Carotid Atherosclerosis In Subjects Research Articles

The effect of homocysteine-lowering therapy on the formation of carotid atherosclerosis: A follow-up study in the rural areas of northwest China

ObjectiveTo explore the risk factors for carotid atherosclerosis in the rural areas of Northwest China, and to assess whether reducing serum homocysteine can prevent carotid atherosclerosis in subjects with hyperhomocysteinemia. MethodThis observational study with 767 participants aged 40 years or older was conducted over 3 years. Color Doppler ultrasonography was performed to measure carotid atherosclerosis. We recorded biochemical indexes and carotid ultrasound results in the first and fourth years. ResultA total of 767 individuals (48.5 % men) were analyzed. Older age, hypertension, and higher levels of baseline low-density lipoprotein cholesterol (LDL-C) were risk factors for increased carotid intima-media thickness (CIMT), carotid plaque, and carotid stenosis (All P < 0.05). No association was found between decreased serum homocysteine (Hcy) levels and CIMT, carotid plaque, or carotid stenosis in individuals with hyperhomocysteinemia. ConclusionOlder age, hypertension, and higher baseline levels of LDL-C were independent risk factors for carotid atherosclerosis. Reducing serum Hcy levels may not prevent carotid atherosclerosis in the general population with hyperhomocysteinemia.

Long-term efficacy and safety of early alogliptin initiation in subjects with type 2 diabetes: an extension of the SPEAD-A study

We previously reported in the study of preventive effects of alogliptin on diabetic atherosclerosis (SPEAD-A) that alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the progression of carotid atherosclerosis in subjects with type 2 diabetes and no history of cardiovascular disease. This extension study of the SPEAD-A trial investigated whether early alogliptin initiation improved long-term cardiovascular outcomes. The SPEAD-A trial randomized 341 subjects with type 2 diabetes to either alogliptin or conventional treatment to investigate the effects of alogliptin on atherosclerosis. All subjects who completed that trial were eligible for this prospective, observational cohort study. The primary endpoint was the first occurrence of a major cardiovascular event, defined as death due to any cause, acute myocardial infarction, or stroke. During the 520-week follow-up period, composite primary outcome events occurred in only a few subjects in each group [8 (5.4%) in the alogliptin group and 9 in the conventional treatment group (5.9%)]. There were no significant differences in the incidence rate of the primary outcome between the two groups. Post hoc Poisson regression analysis showed no significant difference between the two groups in the incidence rate of composite recurrence events for the same outcomes as the primary endpoint. On the other hand, this incidence rate was significantly lower in subjects who received DPP-4 inhibitors before an initial cardiovascular event than in those who did not (5.8 vs. 13.3 per 1000 person-years, respectively, p = 0.04). Early initiation of alogliptin was not associated with a reduced risk of composite cardiovascular disease, which could be attributed to fewer events and/or the addition of DPP-4 inhibitors during the follow-up period.

Serum Urate Levels and Ultrasound Characteristics of Carotid Atherosclerosis across Obesity Phenotypes.

Existing evidence suggests a close link among high levels of serum urate (SU), obesity and carotid atherosclerosis. The aim of the present study was to evaluate the interrelations between SU levels and carotid atherosclerosis in subjects with different obesity phenotypes. In this study, a total of 2076 subjects (mean age 48.1 ± 13.1 years; 1307 women) were recruited: 59 with general obesity, 616 with central obesity, 715 with mixed (general-central) obesity and 686 non-obese. Anthropometric measurements, vascular risk factors, blood biochemistry analysis (including SU levels), and carotid ultrasound were performed. Ultrasound assessment included evaluation of intima-media thickness (IMT) and plaque characteristics, including number, total area and type (vulnerable vs. stable) of plaques. After adjustment for potential confounders, the highest levels of SU were observed in subjects with mixed obesity, followed by subjects with central obesity, general obesity and the non-obese (309.4 ± 82.2 vs. 301.2 ± 73.1 vs. 272.9 ± 61.8 vs. 234.2 ± 59.8 μmol/L, respectively; F = 149.2, post hoc p < 0.001). Similarly, subjects with mixed and central obesity presented higher values of IMT compared to subjects with general obesity and the non-obese (0.68 ± 0.16 vs. 0.67 ± 0.16 vs. 0.62 ± 0.14 vs. 0.57 ± 0.13 mm, respectively; F = 54.2, post hoc p < 0.001). No difference in number, total area and type of plaques among obesity groups were attested (all p > 0.05). Significantly higher IMT values were observed in subjects with increased SU levels compared to subjects with normal SU levels (0.70 ± 0.10 vs. 0.62 ± 0.14 mm, p = 0.02) only within the central obesity group. Increasing levels of SU were associated with a higher frequency of increased IMT only in subjects with central obesity (OR 1.033, 95% CI 1.025-1.041). Similarly, SU levels yielded a satisfactory performance in detecting subjects with increased IMT (AUC 0.65, 95% CI 0.50-0.73, subjects with carotid plaques (0.62, 95% CI 0.55-0.68) and subjects with vulnerable plaque types (0.68, 0.59-0.76) only within the central obesity group. Among the studied obesity types, the association between SU levels and markers of carotid atherosclerosis was of particular significance in subjects with central obesity.

