The renal artery-aorta angle associated with renal artery plaque: a retrospective analysis based on CT.

PURPOSE: To investigate the relationship between renal artery anatomical configuration and renal artery plaque (RAP) based on 320-row CT. METHODS: The abdominal contrast-enhanced CT data from 210 patients was retrospectively analyzed. Among 210 patients, there were 118 patients with RAP and 92 patients with no RAP. The anatomical parameters between lesion group and control group were compared and analyzed by using t-test, χ2-test and logistic regression analysis. RESULTS: (1) There were statistical differences on age, hypertension, diabetes, hypertriglyceridemia and hypercholesterolemia between lesion group and control group. (2) The differences on the distribution and type and of RAP between lesion group and control group were statistically significant. The most common position was the proximal, and the most common type was calcified plaque. (3)There were significant statistical differences on the proximal diameter of renal artery and renal artery-aorta angle A between lesion group and control group. The differences on the other anatomical factors between two groups were not statistically significant. (4) The result of logistic regression analysis showed that right RAP was related to age, hypertension and right renal artery angle A (the AUC of ROC = 0.82), and left RAP was related to high serum cholesterol, age and left renal artery angle A(the AUC of ROC = 0.83). (5) The RAP was associated with renal artery-aorta angle A, but the differences on distribution, type stability of RAP between R1 (L1) group and R2 (L2) group were not statistically significant. CONCLUSIONS: The RAP was associated with age, hypertension, hypercholesterolemia and renal artery-aorta angle A. Adults which had the greater renal artery-aorta angle A and the other above risk factors may be at increased risk for RAP.

Creating a Natural Vascular Scaffold by Photochemical Treatment of the Extracellular Matrix for Vascular Applications.

The development of bioscaffolds for cardiovascular medical applications, such as peripheral artery disease (PAD), remains to be a challenge for tissue engineering. PAD is an increasingly common and serious cardiovascular illness characterized by progressive atherosclerotic stenosis, resulting in decreased blood perfusion to the lower extremities. Percutaneous transluminal angioplasty and stent placement are routinely performed on these patients with suboptimal outcomes. Natural Vascular Scaffolding (NVS) is a novel treatment in the development for PAD, which offers an alternative to stenting by building on the natural structural constituents in the extracellular matrix (ECM) of the blood vessel wall. During NVS treatment, blood vessels are exposed to a photoactivatable small molecule (10-8-10 Dimer) delivered locally to the vessel wall via an angioplasty balloon. When activated with 450 nm wavelength light, this therapy induces the formation of covalent protein-protein crosslinks of the ECM proteins by a photochemical mechanism, creating a natural scaffold. This therapy has the potential to reduce the need for stent placement by maintaining a larger diameter post-angioplasty and minimizing elastic recoil. Experiments were conducted to elucidate the mechanism of action of NVS, including the molecular mechanism of light activation and the impact of NVS on the ECM.

Is the coronary artery calcium score the first-line tool for investigating patients with severe hypercholesterolemia?

BACKGROUND: Coronary artery calcium (CAC) is known as a reliable tool for estimating risk of myocardial infarction, coronary death, all-cause mortality and is even used to evaluate suitable asymptomatic patients. We therefore aimed to evaluate whether CAC scoring can be applied in the algorithm for clinical examination of patients with severe hypercholesterolemia (SH). METHODS: During the period of 2016-2017 a total of 213 asymptomatic adults, underwent computed tomography angiography to evaluate their CAC scoring. The sample consisted of 110 patients with SH and 103 age and sex matched controls without dyslipidemia and established cardiovascular disease. RESULTS: In total there were 79 (37.2%) subjects with elevated (≥25th) CAC percentiles. Out of them 47 (59.5%) had SH and 32 (40.5%) did not. CAC score did not differ between groups (SH (+) 140.30 ± 185.72 vs SH (-) 87.84 ± 140.65, p = 0.146), however there was a comparable difference in how the participants of these groups distributed among different percentile groups (p = 0.044). Gender, blood pressure, tabaco use, physical activity, family history of coronary artery disease and diabetes mellitus were not associated with CAC score (p > 0.05). There were no significant correlations between biochemical parameters and CAC percentiles except for increase in lipoprotein(a) (p = 0.038). Achilles tendon pathology, visceral obesity, body mass index and increased waist-hip ratio were not associated with CAC percentiles either (p > 0.05). CONCLUSIONS: CAC score is not associated with presence of SH. CAC score is not an appropriate diagnostic tool in the algorithm for clinical examination of patients with SH. Further larger studies are needed to support our findings.

