Serum bilirubin improves the risk predictions of cardiovascular and total death in diabetic patients

Chen, Su Chan; Lin, Chia‐Pin; Hsu, Han Lin; Shu, Jiah Hwang; Li, Ying; Hsu, Powen; Wang, Yuan Jen; Ding, Yaw Zon; Liou, Teh Ling; Wang, Ying Wen; Chang, Yung Chang; Chan, Wan Leong; Chen, Jaw Wen; Lin, Shing Jong; Leu, Hsin Bang

doi:10.1016/j.cca.2018.10.028

Cited by 22 publications

(27 citation statements)

References 39 publications

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“…To assess whether the accuracy of predicting adverse cardiac events would improve after adding SII to a baseline model with established risk factors (ie age, gender, hypertension, diabetes, BMI and medications), the C‐index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. A similar analysis has been used in our previous work 24 . Statistical analysis was performed utilizing SPSS software (Version 22, SPSS Inc) and R version 3.2.3 (http://www.R-project.org/; R Foundation for Statistical Computing).…”

Section: Methodsmentioning

confidence: 99%

Systemic immune‐inflammation index (SII) predicted clinical outcome in patients with coronary artery disease

Yang

Wu²,

Hsu³

et al. 2020

Eur J Clin Investigation

422

300

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Background: This study examines the predictive value of a novel systemic immuneinflammation index (SII, platelet × neutrophil/lymphocyte ratio) in coronary artery disease (CAD) patients. Methods: A total of 5602 CAD patients who had undergone a percutaneous coronary intervention (PCI) were enrolled. They were divided into two groups by baseline SII score (high SII vs low SII) to analyse the relationship between SII groups and the long-term outcome. The primary outcomes were major cardiovascular events (MACE) which includes nonfatal myocardial infarction (MI), nonfatal stroke and cardiac death. Secondary outcomes included a composite of MACE and hospitalization for congestive heart failure. Results: An optimal SII cut-off point of 694.3 × 10 9 was identified for MACE in the CAD training cohort (n = 373) and then verified in the second larger CAD cohort (n = 5602). Univariate and multivariate analyses showed that a higher SII score (≥694.3) was independently associated with increased risk of developing cardiac death (HR: 2.02; 95% CI: 1.43-2.86), nonfatal MI (HR: 1.42; 95% CI: 1.09-1.85), nonfatal stroke (HR: 1.96; 95% CI: 1.28-2.99), MACE (HR: 1.65; 95% CI: 1.36-2.01) and total major events (HR: 1.53; 95% CI: 1.32-1.77). In addition, the SII significantly improved risk stratification of MI, cardiac death, heart failure, MACE and total major events than conventional risk factors in CAD patients by the significant increase in the C-index (P < .001) and reclassification risk categories by significant NRI (P < .05) and IDI (P < .05). Conclusions: SII had a better prediction of major cardiovascular events than traditional risk factors in CAD patients after coronary intervention. K E Y W O R D Scoronary artery disease, inflammation, percutaneous coronary intervention 2 of 11 | YANG et Al.

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Section: Methodsmentioning

confidence: 99%

Systemic immune‐inflammation index (SII) predicted clinical outcome in patients with coronary artery disease

Yang

Wu²,

Hsu³

et al. 2020

Eur J Clin Investigation

422

300

View full text Add to dashboard Cite

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“…To assess whether the accuracy of predicting adverse cardiac events would improve after the addition of CONUT to a baseline model with established risk factors (i.e., age, gender, hypertension, diabetes, BMI and medications), the C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated. A similar analysis has been used in our previous work [16]. Statistical analysis was performed utilizing the SPSS software (Version 15.0, IBM Corporation, Armonk, NY, USA) and R version 3.2.3 (http://www.R-project.org/; R Foundation for Statistical Computing, Vienna, Austria).…”

Section: Statistical Analysesmentioning

confidence: 99%

Association between Preoperative Nutritional Status and Clinical Outcomes of Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

Chen

Yang

et al. 2020

Nutrients

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Background: Malnutrition is associated with poor outcomes in patients with cancer, heart failure and chronic kidney disease. This study aimed to investigate the predictive value of the Controlling Nutritional Status (CONUT) score in coronary artery disease (CAD) patients. Methods: We recruited a cohort of 3118 patients with CAD undergoing percutaneous coronary intervention (PCI) from 2005 to 2015. Nutritional status was evaluated using the CONUT score, with higher scores reflecting worse nutritional status. Results: After adjustment for comorbidities and medication, an increased CONUT score was independently associated with a higher risk of acute myocardial infarction (AMI) (HR: 1.13; 95% CI: 1.03–1.24), cardiovascular (CV) death (HR: 1.18; 95% CI: 1.07–1.30), congestive heart failure (CHF) (HR: 1.11; 95% CI: 1.04–1.18), a major adverse cardiovascular event (MACE) (HR: 1.14; 95% CI: 1.07–1.22), and total CV events (HR: 1.11; 95% CI: 1.07–1.15). The subgroup analyses demonstrated that the association of the CONUT score existed independently of other established cardiovascular risk factors. In addition, CONUT significantly improved risk stratification for myocardial infarction (MI), cardiac death, CHF, MACEs and total CV events compared to conventional risk factors in CAD patients by the significant increase in the C-index (p < 0.05) and reclassification risk categories in cardiac death and MACEs. Conclusions: The CONUT score improved the risk prediction of adverse events compared to traditional risk factors in CAD patients after percutaneous coronary intervention (PCI).

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“…Therefore, we focused our study on the analysis of sex-specific GWAS and the exploration of gene-diet interactions. We selected the serum concentrations of total bilirubin as the central phenotype taking into account that there is a growing interest in it due to its potential protection against cardiovascular disease [20,21,22,23], and mainly, because it is highly heritable [24]. Hence, statistically significant results at the GWAS level can be obtained with a relatively small number of study subjects.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population

et al. 2019

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Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55–75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p < 5 × 10−8 (GWAS level). The top-ranked were four SNPs (rs4148325 (p = 9.25 × 10−24), rs4148324 (p = 9.48 × 10−24), rs6742078 (p = 1.29 × 10−23), rs887829 (p = 1.39 × 10−23), and the rs4148324 (p = 9.48 × 10−24)) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men (p = 4.77 × 10−11) and women (p = 2.15 × 10−14), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance (p < 1 × 10−5). We did not detect any gene-MedDiet interaction at p < 1 × 10−5 for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p < 1 × 10−5, and even at the GWAS level for the IL17B gene (p = 3.14 × 10−8). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet.

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Serum bilirubin improves the risk predictions of cardiovascular and total death in diabetic patients

Cited by 22 publications

References 39 publications

Systemic immune‐inflammation index (SII) predicted clinical outcome in patients with coronary artery disease

Systemic immune‐inflammation index (SII) predicted clinical outcome in patients with coronary artery disease

Association between Preoperative Nutritional Status and Clinical Outcomes of Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population

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