Risk of Carotid Atherosclerosis in Subjects with Prediabetes Overlapping Metabolic Syndrome.

Background: While the number of individuals with prediabetes and metabolic syndrome (MetS) is increasing, only a few studies have reported differences in cardiovascular risk according to the presence or absence of MetS in individuals with prediabetes. Here, we examined differences in carotid intima-media thickness (CIMT) and carotid plaques in individuals with prediabetes with or without MetS among subjects who visited a single center in Seoul (Huh Diabetes Center). Methods: A total of 328 participants aged ≥20 years, including the group with normoglycemia, were enrolled in the analysis, of which 273 had prediabetes. Individuals with prediabetes were defined as those who met one or more of the following two criteria: fasting plasma glucose of 100-125 mg/dL and/or HbA1c level of 5.7%-6.4%. Carotid atherosclerosis was determined by mean and maximal CIMT and by the presence of carotid plaques. Results: Eighty-nine subjects (32.6% of prediabetes group) were categorized as having MetS. Those with MetS had significantly higher mean CIMT and maximal CIMT than those without (P < 0.05). Moreover, the group with MetS had a significantly higher prevalence of carotid plaques than the group without MetS [odds ratio (OR): 2.45, 95% confidence interval (CI): 1.43-4.19; P = 0.001]. After adjusting for age, sex, body mass index, and low-density lipoprotein cholesterol, individuals with MetS still had greater mean and maximal CIMT than individuals without MetS (P < 0.05), and the presence of MetS was significantly associated with a higher risk of carotid plaques (OR: 2.55, 95% CI: 1.06-6.15; P = 0.037). Conclusion: These results suggest that MetS is independently associated with increased CIMT and the presence of carotid plaques in prediabetes. Our study indicates that the risk of cardiovascular disease (CVD) is high in prediabetic individuals with MetS, and that more attention is needed on the risk of CVD in these individuals.

Association of α-klotho with subclinical carotid atherosclerosis in subjects with type 1 diabetes mellitus

BackgroundCompelling evidence suggests that the fibroblast growth factor 23 (FGF23) / α-klotho axis is impaired in subjects with diabetes mellitus. We examined the relationship between parameters related to calcium/phosphate homeostasis, including FGF23 and α-klotho, and subclinical carotid atherosclerosis burden in type 1 diabetes mellitus (T1D) subjects.MethodsThis cross-sectional study involved 226 subjects with T1D and 147 age-, sex- and plaque-matched, non-diabetic (non-T1D) subjects, both with normal renal function. Carotid ultrasound was performed to determine the presence and burden of atheromatous plaques. Concentrations of the intact form of FGF23 and α-klotho were assessed by ELISA. Calcium, phosphate, parathyroid hormone, and vitamin D levels were also determined. Negative binomial regression models were used to examine relationship between parameters studied and subclinical carotid atherosclerosis.ResultsOnly FGF23 was increased in T1D compared with non-diabetic subjects (> 2-fold; p < 0.05). α-klotho was higher in subjects with subclinical carotid atherosclerosis (1.4-fold, p < 0.05). Regression analysis revealed that the log α-klotho concentration was positively associated with the presence of subclinical carotid atherosclerosis both in T1D subjects (incidence rate ratio [IRR]: 1.41; 95% confidence interval [CI], 1.06–1.89; p < 0.05) and in non-T1D subjects (IRR: 1.65; 95% CI, 1.02–2.75; p < 0.05). The models also showed that age, smoking and albuminuria-to-creatinine ratio were positively associated with subclinical carotid atherosclerosis in T1D subjects. Interestingly, sex-related protection against plaque was also revealed in T1D women.ConclusionHigher α-klotho was associated with subclinical carotid atherosclerotic in the absence of kidney dysfunction. This finding also points to a new pathophysiological pathway involved in the development and progression of this complication.

