Carotid Artery Intimal Thickness Research Articles

A Study of the Assessment of Serum Adropin Level as a Risk Factor of Ischaemic Heart Disease in Type 2 Diabetes Mellitus Cases

Abstract Background Adropin is a peptide hormone which was discovered in 2008 and originally described as playing an important role in glucose and fatty acid homeostasis that acts on peripheral tissues. We investigate the correlation of adropin and ischaemic heart disease in diabetic patients. Aim Study of the assessment of serum adropin level as a risk factor for ischaemic heart disease in type 2 diabetes mellitus cases. Method This case control study was conducted on 90 subjects, divided into 3 groups: Group (I): 30 T2DM patients with ischaemic heart disease Group (II): 30 T2DM patients without ischaemic heart disease Group (III): 30 healthy subjects as control. Fasting plasma glucose, 2 h post prandial plasma glucose, Carotid artery intimal thickness using ultrasound, HbA1c, Lipid profile (cholesterol, triglycerides, LDL-C, HDL), HOMA IR Serum creatinine, AST, ALT, and Serum Adropin were assessed. Result There was a statistical significant increase in serum Adropin hormone in diabetic patients without ischaemic heart disease than diabetic one with ischaemic heart disease (p value ˂0.001), (26.867 ± 10.037) ng/L vs (87.500 ± 40.509) ng/L respectively. Also Serum Adropin was negatively correlated with fasting insulin and CIMT. Assessment of serum adropin level could be a risk marker for ischaemic heart disease development in type 2 diabetes mellitus patients.

Association of serum thymosin β4 with malnutrition-inflammation-atherosclerosis syndrome in peritoneal dialysis patients: a cross-sectional study

Background Malnutrition-inflammation-atherosclerosis (MIA) syndrome may worsen the prognosis of peritoneal dialysis (PD) patients. Serum thymosin β4 (sTβ4) protects against inflammation, fibrosis and cardiac dysfunction. Objectives The present study aimed to characterize the association between sTβ4 and MIA syndrome as well as to investigate the potential of regulating sTβ4 to improve the prognosis of PD patients. Methods We performed a cross-sectional, single-center pilot study involving 76 PD patients. Demographic characteristics, clinical characteristics, nutritional profiles, inflammatory mediators, atherosclerosis-related factors and sTβ4 levels were collected and subjected to association analysis for sTβ4 and MIA syndrome. Results sTβ4 levels did not significantly vary with sex or primary disease in PD patients. Ages and PD features did not vary between patients with different levels of sTβ4. PD patients with higher levels of sTβ4 had significantly higher levels of nutritional indicators, including subjective global nutritional assessment (SGA) (p < 0.001) and serum albumin (ALB) (p < 0.001) but lower levels of inflammatory and atherosclerotic indicators, including serum C reaction protein (CRP) (p = 0.009), the right common carotid artery (RCCA) intimal thickness (p < 0.001) and the left common carotid artery (LCCA) intimal thickness (p = 0.02). Correlation analysis showed that sTβ4 was positively associated with SGA (p < 0.001) and serum ALB (p < 0.001) but negatively associated with CRP (p = 0.020), RCCA intimal thickness (p < 0.001) and LCCA intimal thickness (p = 0.033). In multiple adjusted models, the prevalence of MIA syndrome was significantly decreased in PD patients with increased levels of sTβ4 when patients without MIA syndrome were compared to those with all indicators of MIA syndrome (OR = 0.996, 95% CI 0.993–0.999, p = 0.003) or those with at least one indicator of MIA syndrome (OR = 0.997, 95% CI 0.995–0.998, p < 0.001). Conclusions The sTβ4 level decreases in PD patients with MIA syndrome. The prevalence of MIA syndrome decreases significantly as the level of sTβ4 increases in PD patients.

Peripheral Vascular Ageing in Pulmonary Arterial Hypertension as Assessed by Common Carotid Artery Intima Thickness and Intima/Media Thickness Ratio: An Investigation Using Non-Invasive High-Resolution Ultrasound.

