Occurrence Of Atherosclerotic Plaques Research Articles

Diagnosis and Vulnerability Risk Assessment of Atherosclerotic Plaques Using an Amino Acid-Assembled Near-Infrared Ratiometric Nanoprobe.

To reduce the risk of atherosclerotic disease, it is necessary to not only diagnose the presence of atherosclerotic plaques but also assess the vulnerability risk of plaques. Accurate detection of the reactive oxygen species (ROS) level at plaque sites represents a reliable way to assess the plaque vulnerability. Herein, through a simple one-pot reaction, two near-infrared (NIR) fluorescent dyes, one is ROS responsive and the other is inert to ROS, are coassembled in an amphiphilic amino acid-assembled nanoparticle. In the prepared NIR fluorescent amino acid nanoparticle (named FANP), the fluorescent properties and ROS-responsive behaviors of the two fluorescent dyes are well maintained. Surface camouflage through red blood cell membrane (RBCM) encapsulation endows the finally obtained FANP@RBCM nanoprobe with not only further reduced cytotoxicity and improved biocompatibility but also increased immune escape capability, prolonged blood circulation time, and thus enhanced accumulation at atherosclerotic plaque sites. In vitro and in vivo experiments demonstrate that FANP@RBCM not only works well in probing the occurrence of atherosclerotic plaques but also enables plaque vulnerability assessment through the accurate detection of the ROS level at plaque sites in a reliable ratiometric mode, thereby holding great promise as a versatile tool for the diagnosis and risk assessment of atherosclerotic disease.

Metabolic changes with the occurrence of atherosclerotic plaques and the effects of statins.

Atherosclerosis is a common cardiovascular disease caused by the abnormal expression of multiple factors and genes influenced by both environmental and genetic factors. The primary manifestation of atherosclerosis is plaque formation, which occurs when inflammatory cells consume excess lipids, affecting their retention and modification within the arterial intima. This triggers endothelial cell (EC) activation, immune cell infiltration, vascular smooth muscle cell (VSMC) proliferation and migration, foam cell formation, lipid streaks, and fibrous plaque development. These processes can lead to vascular wall sclerosis, lumen stenosis, and thrombosis. Immune cells, ECs, and VSMCs in atherosclerotic plaques undergo significant metabolic changes and inflammatory responses. The interaction of cytokines and chemokines secreted by these cells leads to the onset, progression, and regression of atherosclerosis. The regulation of cell- or cytokine-based immune responses is a novel therapeutic approach for atherosclerosis. Statins are currently the primary pharmacological agents utilised for managing unstable plaques owing to their ability to enhance endothelial function, regulate VSMC proliferation and apoptosis by reducing cholesterol levels, and mitigate the expression and activity of inflammatory cytokines. In this review, we provide an overview of the metabolic changes associated with atherosclerosis, describe the effects of inflammatory responses on atherosclerotic plaques, and discuss the mechanisms through which statins contribute to plaque stabilisation. Additionally, we examine the role of statins in combination with other drugs in the management of atherosclerosis.

Atheromatosis of the brain-supplying arteries: Circle of Willis, basilar, vertebral and their branches

PurposeAtherosclerotic plaques in the brain-supplying arteries are slowly-developing alterations of vascular structures that can lead to neurological impairment due to stenosis and insufficient oxygenation of eloquent brain areas. The aim of this study is to provide detailed demographic information related to the incidence of atherosclerotic plaques in the cerebral arteries. Material and methodsForty-eight circles of Willis (21 men, 21 women, mean age: 70.26, six samples unknown) were macroscopically analyzed for length, diameter, and presence of atherosclerotic plaques. Statistical analysis was used to identify potential differences in the locations and frequencies of atherosclerotic plaques in relation to age and sex. ResultsThe study sample revealed 261 atherosclerotic plaques. The key findings were significant correlations between plaque development and age and between plaque location and age; however, there was no significant sex difference. ConclusionThe upper and lower branches of the middle cerebral artery (MCA) were novel locations predisposing to plaque development. A cut-off value at 60 years revealed a significant difference in plaque development and distribution. There were no significant sex differences in the occurrence of atherosclerotic plaques.

