scholarly journals POS0442 RELATIONSHIP BETWEEN PARAOXONASE-1 GENOTYPE, ACTIVITY AND MAJOR ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING TOFACITINIB

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 449.2-450
Author(s):  
C. Charles-Schoeman ◽  
C. Hyde ◽  
S. Guan ◽  
N. Parikh ◽  
J. Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Enzyme Activity ◽  
Lower Risk ◽  
Univariate Analysis ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Major Adverse Cardiovascular Events ◽  
Time Varying ◽  
Paraoxonase Activity ◽  
Cholesterol Levels

Background:Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme with paraoxonase, lactonase and arylesterase activities.1 PON1 contributes to the antioxidant properties of HDL, and is being investigated for its atheroprotective properties.1 Patients (pts) with rheumatoid arthritis (RA) who are homozygous for the RR genotype of the Q192R gene polymorphism on PON1 (rs662) have increased paraoxonase activity, and lower risk of carotid plaques, vs those with QQ or QR genotypes.2 Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA.Objectives:To investigate the relationship between PON1 genotype/activity and risk of major adverse cardiovascular events (MACE) in the tofacitinib RA clinical programme.Methods:In this post hoc analysis, data were pooled from pts enrolled in nine Phase 2/3 studies of tofacitinib in RA. Enzyme activities in pt plasma samples were measured at individual study baseline (BL) and at follow-up visits using three substrates: paraoxon (paraoxonase activity), dihydrocoumarin (lactonase activity) and phenylacetate (arylesterase activity). The effect of the PON1 Q192R genotype (QQ, QR or RR) on BL paraoxonase/lactonase/arylesterase activity was assessed using linear regression for each study, with age and sex as covariates, and then fixed-effect meta-analysis assessed effects across studies. The risk of MACE by enzyme activity was determined using Cox proportional hazards regression stratified by clinical studies. Univariate regression against BL enzyme activity and other risk factors, as well as both minimally and fully adjusted multivariable regressions against time-varying enzyme activity, are presented.Results:The analysis included 1969 pts with RA who received ≥1 dose of tofacitinib and had PON1 activity measures available at BL; 39 pts had ≥1 MACE event. Compared with the QQ genotype, the RR genotype had a highly significant positive association with BL paraoxonase activity, and a highly significant negative association with BL lactonase and arylesterase activity (Table 1). A univariate analysis identified several BL covariates significantly associated with risk of MACE (Figure 1a). Time-varying models found a highly significant association of increased paraoxonase activity over time with lower risk of future MACE, even after controlling for low-density lipoprotein or HDL cholesterol levels, and other traditional cardiovascular (CV) risk factors identified in univariate analysis (Figure 1b), with similar findings for lactonase and arylesterase (data not shown).Table 1.Effect of PON1 genotype (RR vs QQ) on BL enzyme activitynEstimate95% CIp valueCochran’s Q testParaoxonase12291.0350.93, 1.141<0.00010.209Lactonase1188-0.375-0.505, -0.246<0.00010.025Arylesterase1231-1.016-1.382, -0.649<0.00010.251Fixed-effects model; estimate >0 favours RR genotype and <0 favours QQ genotypeBL, baseline; CI, confidence intervalConclusion:Higher activity of the HDL-associated protein PON1 over time was associated with a significantly reduced risk of future MACE in pts with RA receiving tofacitinib, after controlling for traditional CV risk factors and cholesterol levels. Further investigation of PON1 as a novel functional lipid biomarker to assess CV risk in pts with RA is warranted.References:[1]Mackness & Mackness. Gene 2015; 567: 12-21.[2]Charles-Schoeman et al. Arthritis Rheum 2013; 65: 2765-2772.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Jennifer Higginson, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Christina Charles-Schoeman Consultant of: AbbVie, Gilead, Pfizer Inc, Regeneron-Sanofi, Grant/research support from: AbbVie, Bristol-Myers Squibb, Pfizer Inc, Craig Hyde Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Shunjie Guan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Neil Parikh: None declared, Jennifer Wang: None declared, Ani Shahbazian: None declared, Lori Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Andrews Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

scholarly journals Risk factors for cholesterol polyp formation in the gallbladder are closely related to lipid metabolism

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhihao Yu ◽  
Changlin Yang ◽  
Xuesong Bai ◽  
Guibin Yao ◽  
Xia Qian ◽  
...  
Keyword(s):  
Risk Factors ◽  
Low Density Lipoprotein ◽  
Univariate Analysis ◽  
Density Lipoprotein ◽  
High Volume ◽  
Population Characteristics ◽  
Polyp Formation ◽  
Logistic Analysis ◽  
Cholesterol Polyp ◽  
Independent Risk Factors

