and HOMA IR, an insulin resistance index, (r=-0.281, P=0.0084) were negatively correlated with TcPO2 index. Multiple regression analyses showed that association of stiffness beta of the femoral artery or HOMA IR with the TcPO2 index was independent of other factors including age, smoking index, ankle brachial pressure index and IMT of femoral artery. Thus, arterial wall stiffness of femoral artery appears to be a major determinant of peripheral circulation in patients with type 2 diabetes.

Age Factors↗

Non-high-density lipoprotein cholesterol (non-HDL-C) as a predictor of cardiovascular mortality in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) often show lipid abnormalities that may promote atherosclerosis. Although the standard lipid marker is low-density lipoprotein cholesterol (LDL-C) in official recommendations, the need of fasting blood sampling has prevented routine screening for plasma lipids in hemodialysis patients. METHODS: We therefore evaluated the power of non-high-density lipoprotein cholesterol (non-HDL-C) in predialysis (non-fasting) serum as a predictor of cardiovascular mortality in a cohort of 525 hemodialysis patients. RESULTS: During the mean follow-up of 64 months, 120 deaths, including 44 fatal cardiovascular events, occurred. Patients in the highest tertile of non-HDL-C (137 to 285 mg/dL) had a significantly higher risk for cardiovascular mortality (HR, 3.065; 95% CI, 1.357 to 6.925; P = 0.007) [correction] in a univariate Cox analysis. The association between non-HDL-C and cardiovascular mortality remained significant in multivariate Cox models, which included HDL-C, age, gender, duration of hemodialysis, blood pressure, presence of diabetes mellitus, serum albumin, C-reactive protein, and body mass index. CONCLUSION: Non-HDL-C in predialysis serum was a significant and independent predictor of cardiovascular mortality in hemodialysis patients. Non-HDL-C may be a useful marker for risk assessment in routine practice, although predictive powers of this and the standard fasting LDL-C should be compared in future studies.

Adult↗

The association of antibodies against oxidized low-density lipoprotein with atherosclerosis in hemodialysis patients.

BACKGROUND: Immune response to oxidized low-density lipoprotein (oxLDL) may modulate atherogenesis. We recently reported that a high titer of serum anti-oxLDL antibody was an independent predictor of a low risk for cardiovascular death in patients with end-stage renal disease (ESRD). In the present study, we examined a possible association between anti-oxLDL antibody titer and arterial wall thickness in ESRD patients. METHODS: The subjects were 103 ESRD patients treated with hemodialysis. A high resolution B-mode ultrasound method was used to measure intima-media thickness of carotid (CA-IMT) and femoral arteries (FA-IMT). RESULTS: In univariate analysis, anti-oxLDL antibody showed a significant negative correlation with FA-IMT. The inverse association between anti-oxLDL antibody and FA-IMT remained significant in multiple regression analysis, including age, gender, blood pressure, plasma lipids, smoking, C-reactive protein, calcium-phosphate product, serum albumin, body mass index, and duration of dialysis as covariates. The antibody titer showed an inverse trend with CA-IMT without statistical significance. CONCLUSION: These results show for the first time that titer of anti-oxLDL antibody is an independent factor inversely associated with arterial thickness in ESRD, supporting the concept that immunity against oxLDL plays an anti-atherogenic role.

Adult↗

Intima-media thickness of carotid artery predicts cardiovascular mortality in hemodialysis patients.

BACKGROUND: Cardiovascular disease is the leading cause of death in patients with end-stage renal disease (ESRD). Previous studies showed that patients with ESRD had increased intima-media thickness of the carotid artery (CA-IMT). In the present study, we examined whether CA-IMT would predict cardiovascular mortality in patients with ESRD. METHODS: The cohort consisted of 438 patients with ESRD treated with hemodialysis. CA-IMT was measured by high-resolution B-mode ultrasonography. RESULTS: During the follow-up period of 30 months, 82 deaths, including 44 cardiovascular fatal events, occurred. Compared with those with CA-IMT less than 1.0 mm, those with moderately increased CA-IMT (1.0 to 2.0 mm) and those with severely increased CA-IMT (>or=2.0 mm) showed a significantly greater risk for death from cardiovascular causes; odds ratios were 3.17 (95% confidence interval [CI], 1.41 to 7.17; P = 0.005) and 10.20 (95% CI, 3.67 to 28.3; P < 0.0001), respectively, in a multivariate Cox analysis including age, sex, duration of hemodialysis therapy, presence of diabetes mellitus, blood pressure, body mass index, and high-density lipoprotein and non-high-density lipoprotein cholesterol levels as covariates. Conversely, CA-IMT was not significantly associated with noncardiovascular mortality. CONCLUSION: These results indicate that increased CA-IMT is an independent predictor of cardiovascular mortality in the hemodialysis population.

