By Liz Highleyman

Chronic hepatitis C has been linked to numerous co-existing conditions including metabolic abnormalities and cardiovascular disease. While researchers often include strokes when counting cardiovascular events, the association between HCV infection and stroke in particular has not been established.

Mei-Hsuan Lee from National Taiwan University and colleagues performed a study to assess the risk of lethal cerebrovascular diseases -- or problems related to blood flow in the brain -- associated with chronic HCV infection.

Strokes are caused by interruption of the brain's blood supply, either due to blockage (ischemic stroke) or bleeding (hemorrhagic stroke). Blockage can occur when blood clots triggered by atherosclerosis -- especially buildup of plaque in the carotid arteries that supply the brain -- break off and lodge in small blood vessels.

This community-based prospective cohort study enrolled 23,665 Taiwan residents age 30-65 during 1991-1992. Of these, 1307 people, or about 6%, were HCV seropositive. At the time of enrollment participants were interviewed in person using structured questionnaires and provided blood samples for testing. They were followed through 2008, and deaths due to cerebrovascular causes were confirmed using National Death Certification data.

Results

	A total of 255 cerebrovascular deaths were recorded during 382,011 person-years of follow-up.
	The cumulative risk of cerebrovascular deaths was 1.0% for HCV seropositive participants versus 2.7% for HIV seronegative individuals, a significant difference (P < 0.001).
	After adjusting for known stroke risk factors, the hazard ratio of cerebrovascular death for people with HCV was 2.18, or about twice the risk.
	Risk of stroke rose with higher HCV RNA levels:
	Hazard ratio 1.40 for undetectable viral load; Hazard ratio 2.36 for low viral load; Hazard ratio 2.82 for high viral load.
	There was no significant association, however, between stroke risk and HCV genotype.

Based on these findings, the study authors concluded, "Chronic HCV infection is an independent risk predictor of cerebrovascular deaths showing a biological gradient of cerebrovascular mortality with increasing serum HCV RNA level."

"The frequency and intensity of infection might be associated with the progression of atherosclerosis," they suggested in their discussion. "Infection affects atherothrombosis [clotting] by triggering a cascade of immune responses and inflammatory stimuli either locally within vascular tissue or systemically through inflammatory mediators."

"Elevated serum HCV RNA level was associated with an increased risk of cerebrovascular death, suggesting that individuals with an active HCV infection may trigger a stronger inflammation response by host-virus interaction leading to atherothrombosis," they continued. "Whether patients with persistent HCV infection had increased circulating levels of inflammation markers such as C-reactive protein or endothelial progenitor cells may provide insights on the mechanisms of HCV infection and cerebrovascular disease."

Investigator affiliations: Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan; Department of Cardiology, Cardinal Tien Hospital, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan; Department of Microbiology, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

2/1/11

Reference
M-H Lee, H-I Yang, C-H Wang, and others. Hepatitis C virus infection and increased risk of cerebrovascular disease. Stroke 41(12): 2894-2900 (Abstract). December 2010.