Pulmonary arterial hypertension (PAH; WHO Group 1) is associated with increased pulmonary arterial pressure and resistance, with pulmonary vascular remodelling. The vascular anatomy of the systemic arteries has been less well studied. Nineteen (19) patients with PAH, confirmed by right heart catheterisation (RHC), 14 patients with left ventricular heart failure with reduced ejection fraction (LVrEF), and 30 healthy subjects were enrolled. Common carotid artery (CCA) intima thickness, intima/media (I/M) thickness ratio, and intima-media thickness (IMT) were assessed using non-invasive ultrasound (22 MHz centre frequency). The CCA intima thickness was correlated with several RHC variables (all p<0.05). The intima was 56% thicker (+0.05 mm; 95% CI 0.03, 0.06; p<0.0001) and the I/M thickness ratio was 128% greater (+0.21; 95% CI 0.13, 0.28; p<0.0001) in patients with PAH than healthy subjects. These values were also significantly higher than in patients with LVrEF. In ROC curve analysis, the c-values for CCA intima thickness (0.92) and I/M ratio (0.87), but not for IMT, correctly indicated which individuals belonged to the PAH or healthy control groups. The CCA IMT showed no corresponding significant group differences or associations and was of no use according to receiver operating curve analysis. Patients with PAH displayed signs of peripheral vascular remodelling, challenging the common opinion that vascular changes in PAH are restricted to the lung vasculature. Correlations with cardiopulmonary variables from RHC support peripheral vascular coupling and the association with vascular ageing. Results from this pilot study warrant further confirmation.

Association of Elevated Oxidized Low Density Lipoprotein to Low Density Lipoprotein Ratio (Ox LDL/LDL) with Sub Clinical Atherosclerosis in Patients Receiving Maintenance Haemodialysis

Objective: To assess the oxidized low density lipoprotein (ox-LDL) to low density lipoprotein (LDL) ratio as an indicator of subclinical atherosclerosis in haemodialysis patients Methodology: This case control study was carried out at Jinnah Post Graduate Medical Center Karachi, from January to December 2018. The haemodialysis patients were selected from the dialysis center (group B) whereas the controls were recruited from normal healthy population (group A). To access the status of atherosclerosis, doppler ultrasonography technique was employed to detect the intima media thickness (IMT) ratio of common carotid artery of study subjects as well as controls. Lipid peroxidation was detected by serum oxidized LDL (ox-LDL) levels. Results: The mean of carotid artery intima thickness in group A was 0.43±0.02, the mean intima thickness of group B samples was 1.0±0.09. The mean ratio of Ox-LDL/LDL in group A was 0.003±0.001. While in group B the mean of Ox-LDL: LDL was 0.012±0.002. Ox-LDL was found to have a positive linear relationship with mean carotid artery intima media thickness ratio (r=0.8) in haemodialysis group. Conclusion: Ox-LDL to LDL ratio is much enhanced in patients on maintenance haemodialysis showing increased lipid peroxidation. Ox-LDL has a positive linear relationship with mean carotid artery intima media thickness ratio which is a marker of sub clinical atherosclerosis. Early detection of elevated Ox-LDL will help nephrologists in early detection and treatment of sub clinical atherosclerosis.

Correlation between HbA1c and carotid artery intima-media thickening(cIMT) in diabetic patients

Introduction: Correlation between carotid artery intima-media thickening and HbA1c levels in diabetic patients as a non invasive marker of progressive atherosclerosis. Objectives: The aim of this study is to study the role of two non invasive markers, carotid intima media thickening and HbA1c in diabetic patients and establish the usefulness of both the parameters in evaluating early risk factor assessment. Material and methods: 100 patients meeting the required criteria were taken coming to OPD/IPD bases to Dhiraj hospital in the age group of 35-70 years.HbA1c levels were used according to American diabetes association. Carotid intima media thickening was measures on B mode ultrasonography in radiology department.  Results: among the 100 patients, 68 patients were female and 32 patients were male. The mean of HbA1c values were 8.0 ± 2.2%. The mean cIMT values were 0.78 ± 0.3 cm. Conclusion: HbA1c and carotid artery intimal thickness is useful as a diagnostic marker and early risk factor analysis for atherosclerotic changes in diabetic patients.

Association Between Diabetic Retinopathy and Carotid Intima-Media Thickness.

