scholarly journals Increased serum cholesterol and long-chain fatty acid levels are associated with the efficacy of nivolumab in patients with non-small cell lung cancer

Author(s):  
Masato Karayama ◽  
Naoki Inui ◽  
Yusuke Inoue ◽  
Katsuhiro Yoshimura ◽  
Kazutaka Mori ◽  
...  

Abstract Background Lipids have immunomodulatory functions and the potential to affect cancer immunity. Methods The associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab. Results When each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P < 0.001), high-density lipoprotein (HDL)-cholesterol (P = 0.014), total cholesterol (P = 0.007), lauric acid (P = 0.015), myristic acid (P = 0.022), myristoleic acid (P = 0.035), stearic acid (P = 0.028), linoleic acid (P = 0.005), arachidic acid (P = 0.027), eicosadienoic acid (P = 0.017), dihomo-γ-linolenic acid (P = 0.036), and behenic acid levels (P = 0.032) were associated with longer PFS independent of programmed death ligand 1 (PD-L1) expression. Meanwhile, increased LDL-cholesterol (P < 0.001), HDL-cholesterol (P = 0.009), total cholesterol (P = 0.036), linoleic acid (P = 0.014), and lignoceric acid levels (P = 0.028) were associated with longer OS independent of PD-L1 expression. When multiple lipids were evaluated simultaneously, LDL-cholesterol (P = 0.003), HDL-cholesterol (P = 0.036), and lauric acid (P = 0.036) were independently predictive of PFS, and LDL-cholesterol (P = 0.008) and HDL-cholesterol (P = 0.031) were predictive of OS. ORR was not associated with any serum lipid. Conclusions Based on the association of prolonged survival in patients with increased serum cholesterol and long-chain fatty acid levels, serum lipid levels may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Oguri ◽  
K Kato ◽  
H Horibe ◽  
T Fujimaki ◽  
J Sakuma ◽  
...  

Abstract Background The circulating concentrations of triglycerides, high density lipoprotein (HDL)-cholesterol, and low density lipoprotein (LDL)-cholesterol have a substantial genetic component. Although previous genome-wide association studies identified various genes and loci related to plasma lipid levels, those studies were conducted in a cross-sectional manner. Purpose The purpose of the study was to identify genetic variants that confer susceptibility to hypertriglyceridemia, hypo-HDL-cholesterolemia, and hyper-LDL-cholesterolemia in Japanese. We have now performed longitudinal exome-wide association studies (EWASs) to identify novel loci for dyslipidemia by examining temporal changes in serum lipid profiles. Methods Longitudinal EWASs (mean follow-up period, 5 years) for hypertriglyceridemia (2056 case, 3966 controls), hypo-HDL-cholesterolemia (698 cases, 5324 controls), and hyper-LDL-cholesterolemia (2769 cases, 3251 controls) were performed with Illumina Human Exome arrays. The relation of genotypes of 24,691 single nucleotide polymorphisms (SNPs) that passed quality control to dyslipidemia-related traits was examined with the generalized estimating equation (GEE). To compensate for multiple comparisons of genotypes with each of the three conditions, we applied Bonferroni's correction for statistical significance of association. Replication studies with cross-sectional data were performed for hypertriglyceridemia (2685 cases, 4703 controls), hypo-HDL-cholesterolemia (1947 cases, 6146 controls), and hyper-LDL-cholesterolemia (1719 cases, 5833 controls). Results Longitudinal EWASs revealed that 30 SNPs were significantly (P&lt;2.03 × 10–6 by GEE) associated with hypertriglyceridemia, 46 SNPs with hypo-HDL-cholesterolemia, and 25 SNPs with hyper-LDL-cholesterolemia. After examination of the relation of identified SNPs to serum lipid profiles, linkage disequilibrium, and results of the previous genome-wide association studies, we newly identified rs74416240 of TCHP, rs925368 of GIT2, rs7969300 of ATXN2, and rs12231744 of NAA25 as a susceptibility loci for hypo-HDL-cholesterolemia; and rs34902660 of SLC17A3 and rs1042127 of CDSN for hyper-LDL-cholesterolemia. These SNPs were not in linkage disequilibrium with those previously reported to be associated with dyslipidemia, indicating independent effects of the SNPs identified in the present study on serum concentrations of HDL-cholesterol or LDL-cholesterol in Japanese. According to allele frequency data from the 1000 Genomes project database, five of the six identified SNPs were monomorphic or rare variants in European populations. In the replication study, all six SNPs were associated with dyslipidemia-related phenotypes. Conclusion We have thus identified six novel loci that confer susceptibility to hypo-HDL-cholesterolemia or hyper-LDL-cholesterolemia. Determination of genotypes for these SNPs at these loci may prove informative for assessment of the genetic risk for dyslipidemia in Japanese. Funding Acknowledgement Type of funding source: None