Abstract Background The purpose of this study was to assess the risk factors for cholesterol polyp formation in the gallbladder. Methods This was a multicenter retrospective study based on pathology. From January 2016 to December 2019, patients who underwent cholecystectomy and non-polyp participants confirmed by continuous ultrasound follow-ups were reviewed. Patients in the cholesterol polyp group were recruited from three high-volume centers with a diagnosis of pathologically confirmed cholesterol polyps larger than 10 mm. Population characteristics and medical data were collected within 24 h of admission before surgery. The non-polyp group included participants from the hospital physical examination center database. They had at least two ultrasound examinations with an interval longer than 180 days. Data from the final follow-up of the non-polyp group were analyzed. The risk factors for cholesterol polyp formation were analyzed by comparing the two groups. Results A total of 4714 participants were recruited, including 376 cholesterol polyp patients and 4338 non-polyp participants. In univariate analysis, clinical risk factors for cholesterol polyps were age, male sex, higher body mass index (BMI), higher low-density lipoprotein (LDL), lower high-density lipoprotein (HDL), and higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. In multivariate logistic analysis, independent risk factors were age > 50 years (odds ratio [OR] = 3.02, 95% confidence interval [CI] 2.33–3.91, P < 0.001], LDL > 2.89 mmol/L (OR = 1.38, 95% CI 1.08–1.78, P = 0.011), lower HDL (OR = 1.78 95% CI 1.32–2.44, P < 0.001), AST > 40 IU/L (OR = 3.55, 95% CI 2.07–6.07, P < 0.001), and BMI > 25 kg/m 2 (OR = 1.32, 95% CI 1.01–1.72, P = 0.037). Conclusions Age, LDL, HDL, AST, and BMI are strong risk factors for cholesterol polyp formation. Older overweight patients with polyps, accompanied by abnormal lipid levels, are at high risk for cholesterol polyps.

Comparison of atherogenic risk factors among poorly controlled and well-controlled adolescent phenylketonuria patients

2015 ◽  
Vol 26 (5) ◽  
pp. 901-908 ◽  
Author(s):  
Mehmet Gündüz ◽  
Sevim Çakar ◽  
Pınar Kuyum ◽  
Balahan Makay ◽  
Nur Arslan
Keyword(s):  
Risk Factors ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Platelet Volume ◽  
Cholesterol Levels ◽  
The Mean ◽  
Serum Phenylalanine

AbstractBackgroundPrevious studies investigating the known risk factors of atherosclerosis in phenylketonuria patients have shown conflicting results. The primary aim of our study was to investigate the serum atherogenic markers in adolescent classical phenylketonuria patients and compare these parameters with healthy peers. The secondary aim was to compare these atherogenic markers in well-controlled and poorly controlled patients.MethodsA total of 59 patients (median age: 12.6 years, range: 11–17 years) and 44 healthy controls (median age: 12.0 years, range: 11–15 years) were enrolled in our study. Phenylketonuria patients were divided into two groups: well-controlled (serum phenylalanine levels below 360 µmol/L; 24 patients) and poorly controlled patients (serum phenylalanine levels higher than 360 µmol/L).ResultsThe mean high-density lipoprotein cholesterol levels of well-controlled patients (1.0±0.2 mmol/L) were significantly lower compared with poorly controlled patients and controls (1.1±0.2 mmol/L, p=0.011 and 1.4±0.2 mmol/L, p<0.001, respectively). Poorly controlled patients had lower high-density lipoprotein cholesterol levels than healthy controls (p=0.003). Homocysteine levels of both well-controlled (9.8±6.4 µmol/L) and poorly controlled (9.2±5.6 µmol/L) patients were higher compared with controls (5.8±1.8 µmol/L, p<0.01). The mean platelet volume of well-controlled patients (9.5±1.1 fL) was higher than that of poorly controlled patients and controls (8.9±0.8 fL, p=0.024 and 7.7±0.6 fL, p<0.001, respectively).ConclusionLower high-density lipoprotein cholesterol and higher homocysteine and mean platelet volume levels were detected in phenylketonuria patients. In particular, these changes were more prominent in well-controlled patients. We conclude that phenylketonuria patients might be at risk for atherosclerosis, and therefore screening for atherosclerotic risk factors should be included in the phenylketonuria therapy and follow-up in addition to other parameters.

scholarly journals Nutritional status and food consumption in 10–11 year old Dutch boys (Dutch Nutrition Surveillance System)