IntroductionPatients with diabetes having advanced stage of diabetic retinopathy (DR) may predict future risk of coronary artery disease. To predict cardiovascular outcomes carotid intima-media thickness (CIMT) is utilized in diabetic patients. The aim of our study was the evaluation of the relationship between retinopathy and CIMT as two valuable non-invasive methods for early detection of micro- and macrovascular complication of diabetes.MethodsThis comparative cross-sectional study was conducted in the internal medicine ward of tertiary care hospital in Pakistan from November 2020 to January 2021. Three hundred patients with type 2 diabetes mellitus and 300 control subjects were enrolled in the study after taking informed consent. Ophthalmological examination was done to screen patients for DR. CIMT was evaluated by a Doppler ultrasound for both carotid arteries.ResultsCarotid artery intimal thickness was more in patients with retinopathy compared to patients without retinopathy in both right (0.77 ± 0.16 vs. 0.66 ± 0.12; p-value: <0.0001) and left carotid artery (0.77 ± 0.15 vs. 0.65 ± 0.11; p-value: <0.0001).ConclusionIn our study, there was a correlation between DR and CIMT. Screening for DR, which may be a potential early marker for complications, may help detect patients at risk of various macro and microvascular complications.

Arcuate artery calcification on transvaginal sonography may predict coronary artery heart disease

Atherosclerosis is a systematic disease affecting all arteries and is the most common cause of mortality. Our aim was to evaluate the predictive value of the presence of uterine arcuate artery calcification (AAC) for coronary heart disease (CHD) in women. Seventy women presenting with angina pectoris or a finding suggestive of cardiac ischaemia in non-invasive tests, scheduled for angiography between June 2014 and July 2015 were recruited in the study. One day before the coroner artery angiography, all of the patients were examined about the presence of AAC by transvaginal ultrasonography and were classified in the presence of CHD. CHD is classified as obstructive (obstruction >70%) or as non-obstructive (obstruction <70%) according to the severity of stenosis. The association of AAC is evaluated with the presence and severity of CHD that's diagnosed by angiography. CHD was present in 87.2% of women with positive for AAC and in 4.3% of who were negative for AAC (p = .001). AAC positive women were more likely to develop obstructive CHD than non-obstructive CHD (66.6% versus 30.9%, p = .001), respectively. Sensitivity and specificity of AAC for CHD were 97.6% and 78.5%, respectively. AAC detected by transvaginal ultrasound seems to have a strong association with both presences of CHD and the severity of disease.Impact statementWhat is already known on this subject? Atherosclerosis affecting all arteries is the primary cause of mortality and morbidity of coronary heart disease (CHD) (Lim et al. 2011). Uterine artery calcification and its association with atherosclerosis were first reported by Camiel et al. (1967). Ozdemir et al. (2016) found a correlation between carotid artery intima thickness and the presence of uterine arcuate artery calcification (AAC).What do the results of this study add? Very few studies have been performed in this area investigating the relationship of AAC and non-invasive predictors of atherosclerosis or the relationship between arterial calcifications and cardiovascular or systemic disease. Our study is the first to evaluate the correlation between AAC and CHD confirmed using coronary artery angiography at a high sensitivity rate (97.6%).What are the implications of these findings for clinical practice and/or further research? Our study presents an alternative, easy and non-invasive method for the prediction of subclinical CHD in clinical practice. From the view of a gynaecologist, cardiology consultation of patients with AAC detected by transvaginal ultrasonography during the routine gynaecologic examination may be useful and protective against serious cardiac problems. Thus, this study is of great importance in terms of predicting when the majority of CHD patients are asymptomatic or in the subclinical phase.

Carotid Artery Intima Media Thickness in Predicting Coronary Artery Disease in Type II Diabetes Mellitus

