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.

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.

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.

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.

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.

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.

Dietary supplementation of barley and/or dates attenuate hypercholesterolemic-induced endometrial dysfunction in Wistar albino rats via alleviation of apoptotic pathways and enhancing oxidative capacity.

Our study was conducted to characterize the efficacy of barley and/or date palm fruits (10%) in alleviation of hypercholesterolemic endometrial insults in obese rat model. Sixty-four Wistar albino rats were randomized into eight groups (n = 8); control, hypercholesterolemic- and hypercholesterolemic-treated groups. Animals were subjected to treatment for 4 months. After sacrifice, serum and uterine tissues were collected and processed for biochemical, histological, immunohistochemical, and electron microscopic investigations. In hypercholesterolemic rats, the endometrium displayed hyperplasia with necrotic patches in the surface epithelium and its glandular lining cells. Also, there was a remarkable increase in the endometrial thickness and significant decrease in corresponding glandular numbers. Prompted by these findings, immunohistochemical localization revealed that expression of proliferating cell nuclear antigen was downregulated, while cleaved caspase-3 was upregulated in the endometrial cells in hypercholesterolemic group. Accordingly, there was remarkable depletion of antioxidant enzymatic activities associated with increased lipid peroxidation and apoptotic markers. Contradictory, supplementation of barley and/or dates to hypercholesterolemic groups showed intriguing amelioration for the histological architecture of the endometrium and balancing its oxidative redox. In conclusion, the administration of barley and/or dates confers enhanced synergistic effects in attenuation of hypercholesterolemic induced-endometrial dysfunction. This is clear evidence that endometrial amelioration was directly linked to the implication of highly potential antioxidant capacity of barley and/or dates phytochemicals, ß-glucan, polyphenols, and other trace elements, which can be utilized to establish a phyto-therapeutic strategy for activating endometrial cell regeneration. PRACTICAL APPLICATIONS: Barley and dates confer both hypoglycemic and hypocholesterolemic potentials. Therefore, their ingredients would be implicated in the amelioration of uterine functions in obese women. These favorable potentials were directly linked to the restraining of endometrial inflammation and retrieving the oxidative capacity. Furthermore, our findings demonstrated that barley and dates substantially diminished the expression of TNF-α, mitigated DNA damage and prevented leukocytic infiltration in the endometrial tissue; based on their high content of dietary phytochemicals, ß-glucan, polyphenols, and other trace elements.

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.

Endurance exercise training does not limit coronary atherosclerosis in familial hypercholesterolemic swine.

Human studies demonstrate that physical activity reduces both morbidity and mortality of coronary heart disease (CHD) including decreased progression and/or regression of CHD with life-style modification which includes exercise. However, evidence supporting an intrinsic, direct effect of exercise in attenuating the development of CHD is equivocal. One limitation has been the lack of a large animal model with clinically evident CHD disease. Thus, we examined the role of endurance exercise in CHD development in a swine model of familial hypercholesterolemia (FH) that exhibits robust, complex atherosclerosis. FH swine were randomly assigned to either sedentary (Sed) or exercise trained (Ex) groups. At 10 months of age, Ex pigs began a 10 months, moderate-intensity treadmill-training intervention. At 14 months, all pigs were switched to a high-fat, high-cholesterol diet. CHD was assessed by intravascular ultrasound (IVUS) both prior to and after completion of 6 months on the HFC diet. Prior to HFC diet, Ex resulted in a greater coronary artery size in the proximal and mid sections of the LCX compared to SED, with no effect in the LAD. After 6 months on HFC diet, there was a 5-6 fold increase in absolute plaque volume in all segments of the LCX and LAD in both groups. At 20 months, there was no difference in vessel volume, lumen volume, absolute or relative plaque volume in either the LCX or LAD between Sed and Ex animals. These findings fail to support an independent, direct effect of exercise in limiting CHD progression in familial hypercholesterolemia.

Hypocholesterolaemic and antioxidant properties of Olea europaea L. leaves from Chlef province, Algeria using in vitro, in vivo and in silico approaches.

