Association between plasma bilirubin and mortality

Vı́tek, Libor; Hubacek, Jaroslav A.; Pająk, Andrzej; Doryńska, Agnieszka; Kozela, Magdalena; Eremiášová, Lenka; Danzig, Vilém; Stefler, Dénes; Bobák, Martin

doi:10.1016/j.aohep.2019.02.001

Cited by 26 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several studies have examined the relationship between genetically predicted bilirubin and other clinical outcomes with mixed results that possibly reflects differences in the pathophysiological role for oxidative stress, smoking case-mix, age at recruitment, low power for rare outcomes and study design. 34 35 Genome-wide association studies have not identified the UGT1A1 locus in studies of lung cancer, although the number of smokers required to reach the high threshold for genome-wide statistical significance exceeds that available in most cohorts.…”

Section: Discussionmentioning

confidence: 99%

Genetically raised serum bilirubin levels and lung cancer: a cohort study and Mendelian randomisation using UK Biobank

Horsfall¹,

Burgess

Hall

et al. 2020

Thorax

View full text Add to dashboard Cite

BackgroundModerately raised serum bilirubin levels are associated with lower rates of lung cancer, particularly among smokers. It is not known whether these relationships reflect antioxidant properties or residual confounding.ObjectiveThis study aimed to investigate potential causal relationships between serum total bilirubin and lung cancer incidence using one-sample Mendelian randomisation (MR) and UK Biobank.MethodsWe instrumented serum total bilirubin level using two variants (rs887829 and rs4149056) that together explain ~40% of population-level variability and are linked to mild hereditary hyperbilirubinaemia. Lung cancer events occurring after recruitment were identified from national cancer registries. Observational and genetically instrumented incidence rate ratios (IRRs) and rate differences per 10 000 person-years (PYs) by smoking status were estimated.ResultsWe included 377 294 participants (median bilirubin 8.1 μmol/L (IQR 6.4–10.4)) and 2002 lung cancer events in the MR analysis. Each 5 μmol/L increase in observed bilirubin levels was associated with 1.2/10 000 PY decrease (95% CI 0.7 to 1.8) in lung cancer incidence. The corresponding MR estimate was a decrease of 0.8/10 000 PY (95% CI 0.1 to 1.4). The strongest associations were in current smokers where a 5 μmol/L increase in observed bilirubin levels was associated with a decrease in lung cancer incidence of 10.2/10 000 PY (95% CI 5.5 to 15.0) and an MR estimate of 6.4/10 000 PY (95% CI 1.4 to 11.5). For heavy smokers (≥20/day), the MR estimate was an incidence decrease of 23.1/10 000 PY (95% CI 7.3 to 38.9). There was no association in never smokers and no mediation by respiratory function.ConclusionGenetically raised serum bilirubin, common across human populations, may protect people exposed to high levels of smoke oxidants against lung cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetically raised serum bilirubin levels and lung cancer: a cohort study and Mendelian randomisation using UK Biobank

Horsfall¹,

Burgess

Hall

et al. 2020

Thorax

View full text Add to dashboard Cite

show abstract

“…In general, bilirubin is associated with anti-proliferative and antineoplastic activity. In fact, specific polymorphisms in UGT1A1 gene and the consequent hyperbilirubinemia are correlated positively with an increased overall survival in cancer patients (Vitek et al, 2019b), particularly considering colorectal (Jirásková et al, 2012), lung and breast cancers (Wagner et al, 2015). Moreover, reduced bilirubin levels are associated with increased cancer risk (Ching et al, 2002;Zucker et al, 2004).…”

Section: Bilirubin and Tumor Growthmentioning

confidence: 99%

“…Different therapeutic approaches aimed at elevating plasma bilirubin concentration as well as modulating cellular HMOX1 activity have been proposed for the treatment of many disorders, as widely reviewed by others (McCarty, 2007;Vitek et al, 2019b). Here, we focused on that ones in which the modulation of endothelial cell function is pivotal.…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

