HCV, but not HIV, is a risk factor for cerebral small vessel disease

Abstract

Objectives: With the aging of HIV populations, vascular contributions to neuropathogenesis are increasingly important. Indirect analyses of cerebral small vessel disease have been performed, but there have been no direct studies of human brain to elucidate risk factors for arteriolar sclerosis.

Methods: Mean arteriolar wall thickness (sclerotic index, SI) was measured in the deep cerebral white matter of 126 brains (96 HIV+, 30 HIV-). Correlations with SI were performed for age, sex, race, hypertension, hyperlipidemia, diabetes, obesity, cirrhosis, hepatitis C virus (HCV) infection, herpes infection, HIV infection, HIV risk, cocaine use, CD4 count, plasma HIV load, and combination antiretroviral therapy (cART) at the time of death.

Results: Age, hypertension, race, HCV, and cirrhosis were associated with SI; of the HIV variables, only cART at death was associated with SI. To address colinearity, partial correlations were run with HCV and cirrhosis, hypertension and race, and hypertension and age. With HCV controlled, cirrhosis lost significance; with hypertension controlled, age lost significance. For the entire sample, HCV, African American race, and hypertension accounted for 15% of SI variance in multivariate analysis. Each was independently associated with SI, and HCV had the largest effect. For the HIV sample, inclusion of cART in the model increased R (2) to 0.205, with only HCV, hypertension, and cART remaining significant or trend level.

Conclusions: This tissue-based analysis of cerebral arteriolar disease demonstrates that HCV constitutes an independent risk, in addition to African American race, hypertension, and cART. Further study is needed to understand what aspects of HCV and cART contribute to cerebrovascular neuropathogenesis.

Figure. Sclerotic index (SI) calculation

Measurements of the inner diameter (ID) and external diameter (ED) are taken perpendicular to the widest axis of the arteriole (lines separated here for visualization); these are used in calculating the SI = [1−(inner diameter/external diameter)].