Association of serum C1Q/TNF-related protein 4 levels with carotid atherosclerosis in subjects with type 2 diabetes mellitus: A cross-sectional study

BackgroundCarotid atherosclerosis (CAS) is a common manifestation of macroangiopathy in type 2 diabetes mellitus (T2DM). C1Q/TNF-related protein 4 (CTRP4) was found to be involved in regulation of food intake behaviors and glucolipid metabolism, which were also key factors in the development of CAS. However, the relationship between serum CTRP4 and CAS in T2DM remains unclear. MethodsA total of 111 participants with T2DM were enrolled in the study and were divided into 2 groups (T2DM group and T2DM + CAS group) according to the result of carotid ultrasound examinations. Serum CTRP4 levels were measured by enzyme linked immunosorbent assay (ELISA). Trend χ2 test and binary stepwise logistic regression were conducted to assess the association between serum CTRP4 and the risk of CAS in T2DM. ResultsSerum CTRP4 concentrations in T2DM + CAS group were significantly lower compared with those in T2DM group [7.98 (5.53) vs. 11.29 (7.36) ng/ml, P < 0.01]. The risk of CAS in T2DM decreased with the increasing of CTRP4 quartiles (P for trend < 0.01). Binary stepwise logistic regression suggested that serum CTRP4 might be an independent influence factor for CAS in patients with T2DM (P < 0.01) and high concentrations of serum CTRP4 were related to low risk of CAS in T2DM. ConclusionsThe concentrations of serum CTRP4 are lower in T2DM patients with CAS compared to those without CAS. Serum CTRP4 levels are negatively related to the risk of CAS in T2DM.

The association between lipoprotein (a) and carotid atherosclerosis in patients with type 2 diabetes without pre-existing cardiovascular disease: A cross-sectional study

AimsLipoprotein (a) [Lp(a)] has been considered a determinant of residual cardiovascular risk. We aimed to investigate associations between serum Lp(a) levels and carotid atherosclerosis. MethodsThis cross-sectional study included 662 type 2 diabetic patients without cardiovascular disease. The mean value of three right and left measurements was used to indentify increased carotid intima-media thickness (CIMT). A carotid plaque was defined as a focal wall thickening >50% of the surrounding IMT or its CIMT ≥1.5 mm. The presence of carotid atherosclerosis was defined as having CIMT ≥1.0 mm or carotid plaque. ResultsA total of 34.3% of patients had carotid atherosclerosis. The median Lp(a) level was significantly higher in subjects with carotid atherosclerosis (14.6 vs. 10.2 mg/dL, P < 0.001). The log-transformed Lp(a) level per 1-standard deviation increase was significantly associated with higher risk of the presence of carotid atherosclerosis (odds ratio [OR] 1.46; 95% confidence interval [CI] 1.16 – 1.84, P = 0.001) after adjusting other parameters. The log Lp(a) level was still significantly associated with the risk of carotid atherosclerosis in subjects with optimal low-density lipoprotein cholesterol (LDL-C) <100 mg/dL (OR 1.48; 95% CI 1.16 – 1.88, P = 0.001). Higher Lp(a) and LDL-C had an additive effect on the presence of carotid atherosclerosis. ConclusionElevated Lp(a) was significantly associated with the presence of carotid atherosclerosis in patients with type 2 diabetes, independent of conventional cardiometabolic risk factors.

The associations among arterial stiffness, endothelial dysfunction and the progression of carotid atherosclerosis in hypertensive subjects with/without carotid atherosclerosis