Diabetes Mellitus is a chronic, common metabolic disorder characterised by high blood sugar levels over a prolonged period. Atherosclerosis involving the coronary, cerebral and peripheral (lower extremity) arteries is the predominant cause of diabetes related mortality, responsible for up to 70% of all deaths in patients with this disease. Coronary angiography (CAG) has been considered as the gold standard for the assessment of the degree of Coronary atherosclerosis but measurement of carotid intima thickness by ultrasonography is a non invasive and quantitative method of evaluating early atherosclerosis. The aim of this study was to assess carotid artery intima media thickness and to assess any correlation between carotid artery intimal thickness and coronary artery disease in Type II DM. This study was carried out in the department of medicine, Dr. Baba saheb Ambedkar hospital, Delhi to assess carotid intima media thickness (CIMT) as a risk factor for CAD in type II diabetes using Ultrasound B scan to assess CIMT. In this study, 30 patients of DM type II with CAD, 30 patients of DM type II without CAD & 30 patients were age and sex matched controls who did not have any disease. Mean CIMT was found to be significantly increased in DM type 2 with CAD group as compared to DM type 2 without CAD and the difference was found to be statistically significant (P<0.001). Also the mean CIMT was significantly increased in DM type 2 with and without CAD as compared to controls and the difference was statistically significant. Also, patients with more than 3 cardiovascular risk factors had significantly greater CIMT than patients who had less than 3 cardiovascular risk factors and the difference was statistically significant.

The Study of Relationship of Glycated Haemoglobin with Carotid Artery Intimal Thickness in Patients with Ischaemic Stroke

The Study of Relationship of Glycated Haemoglobin with Carotid Artery Intimal Thickness in Patients with Ischaemic Stroke

[Role of ORAI1 in the balloon injury-induced rat carotid artery neointimal formation and the relationship between ORAI1 and sodium and calcium exchange 1].

Objective: To investigate the role of ORAI1 in the balloon injury-induced rat carotid artery neointimal formation and the relationship between ORAI1 and sodium and calcium exchanger(NCX)1. Methods: According to condition of carotid artery balloon injury and observation time, Sprague Dawley rats were divided into 3 groups including sham group, 7 days injury group, and 14 day injury group(n=3 each). According to virus of transfection, Sprague Dawley rats were divided into 2 groups including negative control group (negative lentiviruses particles transfection after establishment of carotid artery balloon injury model, n=3) and siORAI1 group(siORAI1 transfection after operation, n=3). Carotid artery neointimal formation was analyzed after HE staining. The ORAI mRNA expression level was detected using real-time PCR. The proliferating cell nuclear antigen (PCNA), ORAI and NCX1 protein expression level were measured by Western blot. Results: (1) Carotid artery intima was significantly thicker in 7 days and 14 days injury group than in sham group((0.54±0.11)μm2 and (0.89±0.12)μm2 vs.(0.11±0.08)μm2, both P<0.05). Relative expression level of PCNA protein was significantly higher in 7 days and 14 days injury group than in sham group(1.43±0.16 and 1.95±0.16 vs. 1, both P<0.05). Relative mRNA expression level of ORAI1 (1.39±0.14 and 1.78±0.21 vs. 0.56±0.09, both P<0.05) and protein expression level (1.42±0.19 and 1.78±0.22 vs. 1, both P<0.05) were significantly higher in 7 days and 14 days injury group than in sham group.(2) After 14 days, relative expression level of ORAI1 protein was significantly lower in siORAI1 group than in negative control group (0.21±0.161, P<0.05). Carotid artery intima thickness was significantly reduced in siORAI1 group compared to negative control group((0.19±0.14)μm2 vs.(0.91±0.23)μm2,P<0.05). Relative expression level of NCX1 protein was also significantly lower in siORAI1 group than in negative control group(0.53±0.131, P<0.05). Conclusions: ORAI1 may play a key role in the balloon injury-induced neointimal formation and vascular smooth muscle cells proliferation in rat carotid artery.ORAI1 knockdown could down regulate the NCX1 expression and attenuate the balloon injury-induced neointimal formation and vascular smooth muscle cells proliferation in rat carotid artery.

Causes of Thickening of Carotid Intima-Media Thickness in Patients With Alcoholic Liver Disease: A Prospective Observational Study.

