Abstract

Introduction: Hepatitis C and human immunodeficiency virus (HCV, HIV) are associated with cardiovascular disease (CVD). Liver injury is common in HIV and HCV and is associated with pro-atherosclerotic conditions e.g. altered coagulation. We assessed whether liver injury independently predicts CVD risk including among participants without major liver-related co-morbidities. Methods: Participants from the Veterans Aging Cohort Study Virtual Cohort (VACS VC), without CVD at baseline (first clinical visit after 4/1/2003) were included. Liver injury was defined by liver fibrosis index 4 at baseline (FIB4 calculated using age, liver transaminases and platelets) and ICD-9 codes for cirrhosis and hepatic decompensation. Total fatal and non-fatal CVD were assessed using 1) National Death Index cause of death data; 2) VA; 3) VA Fee For Service; and 4) Medicare ICD-9 and procedure codes for acute myocardial infarction, heart failure (HF), coronary heart disease (CHD) and stroke. Follow-up ended after a CVD event, or death, or on 9/30/2012. Cox regression analyses were used to estimate the risk of total CVD, HF, stroke, CHD and AMI by liver injury. Results: Mean (SD) age was 49.6 (9.5) years in this cohort (N=104731, 90% male) followed for a median (IQR) of 7 (3, 9) years. LDL cholesterol and BMI decreased with increasing FIB4 while age increased. African American race, HIV, HCV, HBV, current smoking, type 2 diabetes, alcohol abuse, cocaine use and anemia were more common among participants with FIB4 >1.45 compared to those with FIB4 <1.45. Incident CVD rates increased with increasing FIB4. FIB4 >3.25 or a clinical diagnosis of cirrhosis or hepatic decompensation was independently associated with significantly elevated CVD risk. This association persisted in Veterans without HCV, HBV, HIV, alcohol use disorder and BMI >30 kg/m2. Conclusions: Liver injury is associated with increased risk of CVD. Future studies should assess whether FIB4 improves CVD risk prediction algorithms.

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