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1.
Atherosclerotic cardiovascular disease risk assessment in familial hypercholesterolemia: does one size fit all?
Mata, P, Alonso, R, Pérez de Isla, L
Current opinion in lipidology. 2018;(6):445-452
Abstract
PURPOSE OF REVIEW Familial hypercholesterolemia is a frequent genetic disease associated with lifelong elevation of LDL-cholesterol and premature atherosclerotic cardiovascular disease (ASCVD). Statins are the cornerstone of treatment. However, with the introduction of novel LDL-cholesterol-lowering therapies, it is necessary to identify familial hypercholesterolemia patients presenting a significantly high residual ASCVD risk. The aim of this review is to provide an update on the recent literature concerning cardiovascular risk stratification including the role of coronary imaging. RECENT FINDINGS Several factors have shown to be independent predictors of ASCVD in familial hypercholesterolemia. These include clinical scores with cardiovascular risk factors, coronary imaging and novel protein biomarkers. However, the recent introduction of the SAFEHEART risk-equation (SAFEHEART-RE) could allow a more accurate ASCVD risk prediction in familial hypercholesterolemia. SUMMARY This article highlights the SAFEHEART-RE as a model to predict incident ASCVD in familial hypercholesterolemia. This equation is a simple and widely applicable tool for use in every clinical setting. Furthermore, coronary atherosclerosis assessed by coronary computed-tomographic angiography (coronary-CTA) is independently associated to the cardiovascular risk estimated according to the SAFEHEART-RE. This equation, as well as coronary-CTA and new biomarkers, could increase individual ASCVD risk stratification and could improve the efficiency and the use of new lipid-lowering therapies in familial hypercholesterolemia.
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2.
Lipids and Atherogenic Indices Fluctuation in Rheumatoid Arthritis Patients on Long-Term Tocilizumab Treatment.
Cacciapaglia, F, Anelli, MG, Rinaldi, A, Fornaro, M, Lopalco, G, Scioscia, C, Lapadula, G, Iannone, F
Mediators of inflammation. 2018;:2453265
Abstract
Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events, and the chronic inflammatory state may generate quantitative and qualitative changes in lipoprotein fractions. The anti-IL-6 receptor tocilizumab (TCZ), even if effective in inflammation and joint damage prevention, determined significant alterations to RA patients' lipid levels in randomized controlled trials, but real-world data are lacking. We evaluated the changes in lipid fraction levels and disease activity in a longitudinal cohort of RA patients on long-term treatment with tocilizumab (TCZ) in a community setting. We retrospectively selected 40 naïve-biologic RA patients on treatment with intravenous TCZ compared to 20 RA patients on methotrexate treatment as the control group. Total cholesterol (Tot-Chol), low-density lipoproteins (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured at the baseline and at 12, 24, and 52 weeks thereafter. At the same points, 28-joint disease activity score (DAS28), clinical disease activity index (CDAI), and EULAR clinical responses were also assessed. During the first 24 weeks, we observed in TCZ-treated patients a progressive statistically significant (p < 0.001) increase in Tot-Chol, LDL, HDL, and TG, which returned close to the baseline at 52 weeks. But no changes in the lipid-related CV risk indices Tot-Chol/HDL and LDL/HDL ratios and the atherogenic index (log10 TG/HDL) were detectable. Notably, we observed a statistically significant negative correlation between changes in lipid fractions and DAS28 or CDAI. The prolonged treatment with TCZ was associated to a transient increase in cholesterol's fractions during the first 6 months of treatment, with inverse correlation to disease activity, but with no impact on surrogate lipid indices of atherogenic risk. These findings may aid clinicians in interpreting the RA patient's lipid profile in daily clinical practice.
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3.
Endotoxemia is modulated by quantity and quality of dietary fat in older adults.