Abstract Background While arterial stiffness and endothelial dysfunction, which are diffuse vascular damage, are phenotypes of vascular damage, their associations with the progression of atherosclerosis, which is focal vascular damage, has not been fully clarified. The present prospective observational study was conducted to examine whether arterial stiffness and endothelial dysfunction predict the progression of carotid atherosclerosis in subjects medicated for hypertension with/without carotid atherosclerosis. Methods and results In 617 subjects receiving antihypertensive treatment, we conducted flow-mediated vasodilatation (FMD), brachial-ankle pulse wave velocity (baPWV) and common carotid artery intima-media thickness mean and maximal (IMTmean and IMTmax) at the baseline and the end (3 years' later) of study periods. During the study period, FMD was decreased and baPWV, IMTmean and IMTmax were increased significantly. In subjects without carotid atherosclerosis (IMTmax &amp;lt;1.1mm, n=416), baPWV, but not FMD, at baseline had significant associations with IMTmean and IMTmax at both the baseline and end of study period. As shown in Figure, the changes of IMTmean and also IMTmax during the study period were higher in the highest tertile ranges of baPWV at the baseline than in the lowest tertile range of baPWV. On the other hand, in subjects with carotid atherosclerosis (IMTmax &amp;gt;1.1mm, n=201), both baPWV and FMD were not associated with any markers of carotid atherosclerosis and also their changes during the study period. Conclusion In subjects with hypertension, arterial stiffness rather than endothelial dysfunction may be associated with the progression of carotid atherosclerosis, and this association may be significant in the premature stage of atherosclerosis. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Omron Healthcare, Asahikasei Calpis

The Circulating Fatty Acid Transporter Soluble CD36 Is Not Associated with Carotid Atherosclerosis in Subjects with Type 1 and Type 2 Diabetes Mellitus

This study aimed to determine the association of fatty acid transporter plasma soluble cluster of differentiation 36 (sCD36) with subclinical carotid atherosclerosis (SCA). A cross-sectional study was conducted in 1023 subjects, 225 with type 1 diabetes (T1D), 276 with type 2 diabetes (T2D) and 522 who were nondiabetic. Carotid atherosclerotic plaque (CAP) presence was determined using B-mode carotid ultrasound imaging. sCD36 were analysed by ELISA, and CD36 surface receptor and mRNA expression were measured by flow cytometry and real-time PCR. Logistic regression models were used to evaluate sCD36 as a biomarker of SCA. Up to 376 (36.75%) participants had at least one CAP, 76 T1D, 164 T2D and 136 without diabetes, while the remaining 647 (63.25%) did not have any CAP. There were no differences in sCD36 between patients with and without CAP in T1D (p = 0.287) or T2D (p = 0.513). Although nondiabetic subjects with plaques had lower sCD36 levels than those without (p = 0.023), the multivariate models revealed no association of sCD36 with CAP in any of the three study groups. No differences were found in surface CD36 or CD36 mRNA expression between the patients with and without CAP. sCD36 is not associated with SCA in type 1 or type 2 diabetic or in nondiabetic subjects.

Combined serum free light chain levels are associated with carotid atherosclerosis in type 2 diabetes mellitus

Background:Patients with type 2 diabetes mellitus face an increased risk of cardiovascular events compared to non-diabetic counterparts. Chronic inflammation and activation of the immune system, including B-lymphocyte maturation is believed to play a role in atherosclerosis. Recent investigations suggest combined serum free light chains as a potential biomarker for cardiovascular events. The aim of this analysis was to investigate the association of combined serum free light chain with carotid atherosclerosis in subjects with type 2 diabetes mellitus.Methods:We performed a cross-sectional analysis of data from a prospective single centre 2-year study of 97 patients with type 2 diabetes mellitus and insufficiently controlled cardiovascular risk factors. Complete data on combined serum free light chain, high-sensitivity C-reactive protein were available for 75 subjects.Results:We analysed data of 26 female and 49 male subjects, aged 59 ± 8 years. Their mean body mass index was 31.6 ± 4.4 kg/m2, and the medi...

Association between tongue pressure and subclinical carotid atherosclerosis in relation to platelet levels in hypertensive elderly men: a cross-sectional study