Several studies have reported the relationship between alcoholic liver disease (ALD) and carotid intima-media thickness (CIMT). Few studies, however, have investigated the causes of CIMT thickening in patients with ALD. The authors explored the causes of CIMT thickening in patients with ALD.The authors enrolled 152 patients who were stratified into groups: nonthickening CIMT with ALD (group A); thickening CIMT with ALD (group B); nonthickening CIMT without ALD (group C); and thickening CIMT without ALD (group D).The CIMT was significantly different between patients with and without ALD (χ2 = 3.875, P = 0.049). The patients in groups A, B, and C were significantly younger than group D (P = 0.001, 0.036, and 0.001, respectively). The body mass indexes (BMI) in groups A and B were significantly higher than in group C (P = 0.000 and 0.007, respectively). The blood glucose levels in groups B and D were significantly higher than in group C (P = 0.016 and 0.018, respectively). The blood uric acid levels in group B were significantly higher than in groups A, C, and D (P = 0.009, 0.000, and 0.003, respectively). The blood uric acid in group A was significantly higher than in group C (P = 0.002). The serum total cholesterol (TC) levels of patients in group B were significantly higher than in groups A and C (P = 0.027 and 0.000, respectively) and the serum TC level in group A was significantly higher than in group C (P = 0.048). The serum triglyceride (TG) levels in groups A and B were significantly higher than in group C (P = 0.027 and 0.000, respectively). The serum of very low-density lipoprotein (VLDL) levels in group B were significantly higher than in group C (P = 0.000). Although a comparison of the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) serum levels among the 4 groups indicated no changes. The serum LDL levels in group B were significantly higher than in group A (P = 0.008). No significant differences were observed among the groups with respect to serum homocysteine, C-reactive protein (CRP), interleukin-6 (IL-6), malondialdehyde (MDA), superoxide dismutase (SOD), soluble OX40 ligand (sOX40L), or heat shock protein (HSP) 60 or 70.Alcoholic liver disease may result in CIMT thickening. Carotid intima-media thickness is associated with age and metabolic factors in patients with ALD. In addition, ALD might promote the premature occurrence of CIMT thickening. The thickening of carotid artery intima thickness, however, is not associated with cytokine profiles, oxidative balance, or immune responses in patients with ALD.

The relationship between estrogen levels and carotid atherosclerosis in postmenopausal women with type 2 diabetes

Objective To observe the correlation of estrogen, fasting insulin(FINS), fasting plasma glucose(FPG), glycosylated hemoglobin(Hb A1c), blood lipids and carotid arteries- membrane thickening(IMT) in the postmenopausal women with type 2 diabetes. Methods 63 postmenopausal women with type 2 diabetes were divided into normal IMT group(group A),IMT thickening group(group B),plaque group(group C)according to the vascular ultrasound carotid artery intima thickness,at the same time 15 cases of healthy physical examination as control group(group D).All of the groups were detected the plasma total cholesterol(TC),high- density lipoprotein cholesterol(HDL- C),low density lipoprotein cholesterol(LDL- C),fasting insulin(FINS),fasting plasma glucose (FPG),glycosylated hemoglobin(HbA1c), follicle-stimulating hormone(FSH), estradiol(E2). Results Compared with group A,the levels of FINS,IR,Hb A1c,TC,LDL- C in group C was higher(t= 16.83,14.44,2.50,2.38,2.42, all P< 0.01 or P< 0.05),however,the results of E2,HDL- C was decreased(t= 7.32,5.51,all P< 0.01).The levels of FINS,Hb A1c,TC,LDL- C,FSH,IR in group D was lower than those of group C(t= 19.74,36.44,8.64,7.95, 27.13,6.71,all P< 0.01),On the contrast,the levels of HDL- C,E2 were elevated(t= 11.34,8.72,all P<0.01).The Pearson's correlation analysis showed that E2 had negative correlation with FINS,IR,TC,LDL- C(P< 0.01 or P< 0.05).E2 had positive correlation with HDL- C(P< 0.05).Logistic regression analysis showed that IMT and FINS, IR,Hb A1c,LDL- C were positively correlated(OR= 2.94,72.63,27.30,98.18,all P<0.01),while negatively correlated with E2 levels(OR= 2.94,P<0.01). Conclusion The increased level of estrogen was a protective factor of carotid artery atherosclerosis in postmenopausal women with type 2 diabetes. Key words: Diabetes, mellitus; Estrogens; Carotid athery diseases; Atherosclerosis

Malnutrition and its association with inflammation and vascular disease in children on maintenance dialysis

