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HIV Independently Raises Risk of Ischemic Stroke in 4300-Person US Study
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19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
The association between higher HIV load and stroke suggested to the researchers that "poorer virologic control and associated inflammatory and immunologic sequelae may increase stroke risk." The investigators called for more research to examine the higher stroke risk in younger HIV-positive people and in women with HIV......"aggressive risk modification should be targeted by medical providers for stroke prevention."
Mark Mascolini
HIV infection boosted the risk of ischemic stroke 21% regardless of other stroke risk factors in a US study [1]. HIV made stroke 76% more likely in women, but HIV did not independently raise stroke risk in men.
Because the higher stroke risk with HIV persisted after statistical adjustment for common stroke risk factors, Boston researchers suggested that "stroke risk in the HIV population is attributable, in part, to factors other than established stroke risk factors."
The proportion of ischemic strokes attributed to people with HIV rose in the United States from 1997 to 2006 [2], but stroke risk had not been directly compared in people with and without HIV until this analysis of 4308 HIV-positive people in Boston's Partners HealthCare System and 32,423 HIV-negative people in the same system matched by age, gender, and race. Follow-up continued until the first ischemic stroke or until the end of 2009.
Age averaged 41.6 years in the HIV group and 40.8 in HIV-negative controls (P < 0.001). Women accounted for one third of the study group. Just over half of the group was white, 21% were black and 17% Hispanic. Significantly higher proportions in the HIV group had hypertension (37% versus 31%), diabetes (22% versus 15%), abnormal lipids (40% versus 30%), structural heart disease (16% versus 10%), and acute myocardial infarction (8% versus 5%) (P < 0.001 for all comparisons). A significantly higher proportion of people with HIV smoked (48% versus 30%, P < 0.001) and used warfarin (6% versus 5%, P = 0.004), and a marginally higher proportion of HIV-positive people used aspirin (20% versus 19%, P = 0.07).
Among people with HIV, 67% had used a protease inhibitor and 56% a nonnucleoside. Current and nadir CD4 count averaged 252 and 317, and 73% had a viral load below 400 copies.
Through 233,700 person-years of follow-up, stroke incidence was significantly higher with than without HIV (5.27 versus 3.75 per 1000 person-years, P < 0.001). Among women stroke incidence with and without HIV was 5.02 versus 2.31 per 1000 person-years (P
Overall, people with HIV had a 21% higher risk of ischemic stroke in an analysis accounting for demographic and stroke-related risk factors (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.01 to 1.46, P = 0.043). Among women, HIV hoisted stroke risk 76% (HR 1.76, 95% CI 1.24 to 2.52, P = 0.002). But HIV infection did not independently raise stroke risk among men (HR 1.05, 95% CI 0.84 to 1.32, P = 0.639).
Other factors independently associated with a higher stroke risk in this analysis were hypertension (HR 1.22, 95% CI 1.04 to 1.44, P = 0.013), ever versus never smoking (HR 1.28, 95% CI 1.12 to 1.47, P < 0.001), structural heart disease (HR 2.25, 95% CI 1.91 to 2.65, P < 0.001), atrial fibrillation/flutter (HR 1.34, 95% CI 1.06 to 1.70, P = 0.014), and each additional year of age (HR 1.07, 95% CI 1.06 to 1.08, P < 0.001). Three factors independently lowered the risk of stroke: abnormal lipids (HR 0.71, 95% CI 0.61 to 0.83, P < 0.001), aspirin use (HR 0.77, 95% CI 0.66 to 0.91, P = 0.002), and warfarin use (HR 0.68, 95% CI 0.53 to 0.88, P = 0.003).
An analysis stratified by age determined a higher incidence rate ratio for stroke with HIV in 40-to-49-year-olds, 30-to-39-year-olds, and 18-to-29-year-olds but not in any group 50 or older.
An analysis focused only on people with HIV did not find that gender independently affected stroke risk. Six factors did independently raise or lower stroke risk in this analysis:
Raised stroke risk:
-- Each year of age: HR 1.06, 95% CI 1.03 to 1.09, P < 0.001
-- Each 10-fold higher viral load: HR 1.10, 95% CI 1.04 to 1.17, P = 0.001
-- Atrial fibrillation: HR 3.15, 95% CI 1.26 to 7.87, P = 0.014
-- History of central nervous system infections or malignancy: HR 2.75, 95% CI 1.26 to 6.03, P = 0.011
Lowered risk of stroke:
-- Nonnucleoside use (versus no nonnucleoside use): HR 0.38, 95% CI 0.19 to 0.76, P = 0.006
-- Viral load below 400 copies: HR 0.45, 95% CI 0.25 to 0.81, P = 0.008
Because the study confirmed the impact of traditional stroke risk factors and many such factors are prevalent in HIV-positive people, the researchers suggested "aggressive risk modification should be targeted by medical providers for stroke prevention."
But they added that because the increased stroke risk in HIV-positive people persists even after adjustment for common stroke risk factors, variables other than established risk factors may affect people with HIV.
The association between higher HIV load and stroke suggested to the researchers that "poorer virologic control and associated inflammatory and immunologic sequelae may increase stroke risk." The investigators called for more research to examine the higher stroke risk in younger HIV-positive people and in women with HIV.
References
1. Chow F, Regan S, Fesk S. HIV is an independent risk factor for ischemic stroke: US health care system. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 820. http://www.retroconference.org/2012b/PDFs/820.pdf.
2. Ovbiagele B, Nath A. Increasing incidence of ischemic stroke in patients with HIV infection. Neurology. 2011;76:444-450. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034413/?tool=pubmed.
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