Chronic hepatitis C virus (HCV) infection is associated with an important early warning sign of cardiovascular disease, investigators from the Multicenter AIDS Cohort Study (MACS) report in the online edition of the Journal of Infectious Diseases. Both HIV and HCV infections were independently associated with hardening of the coronary artery, but there was no evidence that HIV/HCV co-infection worsened atherosclerosis. After controlling for HIV infection and other factors associated with heart disease, a consistent relationship was present between chronic HCV infection and coronary artery plaque formation.
“This is the largest study to date to demonstrate that chronic HCV [CHC] infection is associated with subclinical coronary atherosclerosis, an important predictor of future cardiovascular disease [CVD],” write the authors. “The association of CHC with plaque remained significant after adjustment for…recognized CVD risk factors and was independent of HIV infection.”
Both HIV and HCV can cause systemic inflammation and increased immune activation, risk factors for hardening of the arteries. HIV infection has been associated with subclinical arterial disease, but the relationship between HCV infection and atherosclerosis is unclear.
Investigators from the large, on-going MACS study therefore designed a cross-sectional study to evaluate the association between HCV infection and the formation of coronary plaques.
A total of 994 HIV-positive and HIV-negative men (87 with chronic HCV infection) aged between 40 and 70 years who received care before January 2010 were enrolled in the study. All the patients had a coronary CT assessment and 755 also underwent CT angiography. The investigators evaluated the association between chronic HCV and HIV infection and measures of plaque prevalence, extent and stenosis (narrowing of the arteries).
Men with HCV were more likely than HCV-negative men to be HIV-positive (81% vs. 60%), African-American, have low educational attainment, be current smokers, have a history of injecting drug use and to be taking medication for hypertension or diabetes (all differences significant, p < 0.05). Median HCV RNA among the infected men was 2.0x106 iu/ml.
Overall prevalence of coronary artery plaque was significantly higher among men with chronic HCV infection compared to HCV-uninfected men (89% vs. 75%, p = 0.02). Prevalence of non-calcified plaque was also elevated among those with HCV (77V vs. 58%, p < 0.01). However, prevalence did not differ by HCV infection status for coronary artery calcium (CAC) scores, mixed plaque, calcified plaque, or narrowing of the coronary artery by 50% or more.
After taking into account other potential risk factors for arterial disease, both chronic HCV infection and HIV infection were independently associated with prevalence of any plaque (adjusted prevalence ratio [aPR] = 1.26; 95% CI, 1.09-1.45 and 1.12; 95% CI, 1,03-1.22, respectively) and non-calcified plaque (aPR = 1.42; 95% CI, 1.16-1.75 and 1.27; 95% CI, 1.11-1.45, respectively).
Chronic HCV infection (but not HIV) was associated with CAC scores. There was no evidence of an interaction between HCV and HIV; in other words, co-infection did not make prevalence and extent of subclinical coronary atherosclerosis worse.
A higher HCV load was associated with more extensive plaque formation.
The authors’ findings remained robust after taking into account factors such as current injecting drug use, the presence of fatty liver disease, fibrosis, CD4 cell count, HIV load, and the exclusion of individuals with chronic hepatitis B virus (HBV) infection.
“The elevated prevalence of subclinical coronary atherosclerosis among men with chronic HCV infection, especially men with the highest HCV RNA levels, provides further evidence supporting a link between chronic HCV infection and cardiovascular disease,” conclude the authors. “The presence of HCV infection may warrant vigilant cardiovascular risk assessment in these patients.”
McKibben RA et al. Chronic hepatitis C virus infection is associated with subclinical coronary atherosclerosis in the Multicenter AIDS Cohort Study (MACS): a cross-sectional study. J Infect Dis, online edition, 2015.