BackgroundAge-related low-grade inflammation causing endothelial disruption influences sarcopenia, hypertension, and atherosclerosis. We reported previously that maintenance of muscle strength in elderly hypertensive men with high platelet levels is positively associated with subclinical atherosclerosis but not in those with low platelet levels. Since reduced tongue pressure is related to sarcopenia, tongue pressure may be associated with subclinical carotid atherosclerosis in hypertensive elderly subjects, and platelet levels may function as an indicator of the association between tongue pressure and subclinical carotid atherosclerosis.MethodsWe conducted a cross-sectional study of 342 hypertensive elderly Japanese men aged 60–89 who participated in an annual health check-up in 2015 and 2016. Subclinical carotid atherosclerosis was defined as a common carotid intima-media thickness (CIMT) of 1.1 mm or more.ResultsIn the overall study population, 171 subjects demonstrated low platelets (< 21.4 × 104/μL). Tongue pressure was significantly inversely associated with subclinical carotid atherosclerosis in these subjects, but not in subjects with high platelets. The known cardiovascular risk factor adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of subclinical carotid atherosclerosis for a 1 standard deviation (SD) increment in tongue pressure (10.4 kPa) were 0.54 (0.35, 0.85) and 1.31 (0.87, 1.96), respectively.ConclusionTongue pressure is inversely associated with subclinical carotid atherosclerosis in hypertensive elderly men with low platelet levels, but not in those with high levels. This finding may thus constitute an efficient tool for clarifying the background mechanism of age-related diseases such as sarcopenia, hypertension, and atherosclerosis.

Combined serum free light chain levels are associated with carotid atherosclerosis in type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus face an increased risk of cardiovascular events compared to non-diabetic counterparts. Chronic inflammation and activation of the immune system, including B-lymphocyte maturation is believed to play a role in atherosclerosis. Recent investigations suggest combined serum free light chains as a potential biomarker for cardiovascular events. The aim of this analysis was to investigate the association of combined serum free light chain with carotid atherosclerosis in subjects with type 2 diabetes mellitus. We performed a cross-sectional analysis of data from a prospective single centre 2-year study of 97 patients with type 2 diabetes mellitus and insufficiently controlled cardiovascular risk factors. Complete data on combined serum free light chain, high-sensitivity C-reactive protein were available for 75 subjects. We analysed data of 26 female and 49 male subjects, aged 59 ± 8 years. Their mean body mass index was 31.6 ± 4.4 kg/m2, and the median B-score was 2 (interquartile range: 0-3). Significant positive correlations between combined serum free light chain and the B-score ( r = 0.38; p = 0.001) as well as combined serum free light chain and high-sensitivity C-reactive protein ( r = 0.35; p = 0.002) were observed. The adjusted odds ratio for a half standard deviation increase in combined serum free light chain was 1.48 (95% confidence interval: 1.05-2.05) in an ordinal regression model for carotid B-score. In our study, combined serum free light chain was associated with carotid atherosclerosis in subjects with type 2 diabetes mellitus.

Phosphoprotein 1 (osteopontin) gene (rs4754) affects markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus.

Our study was designed to test a possible association between polymorphisms of the SPP1 gene (rs4754, rs28357094) and markers of carotid atherosclerosis (CIMT, number of affected segments of carotid arteries, sum of plaque thickness, presence of carotid plaques, and presence of unstable carotid plaques) in subjects with T2DM. The second aim was to test the possible association between polymorphisms of the SPP1 gene (rs4754, rs28357094) and the progression of carotid atherosclerosis (CIMT progression, change in total plaque thickness, change in the number of sites with plaques) in subjects with T2DM. In the prospective study 595 T2DM subjects were enrolled. Markers of carotid atherosclerosis were assessed ultrasonographically. rs4754 and rs28357094 polymorphisms of the phosphoprotein 1 (SPP1) gene were determined with real-time PCR. In our study we found an association between SPP1 rs4754 and the presence of plaques at the time of recruitment, whereas we did not find any association between SPP1 rs28357094 and subclinical markers of carotid atherosclerosis at the time of recruitment. Moreover, we did not find any statistically significant effect of either rs4754 or rs28357094 on subclinical markers of carotid atherosclerosis progression (CIMT progression, change in total plaque thickness, change in the number of sites with plaques). As shown by the multiple linear regression analysis, genotypes of either rs4754 or rs28357094 did not have a statistically significant effect on the progression of subclinical markers of carotid atherosclerosis (CIMT progression, change in total plaque thickness, change in the number of sites with plaques) after the adjustment for confounding variables. We demonstrated an important effect of the SPP1 rs4754 on subclinical markers of carotid atherosclerosis in subjects with T2DM; however, as demonstrated by the multiple linear regression analysis, neither rs4754 nor rs28357094 had an important impact on the progression of subclinical markers of carotid atherosclerosis in subjects with T2DM.

Polymorphism rs2073618 of the osteoprotegerin gene as a potential marker of subclinical carotid atherosclerosis in Caucasians with type 2 diabetes mellitus.

