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High Serum Cholesterol Is a Novel Risk Factor for Graves' Orbitopathy: Results of a Cross-Sectional Study.
Sabini, E, Mazzi, B, Profilo, MA, Mautone, T, Casini, G, Rocchi, R, Ionni, I, Menconi, F, Leo, M, Nardi, M, et al
Thyroid : official journal of the American Thyroid Association. 2018;(3):386-394
Abstract
BACKGROUND Limited data suggest that treatment with statins is associated with a reduced risk of Graves' orbitopathy (GO) in patients with Graves' disease (GD), attributed to the anti-inflammatory rather than to the hypolipemic effects of these medications. The aim of the present study was to investigate whether there is an association between high cholesterol and GO. The primary outcome was the relation between GO and low-density lipoprotein (LDL)-cholesterol. The secondary outcomes were the relation between severity or activity (the clinical activity score [CAS]) of GO and LDL-cholesterol. METHODS A cross-sectional investigation was conducted in consecutive patients with GD who came under the authors' observation to undergo radioiodine treatment, a stratification aimed at forming two distinct groups of patients under the same conditions. A total of 250 patients were enrolled, 133 with and 117 without GO. Ophthalmological assessments and serum lipids measurements were performed. RESULTS In multivariate analyses with correction for the duration of hyperthyroidism, a variable that differed between patients with respect to the presence or absence of GO, a correlation between the presence of GO and both total (p = 0.01) and LDL-cholesterol (p = 0.02) was observed. In patients with hyperthyroidism lasting <44 months, total and LDL-cholesterol were higher (p = 0.01 and p = 0.008, respectively) among GO patients. In this subgroup, based on the presence/absence of GO, cutoff values were established for total (191 mg/dL) and LDL-cholesterol (118.4 mg/dL), above which an increased risk of GO was observed (total cholesterol relative risk: 1.47; p = 0.03; LDL-cholesterol relative risk: 1.28; p = 0.03). GO severity and CAS did not correlate with serum lipids. However, CAS was found to be higher (p = 0.02) in patients with high total cholesterol. When the analysis was restricted to untreated GO patients, a correlation was found between CAS and both total (p = 0.04) and LDL-cholesterol (p = 0.03), after adjustment for GO duration. CONCLUSIONS In patients with a short duration of hyperthyroidism, total and LDL-cholesterol correlate with the presence of GO, suggesting a role of cholesterol in the development of GO. Depending on GO duration, total and LDL-cholesterol correlate with GO activity, suggesting a role of cholesterol in the clinical expression of GO.
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2.
Supplementation-Dependent Effects of Vegetable Oils with Varying Fatty Acid Compositions on Anthropometric and Biochemical Parameters in Obese Women.
Oliveira-de-Lira, L, Santos, EMC, de Souza, RF, Matos, RJB, Silva, MCD, Oliveira, LDS, Nascimento, TGD, Schemly, PALS, Souza, SL
Nutrients. 2018;(7)
Abstract
Fatty acid (FA) composition is a determinant of the physiological effects of dietary oils. This study investigated the effects of vegetable oil supplementation with different FA compositions on anthropometric and biochemical parameters in obese women on a hypocaloric diet with lifestyle modifications. Seventy-five women (body mass index, BMI, 30⁻39.9kg/m²) were randomized based on 8-week oil supplementation into four experimental groups: the coconut oil group (CoG, n = 18), the safflower oil group (SafG, n = 19), the chia oil group (ChG, n = 19), and the soybean oil placebo group (PG, n = 19). Pre- and post-supplementation weight, anthropometric parameters, and body fat (%BF), and lean mass percentages (%LM) were evaluated, along with biochemical parameters related to lipid and glycidemic profiles. In the anthropometric evaluation, the CoG showed greater weight loss (Δ% = -8.54 ± 2.38), and reduced BMI (absolute variation, Δabs = -2.86 ± 0.79), waist circumference (Δabs = -6.61 ± 0.85), waist-to-height ratio (Δabs = -0.041 ± 0.006), conicity index (Δabs = -0.03 ± 0.016), and %BF (Δabs = -2.78 ± 0.46), but increased %LM (Δabs = 2.61 ± 1.40) (p < 0.001). Moreover, the CoG showed a higher reduction in biochemical parameters of glycemia (Δabs = -24.71 ± 8.13) and glycated hemoglobin (Δabs = -0.86 ± 0.28) (p < 0.001). The ChG showed a higher reduction in cholesterol (Δabs = -45.36 ± 0.94), low-density lipoprotein cholesterol (LDLc; Δabs = -42.53 ± 22.65), and triglycerides (Δabs = -49.74 ± 26.3), but an increase in high-density lipoprotein cholesterol (HDLc; abs = 3.73 ± 1.24, p = 0.007). Coconut oil had a more pronounced effect on abdominal adiposity and glycidic profile, whereas chia oil had a higher effect on improving the lipid profile. Indeed, supplementation with different fatty acid compositions resulted in specific responses.
