scholarly journals Lipid Profiles in Patients With Ulcerative Colitis Receiving Tofacitinib—Implications for Cardiovascular Risk and Patient Management

2020 ◽  
Author(s):  
Bruce E Sands ◽  
Jean-Frédéric Colombel ◽  
Christina Ha ◽  
Michel Farnier ◽  
Alessandro Armuzzi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Major Adverse Cardiovascular Events ◽  
Lipid Levels

Abstract Background Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease vs the general population, despite a lower prevalence of traditional risk factors, including hyperlipidemia. Mechanistic studies in patients with rheumatoid arthritis and psoriasis suggest that tofacitinib restores serum lipids to preinflammation levels by reversing inflammation-induced cholesterol metabolism changes. We reviewed data on lipid levels and cardiovascular events, alongside recommendations for managing lipid levels during tofacitinib treatment in patients with UC, based on up-to-date expert guidelines. Methods Data were identified from a phase 3/open-label, long-term extension (OLE) tofacitinib UC clinical program (cutoff May 27, 2019). Literature was identified from PubMed (search terms “lipid,” “cholesterol,” “lipoprotein,” “cardiovascular,” “inflammation,” “atherosclerosis,” “tofacitinib,” “rheumatoid arthritis,” “psoriasis,” “inflammatory bowel disease,” “ulcerative colitis,” “hyperlipidemia,” and “guidelines”) and author knowledge. Data were available from 4 phase 3 clinical trials of 1124 patients with moderately to severely active UC who received ≥1 dose of tofacitinib 5 or 10 mg twice daily in induction (two identical trials), maintenance, and OLE studies (treatment duration ≤6.8 years; 2576.4 patient-years of drug exposure). Results In the OLE study, tofacitinib treatment was not associated with major changes from baseline in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, total cholesterol/high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol, with lipid levels and ratios generally remaining stable over time. The major adverse cardiovascular events incidence rate was 0.26/100 patient-years (95% confidence interval, 0.11-0.54). Conclusions Lipid levels and ratios remained generally unchanged from baseline in the OLE study after tofacitinib treatment, and major adverse cardiovascular events were infrequent. Long-term studies are ongoing. ClinicalTrials.gov identifiers NCT01465763, NCT01458951, NCT01458574, NCT01470612

scholarly journals Phosphorylation-related SNPs influence lipid levels and rheumatoid arthritis risk by altering gene expression and plasma protein levels

Rheumatology ◽  
2019 ◽  
Vol 59 (4) ◽  
pp. 889-898
Author(s):  
Xingbo Mo ◽  
Yufan Guo ◽  
Qiyu Qian ◽  
Mengzhen Fu ◽  
Huan Zhang
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Lipid Levels ◽  
Low Density Lipoprotein Cholesterol ◽  
Protein Levels

Abstract Objectives Phosphorylation-related single-nucleotide polymorphisms (phosSNPs) are missense SNPs that may influence protein phosphorylation. The aim of this study was to evaluate the effect of phosSNPs on lipid levels and RA. Methods We examined the association of phosSNPs with lipid levels and RA in large-scale genome-wide association studies (GWAS) and performed random sampling and fgwas analyses to determine whether the phosSNPs associated with lipid levels and RA were significantly enriched. Furthermore, we performed QTL analysis and Mendelian randomization analysis to obtain additional evidence to be associated with the identified phosSNPs and genes. Results We found 483 phosSNPs for lipid levels and 243 phosSNPs for RA in the GWAS loci (P < 1.0 × 10−5). SNPs associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, Total cholesterol (TC) and RA were significantly enriched with phosSNPs. Almost all of the identified phosSNPs showed expression quantitative trait loci (eQTL) effects. A total of 48 protein QTLs and 9 metabolite QTLs were found. The phosSNP rs3184504 (p.Trp262Arg) at SH2B3 was significantly associated with RA, SH2B3 expression level, and plasma levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TC, hypoxanthine and 80 proteins, including beta-2-microglobulin. SH2B3 was differentially expressed between RA cases and controls in peripheral blood mononuclear cells and synovial tissues. Mendelian randomization analysis showed that SH2B3 expression level was significantly associated with TC level and RA. Plasma beta-2-microglobulin level was causally associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TC levels and RA. Conclusion The findings suggested that phosSNPs may play important roles in lipid metabolism and the pathological mechanisms of RA. PhosSNPs may influence lipid levels and RA risk by altering gene expression and plasma protein levels.

scholarly journals Inflammation Alters Relationship Between High‐Density Lipoprotein Cholesterol and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From KNOW‐CKD

2021 ◽  
Author(s):  
Jae Young Kim ◽  
Jung Tak Park ◽  
Hyung Woo Kim ◽  
Tae‐Ik Chang ◽  
Ea Wha Kang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Cardiovascular Events ◽  
Primary Outcome ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Major Adverse Cardiovascular Events

Background The function of high‐density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high‐density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease . Methods and Results In total, 1864 patients from the prospective KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high‐density lipoprotein cholesterol (HDL‐C) level. Presence of inflammation was defined by hs‐CRP (high‐sensitivity C‐reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person‐years of follow‐up, overall incidence of the primary outcome was 15.8 per 1000 person‐years. In multivariable Cox analysis after adjusting for confounders, HDL‐C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL‐C for risk of extended major adverse cardiovascular events ( P =0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL‐C levels <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50–1.82), 0.95 (0.50–1.82), and 0.42 (0.19–0.95), respectively, compared with HDL‐C of 40 to 49 mg/dL. However, the significant association for HDL‐C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL‐C groups (HRs [95% CIs], 0.73 [0.37–1.43], 1.24 [0.59–2.61], and 1.56 [0.71–3.45], respectively), but without statistical significance. Conclusions The association between HDL‐C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01630486.

