People with hepatitis C are at higher risk of dying from cardiovascular disease suffering a stroke or developing cardiovascular problems than people with similar risk factors for heart disease who do not have hepatitis C, a meta-analysis of published studies has shown.
The findings, published in the January 2016 edition of Gastroenterology, come from a meta-analysis of 22 epidemiological studies conducted by Salvatore Petta and colleagues at the University of Palermo, Italy.
Studies have produced inconsistent findings previously regarding the risk of cardiovascular disease in people with hepatitis C. These studies have suffered from insufficient numbers or weaknesses in design, limiting the strength of any conclusions. Researchers at the University of Palermo set out to pool data from published studies in order to produce more robust estimates of the risks of heart attack and stroke in people living with hepatitis C.
The researchers identified 22 studies which reported fully on the cardiovascular outcomes of people with hepatitis C in comparison to those of people without hepatitis C.
Their meta-analysis considered three outcomes:
Cardiovascular mortality (death from any cardiovascular cause)
Carotid atherosclerosis as measured by carotid plaques (plaques, composed of cholesterol, calcium and fibrous tissue, build up in the arteries and their presence raises the risk of heart attack and stroke)
Stroke or heart attack (cerebrocardiovascular events).
Cardiovascular mortality
Cardiovascular mortality was calculated from the results of three cohort studies which followed 68,365 people and observed 735 deaths. The pooled estimate showed a 65% increase in the risk of dying from a cardiovascular cause for people with hepatitis C (odds ratio 1.65, 1.07-2.56, p = 0.02). These studies were inconsistent in their recording of risk factors so it was not possible to come up with a pooled estimate which controlled for the prevalence of risk factors.
Carotid atherosclerosis
The prevalence of carotid atherosclerosis was calculated from nine case-control studies, combining data from 9083 people, 1979 had carotid artery plaques. The pooled estimate showed that people with hepatitis C were almost two-and-a-half times more likely to have a carotid plaque (odds ratio 2.27, 95% CI 1.76-2.94, p < 0.01). HCV had a greater effect on the prevalence of carotid plaques when over one in five people in the study population smoked (OR 2.66, 95% CI 1.96-3.61, p < 0.001). The impact of HCV on carotid plaques was not statistically significant in populations where smoking was less common, showing that smoking exacerbates any effect of hepatitis C on the development of cardiovascular disease, unsurprisingly.
Cerebrocardiovascular events
The impact of hepatitis C on the incidence of cardiovascular events, including stroke, was calculated from eight studies, combining data from 390,602 people and 18,388 events. Hepatitis C increased the risk of any event modestly, by 30% (odds ratio 1.30, 95% CI 1.10-1.55, p = .002), and the effect was similar when the analysis was confined to stroke alone (35%) (odds ratio 1.30, 95% CI 1.03-1.82, p = .05). The risk was significantly higher in studies where the background rate of diabetes was above 10%, where the prevalence of high blood pressure was above 20% or where the average age of the study population was above 50 years.
The authors note that even after allowing for the well-established risk factors for heart disease – diabetes, high blood pressure and smoking – the risk of death, cardiovascular disease and carotid artery disease was still elevated in people with hepatitis C. Indeed, they describe the effect of hepatitis C on cardiovascular risk as “especially pronounced” in populations where diabetes, high blood pressure or smoking are common.
The authors suggest that the metabolic abnormalities common in people with hepatitis C may provide one explanation for the increased risk, but they also point to recent evidence showing that hepatitis C promotes inflammation, which contributes to the development of cardiovascular disease.
Petta S et al. Hepatitis C virus infection is associated with increased cardiovascular mortality: a meta-analysis of observational studies. Gastroenterology 150: 145-55, 2016.