Correlation of High‐Density Lipoprotein–Associated Paraoxonase 1 Activity With Systemic Inflammation, Disease Activity, and Cardiovascular Risk Factors in Psoriatic Disease

Husni, M. Elaine; Tang, W.H. Wilson; Lucke, Michael; Chandrasekharan, Unnikrishnan M.; Brennan, Danielle M.; Hazen, Stanley A

doi:10.1002/art.40499

Cited by 22 publications

(23 citation statements)

References 49 publications

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“…Five markers showed a strong level of evidence for no association with PsA in Pso: vitamin D [ 42 – 45 , 130 ], serum glucose [ 42 , 62 , 71 , 76 , 77 , 130 ], serum triglycerides [ 42 , 46 , 62 , 71 , 72 , 76 , 77 ], serum high-density lipoprotein (HDL) [ 42 , 62 , 71 , 72 , 77 ], and serum low-density lipoprotein (LDL) [ 42 , 50 , 51 , 53 , 55 , 62 , 71 , 72 , 76 , 130 ].…”

Section: Resultsmentioning

confidence: 99%

Clinical, laboratory, and genetic markers for the development or presence of psoriatic arthritis in psoriasis patients: a systematic review

et al. 2021

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Twenty to thirty percent of psoriasis (Pso) patients will develop psoriatic arthritis (PsA). Detection of Pso patients that are (at risk for) developing PsA is essential to prevent structural damage. We conducted a systematic search of five bibliographic databases, up to May 2020. We searched for studies assessing markers (clinical, laboratory, genetic) associated with the development or presence of PsA in Pso patients. Study selection and quality assessment of the included studies was performed, followed by a qualitative best evidence synthesis to determine the level of evidence for a marker and its association with concomitant/developing PsA in Pso. Overall, 259 possible markers were identified in 119 studies that met the inclusion criteria. Laboratory markers related to inflammation and bone metabolism reached a strong level of evidence for the association (not prediction) of PsA in Pso. Only CXCL10 showed strong evidence for a positive predictive value for PsA in Pso. The importance of timely detecting PsA in a Pso population, and finding more (bio)markers contributing to early detection, remains high.

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Section: Resultsmentioning

confidence: 99%

Clinical, laboratory, and genetic markers for the development or presence of psoriatic arthritis in psoriasis patients: a systematic review

et al. 2021

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“…The insidious onset of PsA may also mean that patients with PsA are exposed to active disease for longer than patients with other inflammatory diseases, putting them at greater risk for lipid changes . In addition, the burden of systemic inflammation, along with oxidative stress and disease activity, have been demonstrated to play a role in increasing the risk of CVD and therefore MACE in patients with PsA . To further understand the link between lipids and CVD risk in patients with PsA, investigating nontraditional lipid risk factors such as HDL‐associated paraoxonase 1 activity and HDL‐associated serum amyloid A may be beneficial.…”

Section: Discussionmentioning

confidence: 99%

“…To further understand the link between lipids and CVD risk in patients with PsA, investigating nontraditional lipid risk factors such as HDL‐associated paraoxonase 1 activity and HDL‐associated serum amyloid A may be beneficial. Indeed, paraoxonase 1 activity has been found to be decreased in patients with PsA compared with healthy controls , and in patients with psoriasis, treatment with tofacitinib has been found to both increase paraoxonase 1 activity and decrease HDL‐associated serum amyloid A .…”

Section: Discussionmentioning

confidence: 99%

Changes in Lipid Levels and Incidence of Cardiovascular Events Following Tofacitinib Treatment in Patients With Psoriatic Arthritis: A Pooled Analysis Across Phase III and Long‐Term Extension Studies