The influence of ultra-processed food consumption in anthropometric and atherogenic indices of adolescents

2021 ◽  
Vol 34 ◽  
Author(s):  
Larisse Monteles NASCIMENTO ◽  
Nayara Vieira do Nascimento MONTEIRO ◽  
Thiana Magalhães VILAR ◽  
Cyntia Regina Lúcio de Sousa IBIAPINA ◽  
Karoline de Macedo Gonçalves FROTA
Keyword(s):  
High Density Lipoprotein ◽  
Food Consumption ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Atherogenic Index ◽  
Processed Foods ◽  
Atherogenic Indices

ABSTRACT Objective To investigate the influence of ultra-processed food consumption on anthropometric and atherogenic indices. Methods A cross-sectional study was conducted with 327 adolescents aged 14 to 19 years. Sociodemographic, anthropometric, biochemical, and food consumption data were evaluated. The ratios of atherogenic indices were calculated using the Castelli I (Total Cholesterol/High Density Lipoprotein Cholesterol), Castelli II (Low Density Lipoprotein Cholesterol/High Density Lipoprotein Cholesterol), and estimated Low Density Lipoprotein Cholesterol particle size (Atherogenic Index of Plasma=Triglycerides/High-Density Lipoprotein Cholesterol) indices. Logistic regression was used for the unadjusted and adjusted analysis between ultra-processed foods consumption, anthropometric, and atherogenic indices. The level of significance was 5%. Results Most participants were female (59.3%). Girls had a higher consumption of ultra-processed foods (26.6% vs. 20.5%). Of the total number of adolescents, 16.5% were overweight and 65.7% were from public schools. Adolescents with altered values for the Castelli I and II Index, and for the Atherogenic Index of Plasma had significantly higher weights, Waist Circumference, Waist Circumference/ Height and Body Mass Index/ Age values. The adjusted analysis identified a significant association (Odds ratio=2.29; 95% Confidence interval: 1.23-4.28) between the high consumption of ultra-processed foods and the Castelli II index. Conclusion The associations between atherogenic indices and anthropometric indices and the consumption of ultra-processed foods highlight the negative influence of these foods on adolescents’ cardiovascular health.

The Effects of Low-Density Lipoprotein and High-Density Lipoprotein on Blood Viscosity Correlate with their Association with Risk of Atherosclerosis in Humans

1997 ◽  
Vol 92 (5) ◽  
pp. 473-479 ◽  
Author(s):  
Gregory D. Sloop ◽  
David W. Garber
Keyword(s):  
High Density Lipoprotein ◽  
Total Cholesterol ◽  
High Density Lipoprotein Cholesterol ◽  
Blood Viscosity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

1. Increased blood or plasma viscosity has been observed in almost all conditions associated with accelerated atherosclerosis. Cognizant of the enlarging body of evidence implicating increased viscosity in atherogenesis, we hypothesize that the effects of low-density lipoprotein and high-density lipoprotein on blood viscosity correlate with their association with risk of atherosclerosis. 2. Blood viscometry was performed on samples from 28 healthy, non-fasting adult volunteers using a capillary viscometer. Data were correlated with haematocrit, fibrinogen, serum viscosity, total cholesterol, high-density lipoprotein-cholesterol, triglycerides and calculated low-density lipoprotein-cholesterol. 3. Low-density lipoprotein-cholesterol was more strongly correlated with blood viscosity than was total cholesterol (r = 0.4149, P = 0.0281, compared with r = 0.2790, P = 0.1505). High-density lipoprotein-cholesterol levels were inversely associated with blood viscosity (r = −0.4018, P = 0.0341). 4. To confirm these effects, viscometry was performed on erythrocytes, suspended in saline, which had been incubated in plasma of various low-density lipoprotein/high-density lipoprotein ratios. Viscosity correlated directly with low-density lipoprotein/high-density lipoprotein ratio (n = 23, r = 0.8561, P < 0.01). 5. Low-density lipoprotein receptor occupancy data suggests that these effects on viscosity are mediated by erythrocyte aggregation. 6. These results demonstrate that the effects of low-density lipoprotein and high-density lipoprotein on blood viscosity in healthy subjects correlate with their association with risk of atherosclerosis. These effects on viscosity may play a role in atherogenesis by modulating the dwell or residence time of atherogenic particles in the vicinity of the endothelium.

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