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3.
Reducing Cholesterol and Fat Intake Improves Glucose Tolerance by Enhancing β Cell Function in Nondiabetic Subjects.
Tricò, D, Trifirò, S, Mengozzi, A, Morgantini, C, Baldi, S, Mari, A, Natali, A
The Journal of clinical endocrinology and metabolism. 2018;(2):622-631
Abstract
CONTEXT A diet low in cholesterol and fat is commonly recommended to prevent metabolic and cardiovascular diseases; however, its effect on glucose tolerance is largely unknown. OBJECTIVE We examined whether and by which mechanisms a chronic reduction of cholesterol and fat intake affects glucose tolerance in nondiabetic individuals, independently of weight changes. DESIGN AND PARTICIPANTS In this crossover, randomized clinical trial, 30 healthy subjects, including 15 with family history of type 2 diabetes (T2D) (T2D offspring), underwent a 75-g oral glucose tolerance test (OGTT) after two 14-day isocaloric high-cholesterol, high-fat (HChF) or low-cholesterol, and low-fat (LChF) diets. MAIN OUTCOME MEASURES We evaluated changes in glucose tolerance, β cell function, insulin clearance, and insulin sensitivity by modeling plasma glucose, insulin, and C-peptide levels during the OGTT. RESULTS The shift from the HChF to the LChF diet was neutral on body weight but increased glucose tolerance (mean glucose -5%, P = 0.01) and three components of β cell function: glucose sensitivity (+17%, P = 0.01), insulin secretion at fasting glucose (+20%, P = 0.02), and potentiation (+19%, P = 0.03). The LChF diet improved insulin sensitivity (+7%, P = 0.048) only in T2D offspring, who tended to be more susceptible to the positive effect of the diet on glucose tolerance. CONCLUSIONS A chronic and isocaloric decrease in dietary cholesterol and fat intake improves glucose tolerance by diffusely ameliorating β cell function in nondiabetic subjects. Individuals genetically predisposed to develop T2D tend to be more susceptible to the positive effect of this dietary intervention on glucose tolerance and insulin sensitivity.
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4.
Cholesterol granuloma in an antrochoanal polyp. A rare lesion in children.
Val-Bernal, JF, Martino, M, Castaneda-Curto, N, García-Triana, M, Teigeiro-Núñez, V
Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia. 2018;(4):262-266
Abstract
Antrochoanal polyps (ACPs) are an infrequent clinical entity. Cholesterol granulomas (CGs) are commonly associated with chronic middle ear disease but are rare in the paranasal sinuses. We describe a case of a 10-year-old girl with a concomitant CG in an ACP which was surgically excised by nasosinusal endoscopic surgery. To our knowledge, there are only five previously published cases of CGs in ACPs and of these, only two were pediatric cases. We describe a third case in the youngest patient yet reported. Increased intrasinus pressure may affect venous and lymphatic drainage, leading to hemorrhages with hemolysis and deposition of cholesterol crystals and their esters initiating the formation of granulomas in the polyp. In addition, the insufficient lymphatic drainage prevents the complete elimination of lipids, contributing to the formation of cholesterol granulomas. The treatment and the outcome of an ACP associated with a CG are the same as for usual ACPs.
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5.
Inflammation, not Cholesterol, Is a Cause of Chronic Disease.
Tsoupras, A, Lordan, R, Zabetakis, I
Nutrients. 2018;(5)
Abstract
Since the Seven Countries Study, dietary cholesterol and the levels of serum cholesterol in relation to the development of chronic diseases have been somewhat demonised. However, the principles of the Mediterranean diet and relevant data linked to the examples of people living in the five blue zones demonstrate that the key to longevity and the prevention of chronic disease development is not the reduction of dietary or serum cholesterol but the control of systemic inflammation. In this review, we present all the relevant data that supports the view that it is inflammation induced by several factors, such as platelet-activating factor (PAF), that leads to the onset of cardiovascular diseases (CVD) rather than serum cholesterol. The key to reducing the incidence of CVD is to control the activities of PAF and other inflammatory mediators via diet, exercise, and healthy lifestyle choices. The relevant studies and data supporting these views are discussed in this review.
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6.
Hypoxic Signaling and Cholesterol Lipotoxicity in Fatty Liver Disease Progression.
