Assessing Healthcare Outcomes of Hepatitis C Virus (HCV) Positive Patients Counseled for Cardiovascular Disease Risk Factors

Cardiovascular diseases (CVD), including atherosclerosis, are now the leading causes of mortality both in the United States and globally. Unfortunately, the major risk factors that have been targeted by public health programs are all behavioral, and have not met with enough success. Hence, there is an acute need for more tangible interventions that afford new options to reduce disease burden from atherosclerosis.

While the association of Hepatitis C virus (HCV) infection with life threatening complications such as liver cirrhosis and hepatocellular carcinoma (HCC) is well established, the recent discovery of HCV as a risk factor for atherosclerosis presents a new target for CVD control. In the largest epidemiological study of HCV and cardiovascular disease to date, HCV positive individuals were determined to have a significantly higher incidence of myocardial infarction, congestive heart failure, and corrective procedures for coronary artery disease including bypass grafting and angioplasty (1). Subsequent meta- analyses have lent increasing support to this relationship, showing adjusted odds ratios (OR) of 1.76 - 2.24 of carotid atherosclerosis in HCV+ patients (2,3).

The epidemiological evidence supporting the link of HCV and atherosclerosis has been further supported by bench research elucidating the role of HCV in vascular cytotoxicity and systemic inflammation. HCV viral replication has been shown within carotid artery plaques (4), as a result of viral endocytosis through the LDL receptor (5). HCV promotes intracellular oxidative stress, monocyte recruitment, and subsequent endothelial dysfunction leading to the promotion of atherosclerosis (6). In addition, HCV infection leads to a systemic inflammatory state promoting the acceleration of arterial vascular disease (7,8). Robust evidence now supports HCV as strongly pro-atherogenic (2,9), a relationship that is irrespective of HCV genotype or degree of histological liver pathology (10).

Viral RNA load of Hepatitis C has been shown to directly correlate with the atherosclerotic burden (10,11). HCV RNA levels are associated with advanced phase carotid plaques and carotid intima-media thickness (10). In addition, HCV RNA has been found in direct association with serum fibrinogen and C-reactive protein levels, which in turn were independently associated with carotid atherosclerosis (10). Together, such data suggest that managing HCV viral load will, in turn, control the cardiovascular manifestations of this disease.

Similar to atherosclerotic burden, higher viral loads correlate well with increased risk of cardiovascular and cerebrovascular associated mortality (2,9,11). Recent meta-analyses show the HCV+ population with an adjusted OR of 1.3 to 1.97 for cerebrovascular incidents (12) and an adjusted OR of 1.65 for death due to cardiovascular disease (3). Of importance, combination ribavirin and interferon therapy has been shown to decrease such non-hepatic mortality as well as incidence of stroke in HCV+ patients (13,14). Thus, prompt and effective management of HCV can lead to suppression of viral loads, which can result in decreased mortality secondary to cardiovascular events (9,10).