Lopez-Moreno, J, Garcia-Carpintero, S, Gomez-Delgado, F, Jimenez-Lucena, R, Vals-Delgado, C, Alcala-Diaz, JF, Roncero-Ramos, I, Rangel-Zuñiga, OA, Yubero-Serrano, EM, Malagon, MM, et al
Experimental gerontology. 2018;:119-125
Abstract
BACKGROUND Aging is an important determinant of the rate of atherosclerosis development, mainly through low-grade inflammation. Diet, and particularly its fat content, modulates the inflammatory response in fasting and postprandial states. OBJECTIVE We aimed to study the effects of dietary fat on endotoxemia in healthy older adults. MATERIALS AND METHODS Twenty healthy older adults were randomized to three diets, lasting three-weeks each, using a crossover design: 1. A Mediterranean diet enriched in MUFA with virgin olive oil. 2. An SFA-rich diet. 3. A low-fat high-carbohydrate diet enriched in n-3 PUFA (α-linolenic acid of plant origin) (CHO-PUFA diet). At the end of each period, after a 12-h fast, the subjects received a meal with a composition similar to the dietary period just completed. We determined the fasting and the postprandial plasma levels of lipopolysaccharide (LPS) and LPS-binding protein (LBP). RESULTS In the fasting state, we observed lower LPS plasma levels after the consumption of the CHO-PUFA diet (P=0.046) in comparison with the consumption of the Med and SFA-rich diets. In the postprandial measurements, we observed a statistically significant increase in plasma levels of LPS (P=0.044) and a decrease in LBP (P=0.003) after the intake of the CHO-PUFA meal, whereas no postprandial changes were observed after the ingestion of the Med and SFA-rich meals. CONCLUSION Our results, together with those obtained in a previous study, support the concept that the consumption of the Med Diet, in contrast to a low-fat PUFA diet, constitutes a more suitable dietary lifestyle for preventing the development of atherosclerosis in a population at risk, such as older adults.
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4.
Effects of pemafibrate (K-877) on cholesterol efflux capacity and postprandial hyperlipidemia in patients with atherogenic dyslipidemia.
Yamashita, S, Arai, H, Yokote, K, Araki, E, Suganami, H, Ishibashi, S, ,
Journal of clinical lipidology. 2018;(5):1267-1279.e4
Abstract
BACKGROUND Cardiovascular risk is negatively correlated with cholesterol efflux capacity (CEC) from macrophages to high-density lipoproteins (HDLs) and positively correlated with fasting and nonfasting triglyceride-rich lipoproteins (TRLs). Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, robustly decreases the fasting TRL level, increases the HDL cholesterol (HDL-C) level, and improves the atherogenic lipoprotein subclass profile, with an adverse event rate comparable to that of placebo treatment in previous clinical studies. OBJECTIVE This study aimed to investigate the effects of pemafibrate on CEC and postprandial hyperlipidemia. METHODS Using a single-center, double-blind, randomized, two-by-two crossover design, 33 patients were assigned to receive either 0.4 mg/d pemafibrate (twice daily) or placebo first. The assigned study drug was administered for 4 weeks. Subsequently, the alternate study drug was administered for another 4 weeks. CEC was measured using HDLs obtained from fasting blood samples. A meal tolerance test was performed to examine the postprandial lipid levels at weeks 0, 4, and 8. RESULTS CEC, HDL-C, and apolipoprotein A-I levels increased after pemafibrate treatment compared with placebo administration. Moreover, the percent change in CEC was correlated with that of HDL-C and apolipoprotein A-I levels. TRL levels markedly decreased after pemafibrate treatment in both fasting and nonfasting states. CONCLUSIONS These findings suggest that pemafibrate enhances reverse cholesterol transport and may retard the progression and even promote the regression of atherosclerosis by comprehensively ameliorating the atherogenic lipid profile.
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5.
On-treatment lipid profiles to predict the cardiovascular outcomes in ASCVD patients comorbid with chronic kidney disease - The multi-center T-SPARCLE registry study.
Ho, LT, Lin, FJ, Tseng, WK, Yin, WH, Wu, YW, Li, YH, Yeh, HI, Chen, JW, Wu, CC, ,
Journal of the Formosan Medical Association = Taiwan yi zhi. 2018;(9):814-824
Abstract
BACKGROUND The aim of this study is to determine the relationship between the on-treatment lipid profiles and the CV events in CKD and non-CKD population. METHOD This study was a multi-center observational registry, the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. This study follows up patients with CV diseases in Taiwan who have secondary prevention therapies. The primary outcome is the time of first occurrence of a major adverse cardiac events (MACEs). RESULT 5388 patients with ASCVD were included and 1478 (27.4%) had CKD without dialysis. CKD patients had higher TG and lower LDL-C levels. The incidence of recurrent MACEs per 1000 person-years in CKD patients was 19.5 (95% CI 15.5-24.9), compared with 9.1 (95% CI 7.4-11.1) in non-CKD patients. In patients with statin therapy, there were no differences in MACE risk between each level of on-treatment LDL-C, TG and HDL-C level. Higher on-treatment non-HDL-C level was a significant predictor for higher MACE risk in patients without CKD, and borderline significant in CKD patients under statin therapy. Heart failure history was also associated with higher MACE risk in both group. Lower body mass index (BMI < 23 kg/m2) was associated with higher MACE risk in CKD patients. CONCLUSION In ASCVD patients, on-treatment LDL-C was not a good CV outcome predictor. Instead, on-treatment non-HDL-C was a better predictor. Heart failure history was also associated with higher MACE risk in both group of patients. Lower BMI (<23 kg/m2) was associated with higher recurrent MACE risk in CKD patients.