Tirosh, O
Oxidative medicine and cellular longevity. 2018;:2548154
Abstract
Cholesterol is the only lipid whose absorption in the gastrointestinal tract is limited by gate-keeping transporters and efflux mechanisms, preventing its rapid absorption and accumulation in the liver and blood vessels. In this review, I explored the current data regarding cholesterol accumulation in liver cells and key mechanisms in cholesterol-induced fatty liver disease associated with the activation of deleterious hypoxic and nitric oxide signal transduction pathways. Although nonalcoholic fatty liver disease (NAFLD) affects both obese and nonobese individuals, the mechanism of NAFLD progression in lean individuals with healthy metabolism is puzzling. Lean NAFLD individuals exhibit normal metabolic responses, implying that liver damage is not associated with impaired metabolism per se and that direct lipotoxic effects are crucial for disease progression. Several redox and oxidant signaling pathways involving cholesterol are at play in fatty liver disease development. These include impairment of the mitochondrial and lysosomal function by cholesterol loading of the inner-cell membranes; formation of cholesterol crystals and hepatocyte degradation; and crown-like structures surrounding degrading hepatocytes, activating Kupffer cells, and evoking inflammation. The current review focuses on the induction of liver inflammation, fibrosis, and steatosis by free cholesterol via the hypoxia-inducible factor 1α (HIF-1α), a main oxygen-sensing transcription factor involved in all stages of NAFLD. Cholesterol loading in hepatocytes can result in chronic HIF-1α activity because of the decreased oxygen availability and excessive production of nitric oxide and mitochondrial reactive oxygen species.
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7.
Prevalence of the cardiovascular health status in adults: A systematic review and meta-analysis.
Peng, Y, Cao, S, Yao, Z, Wang, Z
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2018;(12):1197-1207
Abstract
BACKGROUND AND AIMS The American Heart Association has outlined seven cardiovascular health (CVH) metrics, including smoking, body mass index, physical activity, dietary pattern, total cholesterol, and fasting plasma glucose, to define and monitor CVH status. Our study was to evaluate the global CVH in adults. METHODS AND RESULTS We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and reference lists of relevant articles for studies published between 1 January 2010 and 30 June 2018. Included studies should report the proportions of ideal status for the seven CVH metrics and/or provide the prevalence of overall poor (having 0-2 ideal metrics) or ideal (having 5-7 ideal metrics) CVH status in adults. 88 articles were identified: 75 for the prevalence of ideal CVH metrics, 58 for the proportion of overall poor CVH status, and 55 for the proportion of overall ideal CVH status. Smoking had the highest prevalence of ideal status (69.1%) while dietary pattern has the lowest (12.1%). 32.2% and 19.6% of participants had overall poor and ideal CVH, respectively. Females and young adults had better CVH status when compared to males and older adults. There existed regional variations in ideal CVH metrics and overall CVH status. The overall CVH status had improved over study time. CONCLUSION The prevalence of ideal status was low for some metrics, such as dietary pattern, and the overall CVH status was still unsatisfactory. We should continue to measure the CVH status and carry out lifestyle interventions to improve the CVH status in the whole population.
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8.
Corn Oil Lowers Plasma Cholesterol Compared with Coconut Oil in Adults with Above-Desirable Levels of Cholesterol in a Randomized Crossover Trial.
Maki, KC, Hasse, W, Dicklin, MR, Bell, M, Buggia, MA, Cassens, ME, Eren, F
The Journal of nutrition. 2018;(10):1556-1563
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Abstract
BACKGROUND Few trials have examined the effects of coconut oil consumption in comparison with polyunsaturated fatty acid-rich oils such as corn oil. OBJECTIVE This trial assessed the effects of consuming foods made with corn oil compared with coconut oil on lipids, glucose homeostasis, and inflammation. METHODS This was a preliminary randomized crossover study of men (n = 12) and women (n = 13) with a mean age of 45.2 y, mean body mass index (in kg/m2) of 27.7, fasting LDL cholesterol ≥115 mg/dL and <190 mg/dL, and triglycerides (TGs) ≤375 mg/dL. Subjects consumed muffins and rolls providing 4 tablespoons (∼54 g) per day of corn oil or coconut oil as part of their habitual diets for 4 wk, with a 3-wk washout between conditions. Fasting plasma lipids and high-sensitivity C-reactive protein (hs-CRP) and glucose metabolism were assessed via an intravenous glucose tolerance test at baseline and 15 and 29 d of treatment. Responses were compared between treatments by ANCOVA. RESULTS Median baseline concentrations of LDL cholesterol, non-HDL cholesterol, total cholesterol (total-C), HDL cholesterol, total-C:HDL cholesterol, and TGs were 123, 144, 188, 46.0, 4.21, and 92.5 mg/dL, respectively. Changes from baseline for corn oil and coconut oil conditions, respectively, were: LDL cholesterol (primary outcome; -2.7% compared with +4.6%), non-HDL cholesterol (-3.0% compared with +5.8%), total-C (-0.5% compared with +7.1%), HDL cholesterol (+5.4% compared with +6.5%), total-C:HDL cholesterol (-4.3% compared with -3.3%), and TGs (-2.1% compared with +6.0%). Non-HDL cholesterol responses were significantly different between corn and coconut oil conditions (P = 0.034); differences between conditions in total-C and LDL cholesterol approached significance (both P = 0.06). Responses for hs-CRP and carbohydrate homeostasis parameters did not differ significantly between diet conditions. CONCLUSIONS When incorporated into the habitual diet, consumption of foods providing ∼54 g of corn oil/d produced a more favorable plasma lipid profile than did coconut oil in adults with elevated cholesterol. This trial was registered at clinicaltrials.gov as NCT03202654.