“…Finally, it is worth noting that senescence and aging processes, strongly associated with accumulation of oxidative damage, are reduced/slowed by bilirubin. Notably, has been recently highlighted the negative relationship among bilirubin concentration and cancer mortality, even though the relationship is missing among bilirubin and CVD mortality (Vitek et al, 2019b). It is conceivable that larger studies focused on older population are needed to explain this lack of association.…”

Section: Conclusion and Future Researchmentioning

confidence: 99%

See 1 more Smart Citation

Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

2020

View full text Add to dashboard Cite

Among antioxidants in the human body, bilirubin has been recognized over the past 20 years to afford protection against different chronic conditions, including inflammation and cardiovascular disease. Moderate increases in plasma concentration and cellular bilirubin generation from metabolism of heme via heme oxygenase (HMOX) in virtually all tissues can modulate endothelial and vascular function and exert antioxidant and antiinflammatory roles. This review aims to provide an up-to-date and critical overview of the molecular mechanisms by which bilirubin derived from plasma or from HMOX1 activation in vascular cells affects endothelial function. Understanding the molecular actions of bilirubin may critically improve the management not only of key cardiovascular diseases, but also provide insights into a broad spectrum of pathologies driven by endothelial dysfunction. In this context, therapeutic interventions aimed at mildly increasing serum bilirubin as well as bilirubin generated endogenously by endothelial HMOX1 should be considered.

show abstract

“…Furthermore, similar inverse associations have now been shown between serum bilirubin concentrations and coronary artery disease [15], coronary heart disease [16], peripheral vascular disease [17], and stroke [18]. Moreover, mildly elevated bilirubin concentrations may protect against cardiovascular and total death [19][20][21], whereas other research indicates that higher levels of bilirubin have increased or null associations with cardiovascular diseases (CVD) [22,23].…”

Section: Introductionmentioning

confidence: 86%

Lower serum bilirubin is a risk factor for cardiovascular mortality in maintenance hemodialysis patients: a retrospective cohort study

Chen

Zhao

Fan

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Although recent studies showed serum bilirubin, an endogenous antioxidant, is protective against cardiovascular diseases, cancer, and diabetic complications, less information is available its association with cardiovascular mortality in hemodialysis patients. This study aimed to investigate the relationship between serum bilirubin and the cardiovascular mortality in maintenance hemodialysis patients.Methods: This retrospective study included 284 chronic hemodialysis patients who started hemodialysis between January 01, 2003, and May 30, 2019. The endpoint was cardiovascular death and all-cause death. A Cox proportional hazards model was used to evaluate the risk factors for cardiovascular death in the maintenance hemodialysis. The cardiovascular mortality was evaluated by Kaplan-Meier analysis.Results: Up to 2019, the median follow-up time was 53 months. In Kaplan–Meier analysis curves, the risk of cardiovascular death in the patients with serum indirect bilirubin (IBIL) levels＜3.0 μmol/L was significantly higher than those with serum IBIL levels≥3.0 μmol/L(p =0.045). In multivariate Cox regression analysis, the risk of cardiovascular mortality in patients with serum IBIL levels ≥3.0 μmol/L was 0.556 times the risk in patients with serum IBIL levels＜3.0 μmol/L (Hazard ratio=0.556, 95% confidence interval 0.334~0.926, p =0.024). However, there was no significant association between serum IBIL and all-cause mortality (p =0.269). Conclusions: Our findings suggest that low serum IBIL level is independently associated with high risk of cardiovascular death in maintenance hemodialysis patients.

show abstract

Association between plasma bilirubin and mortality

Cited by 26 publications

References 34 publications

Genetically raised serum bilirubin levels and lung cancer: a cohort study and Mendelian randomisation using UK Biobank

Genetically raised serum bilirubin levels and lung cancer: a cohort study and Mendelian randomisation using UK Biobank

Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

Lower serum bilirubin is a risk factor for cardiovascular mortality in maintenance hemodialysis patients: a retrospective cohort study

Contact Info

Product

Resources

About