Correlation between Echo-Tracking Parameters and In Vitro Measurements of Arterial Contraction and Relaxation in Rats Fed a High-Cholesterol Diet.

BACKGROUND: Echo-tracking (ET) is a new technique that allows the assessment of arterial function and stiffness. This study aimed to ascertain the utility of the echo-tracking (ET) technique to assess vascular stiffness in rats with hypercholesterolemia and atherosclerosis. MATERIAL AND METHODS: ET was used to measure the arterial stiffness of the aorta in cholesterol-fed Sprague-Dawley rats (group T1, n=10, for 4 weeks; group T2, n=10, for 12 weeks) and normal control rats (group C1, n=10; group C2, n=10). In vitro isometric tension experiments were used to measure the maximum contractile tension (MCT) and maximum relaxation percentage (MRR%) of aortic rings. Indicators of arterial stiffness and aortic MCT and MRR% were compared between groups using linear regression analysis. Light microscopic evaluation was used to demonstrate atherosclerotic changes in the aorta. RESULTS: The rat models were successfully induced; pathological examination of the aortas showed significant atherosclerosis in group T2, but not in groups C1, C2, or T1. The arterial stiffness parameters obtained using ET and aortic rings in vitro showed significant impairments in T1 and T2 rats compared with C1 and C2 controls (all P<0.05 vs. controls). In addition, these impairments were greater in the T2 group than in the T1 group (all P<0.05). Finally, MRR% correlated with the distensibility coefficient (r=0.396, P=0.012), arterial compliance (r=0.317, P=0.047), stiffness parameter b (r=-0.406, P=0.009) and one-point pulse wave ß (r=-0.434, P=0.005). CONCLUSIONS: These results suggest that ET could be used to evaluate the changes in arterial wall elasticity associated with atherosclerosis and hypercholesterolemia.

Systematic study of the effects of lowering low-density lipoprotein-cholesterol on regression of coronary atherosclerotic plaques using intravascular ultrasound.

BACKGROUND: Conflicting results currently exist on the effects of LDL-C levels and statins therapy on coronary atherosclerotic plaque, and the target level of LDL-C resulting in the regression of the coronary atherosclerotic plaques has not been settled. METHODS: PubMed, EMBASE, and Cochrane databases were searched from Jan. 2000 to Jan. 2014 for randomized controlled or blinded end-points trials assessing the effects of LDL-C lowering therapy on regression of coronary atherosclerotic plaque (CAP) in patients with coronary heart disease by intravascular ultrasound. Data concerning the study design, patient characteristics, and outcomes were extracted. The significance of plaques regression was assessed by computing standardized mean difference (SMD) of the volume of CAP between the baseline and follow-up. SMD were calculated using fixed or random effects models. RESULTS: Twenty trials including 5910 patients with coronary heart disease were identified. Mean lowering LDL-C by 45.4% and to level 66.8 mg/dL in the group of patients with baseline mean LDL-C 123.7 mg/dL, mean lowering LDL-C by 48.8% and to level 60.6 mg/dL in the group of patients with baseline mean LDL-C 120 mg/dL, and mean lowering LDL-C by 40.4% and to level 77.8 mg/dL in the group of patients with baseline mean LDL-C 132.4 mg/dL could significantly reduce the volume of CAP at follow up (SMD -0.108 mm3, 95% CI -0.176 ~ -0.040, p = 0.002; SMD -0.156 mm3, 95% CI -0.235 ~ -0.078, p = 0.000; SMD -0.123 mm3, 95% CI -0.199 ~ -0.048, p = 0.001; respectively). LDL-C lowering by rosuvastatin (mean 33 mg daily) and atorvastatin (mean 60 mg daily) could significantly decrease the volumes of CAP at follow up (SMD -0.162 mm3, 95% CI: -0.234 ~ -0.081, p = 0.000; SMD -0.101, 95% CI: -0.184 ~ -0.019, p = 0.016; respectively). The mean duration of follow up was from 17 ~ 21 months. CONCLUSIONS: Intensive lowering LDL-C (rosuvastatin mean 33 mg daily and atorvastatin mean 60 mg daily) with >17 months of duration could lead to the regression of CAP, LDL-C level should be reduced by >40% or to a target level <78 mg/dL for regressing CAP.

