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Cardiovascular events as a function of serum bilirubin levels in a large, statin-treated cohort
Laura J Horsfall1, Irwin Nazareth, Irene Petersen
1Research Department of Primary Care and Population Health, Faculty of Biomedical Sciences, University College London Medical School, Royal Free Campus, Rowland Hill St, London NW3 2PF, UK. laura.horsfall@ucl.ac.uk
Insights
Low serum bilirubin levels, routinely checked before statin prescriptions, are linked to increased cardiovascular disease (CVD) risk. This finding highlights bilirubin as an independent predictor of CVD events and mortality in both men and women.
Area of Science:
- Biochemistry
- Cardiology
- Public Health
Background:
- Serum bilirubin, an endogenous antioxidant, is commonly measured for liver function before statin initiation.
- The association between serum bilirubin and cardiovascular disease (CVD) risk in patients initiating statin therapy has not been previously explored.
Purpose of the Study:
- To investigate the relationship between pre-statin serum total bilirubin levels and the risk of incident CVD.
- To determine if serum bilirubin is an independent predictor of CVD events and all-cause mortality.
Main Methods:
- A retrospective cohort study using a large UK primary care database (The Health Improvement Network).
- Inclusion of 130,052 patients with recorded serum total bilirubin levels prior to statin initiation (2000-2010) and no history of liver disease or CVD.
- Median follow-up of 43 months with analysis of 7,850 CVD events.
Main Results:
- A nonlinear, L-shaped association was observed between serum bilirubin levels and CVD risk after adjusting for conventional risk factors.
- Patients in the lowest bilirubin decile (1-6 μmol/L) exhibited higher CVD incidence compared to those in the highest decile (19-40 μmol/L).
- Lower bilirubin levels (e.g., 5 μmol/L vs. 10 μmol/L) were associated with significantly increased risks of CVD events (18%), myocardial infarction (34%), and all-cause mortality (33%).
Conclusions:
- Serum bilirubin level, measured routinely for liver function assessment before statin prescription, is an independent risk factor for cardiovascular disease.
- Lower serum bilirubin levels are associated with an elevated risk of CVD events, myocardial infarction, and all-cause mortality.
- These findings suggest serum bilirubin may serve as a novel biomarker for CVD risk stratification in patients initiating statin therapy.
Background:
Serum bilirubin is an endogenous antioxidant that is routinely measured before a statin is prescribed primarily to assess liver function, but the association with cardiovascular disease (CVD) in this population has not been explored.
Method And Results:
We identified patients from a United Kingdom primary care database (The Health Improvement Network) with measurements of serum total bilirubin levels recorded 3 months before the first statin treatment between January 1, 2000, and December 31, 2010, and no history of liver disease or CVD. In total, 130 052 patients met the inclusion criteria, and after a median follow-up of 43 months, there were 7850 CVD events. In men, the incidence of CVD in the lowest decile category of bilirubin (1-6 μmol/L [0.06-0.35 mg/dL]) was 215 per 10 000 person-years compared with 163 per 10 000 person-years in the highest decile (19-40 μmol/L [1.1-2.3 mg/dL]). Similar differences were seen for women. After conventional CVD risk factors were accounted for, the associations with bilirubin were nonlinear (L shaped), and the models predicted that, compared with patients with a bilirubin level of 10 μmol/L (0.6 mg/dL), those with a similar CVD risk profile but a bilirubin level of 5 μmol/L (0.3 mg/dL) had an 18% (95% confidence interval, 9-27) higher risk of any CVD event, a 34% (95% confidence interval, 13-56) higher risk of myocardial infarction, and a 33% (95% confidence interval, 21-46) higher risk of death resulting from any cause.
Conclusions:
Serum bilirubin level measured before a statin prescription to assess liver function is an independent risk factor for CVD and death in both men and women.
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