2011 ◽  
Vol 59 (4) ◽  
pp. 445-454 ◽  
Author(s):  
Ewa Skotnicka ◽  
Zbigniew Muszczyński ◽  
Maria Suska

Blood samples were taken from 12 goats during the periparturient period (4 and 1 weeks before and 2, 10 and 30 days after delivery), and from 10 nonpregnant goats. The following variables were determined: total lipids (TL), triacylglycerol (TG), total cholesterol (TCH) and high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol fractions. One week before delivery TL (2.32 ± 0.12 g/l, P ≤ 0.05), TG (0.32 ± 0.16 mmol/l, P ≤ 0.001) and TCH concentrations (1.65 ± 0.42 mmol/l, P ≤ 0.05) were significantly increased as compared to non-pregnant goats (2.08 ± 0.28 g/l, 0.15 ± 0.05 mmol/l, 1.38 ± 0.19 mmol/l, respectively). After delivery, the concentrations of TL, TG, TCH and HDL decreased significantly. The lowest TG concentration was observed 2 days after delivery (0.18 ± 0.02 mmol/l), while TL (1.73 ± 0.21 g/l), TCH (0.95 ± 0.21 mmol/l) and HDL (0.74 ± 0.16 mmol/l) reached the lowest level 10 days after delivery. Two days after delivery a significant increase of LDL concentration was observed (0.38 ± 0.04 mmol/l); however, ten days after delivery a threefold decrease was shown in the LDL concentration (0.12 ± 0.04 mmol/l). A month after delivery all the variables studied reached levels similar to those measured in non-pregnant goats.


1970 ◽  
Vol 14 ◽  
pp. 93-98 ◽  
Author(s):  
MS Saha ◽  
NK Sana ◽  
Ranajit Kumar Shaha

A prospective study was conducted in the Northern region of Bangladesh, to investigate the serum lipid profile viz the level of total cholesterol (TC), Triglyceride (TG), HDL-cholesterol and LDL-cholesterol of hypertensive patients and compares them with levels of control subjects. The results revealed that serum total cholesterol, triglyceride and LDL-cholesterol were significantly markedly raised (p>0.001) whereas the level of HDL-cholesterol was significantly lower (p>0.001) in hypertensive patients as compared to control subjects. No significant changes of serum lipid profile were found between male and female hypertensive patients, but in control subjects, markedly higher levels of serum lipid profile was observed in male compared to that of female. It was concluded that hypercholesterolaemia, hypertrigyceridaemia and low density lipoprotein are the main lipid abnormalities on the incidence of hypertension in the study area. Key words: Hypertension, Total cholesterol (TC), triglyceride (TG), HDL- cholesterol and LDL-cholesterol. J. bio-sci. 14: 93-98, 2006


