Diabetes modifies the relationships among carotid plaque calcification, composition and inflammation.

Type 2 diabetes is associated with more advanced coronary atherosclerosis on multislice computed tomography and virtual histology intravascular ultrasound

Vascular calcification associates independently with cardiovascular events and morbidity. Plaque composition and calcification burden differ between arterial beds. Cardiovascular risk factors (CVRF) affect plaque development differentially between arterial beds. The aim of this study was to evaluate the impact of CVRF on atherosclerotic plaque calcification, and further study molecular arterial heterogeneity that could drive these differences. Histological analysis performed on atherosclerotic plaques (153 carotid, 97 femoral and 28 infrapopliteal arteries) showed that femoral arteries are the most calcified arteries overall. They were highly susceptible to osteoid metaplasia. CVRF showed minor association with plaque calcification types: age and hypertension only affected the presence of calcification overall, but not type of the calcification, which differed significantly between arterial beds. Transcriptome analysis revealed distinct gene expression profiles for each pathological arterial bed, but also for healthy arteries. Canonical pathway analysis showed a preferential involvement of immune-related processes in both atherosclerotic and healthy carotid arteries. Bone remodeling-related genes were among those mostly enriched in atherosclerotic and healthy femoral arteries, which are more prone to develop endochondral calcification. We observed similar findings between cultured SMCs isolated from healthy arteries. These molecular differences translated into functional disparities. SMC from femoral arteries showed the highest propensity to mineralize due to an increase in basal TGFβ signaling. Our results suggest that biological heterogeneity of resident vascular cells between arterial beds, reflected by our transcriptomic analysis, is critical in understanding plaque biology and calcification, and may have strong implications in vascular therapeutic approaches.

Carotid Plaque Composition in Chronic Kidney Disease: A Retrospective Analysis of Patients Undergoing Carotid Endarterectomy

Cardiovascular events are high in patients with type 2 diabetes, whereas their risk stratification is more difficult. The higher risk may be related to differences in coronary plaque burden and composition. The purpose of this study was to evaluate whether differences in the extent and composition of coronary plaques in patients with and without diabetes can be observed using multislice computed tomography (MSCT). MSCT was performed in 215 patients (86 [40%] with type 2 diabetes). The number of diseased coronary segments was determined per patient; each diseased segment was classified as showing obstructive (> or = 50% luminal narrowing) disease or not. In addition, plaque type (noncalcified, mixed, and calcified) was determined. Plaque characteristics were compared in patients with and without diabetes. Regression analysis was performed to assess the correlation between plaque characteristics and diabetes. Patients with diabetes showed significantly more diseased coronary segments than nondiabetic patients (4.9 +/- 3.5 vs. 3.9 +/- 3.2, P = 0.03) with more nonobstructive (3.7 +/- 3.0 vs. 2.7 +/- 2.4, P = 0.008) plaques. Relatively more noncalcified (28 vs. 19%) and calcified (49 vs. 43%) and less mixed (23 vs. 38%) plaques were observed in patients with diabetes (P < 0.0001). Diabetes correlated with the number of diseased segments and nonobstructive, noncalcified, and calcified plaques. Differences in coronary plaque characteristics on MSCT were observed between patients with and without diabetes. Diabetes was associated with higher coronary plaque burden. More noncalcified and calcified plaques and less mixed plaques were observed in diabetic patients. Thus, MSCT may be used to identify differences in coronary plaque burden, which may be useful for risk stratification.

