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Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B.
Suzuki, K, Suda, G, Yamamoto, Y, Abiko, S, Kinoshita, K, Miyamoto, S, Sugiura, R, Kimura, M, Maehara, O, Yamada, R, et al
PloS one. 2022;(1):e0261760
Abstract
For long-term treatment of hepatitis B virus (HBV) infection, switching from tenofovir-disoproxil-fumarate (TDF) to tenofovir-alafenamide (TAF) may prevent renal dysfunction and bone loss. However, the precise effects of this switch on the blood lipid profile remain to be clarified. This is an important issue as TDF is known to have effects on both low- and high-density lipids. Therefore, our retrospective multi-center study aimed to evaluate the effects of switching from TDF to TAF on the lipid profile of patients with HBV infection. Samples were obtained prior to the switch from TDF to TAF and at 6-12 months after TAF initiation. In some cases, additional samples obtained pre- and post-TDF administration were available for analysis. Serum cholesterol levels, including oxidized-low-density lipoprotein (LDL) and non-high-density lipoprotein-cholesterol (HDL-c), and the rate of dyslipidemia, according to the NCEP-ATP III lipid risk classification, were analyzed. The data from 69 patients were analyzed, including 33 patients with pre- and post-TDF-initiation serum samples. Total cholesterol (T-chol), HDL-c, LDL-c, non-HDL-c, and oxidized LDL levels increased significantly after switching to TAF. With regard to sequential changes pre- to post-TAF, TDF was associated with significantly lower serum T-chol, HDL-c, and oxidized LDL-c levels, with T-chol, HDL-c, LDL-c, and oxidized LDL-c levels increasing significantly after the switch. The switch from TDF to TAF was also associated with an increase in the rate of dyslipidemia, from 33% to 39%, with an increase in the rate of severe dyslipidemia of 1.4% and 5.8%, based on T-chol and LDL-c levels. Of note, no cases of severe dyslipidemia were detected pre-TAF treatment. As oxidized LDL-c and non-HDL-c are strongly associated with atherosclerosis development, careful monitoring of lipid is needed after switching from TDF to TAF in this clinical population.
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Lipid profile dysregulation in opium users based on Fasa PERSIAN cohort study results.
Kazemi, M, Bazyar, M, Naghizadeh, MM, Dehghan, A, Rahimabadi, MS, Chijan, MR, Bijani, M, Zahmatkeshan, M, Ghaemi, A, Samimi, N, et al
Scientific reports. 2021;(1):12058
Abstract
One of the main health problems in many societies is the increased opium abuse, which was found to be correlated with many problems like cardiovascular disease. This study aimed to evaluate the correlation of opium use with blood lipoproteins as the risk factor of CVD. This was a cross-sectional study conducted on participants of the first phase of the PERSIAN Cohort study who were aged between 35 and 70 years old. Demographic characteristics; history of smoking, alcohol, and opium consumption; medical history; and medications were asked and the related checklists were filled out. The levels of physical activity and fat intake were also registered. As well, lipoprotein profiles were investigated by blood sampling. The linear and logistic regression was used to analyze the relationship between opium and lipid profile and the statistical significant level was considered as < 0.05. Among 9300 participants with a mean age of 48.06 ± 9.44 years old, 49.6% of them were men. About 24.1% of the participants used opium. In the linear regression models, unlike TG (β = 2.2, p = 0.36), total cholesterol (β = - 2.5, p = 0.02), LDL (β = - 2.0, p = 0.04), and HDL (β = - 1.0, p = 0.04) were significantly lower in people who used opium compared to the others. In the logistic regression models, abnormal level of LDL (OR = 0.78, p = 0.003) and total cholesterol (OR = 0.82, p = 0.008) were less in people who used opium compared to the others. This study showed that there is a correlation between opium usage and lower levels of total cholesterol and LDL; however, the lower level of HDL in normal range was seen in opium users. Considering the current evidences, most of them showed the increased risks of ischemic heart disease, heart attack, hypertension, cerebrovascular disease, and cancer in opium users. Therefore, Healthcare providers and patients should be noticed about the deleterious effects of opium consumption on various vascular events. In addition, it is necessary for managers and policy makers of the health care system to take the necessary measures to raise the level of awareness and health literacy of the general public about the high-risk side effects of opium use and to take necessary and effective strategies to prevent and reduce its use.