Malnutrition is associated with both inflammation and atherosclerotic cardiovascular disease in adults with chronic kidney disease. We studied the prevalence of malnutrition and its possible associations with inflammation and vascular disease in children on chronic dialysis. Thirty-three patients on maintenance dialysis (18 peritoneal dialysis, 15 hemodialysis) and 19 age- and gender- matched healthy controls were studied. Nutritional status was assessed by anthropometric measurements including body mass index (BMI), upper arm measurements, multifrequency bioimpedance analysis (BIA) and serum levels of albumin, prealbumin, and cholesterol. Inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. The carotid artery intima thickness (cIMT) was measured to assess vascular disease. Compared with healthy children, patients had lower anthropometric measurements (P < 0.05) and serum albumin level (P < 0.001), and higher CRP and TNF-alpha (P = 0.030 and P = 0.007, respectively), and higher cIMT-SDS (P < 0.001). Malnutrition was present in 8 (24%) and lower BIA-based fat mass was independently associated with higher IL-6 levels (P = 0.035). An increased cIMT was present in 16 (48.5%); however, there was no difference in cIMT-SDS between patients with and without malnutrition. Carotid IMT did not show any association with nutritional indices; but positively correlated with serum IL-6 (P = 0.037), CRP (P = 0.012), and iPTH (P = 0.009), and independently associated with only iPTH (P = 0.018). Children on dialysis are at an increased risk of malnutrition, inflammation, and vascular disease. Although each of these three conditions exists, there is no interaction among them all. We postulate that the malnutrition-inflammation-atherosclerosis (MIA) complex might not exist in pediatric dialysis patients.

Oxidative stress, endothelial function, carotid artery intimal thickness and their correlates among chronic peritoneal dialysis patients

We evaluated important nontraditional cardiovascular risk factors, endothelial function and oxidative stress (OS) among stable peritoneal dialysis (PD) patients. Their association with carotid intimal medial thickness (CIMT) was also assessed. Thirty-eight adult patients (13 diabetics, 20 males) on PD for >6 months and 15 age and sex-matched controls were studied. Duration of dialysis (DOD), residual urine output (UO), weekly Kt/V urea, detailed biochemical and lipid profile were noted. OS was measured by serum concentration of antioxidants; vitamin C and ferric reducing ability of plasma (FRAP) and pro-oxidant; thiobarbituric acid-reactive substances (TBARS). High-resolution ultrasonography was used to determine CIMT and flow-mediated dilatation of brachial artery [endothelium-dependent dilatation (EDD)] and dilatation subsequent to nitrate spray [endothelium-independent dilatation (EID)]. Mean age, DOD, UO and Kt/V of study population were 49.3 ± 11.6 years, 19.4 ± 11.8 months, 508.2 ± 422.9 ml/day and 1.73 ± 0.24, respectively. As compared to controls PD patients had higher CIMT (0.46 ± 0.05 vs 0.50 ± 0.07 mm, P = 0.003) and TBARS (1.5 ± 0.4 vs 5.1 ± 2.3 nM/ml, P < 0.001) but lower Vitamin C (1.7 ± 0.3 vs 0.6 ± 0.2 mg%, P < 0.001), FRAP (990.8 ± 78.1 vs 328.7 ± 183.5 μM/L, P < 0.001) and EDD (26.2 ± 5.4 vs 9.8 ± 4.6 %, P < 0.001). TBARS correlated positively with DOD and negatively with hemoglobin. Vitamin C and FRAP correlated positively with serum albumin. EDD correlated positively with UO, Kt/V and hemoglobin. CIMT correlated negatively with Kt/V and hemoglobin. Among themselves CIMT correlated negatively with EDD and vitamin C. EDD correlated positively with vitamin C, while FRAP correlated positively with vitamin C and negatively with TBARS. PD patients have higher OS, poorer endothelial function and higher structural atherosclerosis. These parameters are closely linked to each other, hemoglobin, DOD, residual UO, serum albumin and small solute clearances.

Elevated peroxidative glutathione redox status in atherosclerotic patients with increased thickness of carotid intima media.

