Commonly used clinical chemistry tests as mortality predictors: Results from two large cohort studies

Lind, Lars; Zanetti, Daniela; Högman, Marieann; Sundman, Lars; Ingelsson, Erik

doi:10.1371/journal.pone.0241558

Cited by 6 publications

(5 citation statements)

References 34 publications

(37 reference statements)

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“…In the general population, a research conducted using data from NHANES spanning the years 1999 to 2006 revealed that participants with elevated BUN levels, compared to those in the first quartile of BUN levels, exhibited an elevated risk of dying from CVD and all-cause [ 28 ]. However, data from the UK Biobank and Health Screening Survey X69 showed that BUN levels and mortality displayed a U-shaped relationship [ 29 ]. Various similar findings have been observed in clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Association of blood urea nitrogen with all-cause and cardiovascular mortality in hyperlipidemia: NHANES 1999–2018

Shen,

Wang,

Liu

et al. 2024

Lipids Health Dis

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Objective Although blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia. Methods This analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used. Results During the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis. Conclusions This study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.

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Section: Discussionmentioning

confidence: 99%

Association of blood urea nitrogen with all-cause and cardiovascular mortality in hyperlipidemia: NHANES 1999–2018

Shen,

Wang,

Liu

et al. 2024

Lipids Health Dis

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“…Leveraging data from 3,209 participants in the Framingham Heart Study, Wang et al constructed a score comprising five biomarkers (CRP, N-terminal pro-atrial natriuretic peptide, homocysteine, renin, and D-dimer) to predict all-cause mortality, with a C statistic of 0.79 for the model including age, sex, and the score [ 28 ]. In another study examining the predictivity of 11 blood biomarkers (calcium, BUN, bilirubin, ALB, hematocrit, leukocyte count, uric acid, iron, GGT, ALP, and lactate dehydrogenase) for all-cause mortality in two cohorts, adding the biomarkers into a model of traditional risk factors yielded a validated C statistic of 0.76 [ 29 ]. In our study, we excluded participants with prevalent CVD or cancer at baseline to reduce confounding by preexisting diseases.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a blood biomarker score for predicting mortality risk in the general population

Yang

Miao

et al. 2023

J Transl Med

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Background Blood biomarkers for multiple pathways, such as inflammatory response, lipid metabolism, and hormonal regulation, have been suggested to influence the risk of mortality. However, few studies have systematically evaluated the combined predictive ability of blood biomarkers for mortality risk. Methods We included 267,239 participants from the UK Biobank who had measurements of 28 blood biomarkers and were free of cardiovascular disease (CVD) and cancer at baseline (2006–2010). We developed sex-specific blood biomarker scores for predicting all-cause mortality risk in a training set of 247,503 participants from England and Wales, and validated the results in 19,736 participants from Scotland. Cox and LASSO regression analyses were performed to identify independent predictors for men and women separately. Discrimination and calibration were evaluated by C-index and calibration plots, respectively. We also assessed mediating effects of the biomarkers on the association between traditional risk factors (current smoking, obesity, physical inactivity, hypertension, diabetes) and mortality. Results A total of 13 independent predictive biomarkers for men and 17 for women were identified and included in the score development. Compared to the lowest tertile of the score, the highest tertile showed a hazard ratio of 5.36 (95% confidence interval [CI] 5.04–5.71) in men and 4.23 (95% CI 3.87–4.62) in women for all-cause mortality. In the validation set, the score yielded a C-index of 0.73 (95% CI 0.72–0.75) in men and 0.70 (95% CI 0.68–0.73) in women for all-cause mortality; it was also predictive of CVD (C-index of 0.76 in men and 0.79 in women) and cancer (C-index of 0.70 in men and 0.67 in women) mortality. Moreover, the association between traditional risk factors and all-cause mortality was largely mediated by cystatin C, C-reactive protein, 25-hydroxyvitamin D, and hemoglobin A1c. Conclusions We established sex-specific blood biomarker scores for predicting all-cause and cause-specific mortality in the general population, which hold the potential to identify high-risk individuals and improve targeted prevention of premature death.

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“…Notably, several studies have revealed a U-shaped association between total bilirubin concentration and coronary heart disease [ 39 , 40 ], telomere length [ 41 ], and all-cause mortality [ 42 ]. These findings suggest bilirubin’s threshold effect on bone health.…”

Section: Discussionmentioning

confidence: 99%

Association between total bilirubin and bone mineral density level in adolescents

Wang

et al. 2022

BMC Musculoskelet Disord

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Background Increasing bone mass accumulation in adolescence and obtaining greater peak bone mass is one of the effective methods to prevent osteoporosis in the future. We aimed to examine the association between total bilirubin and bone mineral density (BMD) level in adolescents. Methods We used the data from 2005–2010 and 2013–2014 cycles of National Health and Nutrition Examination Survey (NHANES). The BMD levels in the region of lumbar spine and femoral regions, including total femur, femoral neck, trochanter, and intertrochanter were measured. Univariable and multivariable linear regression model were used to assess the relationship between total bilirubin concentration and BMD. Results A total of 3741 participants aged 12–19 years were ultimately included in the study. There were 1997 (53.38%) males and 1744 (46.62%) females. Univariate analysis results showed that age, sex, race, education, income, body mass index, dietary calcium intake, and diabetes were correlated with BMD levels. Compared with the lowest quartile of total bilirubin concentration, the highest quartile of total bilirubin concentration was positively associated with BMD levels in the regions of total femur (β = 0.036, 95% CI = 0.021 to 0.050, P < 0.001), femur neck (β = 0.030, 95% CI = 0.016 to 0.044, P < 0.001), trochanter (β = 0.033, 95% CI = 0.019 to 0.046, P < 0.001), intertrochanter (β = 0.040, 95% CI = 0.023 to 0.056, P < 0.001), and lumbar spine (β = 0.032, 95% CI = 0.018 to 0.045, P < 0.001). We also observe the same trend in sensitivity analysis (P for trend < 0.001). Conclusion Our study demonstrated that total bilirubin concentration was positively associated with BMD levels in adolescents in United States. Total bilirubin concentration might be a protective marker against bone loss in adolescents.

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Commonly used clinical chemistry tests as mortality predictors: Results from two large cohort studies

Cited by 6 publications

References 34 publications

Association of blood urea nitrogen with all-cause and cardiovascular mortality in hyperlipidemia: NHANES 1999–2018

Association of blood urea nitrogen with all-cause and cardiovascular mortality in hyperlipidemia: NHANES 1999–2018

Development and validation of a blood biomarker score for predicting mortality risk in the general population

Association between total bilirubin and bone mineral density level in adolescents

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