Bilirubin in coronary artery disease: Cytotoxic or protective?

Gupta, Nancy; Singh, Tavankit; Chaudhary, Rahul; Garg, Sushil Kumar; Sandhu, Gurprataap S.; Mittal, Varun; Gupta, Rahul; Bodin, Roxana; Sule, Sachin

doi:10.4292/wjgpt.v7.i4.469

Cited by 26 publications

(23 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, our results remain significant when smoking status is adjusted for the analysis. Several prospective studies did not found protective effect of bilirubin on CVD [ 21 ]. However, these studies were limited by its small sample size or patients with high risk profile for CVD.…”

Section: Discussionmentioning

confidence: 99%

“…Low bilirubin levels can be indicative of decreased heme oxygenase activity (a powerful antioxidant) or could be indicative of high oxidative stress in patients leading to consumption of the natural antioxidants including bilirubin. Hence, there is possibility that lower levels of bilirubin are perhaps not the causal factor for CVD but may indicate patients at an increased risk of developing CVD [ 21 ]. Moreover, further large scale long-term study will be required to confirm our results regarding inflammation and IR in the future.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship between serum bilirubin levels and cardiovascular disease

Suh¹,

Cho²,

Park³

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

We tested the hypothesis that higher levels of bilirubin, a bile pigment with antioxidant properties, are associated with a decreased risk of cardiovascular disease (CVD). This study analyzed data from the Korean Health and Genome Study to examine the association between serum total bilirubin (TB) on CVD and CVD death. Serum TB was measured in a total of 8,844 subjects (4,196 males and 4,648 females) and evaluated for the development of new onset CVD from 2001 to 2012 (mean 8.1 years of follow-up). During the follow-up period, 689 cases of incident CVD (7.8%) were identified, and the prevalence of metabolic syndrome (MetS) at baseline was 26.1%. The prevalence of MetS decreased across bilirubin tertile categories. In addition to MetS itself, individual components of MetS significantly decreased with increased bilirubin tertiles. Moreover, the incidence of CVD decreased across bilirubin tertile categories. The hazard ratios (HRs) for developing coronary heart disease (CHD, HR 0.769, 95% CI 0.655–1.000) and CVD death (HR 0.513, 95% CI 0.267–0.985) was significantly lower in the highest tertile group (> 0.63 mg/dL) in comparison to the lowest tertile group (< 0.44 mg/dL) after adjusting for all confounding variables. In the present longitudinal study, a significant negative relationship was demonstrated between baseline bilirubin levels and incident CHD and CVD death.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Relationship between serum bilirubin levels and cardiovascular disease

Suh¹,

Cho²,

Park³

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Ritonavir-boosted atazanavir (ATV/r) has been associated with a lower cardiovascular risk than ritonavir-boosted darunavir [9]. This could be related to the ability of ATV/r to increase bilirubin levels, because bilirubin has been related to cardio-protective anti-oxidant effects [10].…”

Section: Introductionmentioning

confidence: 99%

HIV antiretroviral drugs, dolutegravir, maraviroc and ritonavir-boosted atazanavir use different pathways to affect inflammation, senescence and insulin sensitivity in human coronary endothelial cells

et al. 2020

View full text Add to dashboard Cite

Objectives Aging HIV-infected antiretroviral-treatment (ART)-controlled patients often present cardiovascular and metabolic comorbidities. Thus, it is mandatory that lifelong used ART has no cardiometabolic toxicity. Protease inhibitors have been associated with cardiometabolic risk, integrase-strand-transfer-inhibitors (INSTI) with weight gain and the CCR5 inhibitor maraviroc with improved vascular function. We have previously reported that the INSTI dolutegravir and maraviroc improved, and ritonavir-boosted atazanavir(atazanavir/r) worsened, inflammation and senescence in human coronary artery endothelial cells (HCAEC)s from adult controls. Here, we analyzed the pathways involved in the drugs' effects on inflammation, senescence and also insulin resistance. Methods We analyzed the involvement of the anti-inflammatory SIRT-1 pathway in HCAECs. Then, we performed a transcriptomic analysis of the effect of dolutegravir, maraviroc and atazanavir/r and used siRNA-silencing to address ubiquitin-specific-peptidase-18 (USP18) involvement into ART effects. Results Dolutegravir reduced inflammation by decreasing NFκB activation and IL-6/IL-8/sICAM-1/ sVCAM-1 secretion, as did maraviroc with a milder effect. However, when SIRT-1 was inhibited by splitomicin, the drugs anti-inflammatory effects were maintained, indicating that they were SIRT-1-independant.

show abstract

“…IDB is converted to DB in hepatic cells and excreted into bile acid. 1 Considered to be a waste product at first, bilirubin now has been known to have antioxidative, 2 anti-inflammatory, 3 and antithrombotic effects. 4 However, epidemiologic studies lack consistency.…”

mentioning

confidence: 99%

Relation of Direct, Indirect, and Total bilirubin to Adverse Long-term Outcomes Among Patients With Acute Coronary Syndrome

Dong

Deng

et al. 2019

The American Journal of Cardiology

View full text Add to dashboard Cite

Bilirubin is known as an antioxidant. However, there have been controversies over whether bilirubin is protective against cardiovascular disease or not. In addition, no study has examined the association between subtypes of total bilirubin (direct bilirubin [DB] and indirect bilirubin [IDB]) and long-term outcomes of acute coronary syndrome (ACS) patients. We included 533 consecutive patients with ACS. All the patients were followed up for the composite end point of cardiac death, revascularization, and acute heart failure. At a median follow-up of 2.4 years, Kaplan-Meier curve demonstrated that higher serum DB levels were significantly associated with major adverse cardiac events (MACE) (p <0.05). However, total bilirubin (TB) and IDB were not associated with MACE by Kaplan-Meier analysis. Cox analysis showed that high TB and DB were associated with increased risk of MACE in ACS even after adjustment of cardiovascular risk factors. The receiver operating characteristic curve illustrated that DB had a predictive value of MACE in ACS. In conclusion, we firstly reported that high TB and DB but not IDB were associated with increased risk of MACE in Chinese ACS, and the prognostic value of DB was superior to that of TB or IDB.

show abstract

Bilirubin in coronary artery disease: Cytotoxic or protective?

Cited by 26 publications

References 49 publications

Relationship between serum bilirubin levels and cardiovascular disease

Relationship between serum bilirubin levels and cardiovascular disease

HIV antiretroviral drugs, dolutegravir, maraviroc and ritonavir-boosted atazanavir use different pathways to affect inflammation, senescence and insulin sensitivity in human coronary endothelial cells

Relation of Direct, Indirect, and Total bilirubin to Adverse Long-term Outcomes Among Patients With Acute Coronary Syndrome

Contact Info

Product

Resources

About