Association of cardiometabolic and vascular atherosclerosis phenotypes on non-contrast chest CT with incident heart failure in patients with severe hypercholesterolemia.

BACKGROUND: Coronary artery calcium (CAC), thoracic aorta calcification (TAC), non-alcoholic fatty liver disease (NAFLD), and epicardial adipose tissue (EAT) are associated with atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). OBJECTIVES: We aimed to determine whether these cardiometabolic and atherosclerotic risk factors identified by non-contrast chest computed tomography (CT) are associated with HF hospitalizations in patients with LDL-C≥ 190 mg/dL. METHODS: We conducted a retrospective cohort analysis of patients with LDL-C ≥190 mg/dL, aged ≥40 years without established ASCVD or HF, who had a non-contrast chest CT within 3 years of LDL-C measurement. Ordinal CAC, ordinal TAC, EAT, and NAFLD were measured. Kaplan-Meier curves and multivariable Cox regression models were built to ascertain the association with HF hospitalization. RESULTS: We included 762 patients with median age 60 (53-68) years, 68% (n=520) female, and median LDL-C level of 203 (194-216) mg/dL. Patients were followed for 4.7 (interquartile range 2.75-6.16) years, and 107 (14%) had a HF hospitalization. Overall, 355 (47%) patients had CAC=0, 210 (28%) had TAC=0, 116 (15%) had NAFLD, and median EAT was 79 mL (49-114). Moderate-Severe CAC (log-rank p<0.001) and TAC (log-rank p=0.006) groups were associated with increased HF hospitalizations. This association persisted when considering myocardial infarction (MI) as a competing risk. NAFLD and EAT volume were not associated with HF. CONCLUSIONS: In patients without established ASCVD and LDL-C≥190 mg/dL, CAC was independently associated with increased HF hospitalizations while TAC, NAFLD, and EAT were not.

Obesity and hypercholesterolemia are associated with NOX2 generated oxidative stress and arterial dysfunction.

OBJECTIVE: To analyze the interplay among oxidative stress, NOX2, the catalytic core of nicotinamide-adenine dinucleotide phosphate oxidase, and endothelial dysfunction in children with obesity and/or hypercholesterolemia. STUDY DESIGN: We performed a cross-sectional study comparing flow-mediated arterial dilation (FMD), oxidized low-density lipoprotein, and urinary excretion of isoprostanes (8-iso-PGF2α), as markers of oxidative stress, and NOX2 activity, as assessed by blood levels of soluble NOX2-dp (sNOX2-dp), in a population of 100 children, matched for age and sex, including 40 healthy subjects (HS), 20 children with hypercholesterolemia (HC), 20 obese children (OC), and 20 children with coexistence of hypercholesterolemia and obesity (HOC). RESULTS: HOC had higher sNOX2-dp and oxidized low-density lipoprotein levels compared with HS, HC, and OC. HC, OC, and HOC had lower FMD values compared with HS. Urinary 8-iso-PGF2α excretion was higher in HOC compared with HS. FMD was inversely correlated with sNOX2-dp levels (r = -0.483; P < .001) and with the number of cardiovascular risk factors (r = -0.617; P < .001). Multiple linear regression analysis showed that the number of cardiovascular risk factors was the only independent predictive variable associated with FMD (ß: -0.585; P < .001; R(2) = 35%) and sNOX2-dp (ß: 0.587; P < .001; R(2) = 34%). CONCLUSION: The study suggests that NOX2-generating oxidative stress may have a pathogenic role in the functional changes of the arterial wall occurring in HOC.

Clinical associations in patients with hand osteoarthritis.