Aqueous and ethanol extracts prepared from leaves of Olea europaea L. were evaluated for in vitro antioxidant and in vivo hypocholesterolemic effect. The result of administration of O. europaea leaf extracts on serum total cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in hypercholesterolaemic mice was evaluated. In addition, rutin and luteolin, reported to occur naturally in O. europaea leaves, were docked against HMG-CoA reductase, the rate-limiting enzyme in cholesterol metabolism. Mice treated with both extracts showed reduced total cholesterol (246.6 and 163.4 mg/dl, for mice groups treated with respective extracts) and LDL (150.16 and 81.28 mg/dl, for mice groups treated with respective extracts) levels as compared to the hypercholesterolaemic group (total cholesterol 253.00 mg/dl and LDL 160.00 mg/dl). Mice treated with aqueous extract (200 mg/kg body weight) showed significantly reduced triglyceride and VLDL levels as compared to the group treated with atorvastatine. HDL level of mice administered with O. europaea aqueous extract was comparable to the atorvastatine-treated group. The ethanol extract of O. europeae leaves was a potent antioxidant (IC50 69.15 mg/ml, % inhibition 54.98, 82.63 mg ascorbic acid equivalent/g extract, 7.53 mol of Fe2+/g extract, and % inhibition 49.71, for the DPPH, ß-carotene bleaching, total antioxidant capacity, FRAP, and ferric thiocyanate assays, respectively). Docking studies revealed that rutin showed higher binding affinity with HMG-CoA reductase as compared to luteolin. Data gathered from this study support the development of a prophylactic biomedicine from O. europaea leaves for the management of hypercholesterolemia and atherosclerosis.

THE EFFECT OF APPLICATION OF ANTIOXIDANT THERAPY IN THE TREATMENT OF NON-ALKOHOLIC STEATOHEPATATIS IN CHORNOBYL NPP ACCIDENT SUFFERERS IN THE REMOTE PERIOD AFTER IRRADIATION. / ZASTOSUVANNIa ANTYOKSYDANTNOÏ TERAPIÏ V LIKUVANNI NEALKOGOL'NOGO STEATOGEPATYTU U POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChAES U VIDDALENYI PERIOD PISLIa OPROMINENNIa.

OBJECTIVE: to determine the effectiveness of combined treatment with hepatoprotectors and antioxidant a complexpreparation of vitamins A and E (I) in patients with non-alcoholic steatohepatitis (NASH) who suffered from theChornobyl NPP accident based on the results of evaluation of metabolic changes. MATERIALS AND METHODS: The state of the hepatobiliary system of 72 patients with NASH suffered as a result of theChornobyl accident was studied based on the results of the biochemical analysis of blood, indicators characterizingthe processes of oxidative modification of macromolecules and the state of the antioxidant system (AOS), as well asstructural changes in the liver according to ultrasound investigations in the course of the examination before andafter treatment. RESULTS: The treatment of NASH with hepatoprotectors and antioxidant I in the sufferers of the Chornobyl accidentincreased the level of antioxidant defense products (catalase and superoxide dismutase) with the normalization ofthe integral index of the AOS, and a significant decrease in the number of patients with reduced AOS status (from42.6% to 24, 2%, p <0.05), positive dynamics of biochemical parameters of blood with decreasing frequency ofdetection of cholestasis syndrome, hypercholesterolemia and hyperglycemia were established as well as the positivedynamics of structural changes in the liver according to ultrasound data. CONCLUSION: Combined therapy of NASH with hepatoprotectors and antioxidant I in patients who suffered from theChornobyl NPP accident contributes to the restoration of the prooxidant-antioxidant balance, decreases cholestasis,hypercholesterolemia and hyperglycemia, and promotes positive dynamics of structural changes in the liver.

Hypercholesterolemia after conversion to sirolimus as primary immunosuppression and cardiac allograft vasculopathy in heart transplant recipients.