Relationship between subclasses low-density lipoprotein and carotid plaque.

BackgoundLow-density lipoprotein (LDL) cholesterol can lead to the occurrence of atherosclerotic plaques, but patients with normal LDL still have atherosclerotic plaques in clinical practice. With the proposal of LDL subclass, this experiment investigated the relationship between the LDL content of different subclasses and the stability of carotid plaques.MethodsPlaque stability was suggested by carotid ultrasound results. 37 patients with stable plaques were classified into one group and 41 patients with unstable plaques were classified into another group. The data of age, glycosylated hemoglobin (Ghb), and homocysteine (Hcy) were collected. The contents of LDL subclasses were measured by LIPOPRINT system. The data of total cholesterol (TC), LDL cholesterol, and triglyceride (TG) were collected. The plaque stability was assessed by carotid artery color Doppler ultrasound and the intima-media thickness (IMT) was measured.ResultsThe levels of LDL-1 subclass 19.00 (13.00, 27.50) and LDL-2 subclass (21.62 ± 7.24) in the stable plaque group were higher than those in the unstable plaque group (p < 0.05). The levels of LDL-3 subclass (12.24 ± 4.58), LDL-4 subclass 5.00 (2.00, 9.00), and sd-LDL 0 (0.00, 3.00) in the unstable plaque group were higher than those in the stable plaque group (p < 0.05). LDL-1 subclass (adjusted OR = 0.923 and p < 0.05), and LDL-3 subclass (adjusted OR = 1.176 and p < 0.05) were independent risk factors for plaque stability.ConclusionElevated LDL1 is associated with stable plaques whereas LDL3 was found associated with unstable plaques.

Beneficial Effect of Successful Simultaneous Pancreas-Kidney Transplantation on Plasma Profile of Metalloproteinases in Type 1 Diabetes Mellitus Patients.

It is not fully elucidated whether the restoring of normal glucose metabolism after successful simultaneous pancreas-kidney transplantation (SPK) improves vascular wall morphology and function in type 1 diabetic (T1D) patients. Therefore, we compared arterial stiffness, assessed by pulse wave velocity (PWV), carotid intima-media thickness (IMT), and biomarkers of arterial wall calcification in T1D patients after SPK or kidney transplantation alone (KTA). In 39 SPK and 39 KTA adult patients of similar age, PWV, IMT, circulating matrix metalloproteinases (MMPs) and calcification biomarkers were assessed at median 83 months post transplantation. Additionally, carotid plaques were visualized and semi-qualitatively classified. Although PWV and IMT values were similar, the occurrence of atherosclerotic plaques (51.3 vs. 70.3%, p < 0.01) and calcified lesions (35.9 vs. 64.9%, p < 0.05) was lower in SPK patients. There were significantly lower concentrations of MMP-1, MMP-2, MMP-3, and osteocalcin in SPK subjects. Among the analyzed biomarkers, only logMMP-1, logMMP-2, and logMMP-3 concentrations were associated with log HbA1c. Multivariate stepwise backward regression analysis revealed that MMP-1 and MMP-3 variability were explained only by log HbA1c. Normal glucose metabolism achieved by SPK is followed by the favorable profile of circulating matrix metalloproteinases, which may reflect the vasoprotective effect of pancreas transplantation.

SUN-121 ASSOCIATION BETWEEN A NOVEL BIOMARKER, SERUM MIDKINE, AND ASYMPTOMATIC AND CLINICAL CARDIOVASCULAR DISEASE IN ELDERLY WOMEN