OBJECTIVES: To investigate the clinical associations of hand osteoarthritis (HOA) and their relationships with radiographic features. METHODS: A total of 446 patients with hand osteoarthritis (HOA; 233 with erosive HOA (EHOA) and 213 with non-EHOA) and 307 controls were evaluated. Demographic and clinical data from patients and controls were recorded based on medical records/clinical reports and an anamnesis of drug consumption. Posteroanterior radiographs of both hands were obtained from all HOA patients and were assessed using the Kellgren and Lawrence (K&L) and Kallman scoring systems. RESULTS: After adjustment for age, gender, and body mass index (BMI), HOA patients showed a significantly increased odds ratio (OR) for hypercholesterolaemia [OR 2.10, 95% confidence interval (CI) 1.39-3.16, p < 0.0005] and autoimmune thyroiditis (OR 4.85, 95% CI 1.77-13.29, p = 0.002), as well as for knee (OR 1.63, 95% CI 1.09-2.44, p = 0.018) and hip OA (OR 1.87, 95% CI 1.07-3.27, p = 0.029). No significant increase for systemic hypertension, ischaemic heart disease, and diabetes mellitus was found. Patients with EHOA and non-EHOA showed similar risks for the above-mentioned co-morbidities. A similar occurrence of clinical associations was also observed in patients with HOA alone and in those with generalized OA. No association between radiographic scores and clinical associations was observed. CONCLUSIONS: Patients with HOA present a direct association with hypercholesterolaemia (and autoimmune thyroiditis) but do not show increased ischaemic cardiovascular manifestations compared to controls. No significant association between radiographic scores and co-morbidities was found.

Influence of achieved low-density lipoprotein cholesterol level with atorvastatin therapy on stabilization of coronary plaques: sub-analysis of the TWINS study.

BACKGROUND: Previously the stabilization of coronary plaque with atorvastatin was demonstrated in the TWINS (evaluaTion With simultaneous angIoscopy and iNtravascular ultraSound) study. The influence of the low-density lipoprotein cholesterol (LDL-C) level on plaque stabilization was analyzed. METHODS AND RESULTS: Patients (n=29) with hypercholesterolemia and coronary artery disease (CAD) were analyzed. They received atorvastatin (10-20mg/day) for 80 weeks and were divided into low (< 91 mg/dl) and high (≥ 91 mg/dl) LDL-C groups based on their 80-week LDL-C level. Angioscopy was performed before and after treatment. Yellow coronary plaques were classified into six grades (grades 0 to 5) and mean grade was determined for each patient. The LDL-C levels at week 28 and 80 were reduced in both low LDL-C groups (n=14, 140.3 to 77.9 and 75.9 mg/dl; P<0.001 both groups) and high LDL-C groups (n=15, 151.7 to 93.0 and 99.1mg/dl; P<0.001 both groups). Significant improvement in the mean grade was shown in the low LDL-C groups (1.44 to 1.00 and 1.05; P=0.003 both groups) at week 28 and 80 vs. no significant change in high LDL-C groups (1.43 to 1.23 and 1.28; P=0.032 and P=0.169 respectively). CONCLUSIONS: Adequate reduction of LDL-C is important for the stabilization of coronary plaques.

Contrast ultrasound imaging of the aorta alters vascular morphology and circulating von Willebrand factor in hypercholesterolemic rabbits.

OBJECTIVES: Ultrasound contrast agents (UCAs) are intravenously infused microbubbles that add definition to ultrasonic images. Ultrasound contrast agents continue to show clinical promise in cardiovascular imaging, but their biological effects are not known with confidence. We used a cholesterol-fed rabbit model to evaluate these effects when used in conjunction with ultrasound (US) to image the descending aorta. METHODS: Male New Zealand White rabbits (n = 41) were weaned onto an atherogenic diet containing 1% cholesterol, 10% fat, and 0.11% magnesium. At 21 days, rabbits were exposed to contrast US at 1 of 4 pressure levels using either the UCA Definity (Lantheus Medical Imaging, Inc, North Billerica, MA) or a saline control (n = 5 per group). Blood samples were collected and analyzed for lipids and von Willebrand factor (vWF), a marker of endothelial function. Animals were euthanized at 42 days, and tissues were collected for histologic analysis. RESULTS: After adjustment for pre-exposure vWF, high-level US (in situ [at the aorta] peak rarefactional pressure of 1.4 or 2.1 MPa) resulted in significantly lower vWF 1 hour post exposure (P = .0127; P(adj) < .0762). This difference disappeared within 24 hours. Atheroma thickness in the descending aorta was lower in animals receiving the UCA compared to animals receiving saline. CONCLUSIONS: Contrast US affected the descending aorta, as evidenced by two separate outcome measures. These results may be a first step in elucidating a previously unknown biological effect of UCAs. Further research is warranted to characterize the effects of this procedure.