BACKGROUND: Sirolimus (SRL) attenuates cardiac allograft vasculopathy (CAV) progression after heart transplantation (HT) but often results in hyperlipidemia. In this study we investigated the differential effects of SRL-based and calcineurin inhibitor (CNI)-based immunosuppression on CAV progression and clinical outcomes in HT recipients. METHODS: CAV progression was assessed by coronary intravascular ultrasound (IVUS) as changes in volumetric measurements after correction to time between the first and last follow-up IVUS exams. CAV progression rate and CAV-associated events were compared between patients with mean follow-up low-density lipoprotein (LDL) <100 mg/dl (lower level or LL) and ≥100 mg/dl (higher level or HL) in the SRL and CNI groups. RESULTS: We identified 227 patients on SRL (LL: 118; HL: 109) and 96 on CNI (LL: 56; HL: 40), with a median follow-up of 6.7 years. Clinical characteristics did not differ between the LL and HL groups and all patients were on statins. In the SRL arm, there were no significant differences in CAV progression rate and there were no differences in all-cause mortality and CAV-associated events between the LL and HL groups. In the CNI arm, the Δ change in plaque volume normalized to segment length and time of follow-up (PV/SL/year) (0.55 ± 0.53 vs 1.53 ± 2.32, p = 0.003) and Δ change in plaque index per year (defined as PV/vessel volume ratio) (3.1 ± 3.7% vs 6.3 ± 10.4%; p = 0.034) were significantly lower in the LL than the HL group. After adjusting for patient characteristics, HL was associated with higher rates of advanced CAV requiring coronary angioplasty (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.05 to 9.40, p = 0.040) and higher rates of all CAV-associated events (HR 2.2, 95% CI 1.10 to 4.54, p = 0.026) in these CNI-treated subjects. CONCLUSION: Unlike CNI-based immunosuppression, the effects of SRL on attenuating CAV progression are independent of LDL cholesterol levels post-HT.

In vivo imaging of murine vasodynamics analyzing different mouse strains by optical coherence tomography.

BACKGROUND AND AIMS: We tried to circumvent the limitations of standard organ chamber experiments using in vivo optical coherence tomography (OCT) to analyze the vascular function of small arteries in different mouse strains. METHODS: OCT images were acquired with a two-axis galvanometer scanner head. Time series (3 frames per second, 300 × 512 pixel per frame) of cross-sectional images were analyzed with image processing software measuring the time course of vessel lumen dynamics. Vascular function of murine saphenous artery of male C57BL/6 (wild-type) and hypercholesterolemic LDLR knockout (LDLR-/-) mice was analyzed at 6 weeks and after 14 weeks feeding a control or high-fat diet containing 21.2% butter fat and 2.1 mg/kg cholesterol. Vasoconstriction and vasodilation was analyzed by OCT in response to 80 mM K+ and 1 mM SNP. RESULTS: The OCT technique allowed determination of inner diameter, flow resistance, maximal velocity of diameter change and time to half-maximal diameter change in murine saphenous arteries of wild-type and LDLR-/- mice. LDLR-/- had impaired vasodilation and changes in vasodynamics after 14 weeks on control or high-fat diet, compared to wild-type mice. The diameter of the saphenous artery of LDLR-/- mice was reduced after vasoconstriction (38 ± 7 µm vs 12 ± 6 µm) and vasodilation (245 ± 8 µm vs 220 ± 10 µm) (P < 0.05 vs C57BL/6). CONCLUSION: OCT was used as an innovative method to image vascular function of small arteries of wild-type and hypercholesterolemic LDLR-/- mice after high-fat diet. The method offers the ability to display differences in the vasodynamics at early stages of endothelial dysfunction in vivo.

Carotid intima media thickness in a girl with sitosterolemia carrying a homozygous mutation in the ABCG5 gene.

BACKGROUND: Sitosterolemia is a rare lipid metabolism disorder that involves storage of plant sterols. This disease is associated with atherosclerosis, but detailed vascular endothelial assessment is difficult. CASE PRESENTATION: We report a 5-year-old girl with sitosterolemia who presented with xanthomas at 23 months of age. Her total cholesterol was 868 mg/dL, and her plasma sitosterol level was 9.48 mg/dL. Direct sequencing detected a homozygous mutation in gene ABCG5 (p.Arg389His). Echocardiographic examination revealed that the carotid artery intima media thickness (cIMT) was 0.4 mm with heterogenous hyperechogenicity inside the arterial wall. She was treated using dietary therapy and ezetimibe, which effectively lowered her sitosterol levels. After 3 years of treatment, her cIMT was stable in diameter and arterial wall echogenicity had improved. CONCLUSIONS: Sitosterolemia is a unique disorder in which it is difficult to avoid premature atherosclerosis because of high sitosterol levels. cIMT measurement with arterial wall assessment may improve management.