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The effects of exercise training on lipid profile in patients with sarcoidosis.
Jastrzebski, D, Toczylowska, B, Zieminska, E, Zebrowska, A, Kostorz-Nosal, S, Swietochowska, E, Di Giulio, C, Ziora, D
Scientific reports. 2021;(1):5551
Abstract
This study aimed to determine the use of lipid profiling to assess the effects of moderate intensity exercise training (ET) on patients with sarcoidosis. Fourteen patients with sarcoidosis (mean age, 46.0 ± 9.6 years) were examined before and after 3-week of ET programme in hospital settings. Symptoms (fatigue: FAS, dyspnoea: MRC), lung function tests and physical function tests (6 MWT, muscle force) were measured before and after ET. Proton nuclear magnetic resonance (NMR) spectroscopy combined with orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to determine lipid profile before and after ET. Twenty-five NMR signals from lipid compounds were selected for further analysis as well as serum lipid and inflammatory markers. Three weeks of ET results in improvement of symptoms (FAS: 27.5 vs. 21.0; p < 0.001, MRC: 0.86 vs. 0.14; p = 0.002) and physical function (6MWT: 508.43 vs. 547.29; p = 0.039). OPLS-DA analysis of the lipid profiles of patients with sarcoidosis revealed differences among the samples before and after ET, including decreases in fatty acids (p < 0.017), triglycerides (p < 0.022) and total cholesterol (p < 0.020). Other changes included shifts in fatty acids oxidation products and triacylglycerol esters. A short-time, in-hospital exercise training benefits patients with sarcoidosis by enhancing their physical function. Additionally, positive effect on lipid profile was observed also in this study. It is suggested that lipid profiling could become a new prognostic method to assess effects of pulmonary rehabilitation in patients with sarcoidosis.
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The Prebiotic Effects of Oats on Blood Lipids, Gut Microbiota, and Short-Chain Fatty Acids in Mildly Hypercholesterolemic Subjects Compared With Rice: A Randomized, Controlled Trial.
Xu, D, Feng, M, Chu, Y, Wang, S, Shete, V, Tuohy, KM, Liu, F, Zhou, X, Kamil, A, Pan, D, et al
Frontiers in immunology. 2021;:787797
Abstract
Phytochemicals derived from oats are reported to possess a beneficial effect on modulating dyslipidemia, specifically on lowering total and LDL cholesterol. However, deeper insights into its mechanism remain unclear. In this randomized controlled study, we assigned 210 mildly hypercholesterolemic subjects from three study centers across China (Beijing, Nanjing, and Shanghai) to consume 80 g of oats or rice daily for 45 days. Plasma lipid profiles, short chain fatty acids (SCFAs), and fecal microbiota were measured. The results showed that total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) decreased significantly with both oats and rice intake after 30 and 45 days. The reduction in TC and non-HDL-C was greater in the participants consuming oats compared with rice at day 45 (p = 0.011 and 0.049, respectively). Oat consumption significantly increased the abundance of Akkermansia muciniphila and Roseburia, and the relative abundance of Dialister, Butyrivibrio, and Paraprevotella, and decreased unclassified f-Sutterellaceae. In the oat group, Bifidobacterium abundance was negatively correlated with LDL-C (p = 0.01, r = -0.31) and, TC and LDL-C were negatively correlated to Faecalibacterium prausnitzii (p = 0.02, r = -0.29; p = 0.03, r = -0.27, respectively). Enterobacteriaceae, Roseburia, and Faecalibacterium prausnitzii were positively correlated with plasma butyric acid and valeric acid concentrations and negatively correlated to isobutyric acid. HDL-C was negatively correlated with valeric acid (p = 0.02, r = -0.25) and total triglyceride (TG) was positively correlated to isovaleric acid (p = 0.03, r = 0.23). Taken together, oats consumption significantly reduced TC and LDL-C, and also mediated a prebiotic effect on gut microbiome. Akkermansia muciniphila, Roseburia, Bifidobacterium, and Faecalibacterium prausnitzii, and plasma SCFA correlated with oat-induced changes in plasma lipids, suggesting prebiotic activity of oats to modulate gut microbiome could contribute towards its cholesterol-lowering effect.