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Functional features defining the efficacy of cholesterol-conjugated, self-deliverable, chemically modified siRNAs.
Shmushkovich, T, Monopoli, KR, Homsy, D, Leyfer, D, Betancur-Boissel, M, Khvorova, A, Wolfson, AD
Nucleic acids research. 2018;(20):10905-10916
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Abstract
Progress in oligonucleotide chemistry has produced a shift in the nature of siRNA used, from formulated, minimally modified siRNAs, to unformulated, heavily modified siRNA conjugates. The introduction of extensive chemical modifications is essential for conjugate-mediated delivery. Modifications have a significant impact on siRNA efficacy through interference with recognition and processing by RNAi enzymatic machinery, severely restricting the sequence space available for siRNA design. Many algorithms available publicly can successfully predict the activity of non-modified siRNAs, but the efficiency of the algorithms for designing heavily modified siRNAs has never been systematically evaluated experimentally. Here we screened 356 cholesterol-conjugated siRNAs with extensive modifications and developed a linear regression-based algorithm that effectively predicts siRNA activity using two independent datasets. We further demonstrate that predictive determinants for modified and non-modified siRNAs differ substantially. The algorithm developed from the non-modified siRNAs dataset has no predictive power for modified siRNAs and vice versa. In the context of heavily modified siRNAs, the introduction of chemical asymmetry fully eliminates the requirement for thermodynamic bias, the major determinant for non-modified siRNA efficacy. Finally, we demonstrate that in addition to the sequence of the target site, the accessibility of the neighboring 3' region significantly contributes to siRNA efficacy.
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10.
Statin utilization and lipid goal attainment in high or very-high cardiovascular risk patients: Insights from Italian general practice.
Arca, M, Ansell, D, Averna, M, Fanelli, F, Gorcyca, K, Iorga, ŞR, Maggioni, AP, Paizis, G, Tomic, R, Catapano, AL
Atherosclerosis. 2018;:120-127
Abstract
BACKGROUND AND AIMS Statin utilization and lipid goal achievement were estimated in a large sample of Italian patients at high/very-high cardiovascular (CV) risk. METHODS Patients aged ≥18 years with a valid low-density lipoprotein cholesterol (LDL-C) measurement in 2015 were selected from the IMS Health Real World Data database; non-high-density lipoprotein cholesterol (non-HDL-C) was assessed in those with available total cholesterol measurements. Index dates were defined as the last valid lipid measurement in 2015. Patients were hierarchically classified into mutually exclusive risk categories: heterozygous familial hypercholesterolemia (primary and secondary prevention), atherosclerotic CV disease (including recent acute coronary syndrome [ACS], chronic coronary heart disease, stroke, and peripheral arterial disease), and diabetes mellitus (DM) alone. Statin and non-statin lipid-modifying therapy (LMT) use, and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline-recommended goal attainment, were assessed. RESULTS Among 66,158 patients meeting selection criteria, the overall rate of LMT prescriptions was 53.3%, including 7.7% on high-intensity statin therapy. Statin use was highest for recent ACS and lowest for DM alone. LDL-C goal attainment was 16.0% for <1.8 mmol/l and 45.0% for <2.5 mmol/l; 24.3% reached non-HDL-C <2.6 mmol/l and 52.2% were at <3.3 mmol/l. Goal achievement was greatest with high-intensity statin use. CONCLUSIONS Statin use in this cohort was consistent with previous reports in Italian patients at high/very-high CV risk, and low relative to statin use in other European countries. The low rate of ESC/EAS lipid goal attainment observed was consistent with outcomes of other European studies.