Elevated Midkine (MK) levels have been associated with acute cardiac events in patients with chronic heart failure. However its prognostic value in predicting subclinical and clinical outcomes of CVD in the elderly general population remains unknown. This study aims to determine the relationship between serum MK and asymptomatic measures and clinical outcomes of CVD in a large cohort of elderly women with long-term clinical follow-up. This was a prospective study of ageing women. Serum MK was measured in 1998 (baseline). The univariate association between baseline serum MK with baseline abdominal aortic calcification (AAC) 24 scores was analysed using Spearman’s correlation. Differences in baseline AAC24 scores, change in AAC24 scores at 5 years, and common carotid artery intimal medial thickness (CCA-IMT) at 3 years between medians of serum MK were assessed using analysis of covariance, adjusting for age, body mass index (BMI), baseline estimated glomerular filtration rate (eGFR), smoking history, diabetes, use of blood pressure lowering medications, use of statins, calcium treatment code and prevalent atherosclerotic vascular disease (ASVD). Associations between baseline serum MK and the occurrence of atherosclerotic plaques at 3 years, and atherosclerotic vascular disease (ASVD)-related hospitalisations and deaths at 14.5 years as a composite outcome were examined using logistic and Cox regression analyses respectively, adjusting for similar risk factors. The baseline cohort consisted of women aged over 70 years, with a median age of 75. Throughout the follow-up period of 15 years, there were a total of 206 deaths, and 225 ASVD-related hospitalisations and deaths. Baseline serum MK was correlated with baseline AAC24 scores in the univariate analysis (r = 0.111, p = 0.035). Baseline AAC24 scores were not significantly different between below and above-median baseline serum MK (below-median: 3.15 ± 0.26 vs above-median: 3.30 ± 0.27, p = 0.684), however the increase in AAC24 scores at 5 years was significantly higher in participants with above-median baseline serum MK as compared to those with below-median baseline serum MK (below median: 0.90 ± 0.18 vs above-median 1.64 ± 0.20, p = 0.007) after multivariable-adjustment. At 3 years, mean and maximum CCA-IMT were significantly greater in participants with above-median baseline serum MK as compared to those with below-median baseline serum MK after multivariable adjustment (below median: 0.769 ± 0.011 mm vs above-median: 0.802 ± 0.011 mm, p = 0.035; below-median: 0.910 ± 0.012 mm vs above-median: 0.951 ± 0.013 mm, p = 0.024, respectively), however above-median baseline serum MK was not associated with an increased risk of occurrence of atherosclerotic plaques (odds ratio = 0.99, 95% CI = 0.63-1.55, p = 0.964). Compared to below-median, above-median baseline serum MK was associated with a 1.3-fold increased risk of ASVD-related hospitalisations and deaths at 14.5 years (hazard ratio = 1.37, 95% CI = 1.05, 1.80, p = 0.022) after adjusting for known risk factors. In older women, elevated serum MK is associated with AAC outcomes and asymptomatic measures and clinical outcomes of ASVD. These results suggest that MK could be potential risk factor for CVDs, and further prospective studies are needed to determine the prognostic importance of elevated MK with CVD clinical outcomes.

Blood Lead Levels and Risk of Atherosclerosis in the Carotid Artery: Results from a Swedish Cohort.

Background:Lead exposure has been associated with increased incidence of adverse clinical cardiovascular outcomes. Atherosclerosis has been suggested as one of the underlying mechanisms, and findings from experimental studies support this, but human data are scarce.Objectives:Our objective was to determine the association between environmental lead exposure based on blood lead (B-Pb) concentrations and the prevalence of atherosclerotic plaque in the carotid artery.Methods:We used cross-sectional data from the Malmö Diet and Cancer Study cardiovascular cohort (MDCS-CC; recruitment in 1991–1994) covering 4,172 middle-aged men and women. B-Pb at baseline, measured by inductively coupled plasma mass spectrometry, was used as the exposure biomarker. The presence of atherosclerotic plaque in the carotid artery was determined by B-mode ultrasonography. We used logistic regression to estimate odds ratios (ORs) for prevalence of plaque in the carotid artery according to B-Pb quartiles.Results:The median B-Pb was (range: 1.5–258), and 36% of the cohort had any atherosclerotic plaque. After controlling for confounders and known cardiovascular risk factors, the OR for prevalence of plaque in the highest quartile (Q4) of B-Pb compared with the lowest quartile (Q1) was 1.35 (95% CI: 1.09, 1.66) in the total group, 1.58 (95% CI: 1.20, 2.08) among women, and 1.18 (95% CI: 0.83, 1.69) among men. Among women, associations were limited to those who were postmenopausal [OR for Q4 vs. 1.72 (95% CI: 1.26, 2.34) vs. 0.96 (95% CI: 0.49, 1.89 in premenopausal women)]. Associations were weak and nonsignificant in never-smokers [OR for Q4 vs. 1.14 (95% CI: 0.81, 1.61)].Discussion:Our study shows an association between B-Pb concentrations and occurrence of atherosclerotic plaque in the carotid artery, adding evidence for an underlying pro-atherogenic role of lead in cardiovascular disease. Associations appeared to be limited to postmenopausal (vs. premenopausal) women. https://doi.org/10.1289/EHP5057