2019 ◽  
Vol 77 (12) ◽  
pp. 890-902 ◽  
Author(s):  
Daniel T Dibaba

Abstract Context Vitamin D deficiency is highly prevalent across the world. The existing evidence suggests vitamin D may have beneficial effects on serum lipid profiles and thus cardiovascular health. Objective The objective of this systematic review and meta-analysis was to examine the effect of vitamin D supplementation on serum lipid profiles. Data Source Original randomized controlled trials (RCTs) examining the effect of vitamin D supplementation on serum lipid profiles and published before July 2018 were identified by searching online databases, including PubMed, Google Scholar, and ScienceDirect, using a combination of relevant keywords. Data Extraction Data on study characteristics, effect size, measure of variation, type of vitamin D supplementation, and duration of follow-up were extracted by the author. Data Analysis PRISMA guidelines for systematic reviews were followed. Random effects (DerSimonian and Laird [D-V)] models were used to pool standardized mean differences in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides between the active and the placebo arms of RCT studies. Between-study heterogeneities were assessed using Cochrane Q and I2, and publication bias was assessed using Begg’s test, Egger’s test, and funnel plot. Results A total of 41 RCTs comprising 3434 participants (n = 1699 in the vitamin D supplementation arm and n = 1735 in the placebo arm) were identified and included in the meta-analysis. Approximately 63.4% of study participants were women, with 14 studies conducted entirely among women. Approximately 24% of the trials had follow-up duration >6 months, whereas the remaining 76% had follow-up duration of <6 months. The standardized mean differences (SMDs) and 95% confidence intervals (CIs) for comparing the change from baseline to follow-up between the vitamin D supplementation arm and the placebo (control) arm were as follows: total cholesterol = –0.17 (–0.28 to –0.06); LDL cholesterol = –0.12 (–0.23 to –0.01); triglycerides = –0.12 (–0.25 to 0.01); and HDL cholesterol = –0.19 (–0.44 to 0.06). After removing a trial that was an outlier based on the magnitude of the effect size, the SMD for triglycerides was –0.15 (–0.24 to –0.06) and that for HDL cholesterol was –0.10 (–0.28 to 0.09). The improvements in total cholesterol and triglycerides were more pronounced in participants with baseline vitamin D deficiency. Conclusions Vitamin D supplementation appeared to have a beneficial effect on reducing serum total cholesterol, LDL cholesterol, and triglyceride levels but not HDL cholesterol levels. Vitamin D supplementation may be useful in hypercholesterolemia patients with vitamin D insufficiency who are at high risk of cardiovascular diseases.


2014 ◽  
Vol 20 ◽  
pp. 57-65
Author(s):  
Md Rashidul Hasan ◽  
Parvez Hassan ◽  
Md Abdul Jalil Miah

Context: Abuse of the drug, Phensedyl like any other drug might exert adverse effects on vital organs of th e h u m an body like liver, kidney and heart. Objectives: To determine the effects of Phensedyl intake on the serum biochemical parameters of the addicts in order to access for damages of vital human organs like liver, kidney and heart. Materials and Methods: Study population consisted of 127 male Phensedyl addicts within the ages of 18–55 years of defined criteria from Gaibandha district, a Northern part of Bangladesh, during July 2009 to December 2011. Fifty (50) non-drug dependent healthy men of matched age, height, and socioeconomic status were included as controls from the same community. Biochemical parameters analyzed were – Serum creatinine, SGOT, SGPT and Lipid profiles (total serum cholesterol (TC), Serum triglyceride (TG), serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol determined by semiautomatic biochemistry analyzer using commercially available kits Results: Abuse of Phensedyl appears not to hamper the normal renal and liver function in most of the addicts even after 8 years of Phensedyl intake irrespective of age except in case of 4 abusers. Serum total cholesterol (TC) remained almost unchanged among the addicts abusing Phensedyl for less than 8 years. But very strikingly, addicts taking Phensedyl for more than 8 years had higher trends in serum cholesterol i.e. more than 200 ml/dl. Of the addict’s, 44.36% abusing Phensedyl for less than 8 years had normal triglyceride (TG) values whereas, in 45.66% addicts abusing the drug for more than 8 years had clinically very significantly elevated triglyceride levels, which was also found to be statistically very significant (p value =0.0001), indicating the risk of developing cardiac diseases. Of the total addicts 53.53% had low levels of HDL cholesterol, which is clinically and statistically found to be very significant (p value =0.002). Of the addict’s 43% taking the drug for less than 8 years had normal LDL levels but significantly elevated values were recorded in 34% of the abusers who had been taking the drug for more than 8 years. Conclusion: Long time (> 8 years) Phensedyl abusers are at the high risk of developing Brain stroke, Coronary Heart Disease (CHD), Ischemic stroke or transient ischemic attack (TIA) as there is the triad of: Elevated LDL cholesterol, Low HDL cholesterol and elevated Triglyceride. DOI: http://dx.doi.org/10.3329/jbs.v20i0.17656 J. bio-sci. 20: 57-65, 2012