The aim of this study was to investigate the association between the aortic valve calcium score (AVCS) and the coronary plaque burden using 64-slice multi-detector computed tomography (MDCT). Calcification of the aortic valve without significant aortic stenosis itself has been suggested to be a marker of atherosclerosis. In this study, we attempted to identify a quantitative correlation between AVCS and the coronary plaque burden assumed by the Gensini score. We retrospectively evaluated 200 patients (aged 40 - 88 years) who underwent MDCT and coronary angiography for chest pain. After exclusion of an aortic stenosis (peak velocity ≥ 2.0 m/s), the plaque burden of the coronary artery was determined by the Gensini score based on the plaque composition (calcified, mixed, or noncalcified plaque) of the CT angiogram. The calcific aortic valve group (AVCS > 0) showed no significant difference in the total plaque burden compared to the noncalcific aortic valve group (AVC = 0) (Gensini score 23.6 ± 15.1 versus 21.2 ± 17.5, P = 0.31). However, the calcified plaque burden was higher in the calcific aortic valve group (Gensini score by calcified plaque 9.1 ± 10.4 versus 5.5 ± 8.6, P = 0.008). In the subgroup of patients who had an AVCS of more than 90.0 (upper 75th percentile, n = 20), the AVCS showed a more significant correlation with the Gensini score by calcified plaque (r = 0.618, P < 0.01). Our results suggest that a high level of AVCS is associated with the calcified plaque burden of the coronary artery rather than the total plaque burden.

Calcification has been associated with carotid plaque stability; however, an acceptable in vivo method to define plaques based on this component remains to be developed. The purpose of our study was to compare calcified and noncalcified volumes of carotid artery culprit symptomatic plaques with asymptomatic plaques using multidetector computed tomography. We identified 102 patients with > or =50% stenosis using NASCET criteria by multidetector computed tomography angiography between January 2004 and May 2006, which included 35 symptomatic (stenosis: 82.0+/-11.9%) and 67 asymptomatic patients (stenosis: 79.4+/-10.8%). Total plaque volume, noncalcified plaque volume, calcified plaque volume, and calcified/total ratio were measured for the 102 index plaques causing stenosis. In a model including age, stenosis, and cardiovascular risk factors, calcified plaque volume/total plaque volume was significantly inversely associated with the occurrence of symptoms (P=0.012; odds ratio, 0.047; 95% CI, 0.004 to 0.511). There was a notable overlap in the calcified plaque volume/total plaque volume ratio between 0% and 45% for symptomatic and asymptomatic plaques. However, calcification >45% of the total plaque was very specific: 97.1% (34/35) for absence of symptoms (sensitivity: 28.4% 19/67). No significant association between total plaque volume, noncalcified plaque volume, or calcified plaque volume and symptomatology was found. The proportion of carotid plaque calcification, rather than absolute volume, is associated with stability in patients with stenosis. Specifically, for a subset of patients, plaque calcification >45% of the total volume may represent a clinically useful cutoff. The carotid plaque calcium ratio, determined by multidetector computed tomography volume measurements, may help noninvasively risk stratify patients with asymptomatic stenosis.

Multidetector computed tomography coronary artery plaque predictors of stress-induced myocardial ischemia by SPECT

Individuals with type 2 diabetes are at increased risk of cardiovascular disease (CVD) mortality and display increased levels of subclinical CVD. Genetic variation in PTPN1, a diabetes susceptibility gene, was investigated for a role in diabetic atherosclerosis. The PTPN1 gene encodes protein tyrosine phosphatase-1B, which is ubiquitously expressed and plays a role in the regulation of several signaling pathways. Subclinical atherosclerosis was assessed in 590 Caucasian participants with type 2 diabetes in the Diabetes Heart Study using B-mode ultrasound measurement of carotid intima-media thickness (IMT) and computed tomography measurement of carotid calcified plaque (CarCP) and coronary calcified plaque (CorCP). Twenty-three single nucleotide polymorphisms (SNPs) in PTPN1 were genotyped and assessed for association with IMT, CarCP, and CorCP. A total of 12 SNPs within a block of linkage disequilibrium encompassing the coding sequence of PTPN1 were significantly associated with CorCP (P values from <0.0001 to 0.043) and 3 SNPs also within the block approached significance (P values from 0.058 to 0.066). In addition, a nine-SNP haplotype (GACTTCAGO) was also associated with increased CorCP under a dominant model (P = 0.01). No association was detected with IMT or CarCP. The associated SNPs and haplotype are the same as those observed to be associated with type 2 diabetes, insulin resistance, and fasting glucose in previous studies. With the inclusion of the most likely haplo-genotype for each individual, the heritability estimate of CorCP increased from 0.53 +/- 0.1 to 0.57 +/- 0.1 (P = 8.1 x 10(-10)), suggesting a modest but detectable effect of this gene on the phenotype of CorCP in type 2 diabetic patients.

