Update on Stroke Risks

August 28, 2017

Two new studies shed light on risk factors for stroke and MI, and a third suggests neurologic use s for Zolpidem that don’t involve treating insomnia.

New neurology research indicates cirrhosis is linked to increased stroke risk, particularly hemorrhagic stroke, and that herpes zoster infection significantly raises the risks of stroke and MI. And the insomnia drug zolpidem may treat a variety of neurologic disorders.

Cirrhosis is associated with an increased risk of stroke

A retrospective cohort study[1] identified a random 5% sample of 1,618,059 Medicare beneficiaries older than 66 years. 15,586 had cirrhosis. During > 4 years follow-up, 77,268 patients were hospitalized for stroke.
Patients with cirrhosis had an annual stroke incidence of 2.17% vs 1.11% in those without cirrhosis. Stroke risk was 40% higher in patients with cirrhosis, after adjustment for demographic and other stroke risk factors. The magnitude of increased stroke risk with cirrhosis was greater for intracerebral hemorrhage and subarachnoid hemorrhage than for ischemic stroke.

Cirrhosis was weakly associated with non-embolic stroke but not with embolic stroke. The risk for stroke and all individual stroke types was slightly higher for patients with decompensated cirrhosis. Mild liver disease was not associated with stroke. Risk for stroke was similar in patients with alcoholic or nonalcoholic cirrhosis.

The increase in stroke risk may be due to the mixed coagulopathy seen in cirrhosis, which may aggravate vascular risk factors. Also, underlying causes of cirrhosis, such as alcohol abuse, hepatitis C infection, and metabolic disease, may contribute to stroke risk.

These data suggest the link between stroke and cirrhosis is strong.

Patients with newly diagnosed herpes zoster face significantly higher risks of stroke and MI in the first year after infection.[2]

Data for this study came from 519,880 patients followed from 2003 to 2013 National Health Insurance Service database covering the entire Korean population. The risk of composite of CV events including stroke and MI was assessed in 23,233 patients diagnosed with herpes zoster and matched to the same number of controls without herpes zoster using propensity-score matching.

Herpes zoster was associated with a 41% increased risk of composite CV events; a 35% increase in stroke; and a 59% increased risk of MI. The hazard ratios were highest in those 40 years or younger. The risks of stroke and MI were highest in the first year after infection and tended to decrease with time.

Stroke may result after herpes zoster infection due to varicella-zoster virus (VZV) replication adjacent to an artery, leading to subsequent thrombosis and rupture. Other mechanisms may include repeated subclinical VZV reactivation effects on arteries and transaxonal migration of VZV in a centripetal direction, the researchers suggested.

Further research may classify VZV-related stroke as a new category of stroke and use antiviral therapy or vaccination to potentially prevent further strokes in these patients.

Zolpidem has been observed to transiently treat a large variety of neurologic disorders, most often related to movement disorders and disorders of consciousness.[3]

A systematic review was conducted of 67 studies with a total of 557 patients: it included 31 studies that treated movement disorders, 22 studies that treated disorders of consciousness, and 14 studies that treated other neurologic conditions, including stroke, traumatic brain injury, encephalopathy, and dementia.

Many studies were case reports and small interventional trials. The most common dose was 10 mg zolpidem across all the disorders of consciousness studies.

Zolpidem effects were wide ranging. They included improvement on the JFK Coma Recovery Scale–Revised, the Unified Parkinson Disease Rating Scale, and the Burke-Fahn-Marsden Dystonia Rating Scale, and generally lasted 1 to 4 hours. The drug response rate was 18% or higher for the patients with movement disorders, such as Parkinson's disease or dystonia, and was 5%-7% in those with disorders of consciousness.

Zolpidem appears to help restore equilibrium to circuits in the brain, and may be worthwhile, in particular for patients with disorders of consciousness. Those with injury to information processing and arousal areas may see better outcomes.

References
1. Parikh NS, Navi BB, Jesudian A, Kamel H. Association between cirrhosis and stroke in a nationally representative cohort. JAMA Neurol. 2017; Jun 5. doi: 10.1001/jamaneurol.2017.0923
2. Kim M-C, Yun S-C, Lee H-B, et al. Herpes zoster increases the risk of stroke and myocardial infarction. J Am Coll Cardiol. 2017;70(2). DOI: 10.1016/j.jacc.2017.05.015
3. Bomalaski MN, Claflin ES, Townsend W. Zolpidem for the treatment of neurologic disorders. JAMA Neurol. Published online June 26, 2017. doi:10.1001/jamaneurol.2017.1133

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Update on Stroke Risks

Mark L. Fuerst