Michael Li1,2, Walter W Chan1,2, Stephen D Zucker1,2. 1. Division of Gastroenterology, Hepatology, and Endoscopy Brigham & Women's Hospital Boston MA. 2. Harvard Medical School Boston MA.
Abstract
BACKGROUND: Serum bilirubin is inversely associated with cardiovascular risk. Atazanavir, an HIV protease inhibitor that competitively inhibits bilirubin conjugation, provides a unique opportunity to examine whether selectively increasing bilirubin is cardioprotective. We sought to determine whether patients receiving atazanavir manifest a reduced risk of cardiovascular disease compared with those receiving darunavir, an HIV protease inhibitor that does not increase serum bilirubin. METHODS AND RESULTS: This was a retrospective cohort study of 1020 patients with HIV. The main outcome was time to myocardial infarction or ischemic stroke. Mean follow-up was 6.6±3.4 years, with 516 receiving atazanavir and 504 darunavir. Atazanavir patients exhibited significantly higher serum total bilirubin (1.7 versus 0.4 mg/dL; P<0.001) and longer mean time to ischemic event (10.2 versus 9.4 years; P<0.001). On Cox regression, atazanavir treatment (hazard ratio [HR], 0.38; 95% CI, 0.21-0.71; P=0.002) and serum bilirubin (HR, 0.60; 95% CI, 0.41-0.89; P=0.011) were independently associated with a lower risk of an ischemic event. Notably, when atazanavir and bilirubin were included together in the Cox regression model, atazanavir lost significance (HR, 0.55; 95% CI, 0.24-1.29; P=0.169) consistent with bilirubin being an intermediate variable on the causal pathway between atazanavir and its effect on cardiovascular disease. Patients on atazanavir also had a significantly lower risk of developing new cardiovascular disease (HR, 0.53; 95% CI, 0.33-0.86; P=0.010) and longer mean time to death (12.2 versus 10.8 years; P<0.001). CONCLUSIONS: Patients with HIV on atazanavir manifest a decreased risk of cardiovascular disease when compared with those on darunavir, an effect that appears to be mediated by serum bilirubin.
BACKGROUND: Serum bilirubin is inversely associated with cardiovascular risk. Atazanavir, an HIV protease inhibitor that competitively inhibits bilirubin conjugation, provides a unique opportunity to examine whether selectively increasing bilirubin is cardioprotective. We sought to determine whether patients receiving atazanavir manifest a reduced risk of cardiovascular disease compared with those receiving darunavir, an HIV protease inhibitor that does not increase serum bilirubin. METHODS AND RESULTS: This was a retrospective cohort study of 1020 patients with HIV. The main outcome was time to myocardial infarction or ischemic stroke. Mean follow-up was 6.6±3.4 years, with 516 receiving atazanavir and 504 darunavir. Atazanavirpatients exhibited significantly higher serum total bilirubin (1.7 versus 0.4 mg/dL; P<0.001) and longer mean time to ischemic event (10.2 versus 9.4 years; P<0.001). On Cox regression, atazanavir treatment (hazard ratio [HR], 0.38; 95% CI, 0.21-0.71; P=0.002) and serum bilirubin (HR, 0.60; 95% CI, 0.41-0.89; P=0.011) were independently associated with a lower risk of an ischemic event. Notably, when atazanavir and bilirubin were included together in the Cox regression model, atazanavir lost significance (HR, 0.55; 95% CI, 0.24-1.29; P=0.169) consistent with bilirubin being an intermediate variable on the causal pathway between atazanavir and its effect on cardiovascular disease. Patients on atazanavir also had a significantly lower risk of developing new cardiovascular disease (HR, 0.53; 95% CI, 0.33-0.86; P=0.010) and longer mean time to death (12.2 versus 10.8 years; P<0.001). CONCLUSIONS:Patients with HIV on atazanavir manifest a decreased risk of cardiovascular disease when compared with those on darunavir, an effect that appears to be mediated by serum bilirubin.
Authors: Mohammed Ahmed Akkaif; Abubakar Sha'aban; Arturo Cesaro; Ammar Ali Saleh Jaber; Andrea Vergara; Ismaeel Yunusa; Abubakar Ibrahim Jatau; Mustapha Mohammed; G Saravana Govindasamy; Majed Ahmed Al-Mansoub; Muhamad Ali Sheikh Abdul Kader; Baharudin Ibrahim Journal: Inflammopharmacology Date: 2022-06-14 Impact factor: 5.093
Authors: Laura Saint-Lary; Marc Harris Dassi Tchoupa Revegue; Julie Jesson; Françoise Renaud; Martina Penazzato; Claire L Townsend; John O'Rourke; Valériane Leroy Journal: Front Pediatr Date: 2022-05-23 Impact factor: 3.569