Real-world data to assess changes in low-density lipoprotein cholesterol and predicted cardiovascular risk after ezetimibe discontinuation post reporting of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial.

BACKGROUND: The 2008 Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) study demonstrated ezetimibe + simvastatin vs simvastatin alone had a neutral effect on the surrogate endpoint of carotid intima-media thickness. Subsequent media portrayal of the study prompted ezetimibe discontinuation in many patients. OBJECTIVE: The objective of the study was to assess the impact of ENHANCE reporting on ezetimibe discontinuation, low-density lipoprotein cholesterol (LDL-C) changes, and potential cardiovascular disease (CVD) risk. METHODS: This analysis used claims data in a retrospective, observational study of patients receiving ezetimibe + statin and compared LDL-C for patients who discontinued ezetimibe (n = 970) vs those who continued ezetimibe + statins (n = 3706) after ENHANCE results disclosure. Change in relative CVD risk was estimated from the absolute LDL-C difference between groups per the Cholesterol Treatment Trialists' meta-analysis of statin trials. RESULTS: The rate of ezetimibe discontinuation was 2% in the 6 months before and 21% in the 6 months after reporting of ENHANCE results. Among patients who ultimately discontinued vs continued ezetimibe, respective mean LDL-C levels were 79.8 and 78.3 mg/dL 6 months before reporting of the ENHANCE results and 93.5 and 78.1 mg/dL 6 months after reporting of ENHANCE. Predictive application of the Cholesterol Treatment Trialists' meta-analysis suggested the 13.9 mg/dL increase in mean LDL-C translated to a 9.4% increase in relative CVD risk for those who discontinued ezetimibe. CONCLUSION: After reporting of the neutral ENHANCE results, ezetimibe discontinuation rate increased, LDL-C levels increased, and predicted CVD risk increased among those who discontinued ezetimibe. Characterization of clinical outcomes regarding lipid-altering agents based on surrogate biomarker studies not designed to assess CVD outcomes may be misleading, potentially placing patients at increased CVD risk.

Frequency of Achilles Tendon Xanthoma in Patients with Acute Coronary Syndrome.

AIM: We studied the frequency of Achilles tendon xanthoma (ATX) in patients with acute coronary syndrome (ACS). Furthermore, we investigated the differences in clinical findings between ACS patients with and without ATX. METHODS: Patients with ACS (n=335) were admitted to the coronary care unit of Nippon Medical School between July 2011 and December 2014. Informed consent for the measurement of Achilles tendon thickness (ATT) on a radiograph was obtained from 228 patients without tendon rupture. ATT of each side was measured on the radiograph in patients with ACS and in those with acromegaly (n=18), non-familial hypercholesterolemia (non-FH; n=96), and familial hypercholesterolemia (FH; n=31). RESULTS: ATT of the right and left side in ACS patients were 6.9±1.3 and 7.0±1.6 (mm; mean± SD). In acromegaly, non-FH, and FH patients, ATT of the right/left side were 6.6±1.1/6.7±1.1, 6.2±0.9/6.6±1.0, and 9.4±3.3/10.0±3.1, respectively. ATX (ATT ≥9 mm) was found in 26 (11.4%) patients with ACS. Patients with acromegaly and non-FH had no ATX, whereas all patients with FH had ATX. No differences in age and serum lipid profiles were observed between ACS patients with and without ATX. The levels of body mass index and glycated hemoglobin of ACS patients with ATX were significantly greater than those in ACS patients without ATX (26.8±4.0 vs. 23.9±3.3, p＜0.05, and 6.9±1.4% 6.3±1.3%, p＜0.05, respectively). CONCLUSION: This is the first report in which the frequency of ACS patients with ATX was 11.4%. The serum lipid profiles of ACS patients with ATX were similar to those without ATX. In the future, ACS patients with ATX will be diagnosed as having FH.

Treatment with a human recombinant monoclonal IgG antibody against oxidized LDL in atherosclerosis-prone pigs reduces cathepsin S in coronary lesions.