Adult↗

Preferential stiffening of central over peripheral arteries in type 2 diabetes.

Arterial stiffness affects cardiac functions, peripheral circulation, and cardiovascular mortality. We examined whether arterial stiffness in different regions is equally affected by diabetes and other factors. The subjects were 161 patients with type 2 diabetes and 129 healthy subjects comparable in age and sex. Arterial stiffness was evaluated by measuring pulse wave velocity (PWV) in the heart-carotid, heart-brachial, heart-femoral, and femoral-ankle segments using an automatic device. The diabetic patients had greater PWV than the healthy subjects in the four arterial regions, and the effect of diabetes on PWV was greater in the heart-carotid and heart-femoral segments (central) than in the heart-brachial and femoral-ankle regions (peripheral). PWV increased with age in the four arterial regions, and the effect of age on PWV was greater in the central than in peripheral arteries. In multiple regression analysis, age and systolic blood pressure had significant impacts on PWV of the four regions, whereas diabetes was significantly associated only with PWV of the central arteries. In contrast, sex was associated with PWV of the peripheral arteries. Thus, type 2 diabetes had greater impact on PWV of the central arteries, and different factors were involved in PWV among different arterial regions.

Adult↗

Factors affecting progression of renal failure in patients with type 2 diabetes.

OBJECTIVE: Hyperglycemia and hypertension are known to be risk factors for the development of proteinuria in patients with diabetes. Little is known, however, about predictors of progression of renal failure in diabetic patients. RESEARCH DESIGN AND METHODS: We investigated factors affecting progression of renal failure by measuring the doubling of serum creatinine (s-Cr) as an end point in a cohort of 85 type 2 diabetic patients with chronic renal insufficiency/failure (s-Cr >1.5 and <3.7 mg/dl, 61 +/- 11 years old, 51 men and 34 women, mean s-Cr 2.3 +/- 0.6 mg/dl). RESULTS: The survey period (mean +/- SD) was 14.2 +/- 10.8 months. The cumulative incidence of the end point in patients with insulin therapy (n = 41) was significantly lower than that in patients without it (n = 44) (P = 0.0022, P values by log-rank test). Multivariate Cox analysis revealed insulin therapy (hazard ratio [HR] 0.435, 95% CI 0.252-0.750, P = 0.0027), serum albumin (0.484, 284-0.823, P = 0.0074), mean blood pressure (1.023, 1.004-1.043, P = 0.017), and hemoglobin (0.841, 0.728-0.972, P = 0.0194) to be independent and significant predictors of progression to renal failure, whereas HbA(1c) or serum cholesterol were not. CONCLUSION: In type 2 diabetic patients with renal failure, hypoalbuminemia, anemia, higher mean blood pressure, and lack of use of insulin predict rapid progression of renal failure, but HbA(1c) does not, and insulin therapy may be possibly an indicator of the delay in progression of renal failure.

Age of Onset↗

[Effective utilization of metabolic markers of bone].

Although long-term treatment is essential to reduce osteoporotic fracture, the treatment is often interrupted, because patients or even physicians cannot recognize the effects of the treatment. The less power of the drugs to increase BMD, low precision of BMD measurement, and/or deformity of lumbar spine are responsible for the low recognition. Bisphosphonate and estrogen replacement therapy reduce the resorption of bone, which can be recognized by the measurement of resorption markers, such as NTX or deoxypyridinoline. Measuring these markers before and after the treatment, patients and physicians can recognize the effect within 1-3 months, which magnitude is usually more than the least significant levels. Confirmation of the effectiveness of the treatment through these markers may reduce the dropout rate of the treatment.

Biomarkers↗

Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease.

BACKGROUND: Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family. OPG-deficient mice develop severe osteoporosis and medial arterial calcification of the aorta and renal arteries. OPG immunoreactivity was demonstrated in the normal blood vessels and in early atherosclerotic lesions. A recent clinical study suggests that there is a significant correlation between elevated serum OPG levels and cardiovascular mortality. We examined whether serum OPG levels are associated with the progression of coronary artery disease (CAD). METHODS AND RESULTS: Serum OPG levels were examined in 201 patients who underwent coronary angiography because of stable chest pain. The number of diseased vessels was used to represent the severity of CAD. Serum OPG levels were measured by ELISA and were significantly greater in patients with significant stenosis of the coronary arteries than in those without stenosis. As the severity of CAD increased, there was a significant increase in serum OPG levels. Serum OPG levels were 0.94+/-0.34, 1.04+/-0.38, 1.19+/-0.38, and 1.44+/-0.54 ng/mL (medians 0.91, 0.99, 1.09, and 1.37) for the subjects with normal coronary arteries or luminal irregularities, 1-vessel disease, 2-vessel disease, and 3-vessel disease, respectively. Multivariate logistic regression analysis revealed that serum OPG levels were significantly associated with the presence of CAD [odds ratio, 5.2; 95% confidence interval, 1.7 to 16.0]. CONCLUSIONS: Our data show that serum OPG levels are associated with the presence and severity of CAD, suggesting that OPG may be involved in the progression of CAD.