Effect of the Tyrosine Kinase Inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) On Blood Glucose Levels in Diabetic and Non-Diabetic Patients.

Molecular stabilizing mechanism in calcified carotid plaques

It remains achallenge to determine criteria according to which patients with asymptomatic carotid stenosis could be properly qualified for revascularization treatment. Carotid calcification assessment seems to be here quite attractive. The aim of the study was the histological analysis of various parameters of calcifications in human carotid plaques in relation to the symptomatic/asymptomatic nature of the lesions. The study involved carotid plaques taken from patients who have undergone endarterectomy of the internal carotid artery. Calcified plaques (with enlarged calcifications) were significantly more frequently asymptomatic than non-calcified plaques. The remaining calcification characteristics played no role. Calcified lesions disclosed the dominance of the fibrous component and the small lipid core significantly more frequently than non-calcified plaques. The percentage of females in the patients group with calcified lesions was significantly higher than in the group with non-calcified plaques. The percentage of males was lower. The former patients group used statins and angiotensin inhibitors significantly more frequently than patients with non-calcified plaques. Enlarged calcifications were independently associated with the asymptomatic nature of the carotid plaques. The enlargement of calcifications in carotid plaques is the only calcification parameter important for the clinical outcome of carotid atherosclerosis. Patients with calcified carotid plaques have asignificantly lower risk of ischemic stroke than patients with non-calcified lesions.

Bone mineral density (BMD) and bone metabolism marker may contribute to the progression of carotid and cardiac arterial calcifications. The aim of this study was to investigate whether low bone mass and the change of bone biomarker are associated with the prevalence of calcified atherosclerotic plaque in elderly Chinese. We conducted a five-year prospective study. BMD was measured by dual-energy X-ray absorptiometry scanning. Carotid and cardiac computed tomography angiography (CTA) was conducted using a 64-multidetector row scanner to assess carotid and cardiac arterial plaque at baseline and during follow-up. Of 1571 community residents over 60years of age, 184 (11.7%) subjects developed carotid calcified plaque, 510 (32.5%) subjects developed cardiac calcified plaque and 97 (6.2%) subjects developed co-existence calcified plaques in carotid and cardiac arteries. After adjustment for age and all relevant confounders, Q1, Q2 quartile of BMD, and osteoprotegerin (OPG), osteocalcin (OC), and C-terminal cross-linked telopeptide of type I collagen (CTX) were associated with increased risk of calcified plaques. This study suggested that lower BMD and change of bone metabolism biomarker were associated with a higher risk of carotid and cardiac calcified plaque development.