High-dose atorvastatin enhances impaired cerebral vasomotor reactivity.

The influence of statin therapy on cerebral vasomotor function has not been fully characterized. We report the effects of high-dose atorvastatin therapy on cerebral vasomotor reactivity (VMR) in patients with controlled hypertension and dyslipidemia. We prospectively enrolled 36 patients with controlled hypertension and a low-density lipoprotein (LDL) cholesterol concentration >100 mg/dL. Atorvastatin 80 mg was given daily for 6 months and then discontinued. VMR was assessed by hypercapnic and hypocapnic transcranial Doppler challenge in both the right and left middle cerebral artery (MCA) at baseline, and after 3 and 6 months of therapy. Forty-five days after statin cessation, a repeat VMR was performed. VMR impairment was defined as ≤70%. Blood pressure, lipid levels, liver function, and creatine kinase level were monitored. Mean patient age was 60 years, 16 were men, and 13 had a previous history of subcortical infarction. Mean LDL cholesterol level before treatment was 154 ± 30 mg/dL. Atorvastatin lowered LDL by 53% at 3 months and by 46% at 6 months. Baseline VMR was 71% ± 21% in the right MCA and 70% ± 19% in the left MCA. No significant effect of atorvastatin on VMR was seen at 3 months and 6 months in the study population as a whole. In the subgroup of patients with baseline VMR impairment, atorvastatin therapy was associated with significantly improved VMR at both 3 and 6 months. This effect persisted for at least 45 days after discontinuation of therapy. Our findings indicate that high-dose atorvastatin therapy can significantly improve impaired cerebral VMR, and that the effects of atorvastatin on VMR persist for 1.5 months after discontinuation of therapy. We found no benefit of atorvastatin therapy in patients with preserved baseline vasoreactivity.

Association of mammographic density and benign breast calcifications individually or combined with hypertension, diabetes, and hypercholesterolemia in women ≥40 years of age: a retrospective study.

Recent evidence has linked certain mammographic characteristics, including breast calcifications (Bcs) and mammographic density (MD), with atherosclerotic cardiovascular disease risk factors in women, but data are limited and inconsistent. We aimed to evaluate the association of MD and/or Bcs with hypertension, diabetes, and hypercholesterolemia in women ≥40 years of age. Through hospital electronic records, we retrospectively identified mammograms of non-pregnant women aged ≥40 years and without breast cancer and retrieved reports and relevant data. MD and Bcs were recorded; risk factor status was diagnosed based on treatment profile and clinical and laboratory data. In total, 1406 women were included. MD was inversely related to hypertension, diabetes, hypercholesterolemia, triglyceride levels, age, and body mass index (BMI) (p value for trend <0.001). Bcs were positively associated with hypertension, diabetes, hypercholesterolemia, age, BMI, and elevated creatinine (p<0.05). Controlling for age and BMI, MD category A (MD-A) was independently associated with hypercholesterolemia; Bcs were independently associated with diabetes. Combining MD-A with Bcs did not increase the odds significantly. Analysis for additive interactions revealed a significant interaction between MD-A and BMI, increasing the odds of hypertension, and a trend for increased odds of diabetes by adding MD-A and/or Bcs to BMI. Decreased MD and presence of Bcs are associated with hypertension, diabetes, and hypercholesterolemia in women ≥40 years of age. MD-A may represent a new obesity index independently associated with hypercholesterolemia and additive to hypertension risk. Bcs are independently associated with diabetes. Combining MD and Bcs did not improve the odds significantly, which may reflect mechanistic differences.

Evidence for active regulation of pro-osteogenic signaling in advanced aortic valve disease.