The OPG/RANKL/RANK (osteoprotegerin/receptor-activator of nuclear factor κB ligand/receptor-activator of nuclear factor κB) axis has been recently linked to the development of atherosclerosis and plaque destabilization. We have investigated whether polymorphism rs2073618 of the OPG gene is associated with subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). 595 subjects with T2DM were enrolled in the cross-sectional study. Subclinical markers of carotid atherosclerosis (carotid intima media thickness, plaque thickness, and plaques presence) were assessed with ultrasound at the time of recruitment. Genotyping for rs2073618 (a missense variant located in exon I of the OPG gene) was performed, and OPG serum levels were determined by ELISA. Compared to the GG genotype, the CC genotype of the rs2073618 polymorphism had a significantly increased risk for the presence of carotid plaque (OR = 2.54, 95 % CI = 1.22-5.28, p = 0.01). No statistically significant difference could be detected (p = 0.68) upon comparing median values of serum OPG levels among studied genotype groups in subjects with T2DM. Multivariable linear regression analyses in T2DM subjects demonstrated that GC and CC genotypes (p = 0.03 and p = 0.003), together with statin therapy (p = 0.009), were independent predictors of the number of carotid segments with plaques. Despite the fact that OPG rs2073618 genotypes failed to predict the serum OPG levels as there was no statistical difference among compared genotypes, our results demonstrate that the rs2073618 polymorphism could be a possible genetic marker for the prediction of increased risk for carotid plaque burden as a measure of advanced subclinical atherosclerosis in T2DM subjects.

C-reactive protein as a marker of progression of carotid atherosclerosis in subjects with type 2 diabetes mellitus

This prospective study was designed to evaluate the effect of inflammatory markers on the presence and progression of subclinical markers of carotid atherosclerosis in a 3.8-year follow-up period in patients with type 2 diabetes mellitus (T2DM). A total of 595 subjects with T2DM were enrolled. Subclinical markers of carotid atherosclerosis (carotid intima media thickness (CIMT), plaque thickness, and plaques presence) were assessed with ultrasound at the time of recruitment and again after 3.8 years. Subjects with T2DM were divided into 2 groups according to the plasma high sensitive C-reactive protein (hs-CRP) levels (subjects with hs-CRP ≥ 2 mg/L and subjects with hs-CRP below 2 mg/L). Subjects with T2DM and hs-CRP levels ≥ 2 mg/L had higher CIMT in comparison with subjects with T2DM and hs-CRP levels below 2 mg/L, and higher incidence of plaques/unstable plaques in comparison with subjects with T2DM and hs-CRP levels below 2 mg/L. Multivariate logistic regression analysis found the association between the HDL cholesterol level and presence of plaques, whereas the inflammatory marker hs-CRP was not associated with subclinical markers of progression of carotid atherosclerosis. Multiple linear regression analysis found the association between the hs-CRP levels and either CIMT progression rate or a change in the number of sites with plaques in a 3.8-year follow-up. We demonstrated an association between the inflammatory marker hs-CRP and either CIMT or incidence of plaques/unstable plaques at the time of recruitment in Caucasians with T2DM. Moreover, we found the association between hs-CRP levels and either CIMT progression rate or a change in the number of sites with plaques in a 3.8-year follow-up in subjects with T2DM.

PECAM-1 gene polymorphism (rs668) and subclinical markers of carotid atherosclerosis in patients with type 2 diabetes mellitus.

ABSTRACTThe platelet endothelial cell adhesion molecule 1 (PECAM-1) plays an important role in many inflammatory processes, including the development of atherosclerosis. Polymorphism rs668 of the PECAM-1 gene (373C/G) is functional, and it was reported to be associated with increased serum levels of PECAM-1. We investigated the association between the rs668 polymorphism of PECAM-1 and subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Geno-typing of the PECAM-1 gene polymorphism (rs668) was performed using KASPar assays. The control examinations were performed 3.8 ± 0.5 years after the initial examination. Higher CIMT was found in patients with T2DM in comparison with subjects without T2DM. Statistically sig-nificantly faster progression of the atherosclerotic markers was shown in subjects with T2DM in comparison with the control group. When adjusted to other risk factors, the rs668 GG genotype was associated with an increased risk of carotid plaques in subjects with T2DM. We concluded that our study demonstrated a minor effect of the rs668 PECAM-1 on markers of carotid atherosclerosis in subjects with T2DM.

