Chronic Hepatitis C Virus Infection, a New Cardiovascular Risk Factor?

Fanny Domont; Patrice Cacoub

Disclosures

Liver International. 2016;36(5):621-627. 

In This Article

HCV Infection and Ischaemic Heart Disease

In 2009, an American study showed more cardiovascular events in HCV-seropositive patients than in those who were seronegative (6.2% vs 4%) (Table 3). Similar results were found for heart failure (7.6% vs 2.9%; P < 0.01) and overall mortality (9.3% vs 4.2%; P < 0.01).[35] After adjustment for common cardiovascular risk factors, HCV seropositivity remained independently associated with the risk for heart failure events. In a case–control study, HCV infection emerged as an independent factor of proven coronary artery disease (adjusted OR = 4.2; 95% CI: 1.4–13.0).[11] A recent retrospective Italian study found an increase in ischaemic heart events in HCV-seropositive patients compared to those who were seronegative (22% vs 13%; P < 0.031).[20] HCV-seropositive American veterans showed an increased risk of coronary artery disease [HR 1.25 (95% CI: 1.2–1.3)] although HCV-seropositive vs HCV-seronegative patients had lower levels of plasma cholesterol (175 ± 41 vs 198 ± 41 mg/dl), LDL cholesterol (102 ± 37 vs 119 ± 38 mg/dl) and triglycerides (144 ± 119 vs 179 ± 151 mg/dl) (all P < 0.001).[36] In a UK study, HCV-seropositive patients vs HCV-seronegative patients had less dyslipidemia but higher median glycated haemoglobin levels (6.2% vs 5.7%; 95% CI: 0.3–0.8) and more frequent metabolic syndrome (28% vs 18%; relative risk 1.6; 95% CI: 0.8–3.0).[37] Several inflammatory pro-atherosclerotic biomarkers were increased in HCV-positive vs HCV-negative patients, including C-reactive protein, soluble intracellular adhesion molecule 1 (slCAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble E-selectin. A recent American study has established that in an HCV-positive cohort (1434 persons), patients with detectable HCV RNA had a significantly higher incidence of coronary heart disease events compared with patients HCV antibody positive with no detectable RNA (5.9% vs 4.7%, P = 0.04). In multivariate analyses, both HCV antibody positivity (OR 1.32 95% CI: 1.09–1.60) and HCV RNA positivity (OR 1.59 95% CI: 1.13–2.26) were independent risk factors for incident coronary heart disease.[38] A Japanese study showed elevated concentrations of NT-pro BNP in 42 of 42 patients with HCV antibodies, at a mean level significantly greater than in 1276 patients without HCV antibody (10000 ± 5860 vs 2508 ± 160 pg/ml, respectively; P < 0.0001). This result suggested that HCV infection may be an important cause of myocarditis and heart failure.[9]

Myocardial perfusion was assessed using thallium-201 scintigraphy in HCV-seropositive subjects before and after antiviral treatment.[39] A total of 217 Japanese patients with chronic hepatitis C, without previously known cardiac involvement, underwent thalium-201 myocardial scintigraphy before and after HCV treatment (Interferon/ribavirin). A severity score of ischaemic cardiac involvement was defined by the sum of myocardial defects visualized on the scintigraphy. Before any antiviral treatment, 87% of patients had an abnormal thallium-201 scintigraphy severity score. The severity score was closely correlated with the type of virological response. In patients with SVR, there was a lasting reduction in the severity score. In patients with virological relapse, there was an initial decrease in the severity score followed by an increase in the score during virological relapse. Patients who were non-responders to the antiviral treatment maintained a high severity score throughout this study. Another severity score based on angiographic coronary data was used (modified scoring system of Reardon et al.[40]) to compare HCV-seronegative subjects to seropositive subjects with similar characteristics (i.e. gender, age, common cardiovascular risk factors). The Reardon score is calculated by attributing 1–4 points according to the degree of occlusion (<50%, 50–74%, 75–100%) of proximal coronary arteries. The Reardon score was higher in HCV seropositive than in seronegative patients (8.75 ± 1.69 vs 6.01 ± 1.80; P < 0.001). The levels of C-reactive protein were higher in seropositive vs seronegative patients (2.073 ± 1.358 vs 1.190 ± 1.005 mg/L; P < 0.001), as were those of fibrinogen (5.323 ± 1.567 vs 4.104 ± 1.648 g/L; P < 0.001). Of note, American veterans with HIV-HCV coinfection showed an increased risk of coronary artery disease compared to patients with HIV mono-infection [HR 2.45 (95% CI: 1.02–3.52)] and non-infected subjects [1.46 (95% CI: 1.03–2.07)].[41]

Some data for the risk of coronary artery disease in HCV-infected patients appear to be more discordant. In 126 000 HCV-seropositive veterans paired for age with 126 000 HCV-seronegative veterans, there was a lower prevalence of coronary artery disease in patients with hepatitis C compared to non-infected patients (8.3% vs 10.8%, P = 0.001).[42] However, the subjects' comorbidities prevalence and characteristics were significantly different between the two groups and the follow-up period was relatively short (4 years). A similar methodology was used by the same group in 2009 in another study with contradictory results.[36] Explanations given for this contradiction were the greater frequency of HBV co-infection and the fact that tobacco use, obesity and lipid levels were not taken into account.[33] A retrospective study in the UK showed that the incidence rate of myocardial infarction did not increase in HCV-infected patients.[37] A review of very recent American literature did not confirm the association between hepatitis C and coronary artery disease.[43] An American cohort of young men from the US Military included 292 patients with coronary artery disease and 290 patients without (controls). Some patients were HCV antibody positive, 7.6% in the coronary artery disease group vs 9.8% in controls. In multivariate analysis adjusted for age, gender, smoking, hyperlipidemia, race/ethnicity, education level, marital status, hypertension, overweight/obesity and work stress, no significant association between HCV seropositivity and coronary artery disease was observed (adjusted OR 0.94; 95% CI: 0.52–1.68).[44] An American study has showed that in HCV-infected patients with stable liver function, the rates of major adverse cardiac events (i.e. death, myocardial infarction, target-vessel revascularization) and of all-cause mortality were similar in the Bare-Metal Stents and Drug Eluting Stent groups.[45]

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