Interplay of nitric oxide metabolites and markers of endothelial injury, inflammation, and vascular disease in the spectrum of advanced chronic kidney disease.

Chronic kidney disease is linked to cardiovascular morbidity; therefore, relevant biomarkers are widely investigated. We aimed to assess the relationship between nitric oxide (as measured by its metabolites, NOx), a key endothelial molecule, with markers of endothelial dysfunction, inflammation, antioxidant status, and mineral disorders as well as histologically assessed vascular calcification in uremic and hemodialysis patients with chronic kidney disease. Plasma and serum samples were obtained from 62 patients with renal failure. NOx was assessed by the Griess method, while the other biomarkers were measured by the immunoenzymatic assay. Morphological analysis of arterial calcification was performed in a blinded, semiquantitative manner. Common carotid intima‑media thickness and atherosclerotic plaques were assessed by ultrasonography. In the simple analysis, NOx levels correlated positively with the parameters of renal function, mineral metabolism, endothelial injury, and inflammation. NOx predicted carotid intima‑media thickness in simple (P = 0.014) and multiple analysis (P = 0.036) adjusted for the Framingham risk score, C‑reactive protein, serum creatinine, and parathormone. The occurrence of atherosclerotic plaques in the common carotid artery was correlated with higher NOx concentrations (P = 0.021). In chronic renal failure, NOx is associated with surrogate markers of atherosclerosis, even after adjustment for traditional cardiovascular risk factors, inflammation, and renal function, but not with the presence or grade of medial arterial calcification. Endothelial injury, inflammation, and mineral metabolism markers are associated with NOx levels, though a causal link requires further study.

Is cadmium exposure associated with the burden, vulnerability and rupture of human atherosclerotic plaques?

The general population is exposed to cadmium from food and smoking. Cadmium is a widely spread toxic pollutant that seems to be associated with cardiovascular diseases, although little is known if it contributes to the occurrence of atherosclerotic plaques and the process whereby plaques become vulnerable and are prone to rupture. We tested the hypotheses that cadmium exposure is associated not only with an increased subclinical burden of atherosclerotic plaques in different vascular territories and early signs of plaque vulnerability, but also with cadmium content and plaque-rupture in the clinical phase of the disease. Ultrasound technique was used to measure plaque prevalence and echogenicity in the carotid and femoral arteries in a population sample of women (n = 599) in whom blood cadmium was measured. In addition cadmium was measured in snap-frozen endarterectomies and whole blood obtained from patients who were referred to surgery because of symptomatic carotid plaques (n = 37). Sixteen endarterectomies were divided into three parts corresponding to different flow conditions and plaque vulnerability. In the population sample blood cadmium was associated with the number of vascular territories with plaques (p = 0.003 after adjustment for potential confounders). The cadmium concentrations in symptomatic plaques were 50-fold higher in plaque tissue than in blood. Cadmium levels in blood and plaque correlated, also after adjustment for smoking and other cardiovascular risk factors (p<0.001). Compared with the other parts of the plaque, the cadmium content was double as high in the part where plaque rupture usually occurs. In conclusion, the results show that cadmium exposure is associated with the burden of subclinical atherosclerosis in middle-aged women with different degrees of glucose tolerance, and that the content of cadmium in symptomatic plaques in patients is related to that in blood, but much higher, and preferentially located in the part of plaque where rupture often occurs.