OBJECTIVE: To test the hypothesis that valvular calcium deposition, pro-osteogenic signaling, and function can be altered in mice with advanced aortic valve disease. METHODS AND RESULTS: "Reversa" mice were given a Western-type diet for 12 months and screened for the presence of aortic valve stenosis. Mice with advanced valve disease were assigned to 1 of 2 groups: (1) those with continued progression for 2 months and (2) those with regression for 2 months, in which lipid lowering was accomplished by a genetic switch. Control mice were normocholesterolemic for 14 months. Mice with advanced valve disease had massive valvular calcification that was associated with increases in bone morphogenetic protein signaling, Wnt/ß-catenin signaling, and markers of osteoblastlike cell differentiation. Remarkably, reducing plasma lipids with a genetic switch dramatically reduced markers of pro-osteogenic signaling and significantly reduced valvular calcium deposition. Nevertheless, despite a marked reduction in valvular calcium deposition, valve function remained markedly impaired. Phosphorylated Smad2 levels and myofibroblast activation (indexes of profibrotic signaling) remained elevated. CONCLUSIONS: Molecular processes that contribute to valvular calcification and osteogenesis remain remarkably labile during the end stages of aortic valve stenosis. Although reductions in valvular calcium deposition were not sufficient to improve valvular function in the animals studied, these findings demonstrate that aortic valve calcification is a remarkably dynamic process that can be modified therapeutically, even in the presence of advanced aortic valve disease.

Plaque-stabilizing effect of atorvastatin is stronger for plaques evaluated as more unstable by angioscopy and intravenous ultrasound.

BACKGROUND: The aim of this study was to compare the effect of atorvastatin treatment on high-grade yellow coronary plaques (grade ≥ 2, group H) vs. low-grade yellow plaques (grade ≤ 1, group L). METHODS AND RESULTS: Twenty-nine hypercholesterolemic patients with coronary heart disease were treated with atorvastatin (10-20mg/day) for 80 weeks and were divided into 2 groups by baseline plaque color grade. The angioscopic plaque grade and the vessel, plaque, and luminal volumes were measured by intravascular ultrasound at baseline and in weeks 28 and 80. The plaque color grade decreased significantly from baseline to weeks 28 and 80 in group H (2.27 ± 0.48, 1.47 ± 0.75, and 1.55 ± 0.86, respectively), but not significantly in group L (0.90 ± 0.31, 0.83 ± 0.61, and 0.89 ± 0.56, respectively). The plaque volume of group HP was greater than that of group LP (respectively 158.0 ± 45.8 vs. 107.5 ± 21.9 mm(3) at baseline, 144.5 ± 41.1 vs. 97.5 ± 24.8mm(3) in week 28, and 128.8 ± 31.5 vs. 87.9 ± 31.5mm(3) in week 80 (P < 0.001 by ANCOVA between groups). CONCLUSIONS: The plaque-stabilizing effect of atorvastatin was stronger for more vulnerable plaques with a higher color grade, although regression of plaque during atorvastatin therapy was noted irrespective of plaque vulnerability.

Increased intima-media thickness in carriers of the ldl-receptor defective gene versus noncarriers with newly detected asymptomatic severe hypercholesterolemia.

BACKGROUND: The data on the examination of early vascular alterations in carriers of molecular defects of the low-density lipoprotein-receptor (LDL-R) in comparison to noncarriers with severe hypercholesterolemia are controversial. AIMS: To examine the difference between patients with severe hypercholesterolemia, who are carriers and noncarriers of LDL-R defective gene, with respect to their functional (flow-mediated vasodilation) and structural (intima-media thickness of carotid artery) characteristics of arterial wall. A total of 250 hypercholesterolemic patients were enrolled. Biochemistry parameters were examined by routine methods. The molecular biological analysis included-R3500Q-mutation in the Apolipoprotein-B (Apo-B) gene, LDL-R gene mutation and polymorphism (and the promoter region), as large rearrangements. Determination of flow-mediated vasodilation and intima-media thickness of common carotid artery was performed with Hewlett Packard Sonos 5500, using automated computer software MedicaSoft. IMT.lab. RESULTS: There was no significant difference between the groups with respect to total cholesterol, LDL, HDL, Apo-B, Apolipoprotein A(1) (Apo-A(1) ), asymmetric dimethylarginine (ADMA), homocysteine, and cellular adhesion molecules. The Apo-B/Apo A(1) index differed significantly (t = 11.23, P < 0.001) between the two groups and this difference was found even after adjustment for age and gender. There was no significant difference with respect to the endothelial dependent and independent vasodilatation between the examined groups (P > 0.05). We were founded a significantly higher carotid IMT in the carriers versus noncarriers. This significant difference was confirmed after adjustment for age and gender. Statistically significant correlations we were founded between IMT mean and age (log) (r(xy) = 0.45; P < 0.01), cholesterol × years score (log) (r(xy) = 0.53; P < 0.01), Apo-B/A(1) (log) (r(xy) = 0.66; P < 0.001) in the group of the carriers. Backward selection process selected Apo-B/A(1) as the most important statistically significant factor related to IMT mean of common carotid artery (F = 105.22; P = 0.001; R(2) = 0.72). CONCLUSION: Our data demonstrate that carriers of the LDL-R defective gene have a higher carotid IMT and Apo B/Apo A(1) index than noncarriers, whereas no difference between the groups was found with respect to the level of lipid parameters, ADMA, total homocysteine, cell adhesion molecules and %FMD. Apo-B/A(1) is a predictor of IMT mean in the group of the carriers of the LDL-receptor gene.