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11βHSD1 Inhibition with AZD4017 Improves Lipid Profiles and Lean Muscle Mass in Idiopathic Intracranial Hypertension.
Hardy, RS, Botfield, H, Markey, K, Mitchell, JL, Alimajstorovic, Z, Westgate, CSJ, Sagmeister, M, Fairclough, RJ, Ottridge, RS, Yiangou, A, et al
The Journal of clinical endocrinology and metabolism. 2021;(1):174-187
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Abstract
BACKGROUND The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH). METHODS We conducted a UK multicenter phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017. Serum markers of glucose homeostasis, lipid metabolism, renal and hepatic function, inflammation and androgen profiles were determined and examined in relation to changes in fat and lean mass by dual-energy X-ray absorptiometry. RESULTS Patients receiving AZD4017 showed significant improvements in lipid profiles (decreased cholesterol, increased high-density lipoprotein [HDL] and cholesterol/HDL ratio), markers of hepatic function (decreased alkaline phosphatase and gamma-glutamyl transferase), and increased lean muscle mass (1.8%, P < .001). No changes in body mass index, fat mass, and markers of glucose metabolism or inflammation were observed. Patients receiving AZD4017 demonstrated increased levels of circulating androgens, positively correlated with changes in total lean muscle mass. CONCLUSIONS These beneficial metabolic changes represent a reduction in risk factors associated with raised intracranial pressure and represent further beneficial therapeutic outcomes of 11β-HSD1 inhibition by AZD4017 in this overweight IIH cohort. In particular, beneficial changes in lean muscle mass associated with AZD4017 may reflect new applications for this nature of inhibitor in the management of conditions such as sarcopenia.
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Lipid Profiles and Heart Failure Risk: Results From Two Prospective Studies.
Wittenbecher, C, Eichelmann, F, Toledo, E, Guasch-Ferré, M, Ruiz-Canela, M, Li, J, Arós, F, Lee, CH, Liang, L, Salas-Salvadó, J, et al
Circulation research. 2021;(3):309-320
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Abstract
RATIONALE Altered lipid metabolism has been implicated in heart failure (HF) development, but no prospective studies have examined comprehensive lipidomics data and subsequent risk of HF. OBJECTIVE We aimed to link single lipid metabolites and lipidomics networks to the risk of developing HF. METHODS AND RESULTS Discovery analyses were based on 216 targeted lipids in a case-control study (331 incident HF cases and 507 controls, matched by age, sex, and study center), nested within the PREDIMED (Prevención con Dieta Mediterránea) study. Associations of single lipids were examined in conditional logistic regression models. Furthermore, lipidomics networks were linked to HF risk in a multistep workflow, including machine learning-based identification of the HF-related network clusters, and regression-based discovery of the HF-related lipid patterns within these clusters. If available, significant findings were externally validated in a subsample of the EPIC-Potsdam cohort (2414 at-risk participants, including 87 incident HF cases). After confounder-adjustments, 2 lipids were significantly associated with HF risk in both cohorts: CER (ceramide) 16:0 (relative risk [RR] per SD in PREDIMED, 1.28 [95% CI, 1.13-1.47]) and phosphatidylcholine 32_0 (RR per SD in PREDIMED, 1.23 [95% CI, 1.08-1.41]). Additionally, lipid patterns in several network clusters were associated with HF risk in PREDIMED. Adjusted for standard risk factors, an internally cross-validated score based on the significant HF-related lipids that were identified in the network analysis in PREDIMED was associated with a higher HF risk (20 lipids, RR per SD, 2.33 [95% CI, 1.93%-2.81%). Moreover, a lipid score restricted to the externally available lipids was significantly associated with HF incidence in both cohorts (6 lipids, RRs per SD, 1.30 [95% CI, 1.14-1.47] in PREDIMED, and 1.46 [95% CI, 1.17-1.82] in EPIC-Potsdam). CONCLUSIONS Our study identified and validated 2 lipid metabolites and several lipidomics patterns as potential novel biomarkers of HF risk. Lipid profiling may capture preclinical molecular alterations that predispose for incident HF. Registration: URL: https://www.isrctn.com/ISRCTN35739639; Unique identifier: ISRCTN35739639.