BACKGROUND: Immunization with oxidized LDL (oxLDL) reduces atherosclerosis in rodents. We tested the hypothesis that treatment with a human recombinant monoclonal antibody against oxLDL will reduce the burden or composition of atherosclerotic lesions in hypercholesterolemic minipigs. METHODS AND RESULTS: Thirty-eight hypercholesterolemic minipigs with defective LDL receptors were injected with an oxLDL antibody or placebo weekly for 12weeks. An 18F-fluorodeoxyglucose positron emission tomography (FDG PET) scan (n=9) was performed before inclusion and after 3months of treatment. Blood samples were obtained prior to each injection. Following the last injection all animals were sacrificed, and the heart, aorta, and iliac arteries were removed. The left anterior descending coronary artery was sectioned at 5mm intervals for quantitative and qualitative assessments of atherosclerosis, including immunohistochemical phenotyping of macrophages using a pan-macrophage marker (CD68) and markers for putative pro-atherogenic (cathepsin S) and atheroprotective (CD163) macrophages. Aorta, right coronary artery, and left iliac artery were stained en face with Sudan IV and the amount of atherosclerosis quantified. There was no effect of treatment on plasma lipid profile, vascular FDG-PET signal or the amount of atherosclerosis in any of the examined arteries. However, immunostaining of coronary lesions revealed reduced cathepsin S positivity in the treated group compared with placebo (4.8% versus 8.2% of intima area, p=0.03) with no difference in CD68 or CD163 positivity. CONCLUSIONS: In hypercholesterolemic minipigs, treatment with a human recombinant monoclonal antibody against oxLDL reduced cathepsin S in coronary lesions without any effect on the burden of atherosclerosis or aortic FDG-PET signal.

Serum level of LOX-1 ligand containing ApoB is associated with increased carotid intima-media thickness in Japanese community-dwelling men, especially those with hypercholesterolemia LOX-1 ligand and IMT in Japanese.

BACKGROUND: The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than usual lipid parameters; however, the relationship between LAB and carotid intima-media thickness (IMT) was not clear even in Asian populations. METHODS: A total of 992 community-dwelling Japanese men, aged 40 to 79 years, were enrolled in the present study. Serum LAB levels were measured by enzyme-linked immunosorbent assays (ELISAs) with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody. RESULTS: Serum LAB levels (median [interquartile range], µg cs/L) were 5341 µg cs/L (4093-7125). The mean average IMT of the common carotid artery was highest in the fourth LAB quartile (842 µm) compared with the first quartile (797 µm) after adjustment for age, high-density lipoprotein cholesterol, triglyceride, body mass index, hypertension, diabetes, high sensitivity C-reactive protein, smoking, and alcohol drinking. However, this statistically significant difference was lost after further adjustment for total cholesterol (TC). After stratification using the combination of median LAB and hypercholesterolemia (serum TC ≥ 6.21 mmol/L and/or lipid-lowering medication), the adjusted mean average IMT (standard error) in the high LAB/hypercholesterolemia group was 886 µm (12.7), 856 µm (16.7) in the low LAB/hypercholesterolemia group, and 833 µm (8.4) in the low LAB/normal cholesterol group (P = .004). After further adjustment for TC, mean average IMT in the high LAB group was significantly higher than that measured in the low LAB group in hypercholesterolemic participants not taking lipid-lowering medication. CONCLUSION: Serum LAB was associated with an increased carotid IMT in Japanese men, especially those with hypercholesterolemia.

Hypercholesterolemia is Accounted for Atherosclerosis at the Proximal Arterial Segments of Myocardial Bridging: A Pilot Study.

Arterial shear stress was generally implicated in the development of atherosclerotic plaque (AP). Atherosclerotic plaque may be associated with myocardial bridging (MB). We evaluated the metabolic abnormalities which could determine the localization of AP at the proximal coronary segment of MB. We analyzed the patients with MB, AP&MB, and AP on left anterior descending (LAD) artery who were diagnosed by multislice computed tomography coronary angiography. Serum levels of metabolic parameters were compared among study groups. Patients with MB&AP and AP were significantly older than those in the MB group. Patients with MB&AP had AP and MB at the proximal and middle segments of LAD artery, respectively. Total cholesterol, low-density lipoprotein (LDL) cholesterol and very LDL, and triglyceride levels were significantly higher in patients with MB&AP and AP compared to only MB. Low-density lipoprotein cholesterol was significantly correlated with the type of coronary artery disease in multiple regression analysis. Myocardial bridging may be an anatomical determinant for the localization of AP proximal to itself in the presence of hypercholesterolemia.