Atherosclerosis is a chronic inflammatory disease. Accumulated evidences suggest a deep involvement of oxidative damage in the development of atherosclerosis, but little is discussed over the relationship between plasma glutathione redox status as the most important intrinsic antioxidant defensive mechanism and the atherosclerosis. A total of 132 patients suspected with atherosclerosis were assigned to three groups by high frequency ultrasonic examination of the carotid artery. With the thickness of intima of the carotid artery as an index of degree of atherosclerosis progression, 56 were included in plaque-forming group (A), 42 in carotid artery intima-thickening group (B), and 34 in normal carotid artery intima-thickness group (C). All patients were subjected to the measurement of plasma glutathione (GSH) (reduced form GSH and oxidized form GSSG), nicotinamide adenine dinucleotide phosphate (NADP) (reduced form NADPH and oxidized form NADP(+)), oxidized low density lipoprotein (oxLDL), and malondialdehyde (MDA). The GSH/GSSG and NADPH/NADP(+) redox potentials were calculated according to the Nernst equation, and their correlation with intima thickness and oxLDL was analyzed. With the thickening of artery intima (from group C to A), GSH concentration and the ratio of GSH/GSSG gradually reduced, and GSSG and GSH/GSSG redox potential gradually increased (more positive) (P < 0.05). The NADPH and NADPH/NADP(+) redox status also showed similar but milder changes. The products of oxidative stress oxLDL and MDA increased significantly along with the thickening of artery intima (P < 0.05). The analysis of the relationship between GSH/GSSG redox potential, intima thickness, and oxLDL showed positive correlations (P < 0.05). The plasma GSH/GSSG redox status was positively correlated with the intima thickness of the carotid artery and the oxidized injury of LDL. The redox status shifted to oxidizing direction along with the intima thickening and plaque-forming. Elevated peroxidative glutathione redox status was deeply implicated in atherosclerosis progressing, and it may be a sensitive and reliable index for monitoring oxidative status in atherosclerosis.

Mis-SHAPEing Public Health Policy

On June 19, 2009, the Heart Attack Prevention Bill, a bill mandating health insurance coverage of radiographic screening tests to detect asymptomatic atherosclerosis, was passed through the Texas legislature and enacted in September.1 The bill, written by the SHAPE (Screening for Heart Attack Prevention and Education) Task Force and championed by Representative Rene O. Oliveira, was first introduced in 2007, but failed at that time because of a lack of scientific data. However, without further evidence or modification, the bill was recently reintroduced and passed, requiring health insurance companies to cover the costs for either cardiac computed tomography (CT) scan to measure coronary artery calcium score or ultrasound to measure carotid artery intimal thickness every 5 years for all men aged 45 to 75 and women aged 55 to 75, along with persons of any age who have diabetes mellitus or an intermediate Framingham Risk Score.1 The Heart Attack Prevention Bill introduces complex questions about the level of scientific evidence needed to support legislative mandates for medical coverage. Neither screening test has demonstrated clinical efficacy in preventing acute myocardial infarctions nor is supported as a primary prevention strategy by any of the major guideline committees.2 In the absence of validating data, mandating medical coverage for these procedures raises concerns of unwarranted costs or harm to patients and potential for conflicts of interest. This article (1) considers the rationale for mandating insurance coverage, (2) considers criteria for evaluating the merits of such policies, and (3) applies these criteria to evaluate the rationale and merits of the Heart Attack Prevention bill, including the political, economic, and social forces at play. As health coverage and payment reform efforts gain increasing momentum, it is critical that legislative coverage mandates qualify as effective public health policy. Currently, most health insurance coverage decisions …

Measurement of the Intimal Thickness of the Carotid Artery: Comparison Between 40 MHz Ultrasound and Histology in Rats

Common carotid artery intimal thickness (IT) has been shown to be as useful as a measurement of the whole layer of intima-media thickness (IMT) for evaluating the early phase of atherosclerosis. The aim of this study was to elucidate the relationship between high echogenic intimal thickening (HEIT), which was measured using a 40 MHz ultrasound biomicroscope (UBM), and the histologically determined IT in rat carotid arteries. HEIT was estimated in 10 Wistar-Kyoto rats (group I), 15 spontaneous hypertensive rats (SHR) fed a standard diet (group II) and 10 SHR fed a high-fat diet (group III). IT and IMT measurements were determined in Masson trichrome-stained tissues and were compared with the HEIT and IMT evaluated using the UBM. In group I, the HEIT and the IT were 33 ± 4 μm and 12 ± 1 μm, respectively. In group II, the HEIT and the IT were 68 ± 8 μm and 16 ± 2 μm, respectively. In group III, the HEIT and the IT were 65 ± 26 μm and 33 ± 14 μm, respectively. In SHR, the HEIT and the mean IMT measured with echography were significantly correlated with the IT and the IMT that were determined by histologic measurement ( r = 0.60, p = 0.003 and r = 0.53, p = 0.01, respectively). Moreover, HEIT may be associated with the intimal pathology and atherosclerotic burden. The HEIT measurement is a noninvasive method that may be used to assess atherosclerosis in humans. (E-mail: younhj@catholic.ac.kr)