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6.
Drug effect of atorvastatin on middle cerebral atherosclerotic stenosis and high resolution NMR diagnosis.
Chen, X, Wang, S, Lin, L, Li, Y, Zhang, H
Pakistan journal of pharmaceutical sciences. 2018;(3(Special)):1169-1173
Abstract
Atherosclerosis (AS) is a chronic inflammatory reaction with the pathological changes in the lipid deposition of arterial intima. The disorder of blood lipid metabolism is the main factor of the occurrence and development of AS, and the inflammatory reaction and autoimmune reaction also run through the development of AS. In this study, we compared the efficacy and safety of atorvastatin, simvastatin, pravastatin and rosuvastatin in the treatment of AS. At the same time, we used high resolution magnetic resonance imaging (MRI) to assess the changes in plaque area in the middle cerebral artery and the patch area before and after drug treatment. After 6 months of treatment, the number of intima-media thickness (IMT), plaque and plaque in each group were significantly lower than that before the same group. The results showed that statin treatment of AS could significantly reduce the level of blood lipids, but rosuvastatin and atorvastatin had better effects on anti inflammation and maintaining plaque stability and the drug safety was good.
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7.
The Central European diet as an alternative to the Mediterranean diet in atherosclerosis prevention in postmenopausal obese women with a high risk of metabolic syndrome - a randomized nutrition-al trial.
Duś-Żuchowska, M, Bajerska, J, Krzyżanowska, P, Chmurzyńska, A, Miśkiewicz-Chotnicka, A, Muzsik, A, Walkowiak, J
Acta scientiarum polonorum. Technologia alimentaria. 2018;(4):399-407
Abstract
BACKGROUND Metabolic syndrome (MS) is a powerful risk factor for atherosclerosis (AT). The crucial meth- od of minimizing the development of atherosclerosis and its clinical manifestations is lifestyle modifications, including following a healthy diet. The aim of the study was to check if the Central European Diet (CED) could be an alternative to the Mediterranean Diet (MED) in the prevention of AT in patients with a risk of MS. METHODS The randomized, single-blind nutritional trial involved 144 obese women with a risk of MS. The subjects were randomly assigned to two groups and followed MED (n = 72) or CED (n = 72) for 16 weeks. The concentrations of high-sensitivity C-reactive protein (hs-CRP) and asymmetrical dimethylarginine (ADMA) were measured before and after nutritional intervention. RESULTS In both studied groups, the concentrations of hs-CRP decreased significantly after the nutritional in- tervention (CED: p = 0.0107; MED: p = 0.0002). The ADMA levels were significantly lower after nutritional intervention in the CED group (p = 0.0187) but not in the MED group (p = 0.8354). However, the observed changes of hs-CRP concentrations (Δhs-CRP) and ADMA levels (ΔADMA) were not different between the groups (p = 0.5307 and p = 0.0905, respectively). CONCLUSIONS In the Central European post-menopausal obese population, a well-designed, energy-restricted diet with the use of food items traditional for the region (CED) could be a good alternative to MED in terms of AT prevention.
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8.
HDLs and the pathogenesis of atherosclerosis.
Schwertani, A, Choi, HY, Genest, J
Current opinion in cardiology. 2018;(3):311-316
Abstract
PURPOSE OF REVIEW Plasma levels of HDL cholesterol are a biomarker of cardiovascular health but not a therapeutic target, as demonstrated by the failure of pharmacological modulation of HDL cholesterol to prevent or treat atherosclerotic cardiovascular disease. In health, HDL particles exert pleiotropic effects against atherosclerosis, including cholesterol removal from foam cells, vasodilatory effects through vascular endothelial cell nitric oxide production, decreased vascular inflammation and oxidative damage, endothelial cell proliferation and antiapoptotic effects. RECENT FINDINGS These functional effects of HDL are independent of the cholesterol mass and are related to the proteome and lipidome. In disease states and with the ageing process, HDL components are extensively modified and may no longer play a beneficial role but are retained in the atheroma and contribute to atherosclerosis. We have recently shown that desmocollin 1 (DSC1) acts as an apolipoprotein (apo) A-I binding protein that is highly expressed in atherosclerotic plaques and inhibits atheroprotective HDL functions by retaining apoA-I. The apoA-I retention hypothesis proposes that macrophages express DSC1 in a maladaptive process that renders apoA-I inactive and contributes to atherosclerosis. SUMMARY HDL loses their beneficial properties in ageing and disease states. Novel pathways may present new therapeutic avenues to restore their biological functions.