Carotid sheath xanthoma: A rare manifestation of lipid disorders.

Xanthomas are visibly deformed cholesterol deposits that are commonly associated with lipid disorders, such as familial hypercholesterolemia (FH) or rare sitosterolemia. We present the first report of two cases of carotid sheath xanthomas in patients with lipid disorders. Case 1 involved a 26-year-old woman presenting with two heterogeneous mutations on the ABCG5 gene-as noted on genetic testing-who was finally diagnosed with sitosterolemia. Ultrasonography (US) revealed hypoechoic masses centered in the bilateral carotid sheath, which gradually reduced in size after diet control and the use of ezetimibe. Case 2 involved a 27-year-old man who was diagnosed with possible FH and had recurrent bilateral buttock xanthomas, as well as bilateral carotid sheath masses detected by US. Postoperative pathological examination of the resected right neck mass confirmed a xanthoma with proliferation of multinucleated giant cells and deposition of cholesterol clefts.

Effects of external irradiation of the neck region on intima media thickness of the common carotid artery.

BACKGROUND: Several studies have shown that common carotid intima-media thickness (IMT) is increased after radiotherapy (RT) to the head and neck. However, further studies are needed to define the exact mechanism of radiation-induced injury in large vessels, investigate the relationship between radiation dose and large vessel injury and evaluate the rate of progress of atherosclerosis in irradiated vessels. OBJECTIVES: To investigate whether external irradiation to the carotid area has any effect on IMT of the common carotid artery in a group of patients who received RT vs control group matched for age, gender and race. METHODS: We studied 19 patients (10 male; 47.8 +/- 17.4 years) during a 5-month period (January 2009-July 2009); they had completed RT with a mean of 2.9 years before (range: 1 month-6 years) The mean radiation dose to the neck in the irradiated patients was 41.2 +/- 15.6 Gy (range: 25-70 Gy). Common carotid IMT was measured with echo-color Doppler. Nineteen healthy adult patients (10 male; 47.8 +/- 17.6) were recruited as a control group. RESULTS: IMT was not significantly higher in patients when compared to the control group (0.59 +/- 0.16 vs 0.56 +/- 0.16 mm, p = 0.4). There was no significant difference between the two groups in relation to the absence (p = 0.7) or presence (p = 0.6) of vascular risk factors. Although the difference did not reach statistical significance (p = 0.1), the irradiated young patients (age < or = 52 years) had IMT measurements higher (0.54 +/- 0.08 mm) than the non-irradiated young patients (0.49 +/- 0.14 mm). The mean carotid IMT increased with increasing doses of radiation to the neck (p = 0.04). CONCLUSION: This study shows that increased IMT of the common carotid artery after RT is radiation-dose-related. Therefore it is important to monitor IMT, which can be used as an imaging biomarker for early diagnosis of cerebrovascular disease in patients who have had radiotherapy for treatment of cancer of the head and neck and who are at increased risk for accelerated atherosclerosis in carotid arteries.

Relationship between reactive oxygen metabolites and carotid intima-media thickness in subjects with hypercholesterolemia.