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High-Sensitivity C-Reactive Protein Discordance With Atherogenic Lipid Measures and Incidence of Atherosclerotic Cardiovascular Disease in Primary Prevention: The ARIC Study.
Quispe, R, Michos, ED, Martin, SS, Puri, R, Toth, PP, Al Suwaidi, J, Banach, M, Virani, SS, Blumenthal, RS, Jones, SR, et al
Journal of the American Heart Association. 2020;(3):e013600
Abstract
Background Inflammation is an independent causal risk factor for atherosclerotic cardiovascular diseases (ASCVDs). However, whether hsCRP (high-sensitivity C-reactive protein) is prognostic across various levels of atherogenic lipid measures such as low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B and total cholesterol/high-density lipoprotein cholesterol in primary prevention is unknown. Methods and Results We studied 9748 ARIC (Atherosclerosis Risk in Communities) study participants who were free of ASCVD at baseline (visit 4, 1996-1998) and had measurements of lipids, apolipoprotein B, and hsCRP. We used multivariable adjusted Cox models to estimate the risk of incident ASCVD events associated with hsCRP levels (less than/greater than or equal to median) in individuals where triple lipid measures combined (low-density lipoprotein cholesterol + non-high-density lipoprotein cholesterol + apolipoprotein B) or quadruple measures combined [triple + total cholesterol/high-density lipoprotein cholesterol] were less than versus greater than or equal to median cut points. Mean age of participants was 62.6±5.6 years; 59% women, 22% black. There were 1574 ASCVD events over median (interquartile range) follow-up of 18.4 (12.8-19.5) years, and discordance between hsCRP and lipid measures was prevalent in 50% of the population. hsCRP greater than or equal to median (2.4 mg/L), compared with less than median, was associated with an increased risk of ASCVD in individuals with less than median levels of the triple (adjusted hazard ratio, 1.33; 95% CI, 1.09-1.60) and quadruple (adjusted hazard ratio,1.47; 95% CI, 1.18-1.85) lipid measures. Such increased risk was consistent among individuals with low (<7.5%) or high (≥7.5%) estimated risk by the pooled cohort equation. There were no interactions by sex, diabetes mellitus, or statin use. Conclusions Our findings suggest that inflammation is independently associated with ASCVD regardless of atherogenic lipid levels and pooled cohort equation risk score in individuals without known ASCVD.
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Lipid-lowering treatment and low-density lipoprotein cholesterol target achievement in patients with type 2 diabetes and acute coronary syndrome.
Ferrières, J, Lautsch, D, Bramlage, P, Horack, M, Baxter, CA, Ambegaonkar, B, Toth, PP, Poh, KK, De Ferrari, GM, Gitt, AK
Archives of cardiovascular diseases. 2020;(10):617-629
Abstract
BACKGROUND Patients with type 2 diabetes mellitus characteristically display an atherogenic lipid profile with high triglyceride concentrations, low high-density lipoprotein cholesterol (HDL-C) concentrations and low-density lipoprotein cholesterol (LDL-C) concentrations not always elevated. It is unclear if patients with diabetes who present with an acute coronary syndrome (ACS) receive different or more-potent lipid-lowering therapy (LLT). AIMS To investigate lipid abnormalities in patients with and without type 2 diabetes hospitalised for an ACS, and use of LLT before admission and 4 months after the event. METHODS Patients were included in the observational DYSIS II study if they were hospitalised for an ACS and had a full lipid profile. RESULTS Of 3803 patients, diabetes was documented in 1344 (54.7%). Compared to patients without diabetes, those with diabetes had a lower mean LDL-C (101.2 vs. 112.0mg/dL; 2.6 vs. 2.9mmol/L; P<0.0001), with a greater proportion attaining concentrations<70mg/dL (1.8mmol/L) (23.9% vs. 16.0%; P<0.0001) and<55mg/dL (1.4mmol/L) (11.3% vs. 7.3%; P<0.0001), a higher mean triglyceride concentration (139.0 vs. 121.0mg/dL; 1.6 vs. 1.4mmol/L; P<0.0001) and a lower HDL-C concentration. LLT was more commonly given to patients with diabetes (77.5% vs. 58.8%; P<0.0001); there were no differences in types of therapy prescribed. Four months after hospitalisation, most patients from both groups were being treated with LLT (predominantly statin monotherapy). CONCLUSIONS Despite the different lipid profiles, the type of LLT prescribed did not vary depending on the presence or absence of type 2 diabetes. There was no difference in LLT in patients with and without diabetes at 4-month follow-up, except for fibrates, which were used in 2% of patients with and 1% of patients without diabetes. Statin monotherapy of intermediate potency was the predominant treatment in both groups.