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9.
PCSK9: A potential regulator of apoE/apoER2 against inflammation in atherosclerosis?
Bai, XQ, Peng, J, Wang, MM, Xiao, J, Xiang, Q, Ren, Z, Wen, HY, Jiang, ZS, Tang, ZH, Liu, LS
Clinica chimica acta; international journal of clinical chemistry. 2018;:192-196
Abstract
Atherosclerosis is characterized by chronic inflammation and lipid accumulation in arterial walls, resulting in several vascular events. Proprotein convertase subtilisin kexin 9 (PCSK9), a serine protease, has a pivotal role in the degradation of hepatic low-density lipoprotein receptor (LDLR). It can increase plasma concentrations of low-density lipoprotein cholesterol and affect lipid metabolism. Recently, PCSK9 has been found to accelerate atherosclerosis via mechanisms apart from that involving the degradation of LDLR, with an emerging role in regulating the inflammatory response in atherosclerosis. Apolipoprotein E receptor 2 (apoER2), one of the LDLR family members expressed in macrophages, can bind to its ligand apolipoprotein E (apoE), exhibiting an anti-inflammatory role in atherosclerosis. Evidence suggests that apoER2 is a target of PCSK9. This review aims to discuss PCSK9 as a potential regulator of apoE/apoER2 against inflammation in atherosclerosis.
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10.
Anthropometric features as predictors of atherogenic dyslipidemia and cardiovascular risk in a large population of school-aged children.
Furtado, JM, Almeida, SM, Mascarenhas, P, Ferraz, ME, Ferreira, JC, Vilanova, M, Monteiro, MP, Ferraz, FP
PloS one. 2018;(6):e0197922
Abstract
BACKGROUND Autopsy studies reveal that atherosclerosis lesions can be found as early as two years of age. To slow the development of this early pathology, obesity and dyslipidemia prevention should start from childhood making it urgent to explore new ways to evaluate dyslipidemia risk in children that can be applied widely, such as the non-invasive anthropometric evaluation. OBJECTIVE Assess the metabolic profile of a pediatric population at a specific age to describe the association between anthropometric and biochemical cardiovascular disease risk factors; and evaluate selected anthropometric variables as potential predictors for dyslipidemic cardiovascular risk. DESIGN AND METHODS Anthropometric features, bioimpedance parameters and fasting clinical profile were assessed in Lisbon and the Tagus Valley region pre-pubertal nine-year-old children (n = 1.496) from 2009-2013 in a descriptive, cross-sectional study. Anthropometric variables predictive power was evaluated through regression analysis. RESULTS At least one abnormal lipid parameter was found in 65% of "normal weight", 73% of "overweight" and 81% of "obese" children according to the International Obesity Task Force (IOTF) standards. Dyslipidemia was present in 67.8% of children. Waist-hip ratio (WHR) explained 0.4% of total cholesterol (TC) variance. Waist circumference (WC) explained 2.8% of apolipoprotein (APO) A1 variance. Waist-circumference-to-height-ratio (WHtR) explained 2.7%, 2.8% and 1.9% of low-density lipoprotein cholesterol (LDL-c), APO B, and N_HDL-c variance, respectively. Children with abnormally high WHR levels had an increase in risk of 4.49, 3.40 and 5.30 times, respectively, for developing cardiovascular disease risk factors measured as high-risk levels of TC, LDL-c and non-HDL-c (N_HDL-c) (p<0.05). Only 29.9% of "normal weight" children had no anthropometric, bioimpedance or biochemical parameters associated with CV risk. CONCLUSION A large proportion of school age children have at least one lipid profile abnormality. BMI, zBMI, calf circumference (CC), hip circumference (HC), WC, and WHR are directly associated with dyslipidemia, whereas HC and calf circumference (CC) adjusted to WC, and mid-upper arm circumference (MUAC), are all inversely associated with dyslipidemia. Selected anthropometric variables are likely to help predict increased odds of having CV risk factors.