Adult↗

Detecting functional asymmetries through the dipole moment of magnetoencephalography.

To assess the accuracy of magnetoencephalography (MEG) as a tool for quantitative detection of neuronal activity, the dipole moment was estimated at N20m of somatosensory evoked fields (SEFs) produced by median nerve stimulation. Neurologically stable patients were examined twice within 2 weeks. Since the estimated moment values of the two examinations should be essentially the same, we assessed the margin of error for our measurement system. The results showed that a change of more than 5.2 nAm is statistically significant (p=0.05; n=91). The patients were classified as without or with functional asymmetries by measuring the conventional cerebral blood flow (CBF) with single photon emission CT (SPECT), and the dipole moment difference between hemispheres was measured. Hemispheric moment differences were statistically larger for the group with CBF laterality, indicating consistency between conventional CBF results and the moment measurements as a group. Moreover, MEG was able to detect more functional asymmetries than CBF study. The dipole moment provided a reliable quantitative index of cortical response to somatosensory stimulus, and the moment measurement thus holds promise as a clinical tool for direct quantification of cortical response.

Adult↗

Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis.

OBJECTIVE: To determine whether arterial wall thickening is advanced in rheumatoid arthritis (RA) patients compared with healthy controls by measuring the intima-media thickness (IMT) of the common carotid and femoral arteries, and to evaluate the factors associated with arterial IMT in patients with RA. METHODS: We studied 138 RA patients and 94 healthy controls (matched for age, sex, and other major risk factors for atherosclerosis). IMT was measured on digitized still images of the common carotid and femoral arteries obtained by high-resolution ultrasonography (10-MHz in-line Sectascanner). Laboratory variables relevant to RA activity were measured by routine methods. The degree of RA progression was assessed by scoring (Larsen method) metacarpophalangeal (MCP) joints on hand radiographs. Activities of daily living were determined by a modified Health Assessment Questionnaire (M-HAQ) score, and physical activity levels were assessed by ultrasound measurement of the calcaneus (expressed as the osteo-sono assessment index [OSI] Z score). RESULTS: Common carotid and femoral artery IMTs were significantly higher (P < 0.05) in RA patients (mean +/- SD 0.641 +/- 0.127 and 0.632 +/- 0.125 mm, respectively) compared with controls (0.576 +/- 0.115 and 0.593 +/- 0.141 mm, respectively). Multiple regression analysis revealed a significant association between RA and the common carotid artery IMT. Moreover, the common carotid artery IMT in RA patients was positively associated with disease duration, the MCP joint Larsen score, and the M-HAQ score, and was negatively associated with the calcaneus OSI Z score. No significant association was found between corticosteroid treatment and common carotid artery IMT. CONCLUSION: RA patients exhibited greater thickness of the common carotid and femoral arteries than healthy controls. The duration and severity of RA and decreased activities of daily living, but not corticosteroid treatment, were independently associated with the increased arterial wall thickness.

Adrenal Cortex Hormones↗

Antibody to oxidized low-density lipoprotein and cardiovascular mortality in end-stage renal disease.

BACKGROUND: Immune response to oxidized low-density lipoprotein (oxLDL) may modulate the process of atherogenesis and cardiovascular disease. METHODS: We performed a prospective, observational cohort study in 249 patients with end-stage renal disease (ESRD) to examine whether the serum titer of anti-oxLDL antibody can predict cardiovascular mortality. RESULTS: The median anti-oxLDL antibody titer was 320 mU/mL at baseline. During the follow-up (63 +/- 23 months), 72 deaths including 34 cardiovascular deaths occurred. When the subjects were divided into two groups by the median titer, the high titer group showed a lower risk for cardiovascular mortality (P = 0.040 by Kaplan-Meier analysis and log-rank test). Multivariate Cox proportional hazards model indicated that the lower risk of cardiovascular death in the high titer group remained significant (hazard ratio of 0.46, 95%CI 0.23-0.95, P = 0.037) and independent of age, presence of vascular complications, presence of diabetes mellitus, and elevated C-reactive protein. In contrast, anti-oxLDL antibody titer was not associated with non-cardiovascular mortality. CONCLUSIONS: These results demonstrate, to our knowledge for the first time, that serum anti-oxLDL antibody titer is an independent predictor of cardiovascular mortality in a cohort of patients with ESRD.

Adult↗

Clinical usefulness of the serum N-terminal propeptide of type I collagen as a marker of bone formation in hemodialysis patients.