OBJECTIVE: It was the aim of this study to investigate whether there is any relationship between oxidative stress, as assessed by the diacron reactive oxygen metabolite (d-ROM) test, and carotid atherosclerosis among hypercholesterolemic patients. SUBJECTS AND METHODS: A well-defined group of patients with type II hypercholesterolemia (n = 81, mean age 59 years) was studied to observe the correlation between the levels of serum d-ROMs and carotid artery intima-media thickness (IMT) using B-mode ultrasound, in relation to the traditional atherosclerotic risk factors (age, sex, smoking, body mass index, blood pressure, glucose and lipid panels). RESULTS: The mean level in low-density lipoprotein cholesterol (LDL-C) in this population was 4.45 mmol/l, d-ROMs were 323.2 Carr U, and IMT was 0.91 mm. A multiple regression analysis revealed a positive and significant correlation between IMT and d-ROMs (ß = 0.27, p < 0.05), along with age and LDL-C. CONCLUSION: These results indicate that the increased oxidative stress levels using the d-ROM test, independent of aging and increased LDL-C levels, may be associated with carotid atherosclerosis even in hypercholesterolemic patients.

Intravenous Statin Administration During Myocardial Infarction Compared With Oral Post-Infarct Administration.

BACKGROUND: Beyond lipid-lowering, statins exert cardioprotective effects. High-dose statin treatment seems to reduce cardiovascular complications in high-risk patients. The ideal timing and administration regime remain unknown. OBJECTIVES: This study compared the cardioprotective effects of intravenous statin administration during myocardial infarction (MI) with oral administration immediately post-MI. METHODS: Hypercholesterolemic pigs underwent MI induction (90 min of ischemia) and were kept for 42 days. Animals were distributed in 3 arms (A): A1 received an intravenous bolus of atorvastatin during MI; A2 received an intravenous bolus of vehicle during MI; and A3 received oral atorvastatin within 2 h post-MI. A1 and A3 remained on daily oral atorvastatin for the following 42 days. Cardiac magnetic resonance analysis (days 3 and 42 post-MI) and molecular/histological studies were performed. RESULTS: At day 3, A1 showed a 10% reduction in infarct size compared with A3 and A2 and a 50% increase in myocardial salvage. At day 42, both A1 and A3 showed a significant decrease in scar size versus A2; however, A1 showed a further 24% reduction versus A3. Functional analyses revealed improved systolic performance in A1 compared with A2 and less wall motion abnormalities in the jeopardized myocardium versus both groups at day 42. A1 showed enhanced collagen content and AMP-activated protein kinase activation in the scar, increased vessel density in the penumbra, higher tumor necrosis factor α plasma levels and lower peripheral blood mononuclear cell activation versus both groups. CONCLUSIONS: Intravenous administration of atorvastatin during MI limits cardiac damage, improves cardiac function, and mitigates remodeling to a larger extent than when administered orally shortly after reperfusion. This therapeutic approach deserves to be investigated in ST-segment elevation MI patients.

Hypercholesterolemia and myocardial function evaluated via tissue doppler imaging.

OBJECTIVE: To establish a link between hypercholesterolemia and myocardial dysfunction. BACKGROUND: Heart failure is a complex disease involving changes in systolic and diastolic function. Newer echocardiographic imaging modalities may be able to detect discreet changes in myocardial function associated with hypercholesterolemia. Therefore we sought to establish a link between hypercholesterolemia and myocardial dysfunction with tissue Doppler imaging (TDI). METHODS: Twenty-seven rabbits were studied: 7 were fed normal chow (group 1) and 20 a high cholesterol diet (10 with ezetimibe, 1 mg/kg/day; group 2 and 10 without, group 3). Echocardiographic images were obtained under general anesthesia. Serum cholesterol levels were obtained at baseline, 3 and 6 months and myocardial cholesterol levels measured following euthanasia. RESULTS: Doppler measurements, including E/A, E'/A' and S' were significantly lower in group 3 compared to both groups 1 and 2 but no significant differences were noted in chamber sizes or ejection fraction among the groups. Average serum cholesterol was higher in group 3 compared to groups 1 and 2 respectively (495 +/- 305 mg/dl vs. 114 +/- 95 mg/dl and 87 +/- 37 mg/dl; p < 0.01). Myocardial cholesterol content was also higher in group 3 compared to group 2 (0.10 +/- 0.04 vs. 0.06 mg/dl +/- 0.02; p = 0.05). There was significant correlation between S', E'/A', E/E' and serum cholesterol (r2 = 0.17 p = 0.04, r2 = 0.37 p = 0.001 and r2 = 0.24 p = 0.01). CONCLUSION: Cholesterol load in the serum and myocardium was significantly associated with decreased systolic and diastolic function by TDI. Moreover, lipid lowering was protective.