The Inverse Association of Elevated Serum Bilirubin Levels with Subclinical Carotid Atherosclerosis

Vı́tek, Libor; Novotný, Ladislav; Sperl, M; Holaj, Robert; Spáčil, J

doi:10.1159/000091966

Cited by 97 publications

(87 citation statements)

References 26 publications

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“…As a result, in this large representative population of males (N = 3408), we found an independent association between increasing concentration of serum total bilirubin and decreasing CAC score, a predictor for CHD risk. 12,13 Our findings were in line with those of previous reports concerning the inverse relation between bilirubin and prevalence of carotid plaque, 23 carotid IMT, 9,11 and PAD. 10 However, a recent study has reported that CAC score is a better predictor of subsequent CHD events than carotid IMT.…”

Section: Discussionsupporting

confidence: 93%

Inverse Relation of Total Serum Bilirubin to Coronary Artery Calcification Score Detected by Multidetector Computed Tomography in Males

Zhang

Bian

Kim

et al. 2012

Clinical Cardiology

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Background:Serum total bilirubin has been suggested to have potential anti‐inflammatory and antioxidant effects on the vasculature, acting against plaque formation and subsequent atherosclerosis. This study was designed to assess the association of serum total bilirubin with coronary artery calcification (CAC).Hypothesis:Individuals with higher bilirubin level would be less likely to develop CAC.Methods:Male subjects (N = 3408) underwent evaluation of CAC by cardiac computed tomography. Correlation and logistic regression analysis were performed to assess the relationships between CAC score and other variables.Results:Subjects with a higher CAC score had significantly lower total bilirubin level (P = 0.001). Total bilirubin level was negatively correlated with CAC score (r = −0.052, P = 0.002). A 0.1‐mg/dL increase in bilirubin was associated with a reduced odds ratio (OR) of the risk by 29.2% for a CAC score above 100 (OR: 0.708, 95% confidence interval: 0.542‐0.927, P = 0.012) after adjustment for several variables. Bilirubin was inversely correlated with high‐sensitivity C‐reactive protein (hsCRP) (r = −0.117, P < 0.001).Conclusions:This study demonstrated an independent inverse association between serum total bilirubin and CAC score in males. Low serum bilirubin concentration would be useful as a potential risk factor for CAC in males. Additionally, reduced hsCRP may be 1 of the mechanisms for how bilirubin reduces CAC. © 2012 Wiley Periodicals, Inc.Additional Supporting Information may be found in the online version of this article.Zheng‐Yun Zhang, MD, and Lu‐Qin Bian, MD, contributed equally to this work.The authors have no funding, financial relationships, or conflicts of interest to disclose.

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Section: Discussionsupporting

confidence: 93%

Inverse Relation of Total Serum Bilirubin to Coronary Artery Calcification Score Detected by Multidetector Computed Tomography in Males

Zhang

Bian

Kim

et al. 2012

Clinical Cardiology

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“…Our study therefore for the first time extends these findings to amputation events. This inverse association is further supported by studies showing a similar relationship between bilirubin levels and CHD, ischaemic stroke, and surrogate markers of atherosclerosis including endothelial dysfunction and carotid intima-media thickness [12,14,[29][30][31][32][33][34][35][36][37][38][39][40][41][42]. A number of prospective studies found a Uor reversed J-shaped relationship rather than an inverse relationship between bilirubin levels and CHD [4,5,27,28,30,33,34,37].…”

Section: Discussionmentioning

confidence: 78%

Plasma total bilirubin levels predict amputation events in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

et al. 2013

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Aims/hypothesis Bilirubin has antioxidant and antiinflammatory activities. Previous studies demonstrated that higher bilirubin levels were associated with reduced prevalence of peripheral arterial disease (PAD). However, the relationship between bilirubin and lower-limb amputation, a consequence of PAD, is currently unknown. We hypothesised that, in patients with type 2 diabetes, bilirubin concentrations may inversely associate with lower-limb amputation.Methods The relationship between baseline plasma total bilirubin levels and amputation events was analysed in 9,795 type 2 diabetic patients from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. The analysis plan was pre-specified. Lower-limb amputation was adjudicated blinded to treatment allocation. Relevant clinical and biochemical data were available for analyses. Amputation was a pre-specified tertiary endpoint. Results Bilirubin concentrations were significantly inversely associated with lower-limb amputation, with a greater than M. K. C. Ng and A. C. Keech are joint senior authors of this study Electronic supplementary material The online version of this article

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“…7,8 On the other hand, the question of a protective effect of Crigler -Najjar causing alleles at the heterozygote state against oxidative damages such as heart coronary diseases is not clear. Vitek et al 21 pointed that patients with mild increase of serum bilirubin could be protected against heart disease. But on the other hand, Bosma et al 22 and Gajdos et al 23 in two different studies did not find any correlation between mutations in UGT1A1 gene promoter and protection against heart disease.…”

Section: Discussionmentioning

confidence: 99%

The Tunisian population history through the Crigler–Najjar type I syndrome

et al. 2008

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Crigler-Najjar syndrome type I (CN-I) is a rare and severe metabolic disorder. A recurrent mutationc.1070A4G in exon 3 -was identified in the Tunisian population, suggesting a founder effect. In 2004, the detection of this mutation in two Kuwaiti Bedouin families has called the Tunisian founder effect in question again. To determine the origin of this mutation, 21 Tunisian and 2 Kuwaiti Bedouin CN-I patients were screened using nine genetic markers. Haplotype analysis confirmed the founder effect hypothesis and dated the appearance of this mutation some 32 generations ago in the Tunisian population. Using the same genetic analysis, the ancestor haplotype was identified in these two families. This result genetically confirms the blending of the Bedouin nomads within today's Tunisian population. After population migration from east to west, this mutation was introduced into the Tunisian population, and then perpetuated, probably because of marriages in isolated communities.

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The Inverse Association of Elevated Serum Bilirubin Levels with Subclinical Carotid Atherosclerosis

Cited by 97 publications

References 26 publications

Inverse Relation of Total Serum Bilirubin to Coronary Artery Calcification Score Detected by Multidetector Computed Tomography in Males

Inverse Relation of Total Serum Bilirubin to Coronary Artery Calcification Score Detected by Multidetector Computed Tomography in Males

Plasma total bilirubin levels predict amputation events in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

The Tunisian population history through the Crigler–Najjar type I syndrome

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