Background Heart failure (HF) is the most common cardiovascular causes of hospitalization in people over 60 years affecting about 64.3 million people worldwide. Few studies have investigated sodium glucose like transporter-2 inhibitors (SGLT-2I) role in diabetic and non-diabetic patients with HF. Objective We conducted our meta-analysis to further investigate SGLT-2I role in diabetic and non-diabetic HF patients. Methods PubMed, Scopus, web of science, and Embase were searched. All clinical trials that compared the effect of SGLT2 inhibitors versus placebo on heart failure patients were included. Dichotomous data were extracted, pooled as risk ratio (RR) with 95% confidence interval, and analyzed via RevMan version 5.3 for windows using Mantel Haenszel (M-H) method. Results Twelve randomized clinical trials were included for analysis with a total number of 69024 patients. SGLT2I significantly lowered the risk of hospitalization for heart failure (HHF) in diabetic (RR=0.68, 95% CI 0.63–0.74) and non-diabetic patients (RR=0.75, 95% CI 0.62–0.89). Also, it significantly lowered mortality risk in both diabetic (RR=0.87, 95% CI 0.77–0.99) and non-diabetic patients (RR=0.93, 95% CI 0.70–1.23). Further analyses for serious adverse events were conducted, and SGLT-2I showed a significant lower risk in diabetic (RR=0.94, 95% CI 0.90–0.98) and non-diabetic patients (RR=0.72, 95% CI 0.38–1.39), yet with no observed difference over placebo in the risk of stroke. Conclusion SGLT2 inhibitors showed a favorable effect in lowering cardiovascular mortality, HHF, and stroke in diabetic patients with heart failure. In non-diabetic patients, they significantly reduce HHF, yet with no difference on cardiovascular mortality and stroke. Therefore, more trials are needed to establish their effect in non-diabetic patients. Funding Acknowledgement Type of funding sources: None.

To compare serum protein levels between diabetic and non-diabetic patients with retinopathy. Comparative study. Ziauddin Medical University and Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from 2000 to 2002. Sixty patients were selected. Among them, 21 were diabetic patients without any clinical evidence of chronic diabetic complications; 20 were diabetic patients with retinopathy and 19 were non-diabetic patients with retinopathy. Twenty-one apparently normal, age, gender and weight-matched control subjects were also inducted. All these patients were selected on clinical grounds. Blood values, fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, glycosylated plasma protein, hexosamine, sialic acid and total serum proteins were determined and compared. Fasting plasma glucose was high in all diabetic patients and correlated significantly with glycosylated hemoglobin, glycosylated plasma proteins and serum fructosamine concentrations. Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein were increased in diabetic patients with retinopathy and diabetic patients without any complications. These values were not different in diabetic patients with retinopathy and diabetic patients without chronic complications as compared with control subjects. Alpha-1 and alpha-2 globulins were significantly increased in diabetic patients with retinopathy, diabetic patients without complications and non-diabetic patients with retinopathy as compared with control subjects. Beta globulin was significantly increased in diabetic patients with retinopathy as compared with non-diabetic patients with retinopathy, diabetic patients without complication and control subjects. Gamma globulin was significantly decreased in diabetic and non-diabetic patients with retinopathy. Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein were increased in diabetic patients with and without complications but these parameters remained within normal limits in non-diabetic patients with retinopathy. The decrease in gamma globulins may be associated with a retinopathy.

Vascular calcification is a strong and independent predictive factor for cardiovascular complications and mortality. Our previous work identified important discrepancies in plaque composition and calcification types between carotid and femoral arteries. The objective of this study is to further characterize and understand the heterogeneity in vascular calcification among vascular beds, and to identify molecular mechanisms underlying this process. We established ECLAGEN biocollection that encompasses human atherosclerotic lesions and healthy arteries from different locations (abdominal, thoracic aorta, carotid, femoral, and infrapopliteal arteries) for histological, cell isolation, and transcriptomic analysis. Our results show that lesion composition differs between these locations. Femoral arteries are the most calcified arteries overall. They develop denser calcifications (sheet-like, nodule), and are highly susceptible to osteoid metaplasia. These discrepancies may derive from intrinsic differences between SMCs originating from these locations, as microarray analysis showed specific transcriptomic profiles between primary SMCs isolated from each arterial bed. These molecular differences translated into functional disparities. SMC from femoral arteries showed the highest propensity to mineralize due to an increase in basal TGFβ signaling. Our results suggest that biological heterogeneity of resident vascular cells between arterial beds, reflected by our transcriptomic analysis, is critical in understanding plaque biology and calcification, and may have strong implications in vascular therapeutic approaches.