Gladman

Charles‐Schoeman

McInnes

et al. 2019

Arthritis Care & Research

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Objective. The risk of cardiovascular (CV) disease is higher in patients with psoriatic arthritis (PsA) versus the general population. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. As tofacitinib increases circulating lipid levels in some patients, we evaluated CV risk factors and major adverse cardiovascular events (MACE) in patients with active PsA receiving tofacitinib 5 or 10 mg twice daily plus conventional synthetic disease-modifying antirheumatic drugs. Methods. Data were pooled from two Phase 3 studies (OPAL Broaden [NCT01877668] and OPAL Beyond [NCT01882439]) and one ongoing long-term extension (OPAL Balance [NCT01976364]; data cut-off January 2017; database not locked). Outcomes included fasting lipid levels, blood pressure (BP), hypertension-related adverse events (AEs; including ‘hypertension’, ‘high blood pressure’, and ‘increased blood pressure’), and MACE. Results. Overall, 783 tofacitinib-treated patients were included. Percentage increases from baseline in low-density and high-density lipoprotein cholesterol levels (LDL-c and HDL-c, respectively) ranged from 9–14% for tofacitinib 5 and 10 mg at 3 and 6 months; no meaningful changes in LDL-c/HDL-c or total cholesterol/HDL-c ratios were observed. BP remained stable over 24 months. Fifty-eight (7.4%) patients had hypertension-related AEs; none were fatal (incidence rate [IR] per 100 patient-years: 4.81; 95% confidence interval [CI]: 3.65–6.22). Five (0.6%) patients had MACE (IR: 0.24; 95% CI: 0.05–0.70); two were fatal. Conclusion. Serum lipid level increases at month 3 following tofacitinib treatment in PsA were consistent with observations in rheumatoid arthritis and psoriasis. The incidence rate of hypertension-related AEs and MACE was low; long-term follow-up is ongoing.

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“…Therefore, PON1 downregulation might be increased by complicated internal mechanisms related to cell division, proliferation, and migration, which could also explain why the expression of PON1 was related to tumor recurrence and clinical outcomes. However, a decrease in PON1 might still cause changes in tumor cells, especially tumor-derived inflammation, autophagy, and apoptosis [ 38 , 39 ]. However, we still need more experimental evidence to prove our conclusions from sequencing data and pathological results.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the prognostic value of paraoxonase 1 in the recurrence and metastasis of hepatocellular carcinoma and establishment of a liver-specific predictive model of survival

Fan

et al. 2018

J Transl Med

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BackgroundHepatocellular carcinoma is a malignant tumor with a highly invasive and metastatic phenotype, and the detection of potential indicators associated with its recurrence and metastasis after surgical resection is critical for patient survival.MethodsTranscriptome data for large cohorts (n = 1432) from multicenter sources were comprehensively analyzed to explore such potential signatures. The prognostic value of the selected indicators was investigated and discussed, and a comparison with conventional clinicopathological features was performed. A survival predictive nomogram for 5-year survival was established with the selected indicator using the Cox proportional hazards regression. To validate the indicator at the protein level, we performed immunohistochemical staining with paraffin-embedded slides of hepatocellular carcinoma samples (n = 67 patients) from our hospital. Finally, a gene set enrichment analysis (GSEA) was performed to detect the underlying biological processes and internal mechanisms.ResultsThe liver-specific protein paraoxonase 1 (PON1) was found to be the most relevant indicator of tumor recurrence, invasiveness, and metastasis in the present study, and the downregulation of PON1 might reveal poor survival for patients with hepatocellular carcinoma. The C-index of the PON1-related nomogram was 0.714, thus indicating a more effective predictive performance than the 7th American Joint Committee on Cancer (AJCC) tumor stage (0.534), AJCC T stage (0.565), or alpha-fetoprotein (0.488). The GSEA revealed that PON1 was associated with several hepatocellular carcinoma-related pathways, including the cell cycle, DNA replication, gap junction and p53 downstream pathways.ConclusionsThe downregulation of paraoxonase 1 may suggest worse outcomes and a higher recurrence rate. Thus, paraoxonase 1 might represent an indicator for predicting the survival of patients with hepatocellular carcinoma.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1707-0) contains supplementary material, which is available to authorized users.

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Correlation of High‐Density Lipoprotein–Associated Paraoxonase 1 Activity With Systemic Inflammation, Disease Activity, and Cardiovascular Risk Factors in Psoriatic Disease

Cited by 22 publications

References 49 publications

Clinical, laboratory, and genetic markers for the development or presence of psoriatic arthritis in psoriasis patients: a systematic review

Clinical, laboratory, and genetic markers for the development or presence of psoriatic arthritis in psoriasis patients: a systematic review

Changes in Lipid Levels and Incidence of Cardiovascular Events Following Tofacitinib Treatment in Patients With Psoriatic Arthritis: A Pooled Analysis Across Phase III and Long‐Term Extension Studies

Evaluation of the prognostic value of paraoxonase 1 in the recurrence and metastasis of hepatocellular carcinoma and establishment of a liver-specific predictive model of survival

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