Polymorphism rs5498 of the ICAM-1 gene affects the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus.

BackgroundAdhesion molecules are involved in the development of atherosclerosis. An increased level of the ICAM 1 molecule is associated with numerous inflammatory diseases including atherosclerosis of carotid arteries. The rs5498 (K469E) polymorphism of the ICAM-1 gene leads to an increase in the level of serum ICAM. We investigated the association between the rs5498 (K469E) polymorphism of the ICAM-1 gene and the progression of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). MethodsThe study included 595 patients with T2DM and 200 subjects in the control group without T2DM. The control examination was made 3.8 years after the initial examination. Indicators of atherosclerosis (carotid intima-media thickness (CIMT), total plaque sum and sum of the plaques thickness) were detected by ultrasound examination. Genetic analyses of the polymorphism rs5498 of the ICAM-1 gene were made by RT-PCR.ResultsThe distribution of genotypes and frequencies of rs5498 polymorphism was not significantly different between the group with type 2 diabetes ( T2DM) and the control group. Genotype EE K469E polymorphism is associated with a statistically significant annual plaques growth.ConclusionThe EE genotype of the rs5498 of the ICAM-1 gene was associated with a more rapid progression of carotid atherosclerosis in patients with T2DM in comparison with other genotypes.

Polymorphisms rs699 and rs4762 of the Angiotensinogen Gene and Progression of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

Background: The aim of the study was to investigate the association between two polymorphisms of the angiotensinogen (AGT) gene (rs699 and rs4762) and subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). Patients and methods: In this cross-sectional study 599 subjects with T2DM and 200 subjects without T2DM (control group) were enrolled. The CIMT and plaque characteristics (presence/absence and plaque thickness) on both the near and the far walls in the common carotid artery, bulb and internal carotid arteries, bilaterally were assessed ultrasonographically. After several years (3.8 ± 0.5 years), patients were re-assessed and changes in subclinical markers of carotid atherosclerosis were calculated. Polymorphisms rs699 and rs4762 of the AGT gene were genotyped by using allele-specific PCR (KASPar) assay. Results: The highest increase in carotid plaque thickness was observed in homozygote carriers of the A allele, even after adjustment for confounding variables. Polymorphism rs699 did not affect the progression of CIMT in the increase of number of segments with plaques. Conclusions: In the study we have found that the rs699 of the AGT gene is a potential genetic marker of carotid atherosclerosis progression (expressed as increase in carotid plaque thickness) in Slovenian patients with T2DM. It did not affect other ultrasonographic markers of carotid atherosclerosis progression. Polypmorphism rs4762 was not associated with carotid atherosclerosis progression in Slovenian patients with T2DM.

Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM.

Impact of Adapted Sports Activities on the Progression of Carotid Atherosclerosis in Subjects With Spinal Cord Injury

ObjectiveTo determine whether regular performance of adapted sports is associated with long-term changes in carotid atherosclerosis in subjects with spinal cord injury (SCI). DesignProspective observational study. SettingAcademic medical center. ParticipantsMen with chronic (>1y) SCI and no preserved motor function below the injury level were evaluated in 2007 and 2012 (N=17). Nine subjects did not perform physical activity between the studied time points (control group), whereas 8 subjects entered competitive upper-body sports programs (rugby: n=5, basketball: n=1, jiu-jitsu: n=1, and tennis: n=1) after baseline and were regularly training at the time of the second evaluation (sports group). InterventionsNot applicable. Main Outcome MeasuresClinical, laboratory, hemodynamic, and carotid ultrasonography analysis. ResultsThe studied groups showed no differences in all studied variables at baseline. After 5 years of follow-up, the control group showed increases in heart rate (87.0±3.1 vs 74.7±3.8 beats per minute; P=.004), but the participants had no significant changes in carotid intima-media thickness (IMT) (.65±.05 vs .67±.03mm; P=.73) or IMT/diameter (.118±.007 vs .136±.013; P=.24). In contrast, the sports group showed long-term decreases in carotid IMT (.56±.05 vs .74±.05mm; P=.001) and IMT/diameter (.097±.006 vs .141±.009; P<.001), but the participants did not show any variation in the other studied variables at follow-up. ConclusionsRegular upper-body sports activities are associated with long-term reductions in carotid atherosclerosis in subjects with SCI and might be a potential prevention strategy aiming to reduce cardiovascular risk in this population.