Is atherosclerosis accelerated in systemic sclerosis? Novel insights.

During the last few decades, the death rate due to cardiovascular disease in systemic sclerosis (SSc) patients has substantially increased. Whether this is because of accelerated atherosclerosis, similar to what has been demonstrated in rheumatoid arthritis and systemic lupus erythematosus, remains to be established. In this review, the main recent evidence about potential pathogenic mechanisms of accelerated atherosclerosis, microvascular disease and macrovascular disease in SSc, and the results from the surrogate measures for detecting and quantifying subclinical atherosclerosis in SSc patients are reviewed. Significantly higher risk of coronary heart disease in SSc patients compared with the general population has been found in the largest cohort studies. However, no difference in either atherosclerotic plaque occurrence or intima-media thickness was detected. The diagnostic utility of other techniques, such as cardiac MRI, in order to improve detection and characterization of SSc heart disease remains to be determined. Although microvascular disease is a hallmark of SSc, mechanistic insights explaining the presence of accelerated atherosclerosis, and the presence and extent of macrovascular disease in SSc patients are lacking. Future challenges will be to unravel the genetic, environmental and ethnic determinants of such processes.

Evidence for Contribution of the Y Chromosome in Atherosclerotic Plaque Occurrence in Men

Diseases such as atherosclerosis and coronary artery disease demonstrate disparate population prevalence or present with variable severity in men and women. While the usual explanation points to hormonal status, the role of the Y chromosome has been implicated, but not sufficiently studied. We genotyped six markers of the male-specific region of the Y chromosome, representing the major haplogroups (YAP, G, I, J, K, and R) in 373 male participants of the "Cyprus Study" with ultrasonic data on subclinical atherosclerosis. Of the five major haplogroups identified, two (J and K) accounted for roughly 67% of the Y-chromosome variance among these Greek Cypriot men. Carriers of haplogroup K had a 2.5-fold higher age-adjusted risk for having an atherosclerotic plaque present in any of the four bifurcations scanned, compared to men with other Y-chromosome lineages (OR=2.51; 95% CI=1.18 to 5.33; p=0.017). Carriers of the YAP haplogroup had about 50% less risk for having a plaque in the femoral bifurcation versus the rest (OR=0.46; 95% CI=0.27 to 0.77; p<0.001). We show a possible contribution of the Y chromosome in atherosclerotic phenotypes in men adding to the previous findings for coronary artery disease. Additional studies are warranted as evidence suggests that the Y chromosome could serve as a biomarker for the health status of men.

Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis

Soluble receptor for advanced glycation end products RAGE (sRAGE), a secretory form of RAGE, plays an important role in suppressing RAGE signals that induce pro-inflammatory gene activation in a range of inflammatory diseases, such as Alzheimer's disease, complications of diabetes mellitus and atherosclerosis. Recent studies have suggested that fluid shear stress generated by laminar blood flow protects blood vessels from atherosclerosis, whereas low and oscillatory shear stress (OSS) generated by disturbed blood flow causes atherosclerosis. Although RAGE levels are increased in atherosclerotic plaque, the regulatory mechanisms of sRAGE in the occurrence of atherosclerotic plaque induced by disturbed blood flow remain largely unknown. This study aimed to determine the effects of sRAGE as a competitive inhibitor of RAGE in atherogenesis induced by disturbed blood flow. To determine the role of sRAGE in atherosclerosis induced by disturbed blood flow, we used a mouse model of partial carotid artery ligation using ApoE(-/-) and C57BL/6 mice. Our results revealed that the expression of RAGE was significantly increased in the region of atherosclerotic plaque and that treatment with sRAGE attenuated the development of plaque formation. We found that the expression levels of RAGE and high mobility group box 1 (HMGB1), the agonistic ligand of RAGE, were significantly increased in human umbilical vein endothelial cells (HUVECs) under shear stress conditions induced by disturbed blood flow and suppressed following treatment with sRAGE. We further observed that treatment with sRAGE decreased the expression of vascular cell adhesion molecule‑1 (VCAM-1) and markedly attenuated monocyte-endothelial cell adhesion. Taken together, our results reveal that sRAGE exerts anti-atherogenic effects by blocking the activation of the RAGE signaling pathway induced by disturbed blood flow and may thus be a potential therapeutic target for the prevention of atherosclerosis.