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Lipid Profile Results after Cardiovascular Prevention Programme: Euroaction Model in Spain.
Buigues, C, Queralt, A, De Velasco, JA, Salvador-Sanz, A, Jennings, C, Wood, D, Trapero, I
Endocrine, metabolic & immune disorders drug targets. 2020;(9):1412-1418
Abstract
BACKGROUND Cardiovascular prevention and rehabilitation programmes (CVPRP) are an established model of care designed to improve risk factor management. They have been successfully implemented in a variety of settings, in patients with coronary heart disease (CHD). OBJECTIVE To assess the long term impact of a nurse-coordinated, multidisciplinary, CVPRP in patients with CHD in the reduction of lipid profile and medication prescription in clinical practice. METHODS The study used an analytical, experimental, population based, prospective and longitudinal design. In Spain, the study was conducted in the Valencian Community, including two randomized hospitals. Coronary patients were prospectively and consecutively identified in both hospitals. The intervention hospital carried out an 8-week CVPRP. RESULTS The proportion of patients achieving improved standards of preventive care increased in the intervention hospital compared with the usual care hospital, mainly regarding LDL-C concentrations. Furthermore, an increased prescription of statins was found in the intervention group. However, there were no statistically significant differences in triglycerides and glucose levels. CONCLUSION The EUROACTION nurse-led CVPRP enabled coronary patients to control lipid profile to the European targets. A large proportion of patients were prescribed statin therapy as cardioprotective medication with favorable changes in medication for coronary patients. To improve the potential for cardiovascular prevention, we need local preventive cardiology programmes adapted to the health policy of individual countries.
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Uncovering pathophysiological changes in frontotemporal dementia using serum lipids.
Phan, K, He, Y, Pickford, R, Bhatia, S, Katzeff, JS, Hodges, JR, Piguet, O, Halliday, GM, Kim, WS
Scientific reports. 2020;(1):3640
Abstract
Blood serum is enriched in lipids and has provided a platform to understand the pathogenesis of a number of human diseases with improved diagnosis and development of biomarkers. Understanding lipid changes in neurodegenerative diseases is particularly important because of the fact that lipids make up >50% of brain tissues. Frontotemporal dementia (FTD) is a common cause of early onset dementia, characterized by brain atrophy in the frontal and temporal regions, concomitant loss of lipids and dyslipidemia. However, little is known about the link between dyslipidemia and FTD pathophysiology. Here, we utilized an innovative approach - lipidomics based on mass spectrometry - to investigate three key aspects of FTD pathophysiology - mitochondrial dysfunction, inflammation, and oxidative stress. We analyzed the lipids that are intrinsically linked to neurodegeneration in serum collected from FTD patients and controls. We found that cardiolipin, acylcarnitine, lysophosphatidylcholine, platelet-activating factor, o-acyl-ω-hydroxy fatty acid and acrolein were specifically altered in FTD with strong correlation between the lipids, signifying pathophysiological changes in FTD. The lipid changes were verified by measurement of the common disease markers (e.g. ATP, cytokine, calcium) using conventional assays. When put together, these results support the use of lipidomics technology to detect pathophysiological changes in FTD.