Statins and Children

Although the debate about when, whom, and how to treat adults with elevated low-density-lipoprotein cholesterol (LDLc) is essentially over because of a huge amount of data generated by large, clinical end-point, placebo-controlled trials with HMG CoA reductase inhibitors (statins),1–3 the issue in children and adolescents is not yet settled. In this issue of Circulation , Rodenburg and colleagues4 provide important further evidence for both the potential benefit of long-term LDLc reduction and the safety of treating children and adolescents with familial hypercholesterolemia (FH) with statins. This latest trial is an extension of an earlier double-blind, placebo-controlled, 2-year study in just over 200 FH children 8 to 17 years of age at entry.5 The initial trial was the first demonstration that even a moderate reduction in LDLc of 25% to 30% resulted in a significant decrease in the rate of thickening of the carotid artery intima thickness and thus moved the focus of lipid-lowering therapy in children from a plasma marker to a well-established anatomic surrogate of atherosclerosis. In the present 2-year extension in which all children were treated with the statin, Rodenburg and colleagues demonstrate that the age at which statin treatment was started was positively associated with carotid artery intima thickness on follow-up and strongly argue that, on the basis of their data, when it comes to treating children with FH, “the earlier, the better.” This would by implication include children at least as young as 8 years of age, the entry age in their trial. This is a few years younger than all current recommendations, including the recently released scientific statement on drug …

The Effect of Pioglitazone on Carotid Artery Intimal Thickness in Healthy Obese Subjects

The Effect of Pioglitazone on Carotid Artery Intimal Thickness in Healthy Obese Subjects

Altered Transcapillary Escape of Albumin and Microalbuminuria Reflects Two Different Pathogenetic Mechanisms

We studied the following in normo- and microalbuminuric hypertensive type 2 diabetic patients: 1) transcapillary escape rate of albumin (TERalb) and 2) expression of mRNA slit diaphragm and podocyte proteins in renal biopsies. Normoalbuminuric subjects had renal cancer, and kidney biopsy was performed during surgery. TERalb was evaluated by clearance of (125)I-albumin. Real-time PCR of mRNA slit diaphragm was measured in kidney specimens. Albumin excretion rate (AER) was by definition lower in normoalbuminuric subjects than in microalbuminuric subjects with typical diabetic glomerulopathy (group 1), in microalbuminuric subjects with normal or near-normal glomerular structure (group 2), and in microalbuminuric subjects with atypical diabetic nephropathy (group 3). This classification was based on light microscopy analysis of renal tissue. TERalb (%/h) was similar in normoalbuminuric and microalbuminuric group 1, 2, and 3 diabetic patients (medians: 14.1 vs. 14.4 vs. 15.7 vs. 14.9, respectively) (ANOVA, NS). mRNA expression of slit diaphragm proteins CD2AP, FAT, Actn 4, NPHS1, and NPHS2 was higher in normoalbuminuric patients than in microalbuminuric patients (groups 1, 2, and 3) (ANOVA, P < 0.001). All diabetic patients had greater carotid artery intimal thickness than normal control subjects using ultrasound technique (ANOVA, P < 0.01). In conclusion, the present study suggests that microalbuminuria identifies a subgroup of hypertensive type 2 diabetic patients who have altered mRNA expression of slit diaphragm and podocyte proteins, even before glomerular structure shows abnormalities using light microscopy analysis. On the contrary, altered TERalb and increased carotid artery intimal thickness are shown by all hypertensive type 2 diabetic patients, both with normal and altered patterns of AER.