Blood flow patterns in the proximal human coronary arteries: relationship to atherosclerotic plaque occurrence.

Atherosclerotic plaques in human coronary arteries are focal manifestations of systemic disease, and biomechanical factors have been hypothesized to contribute to plaque genesis and localization. We developed a computational fluid dynamics (CFD) model of the ascending aorta and proximal sections of the right and left coronary arteries of a normal human subject using computed tomography (CT) and magnetic resonance imaging (MRI) and determined the pulsatile flow field. Results demonstrate that flow patterns in the ascending aorta contribute to a pro-atherosclerotic flow environment, specifically through localization of low and oscillatory wall shear stress in the neighborhood of coronary orifices. Furthermore, these patterns differ in their spatial distribution between right and left coronary arteries. Entrance effects of aortic flow diminish within two vessel diameters. We examined relationships between spatial distributions of wall shear stress and reports of plaque occurrence in the literature. Results indicate low wall shear stress is co-located with increased incidence of lesions, and higher wall shear stresses are associated with lesion-resistant areas. This investigation does not consider plaque progression or advanced lesions, inasmuch as the CFD model was developed from a normal individual and the clinical data used for comparisons were obtained from autopsy specimens of subjects who died from non-cardiovascular causes. The data reported are consistent with the hypothesis that low wall shear stress is associated with the localization of atherosclerotic lesions, and the results demonstrate the importance of aortic flow on flow patterns in the proximal segments of the coronary arteries.

Androgen Deficiency and Endothelial Dysfunction in Men with End-Stage Kidney Disease Receiving Maintenance Hemodialysis

Objectives and Methods: Two thirds of men with end-stage kidney disease (ESKD) have serum testosterone levels in the hypogonadal range. We examined if low serum testoster- one levels were correlated with measures of endothelial dysfunction in ESKD. Bilateral common carotid artery (CCA) intima-media thickness (IMT) and atherosclerotic plaque occurrence, left ventricular mass index, flow- (FMD) and nitrate-mediated vasodilatation (NMD) of the brachial artery were determined by ultrasound imaging in 100 nondiabetic men with ESKD (50 men exhibited androgen deficiency; serum testosterone concentrations <300 ng/dl). Results: Left-ventricular mass index, CCA diameter, CCA-IMT and atherosclerotic plaque occurrence were all significantly increased in ESKD patients with androgen deficiency compared with patients without androgen deficiency (p < 0.05). Also, FMD and NMD measurements were significantly reduced in the former compared with the latter (p < 0.05). Testosterone levels were inversely correlated with age and duration of hemodialysis therapy (r = –0.44 and r = –0.55; p < 0.001). Testosterone levels were negatively correlated to CCA-IMT and atherosclerotic plaque occurrence in patients with androgen deficiency (r = –0.32, p < 0.003, and r = –0.23, p < 0.04, respectively). FMD and NMD measurements were positively correlated to total (r = 0.65 and r = 0.61; both p < 0.0001) and free (r = 0.52 and r = 0.48; both p < 0.001) testosterone levels in patients with low androgenicity. Conclusion: The present results indicated that ESKD patients with androgen deficiency had increased CCA-IMT, atherosclerotic plaque occurrence and reduced FMD and NMD compared with patients without androgen deficiency. Testosterone serum levels were negatively correlated to CCA-IMT and positively correlated to endothelium-dependent vasodilatation in ESKD patients with androgen deficiency.