1991 ◽  
Vol 66 (2) ◽  
pp. 161-169 ◽  
Author(s):  
Geert Van Poppel ◽  
Petra Schneijder ◽  
Michiel R. H. Löwik ◽  
Jaap Schrijver ◽  
Frans J. Kok
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Total Cholesterol ◽  
Cardiovascular Risk Factors ◽  
Food Consumption ◽  
Surveillance System ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Cholesterol Levels

As part of the Dutch Nutrition Surveillance System, cardiovascular risk factors and food consumption (24 h recall) as well as haematological, Fe and vitamin status (A, B6, C) were assessed in 126 Dutch boys aged 10–11 years (response 71 %). Body mass index (BMI) and the sum of four skinfolds were strongly associated (r0.85,P< 0.01) and 8% of the boys were overweight (BMI > 20.1 kg/m2). Elevated serum total cholesterol levels (> 4.4 mmol/l) were observed in 38 %; total cholesterol and low-density-lipoprotein-cholesterol levels were strongly associated (r0.88,P< 0.001). Intake of fat was high (38 % of energy) and too much fat was saturated (polyunsaturated: saturated 0.44, guideline: 0.5–1.0), whereas intake of carbohydrate (49% of energy) and dietary fibre was low. About 12% of the boys had insufficient Fe stores (plasma ferritin < 12.0 μg/l) and the mean Fe intake (9.0 mg/d) was below recommended daily allowance (10.0 mg/d). Plasma ferritin was, however, not associated with haematological indices and no frank anaemias were observed. No marginal values were observed for vitamins A, B6and C status. In conclusion, the main nutritional risks in boys aged 10–11 years are cardiovascular risk factors and Fe nutrition.

scholarly journals Hyperphosphatemia and hs-CRP Initiate the Coronary Artery Calcification in Peritoneal Dialysis Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Da Shang ◽  
Qionghong Xie ◽  
Bin Shang ◽  
Min Zhang ◽  
Li You ◽  
...  
Keyword(s):  
Risk Factors ◽  
Peritoneal Dialysis ◽  
Coronary Artery ◽  
Coronary Artery Calcification ◽  
Univariate Analysis ◽  
Density Lipoprotein ◽  
Binary Logistic Regression ◽  
Dialysis Patients ◽  
Independent Risk Factors ◽  
Hs Crp

Background.Coronary artery calcification (CAC) contributes to high risk of cardiocerebrovascular diseases in dialysis patients. However, the risk factors for CAC initiation in peritoneal dialysis (PD) patients are not known clearly.Methods.Adult patients with baseline CaCS = 0 and who were followed up for at least 3 years or until the conversion from absent to any measurable CAC detected were included in this observational cohort study. Binary logistic regression was performed to identify the risk factors for CAC initiation in PD patients.Results.70 patients recruited to our study were split into a noninitiation group (n=37) and an initiation group (n=33) according to the conversion of any measurable CAC during their follow-up or not. In univariate analysis, systolic blood pressure, serum phosphorus, fibrinogen, hs-CRP, serum creatinine, and triglycerides were positively associated with the initiation of CAC, while the high density lipoprotein and nPCR did the opposite function. Multivariate analysis revealed that hyperphosphatemia and hs-CRP were the independent risk factors for CAC initiation after adjustments.Conclusions.Hyperphosphatemia and hs-CRP were the independent risk factors for CAC initiation in PD patients. These results suggested potential clinical strategies to prevent the initiation of CAC in PD patients.

scholarly journals Functionally Defective High-Density Lipoprotein and Paraoxonase: A Couple for Endothelial Dysfunction in Atherosclerosis

Cholesterol ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Esin Eren ◽  
Necat Yilmaz ◽  
Ozgur Aydin
Keyword(s):  
Risk Factors ◽  
Endothelial Dysfunction ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Oxidized Lipids ◽  
No Production ◽  
Inductive Effects ◽  
Near Future ◽  
Atherosclerotic Risk Factors ◽  
Dysfunctional Hdl

The endothelium is the primary target for biochemical or mechanical injuries caused by the putative risk factors of atherosclerosis. Endothelial dysfunction represents the ultimate link between atherosclerotic risk factors that promote atherosclerosis. HDL-C is thought to exert at least some parts of its antiatherogenic facilities via stimulating endothelial NO production, nearby inhibiting oxidative stress and inflammation. HDL-C is capable of opposing LDL’s inductive effects and avoiding the ox-LDL’s inhibition of eNOS. Paraoxonase 1 (PON1) is an HDL-associated enzyme esterase which appears to contribute to the antioxidant and antiatherosclerotic capabilities of HDL-C. “Healthy HDL,” namely the particle that contains the active Paraoxonase 1, has the power to suppress the formation of oxidized lipids. “Dysfunctional HDL,” on the contrary, has reduced Paraoxonase 1 enzyme activity and not only fails in its mission but also potentially leads to greater formation of oxidized lipids/lipoproteins to cause endothelial dysfunction. The association of HDL-C PON1 and endothelial dysfunction depends largely on the molecules with exact damaging effect on NO synthase coupling. Loss of nitric oxide bioavailability has a pivotal role in endothelial dysfunction preceding the appearance of atherosclerosis. Analyses of HDL-C and Paraoxonase1 would be more important in the diagnosis and treatment of atherosclerosis in the very near future.