2002 ◽  
Vol 227 (4) ◽  
pp. 266-275 ◽  
Author(s):  
Dana R. Smith ◽  
Randall Wood ◽  
Stephen Tseng ◽  
Stephen B. Smith

The objective of this research was to compare the effects of a lean beef enriched in oleic acid to a beef that is typical of the commercial beef consumed in the United States. Ten mildly hypercholesterolemic men, ages 34-58 years old, were selected from the Texas A&M University faculty and staff. Subjects were randomly assigned to one of two diets for a 6-week duration followed by a crossover after a 4-week habitual diet washout period. Diets were consumed daily for a 6-week study period. Participants substituted lean beef obtained from Wagyu bullocks or commercial beef for the meat typically consumed. Total cholesterol, apolipoproteins A-I and B, triacylglycerols, and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were measured in serum samples collected weekly. Beef type had no effect on any measured variable. There were no significant differences between baseline HDL or LDL cholesterol concentrations after the consumption of the beef test diets. Apolipoprotein A-I, serum glucose, and uric acid concentrations were elevated by the additional dietary beef. Analysis of records of customary diets indicated that one group consumed 160 g of beef daily, whereas the other group consumed only 26 g of beef daily. Therefore, post hoc analyses tested the habitual beef intake x treatment time interaction. LDL cholesterol concentration was markedly higher in the group with low habitual beef Intake (180 vs 144 mg/dl), and HDL cholesterol was slightly higher (44 vs 40 mg/dl; post-test values) than for the group with high habitual beef intake, but there were no habitual intake x time interactions for LDL or HDL cholesterol. Creatinine and blood urea nitrogen concentrations also were greater in the individuals habitually consuming less beef. This study had three important findings: i) a lean beef source enriched with oleic acid was no different from commercial beef in its effect on lipoprotein fractions; ii) neither previous level of beef intake nor baseline LDL cholesterol concentration influenced the serum cholesterol response to added dietary beef. which was negative; and iii) apolipoprotein A-I, but not HDL or LDL cholesterol, was sensitive to the additional dietary beef.


2011 ◽  
Vol 18 (01) ◽  
pp. 142-146
Author(s):  
MUHAMMAD ANWAR BURIRO ◽  
MUHAMMAD TAYYAB ◽  
ALLAH DITTA

The increased level of LDL-c in the serum has a high risk and the increased serum HDL-c level has a low risk for the development of atherosclerosis. The effect of Nigella Sativa on levels of cholesterol fractions were determined in this study on rats. Methods: 24 albino rats of 08 weeks age having equal number of males and females were kept at optimum atmospheric condition. The blood samples were taken at the start and different control and experimental diets were given for 24 weeks. The experimental diets were added with Nigella Sativa as 30 mg/kg body weight. The blood samples were taken at the end of study. The blood samples drawn at the start and end of the study were estimated for serum cholesterol. The results of control and experimental groups were compared. Results: Total serum cholesterol in the control group showed increase from 8.3±3.30 to 13.96±9.3 at 24 weeks. The serum HDL cholesterol showed increase from 44.4±6.12 to 80.45±5.95 level at 24 weeks. The serum LDL cholesterol showed increase from 8.3±3.30 to 13.96±9.3 at 24 weeks. The total serum cholesterol in experimental group was increased from 76.9±6.5 to 117.5± 6.65 at 24 weeks. The serum HDL cholesterol levels was increased from 41.7±4.9 to 83.42±5.92 at 24 weeks as compared with control group. The LDL cholesterol levels were decreased from 12.7±6.9 to 8.5±7.8 at 24 weeks. Conclusions: This study shows significant decrease in serum low density lipoprotein cholesterol level, and increase in serum high density lipoprotein cholesterol levels.