Adiponectin and Cardiovascular Remodeling in End-Stage Renal Disease and Co-Morbid Diabetes Mellitus

Objectives and Methods: Altered plasma high-sensitivity C-reactive protein (hs-CRP) and adiponectin (ADP) may contribute to increased vascular inflammation and accelerated atherosclerosis in patients with end-stage renal disease (ESRD) and co-morbid diabetes. Common carotid artery intima-media thickness (CCA-IMT) and atherosclerotic plaque occurrence, left-ventricular mass index (LVMI), and pulse wave velocity of the proximal aorta (PWVr) were determined by ultrasound imaging in 120 ESRD (55 diabetic) patients, and 83 age-, sex-, and blood pressure-matched controls. Also, plasma levels of ADP and hs-CRP were determined and their relationships with the above cardiovascular alterations were analyzed. Results: LVMI, PWVr, CCA-IMT and atherosclerotic plaque occurrence were all increased in ESRD patients compared to controls (all p < 0.001). LVMI (p < 0.05), PWVr (p < 0.001), CCA-IMT (p < 0.001) and atherosclerotic plaque occurrence (p < 0.001) were increased in diabetic compared to nondiabetic ESRD patients. Hs-CRP levels were increased and ADP levels were decreased in diabetic compared to nondiabetic ESRD patients (both p < 0.001). ADP levels correlated inversely with hs-CRP (r = –0.473, p < 0.0001) in ESRD patients. Hs-CRP was positively correlated with LVMI (r = 0.365, p < 0.0001), PWVr (r = 0.42, p < 0.0001) and CCA-IMT (r = 0.18, p = 0.047) while ADP inversely correlated with PWVr (r = –0.263, p = 0.0035) and CCA-IMT (r = –0.207, p = 0.022) in ESRD patients. Conclusion: The present results indicate diabetic disease-specific alterations in the biochemical parameters of hs-CRP and ADP in ESRD patients. The above biochemical parameters were intimately linked to the cardiovascular measurements of LVMI, PWVr and CCA-IMT in patients with ESRD and co-morbid diabetes mellitus.

Atherosclerosis in the vertebral artery: an intrinsic risk factor in the use of spinal manipulation?

The presence of atherosclerotic plaques and their influence on the vertebral artery is of clinical importance within the scope of spinal manipulation. Manipulation may stimulate the development of atherosclerotic plaques, could detach an embolus with ensuing infarction, injure the endothelium or may directly cause a dissection in the presence of atherosclerotic plaques. In order to identify the sites and frequency of atherosclerotic plaques and to determine its relation to the tortuous course of the vertebral artery, a cadaveric study was performed. The vertebral arteries of 57 human cadavers were studied. The vertebral artery was virtually divided into four segments: the pre-vertebral (V1), the vertebral (V2), the atlanto-axial (V3), and the intracranial segment (V4). Abnormalities in the origin and course of the vertebral artery were noted, along with any associated osseous, or cartilaginous anomalies in the neck. After dissection, the artery was opened and macroscopically screened for the presence of atherosclerotic plaques. In 22.8% of the cases, no atherosclerotic plaques were present. In 35.1% of the cases, the atherosclerotic plaques were unilateral, of which 60.0% was on the left side, 40.0% on the right side, and in 42.1%, the occurrence was bilateral. Atherosclerotic plaques were significantly more present in the V3 segment than in the V1 (0.007) and V2 segment (0.049). In the V1 (P=0.008) and V2 segment (P=0.002), there was a correlation between a tortuous course of the vessel and the occurrence of atherosclerotic plaques. In individuals with marked atherosclerotic disease, stretching and compression effects of rotational manipulative techniques on atherosclerotic vessels impose a further risk factor for vertebrobasilar insufficiency. As direct evidence of atherosclerotic plaques are rarely available, therapists should avoid manipulative techniques at all levels of the cervical spine in the presence of any indirect sign of atherosclerotic disease or in the presence of calcified arterial walls or tortuosities of the vessels visible on routinely available X-ray images of the cervical or thoracic spine. It is strongly recommended, that if any doubt exists about the nature of a clinical presentation, vigorous manual procedures should be avoided until either the diagnosis is definitive or gentle manual therapy has proven effective.