BACKGROUND: An intact collagen I amino-terminal propeptide (PINP) assay has been developed as a useful assay for bone formation. The present study was performed to investigate the clinical usefulness of serum PINP as a bone-formation marker in hemodialysis (HD) patients. METHODS: PINP and other bone-formation markers, ie, bone alkaline phosphatase (BAP) and intact osteocalcin (OC), were determined in serum samples collected from 209 HD patients. RESULTS: Serum PINP levels, in contrast to serum BAP and OC levels, did not change significantly during a single HD session (P = 0.069; n = 14). There were significant positive correlations between serum PINP and BAP (r = 0.723; P < 0.001) and OC values (r = 0.739; P < 0.001), as well as intact parathyroid hormone (r = 0.652; P < 0.001) and bone-resorption marker values: deoxypyridinoline (DPD; r = 0.823; P < 0.001), pyridinoline (PYD; r = 0.735; P < 0.001), and beta-crosslaps (r = 0.705; P < 0.001). Serum PINP values correlated significantly more strongly than serum BAP values with all bone-resorption markers. Serum PINP values significantly correlated negatively with annual changes in bone mineral density (BMD) in the distal third of the radius (r = -0.286; P < 0.001). When subjects were divided into tertiles according to degree of bone loss, subjects with greater bone loss had significantly greater serum PINP, BAP, and OC levels, although PINP and OC provided greater discrimination than BAP. PINP-PYD and PINP-DPD ratios, indices of osteoblast function not confounded by enhanced bone resorption, significantly positively correlated with annual BMD changes in the distal third of the radius (PINP-PYD ratio, P = 0.008; PINP-DPD, P = 0.015). CONCLUSION: Serum PINP may provide a better marker of osteoblast function in HD patients and thus be clinically useful for predicting radius bone loss.

Absorptiometry, Photon↗

Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease.

Insulin resistance is closely associated with atherosclerosis and cardiovascular mortality in the general population. Patients with end-stage renal disease (ESRD) are known to have insulin resistance, advanced atherosclerosis, and a high cardiovascular mortality rate. We evaluated whether insulin resistance is a predictor of cardiovascular death in a cohort of ESRD. A prospective observational cohort study was performed in 183 nondiabetic patients with ESRD treated with maintenance hemodialysis. Insulin resistance was evaluated by the homeostasis model assessment method (HOMA-IR) using fasting glucose and insulin levels at baseline, and the cohort was followed for a mean period of 67 mo. Forty-nine deaths were recorded, including 22 cardiovascular deaths. Cumulative incidence of cardiovascular death by Kaplan-Meier estimation was significantly different between subjects in the top tertile of HOMA-IR (1.40 to 4.59) and those in the lower tertiles of HOMA-IR (0.28 to 1.39), and the hazard ratio (HR) was 2.60 (95% confidence interval [CI], 1.12 to 6.01; P = 0.026) in the univariate Cox proportional hazards model. In multivariate Cox models, the positive association between HOMA-IR and cardiovascular mortality remained significant (HR, 4.60; 95% CI, 1.83 to 11.55; P = 0.001) and independent of age, C-reactive protein, and presence of preexisting vascular complications. Further analyses showed that the effect of HOMA-IR on cardiovascular mortality was independent of body mass index, hypertension, and dyslipidemia. In contrast, HOMA-IR did not show such a significant association with noncardiovascular mortality. These results indicate that insulin resistance is an independent predictor of cardiovascular mortality in ESRD.

Aged↗

The 807T allele in alpha2 integrin is protective against atherosclerotic arterial wall thickening and the occurrence of plaque in patients with type 2 diabetes.

Polymorphism of alpha2 integrin (C807T) is shown to be associated with an increased incidence of thrombotic cardiovascular events. However, it is not clear whether this polymorphism is associated with atherosclerotic arterial wall thickening. In this study, we examined the association of C807T polymorphism with arterial wall thickness in 265 control subjects and 272 patients with type 2 diabetes. In all subjects, intima-media thickness of the right carotid artery in the 807TT group (0.649 +/- 0.028 mm [SE]) was significantly (P = 0.0228, Scheffe's F test) less than in the 807CC group (0.767 +/- 0.033). This effect of polymorphism is gene dose dependent (P = 0.0227, ANOVA). The similar association was also observed in patients with diabetes but not in control subjects. Multiple regression analysis in all subjects revealed that the T allele was inversely (beta = -0.095, P = 0.021) associated with intima-media thickness independent of age, HbA(1c), and HDL cholesterol. Finally, an inverse relation between the occurrence of carotid plaque and the T allele was observed in patients with diabetes with an adjusted odds ratio of 0.487 (P = 0.031) in multiple logistic regression analyses. These results suggest that the number of 807T alleles in alpha2 integrin is protective against atherosclerotic arterial wall thickening and the occurrence of plaque in patients with type 2 diabetes.

Adult↗