2018 ◽  
Vol 108 (4) ◽  
pp. 675-687 ◽  
Author(s):  
Nisha Panth ◽  
Kylie A Abbott ◽  
Cintia B Dias ◽  
Katie Wynne ◽  
Manohar L Garg

Abstract Background Medium-chain saturated fatty acids (MCFAs) may affect circulating lipids and lipoproteins differently than long-chain saturated fatty acids (LCSFAs), but the results from human intervention trials have been equivocal. Objective The aim of this study was to determine whether MCFAs and LCSFAs have differential impacts on blood lipids and lipoproteins. Design Five databases were searched (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus) until April 2018, and published clinical trials investigating the differential effects of dietary MCFAs and LCSFAs on blood lipids were included. Searches were limited to the English language and to studies with adults aged >18 y. Where possible, studies were pooled for meta-analysis using RevMan 5.2. The principle summary measure was the mean difference between groups calculated using the random-effects model. Results Eleven eligible crossover and 1 parallel trial were identified with a total of 299 participants [weighted mean ± SD age: 38 ± 3 y; weighted mean ± SD body mass index (kg/m2): 24 ± 2]. All studies were pooled for the meta-analysis. Diets enriched with MCFAs led to significantly higher high-density lipoprotein (HDL) cholesterol concentrations than diets enriched with LCSFAs (0.11 mmol/L; 95% CI: 0.07, 0.15 mmol/L) with no effect on triglyceride, low-density lipoprotein (LDL) cholesterol, and total cholesterol concentrations. Consumption of diets rich in MCFAs significantly increased apolipoprotein A-I (apoA-I) concentrations compared with diets rich in LCSFAs (0.08 g/L; 95% CI: 0.02, 0.14 g/L). There was no evidence of statistical heterogeneity for HDL cholesterol, apoA-I, and triglyceride concentrations; however, significant heterogeneity was observed for the total cholesterol (I2 = 49%) and LDL cholesterol analysis (I2 = 58%). Conclusion The findings of this research demonstrate a differential effect of MCFAs and LCSFAs on HDL cholesterol concentrations. Further investigations are warranted to elucidate the mechanism by which the lipid profile is altered. This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42017078277.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Hansol Choi ◽  
Ju-Mi Lee ◽  
YooSik Youm ◽  
Yumie Rhee ◽  
Chang Oh Kim ◽  
...  

Importance: Sleep duration has been considered as a risk factor for cardiometabolic disease and mortality. Several studies suggest that sleep duration can influence the serum lipid levels, but the association remains unclear. Objective: The aim of present study is to assess the association of sleep duration with serum lipid levels in an elderly Korean population. Methods: The KURE study is a cohort study to investigate risk factors for major disorders of the elderly. This cross-sectional analysis was conducted among 926 participants (302 men and 624 women aged 64-87 years) who completed baseline health examination in 2012. Sleep duration was measured by the interviewer-assisted questionnaire. Habitual sleep time was calculated based on the response to the questions about hour of bedtime, hour of rising, and hours of nap during the passing year. Total cholesterol, triglyceride and high density lipoprotein (HDL) cholesterol concentrations in serum were measured from overnight fasting blood samples. Low density lipoprotein (LDL) cholesterol was calculated from total cholesterol, HDL cholesterol and triglyceride levels using Friedewald’s formula. Multiple linear regression models were conducted to examine whether sleep duration was associated with serum lipid levels. Results: Sleep duration was not significantly associated with total cholesterol (β=-0.154mg/dL per sleep hour, p =0.843), triglyceride (β=-1.000, p =0.506) and LDL cholesterol (β=0.678, p =0.339) after adjusting for age, sex, body mass index, systolic blood pressure, tobacco smoking, alcohol intake, physical activity, diabetes mellitus, myocardial infarction and stroke. However sleep duration was inversely associated with HDL cholesterol (β=-0.644, p =0.015) in fully adjusted model. In the sex-specific analysis, sleep duration was marginally associated with HDL cholesterol in men (β=-0.770, p =0.078) and significantly associated with HDL cholesterol in women (β=-0.685, p =0.037) after fully adjustment. Conclusions: Our findings suggest that longer sleep duration was associated with lower serum HDL cholesterol level in an elderly Korean population. Keywords: Sleep duration, lipids, HDL cholesterol, elderly


Sign in / Sign up

Export Citation Format

Share Document