Concentration of blood-borne agonists at the endothelium

The delivery of endothelial ligands and macromolecules, such as lipoproteins, from the circulation to the arterial wall is of central importance in modulating endothelial cell function and physiology and, consequently, in the onset of vascular disease. Given the strong spatial correlation between areas of disturbed blood flow and occurrence of atherosclerotic plaque, a detailed understanding of the effects of different fluid flow characteristics on the delivery of factors in the bloodstream to the endothelium is an essential step towards understanding the observed localization of vascular disease to certain focal sites within the vasculature. In this paper, a model of biochemical mass transport in a two-dimensional flow chamber with spatially varying wall shear stress is presented. The advantage of the relatively simple arterial geometry is that all the essential features of blood flow in vivo are captured, but the underlying effects on mass transport, and, hence, on endothelial cell function, are not masked by complex three-dimensional flow. Indeed, it is demonstrated that a previously derived similarity solution, in terms of the shear stress on the endothelial wall, is an asymptotically close approximation to the exact solution to the advection–diffusion equation. The mathematical analysis is then used to identify fundamental links between the wall shear stress and the distribution of chemical species along the endothelium. The physiological implications of these links are discussed, in particular the location of maximum chemical concentration on the endothelium, which is of great significance to the regulation of intracellular signalling and, consequently, endothelial cell function.

Hormone replacement therapy use is associated with a lower occurrence of carotid atherosclerotic plaques but not with intima-media thickness progression among postmenopausal women. The vascular aging (EVA) study

Background: Information on the impact of hormone replacement therapy (HRT) on carotid atherosclerosis is limited. Moreover, transdermal estrogens have not been investigated. Methods: We examined association of HRT use with ultrasonographically assessed carotid atherosclerotic plaque occurrence and mean common carotid artery intima-media thickness (CCA–IMT) progression. Within the Vascular Aging (EVA) Study, a community-based cohort, 815 postmenopausal women aged 59–71 have been followed during 4 years. Among these women, 166 had already used HRT. Results: Women who had ever used HRT experienced a lower occurrence of plaques (8.6 versus 19.1%, P=0.003). After adjustment for the main cardiovascular risk factors, odds-ratio for plaque occurrence was 0.41 (95% confidence interval 0.21–0.78, P=0.01) among ever users of HRT compared with never users. When transdermal route of estrogen administration was used, adjusted odds-ratio was 0.66 (95% confidence interval 0.47–0.99, P=0.04). The progression of IMT, which was measured at a plaque-free site and adjusted on initial levels of CCA–IMT did not differ between ever and never users of HRT. It was 0.011 mm per year among ever users and 0.012 mm per year among never users ( P=0.61). Conclusion: These data suggest that HRT use may prevent the development of atherosclerotic plaques in postmenopausal women, especially when estrogens are administered by transdermal route.

Dietary and circulating antioxidant vitamins in relation to carotid plaques in middle-aged women

The results of the few studies conducted on the relation between antioxidant vitamins and carotid atherosclerosis have been inconclusive. We evaluated the association between preclinical carotid atherosclerosis, as determined by high-resolution B-mode ultrasound, and both the intake amounts and plasma concentrations of antioxidant vitamins. Among 5062 participants in Progetto Atena, a population-based study on the etiology of cardiovascular disease and cancer in women, 310 women were examined by B-mode ultrasound to detect early signs of carotid atherosclerosis. The participants answered a food-frequency questionnaire, and their plasma concentrations of vitamin E, vitamin A, and carotenoids were measured. None of the women took vitamin supplements. The occurrence of atherosclerotic plaques at the carotid bifurcation was inversely associated with tertiles of vitamin E intake; the test for a linear trend across tertiles was significant (P < 0.05). Similarly, the ratio of plasma vitamin E to plasma cholesterol was inversely related to the presence of plaques at the carotid bifurcation; the test for a linear trend across tertiles was significant (P < 0.02). No association was found between the intake of other antioxidant vitamins (vitamins A and C and carotenoids) or their plasma concentrations and the presence of carotid plaques. An inverse association was found between both the intake amount and plasma concentration of vitamin E and preclinical carotid atherosclerosis in middle-aged women. This association was independent of other cardiovascular risk factors, was not related to vitamin supplements, and supports the hypothesis that low vitamin E intake is a risk factor for early atherosclerosis.

Abstracts of literature

Abstracts of literature