Total serum bilirubin and risk of cardiovascular disease in the Framingham offspring study

Djoussé, Luc; Levy, Daniel; Cupples, L. Adrienne; Evans, Jane C.; D’Agostino, Ralph B.; Ellison, R. Curtis

doi:10.1016/s0002-9149(01)01494-1

Cited by 242 publications

(196 citation statements)

References 18 publications

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“…12,13 Our findings are consistent with previous evidence that most of the established CHD risk factors are determinants of CAC. 25 Thus, to eliminate the effect of these factors, statistical models were adjusted for age, overweight, diabetes mellitus, hypertension, hypercholesterolemia, hypertriglyceridemia, low HDL cholesterolemia, MetS, hsCRP, elevated serum uric acid, serum creatinine, smoking status, liver function, and statin treatment. Adjustment for these factors, however, did not abolish the significant association of total bilirubin level with CAC score, suggesting that total bilirubin was independently associated with CAC score.…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

“…35, 5, 301-306 (2012) CHD varies by gender. 25,26 Therefore, a larger population of female subjects is required for confirmation.…”

Section: Discussionmentioning

confidence: 99%

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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“…The latter suggested higher bilirubin levels to be associated with a lower cardiovascular risk in men, but the pattern was unclear in women. 18 Ten-year follow-up mortality data from Belgium observed an inverse association between bilirubin levels and all-cause and cancer mortality but not cardiovascular mortality in men. None of these associations was observed in women.…”

Section: Discussionmentioning

confidence: 99%

A genome scan for loci influencing anti-atherogenic serum bilirubin levels

et al. 2002

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Epidemiological studies have shown an association of decreased serum bilirubin levels with coronary artery disease. Two segregation analyses in large pedigrees have suggested a major gene responsible for high bilirubin levels occurring in about 12% of the population. Based on a recessive model from a previous segregation analysis, we performed a genome scan using 587 markers genotyped in 862 individuals from 48 Utah pedigrees to detect loci linked to high bilirubin levels. As a complementary approach, non-parametric linkage (NPL) analysis was performed. These two methods identified four regions showing evidence for linkage. The first region is on chromosome 2q34 -37 with multipoint LOD and NPL scores of 3.01 and 3.22, respectively, for marker D2S1363. This region contains a previously described gene, uridine diphosphate glycosyltransferase 1, which has been associated with high bilirubin levels. A polymorphism in the promoter of this gene was recently shown to be responsible for Gilbert syndrome which is associated with mild hyperbilirubinemia. The other regions were found on chromosomes 9q21, 10q25 -26, and 18q12 with maximum NPL scores of 2.39, 1.55, and 2.79, respectively. Furthermore, we investigated in these pedigrees the association between bilirubin levels and coronary artery disease. One-hundred and sixty-one male and 41 female subjects had already suffered a coronary artery disease event. Male patients showed significantly lower bilirubin concentrations than age-matched controls. This association, however, was not observed in females. These results provide evidence that loci influencing bilirubin variation exist on chromosomes 2q34 -37, 9q21, 10q25 -26, and 18q12 and confirms the association of low bilirubin levels with coronary artery disease in males.

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“…In addition, serum bilirubin has been shown to be inversely related to cardiovascular disease, suggesting a potentially athero-protective effect of bilirubin (7)(8)(9)(10). However, the relationship of serum bilirubin with the future risk of cardiovascular events appears to be more complex.…”

Section: Introductionmentioning

confidence: 99%

Relationship of serum bilirubin concentrations to kidney function and albuminuria in the United States adult population. Findings from the National Health and Nutrition Examination Survey 2001–2006

Targher

Bosworth

Kendrick

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: The association of serum bilirubin concentrations with kidney function and albuminuria has not been established in the US general population. Methods: We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) [2001][2002][2003][2004][2005][2006] and examined the associations of serum total bilirubin concentrations with estimated glomerular filtration rate (eGFR) and albuminuria in a nationally representative sample of 13,184 adults aged 20 years or older. eGFR was estimated using the abbreviated Modification of Diet in Renal Disease equation. Urinary albumin excretion was measured using the albumin/creatinine ratio. Results: An eGFR -60 mL/min/1.73 m 2 and urinary albumin/creatinine ratio G30 mg/g were present in 8.1% (ns1072) and 10.6% (ns1402) of participants, respectively. A total of 427 (3.2%) individuals had a

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Total serum bilirubin and risk of cardiovascular disease in the Framingham offspring study

Cited by 242 publications

References 18 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

A genome scan for loci influencing anti-atherogenic serum bilirubin levels

Relationship of serum bilirubin concentrations to kidney function and albuminuria in the United States adult population. Findings from the National Health and Nutrition Examination Survey 2001–2006

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