Independent associations between liver fat, visceral adipose tissue, and metabolic risk factors in men

2007 ◽  
Vol 32 (2) ◽  
pp. 265-272 ◽  
Author(s):  
Kathleen P. McMillan ◽  
Jennifer L. Kuk ◽  
Timothy S. Church ◽  
Steven N. Blair ◽  
Robert Ross
Keyword(s):  
Risk Factors ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Metabolic Profile ◽  
Univariate Analysis ◽  
Density Lipoprotein ◽  
Metabolic Risk Factors ◽  
Liver Fat ◽  
Metabolic Risk ◽  
Visceral Adipose

The independent associations between liver fat, visceral adipose tissue (AT), and metabolic risk factors are unclear. Although it has been reported that visceral AT is the strongest predictor of metabolic risk, liver fat has also been reported as a strong independent associate of a deleterious metabolic profile. We examined the independent associations between liver fat, visceral AT, and metabolic risk factors in a sample of 293 men varying widely in adiposity. Liver fat and abdominal AT were measured by computed tomography (CT). Univariate analysis revealed that liver fat was associated (p < 0.05) with triglycerides (TG), systolic blood pressure (SBP), and total cholesterol (TC), but not with glucose or high-density lipoprotein cholesterol (HDLC). Liver fat remained a significant correlate (p < 0.05) of TG and TC after control for age and subcutaneous AT or cardiorespiratory fitness (CRF), but not after adjustment for visceral AT alone. Conversely, visceral AT remained significantly associated with TG, SBP, glucose, HDLC (p < 0.01), and TC (p = 0.05) independent of liver fat, subcutaneous AT, CRF, and age. Both liver fat and visceral AT were associated with metabolic risk in men. However, when controlled for each other, visceral AT was the only independent associate of metabolic risk.

Paraoxonase 1 (PON1) and its relationship to lipid variables, age and gender in healthy volunteers

Biologia ◽  
2006 ◽  
Vol 61 (6) ◽  
Author(s):  
Katarína Sumegová ◽  
Pavel Blažíček ◽  
Bianca Fuhrman ◽  
Iveta Waczulíková ◽  
Zdeňka Ďuračková
Keyword(s):  
Lipid Profile ◽  
Serum Lipid ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Atherogenic Index ◽  
Paraoxonase 1 ◽  
Serum Lipid Profile ◽  
Positive Correlation ◽  
Paraoxonase Activity

AbstractRecent studies implied that low-density lipoprotein (LDL) modified predominantly by oxidation or glycation, significantly contributes to the formation of atherosclerotic lesions. In contrast to oxidized LDL (ox-LDL), high-density lipoprotein (HDL) is able to prevent accumulation of ox-LDL in arterial walls. This antiatherogenic property of HDL is attributed in part to several enzymes associated with the lipoprotein, including HDL-associated paraoxonase 1 (PON1). In this study we analyzed PON1 arylesterase/paraoxonase activities in relation to serum lipid profile, gender and age in thirty clinically healthy Slovak volunteers. Our results showed that PON1 arylesterase and paraoxonase activities were lower in citrated plasma than in serum by 16.6% and 27.3%, respectively. Among serum lipoproteins, only HDL-cholesterol level showed significant positive correlation with PON1 arylesterase activity (p = 0.042). Likewise, we found a significant relationship between atherogenic index (AI = total cholesterol/HDL-cholesterol) and PON1 arylesterase activity (p = 0.023). No significant correlation could be demonstrated between PON1 paraoxonase activity and serum lipid profile, age or gender. Furthermore, it was found that PON1 paraoxonase/arylesterase activities were higher in women compared with both investigated activities in men, but these differences were not statistically significant. These results confirmed a positive correlation between HDL-cholesterol and PON1 arylesterase activity. Moreover, it was found out that PON1 paraoxonase activity is not influenced either by gender or by age. PON1 arylesterase activity was however affected by gender to a limited extent.

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