July 7, 2008 — Compared with control subjects, patients who had sudden loss of hearing had a 1.64-fold greater risk for stroke during a 5-year period, after adjustment for confounding factors, in a preliminary study from Taiwan, published in the June 26 Online First issue of Stroke.

Using data from a national database, the investigators compared the incidence of stroke during a 5-year period among 1423 patients hospitalized for an acute episode of sudden sensorineural hearing loss (SSNHL) vs 5692 patients who had been hospitalized for an appendectomy (a surrogate for the general population).

"We suggest that SSNHL patients, in particular those with other vascular conditions or elderly patients, should undergo a comprehensive hematologic and neurological examination to help clinicians identify those who are potentially at risk for stroke in the near future," the group, led by Herng-Ching Lin, PhD, at Taipei Medical University, in Taipei, Taiwan, writes.

"Because approximately half of the strokes occurred more than 2 years after SSNHL onset, routine follow-up examinations should be executed for at least several years after patients are discharged from hospitals for treatment of SSNHL," they add.

Sudden Hearing Loss, Unknown Cause

SSNHL occurs abruptly, developing rapidly within 72 hours, and is a frightening experience, although it has a high spontaneous rate of recovery (40% - 65%), the group writes.

The estimated incidence of SSNHL is 5 to 20 cases per 100,000 people in Taiwan and in Western countries, Dr. Lin told Medscape Neurology & Neurosurgery. Possible causes may include virus or bacterial infection, circulatory disturbance in the area of the anterior inferior cerebellar artery, acoustic tumor, perilymphatic fistula, environment, diet, or weather, he added.

A few investigators suggest that SSNHL could be an early sign of stroke, but to the best of their knowledge, no study investigated the incidence or risk for cerebrovascular diseases after the onset of sudden hearing loss, the group writes.

They aimed to investigate this using data from Taiwan's national health insurance program.

The study sample consisted of 2 groups of patients hospitalized in 1998: 1423 patients with a principal diagnosis of SSNHL and 5692 control patients who had an appendectomy (4 patients for every patient with SSNHL).

The subjects were matched by age (< 45 years, 45 - 64 years, 65 - 74 years, and > 75 years) and were observed from an index hospitalization in 1998 until the end of 2003 to determine the incidence of stroke.

At the time of index hospitalization, the patients with SSNHL were significantly more likely than control subjects to have hypertension, diabetes, hyperlipidemia, higher incomes, and residence in the most urbanized areas in northern Taiwan.

Average Stroke Onset Occurred After 2 Years

A total of 180 (12.7%) of the 1423 patients with SSNL and 441 (7.8%) of the 5692 control patients had strokes during the 5-year follow-up.

Patients with SSNHL had significantly lower 5-year stroke-free survival rates than patients with appendectomy (P < .001).

After adjustment for sex, income, level of urbanization, and comorbid medical disorders, the hazard of stroke during a 5-year period was 1.64 times (95% CI, 1.31 - 2.07; P < .001) greater for patients with SSNHL than patients with appendectomy.

The adjusted hazard ratios for stroke during the follow-up periods of 1, 2, 3, and 4 years were 1.94, 1.62, 1.63, and 1.61 times greater, respectively, for patients with SSNHL vs patients with appendectomy.

The average time to the onset of stroke among the patients with SSNHL was 804 (± 624) days after the hospitalization for hearing loss.

"Our findings support the previous report that SSNHL can be an early warning of an impending stroke," the group concludes.

Preliminary Findings, Results Should Be Interpreted Cautiously

Strengths of the study include the large database, the group writes. Limitations include the absence of a clear, universal definition for SSNHL and the lack of database information about extent of hearing loss and hearing recovery, tobacco use, body mass index, and medical history of cardiovascular disease or atrial fibrillation.

"Because this is the first time any association has been suggested, and because there were many limitations in the data, the results need to be interpreted cautiously until additional independent studies are performed," said Dr. Lin, in a press release.

The actual mechanisms contributing to the association between SSNHL and the subsequent development of stroke remain unclear, the group notes. They speculate that SSNHL may share a common etiology with stroke, because recent studies have consistently shown that vs the general population, patients with SSNHL have significantly higher levels of plasma fibrinogen and cholesterol.

This study is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health, Taiwan, and managed by the National Health Research Institutes. The interpretations and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health, or the National Health Research Institutes.

Stroke. Published online June 26, 2008.

Clinical Context

Study Highlights

• The objective of this study was to estimate the risk for the development of stroke among patients with SSNHL during a 5-year follow-up period after hospitalization for acute episodes of SSNHL.
• This study used Taiwan's National Health Insurance Research Database, a nationwide, population-based dataset begun in March 1995, allowing tracking of all medical service utilization history for all citizens.
• The study cohort consisted of all 1423 patients hospitalized in 1998 for sudden hearing loss. Patients with readmissions were excluded.
• As a surrogate for the general population, the control cohort consisted of 5692 patients hospitalized in 1998 for appendectomy. These patients were matched to control subjects, 4:1, by age.
• Patients were tracked from hospitalization in 1998 until the end of 2003.
• After adjustment for possible confounding factors, Cox proportional hazard regressions allowed determination of 5-year stroke-free survival rates.
• During the 5-year follow-up period, 621 (8.7%) patients had strokes, including 180 (12.7%) of patients with SSNHL and 441 (7.8%) of control patients.
• After adjustment for other factors, patients with hypertension, diabetes, and hyperlipidemia had a greater likelihood of stroke, but patient income and level of urbanization were not significantly related to stroke.
• Compared with control patients, patients with SSNHL had a 1.64-fold greater hazard of stroke during the 5-year follow-up period (95% CI, 1.31 - 2.07; P < .001), after adjustment for other variables.
• This association was totally independent of initial comorbid hypertension, diabetes, hyperlipidemia, renal disease, and demographic factors.
• Approximately half of the strokes occurred 2 years after onset of SSNHL. Only 12.2% of strokes occurred within 3 months after SSNHL onset, 31.4% occurred in the first year, and half (50.6%) occurred in the first 2 years.
• For patients with SSNHL vs control patients, adjusted hazard for stroke was 1.94 times greater by year 1, 1.62 times greater by year 2, 1.63 times greater by year 3, and 1.61 times greater by year 4 (P < .001 for each).
• The investigators suggest that SSNHL can be an early warning sign of impending stroke and that patients with SSNHL should undergo a comprehensive hematologic and neurologic examination to help identify those potentially at risk for stroke in the near future, and these should continue for at least several years after patients are discharged from hospitals for treatment of SSNHL.
• Limitations of the study include lack of clear universal definition for SSNHL and lack of data regarding severity of hearing loss, extent of hearing recovery, tobacco use, body mass index, and a history of cardiovascular disease and atrial fibrillation.

Pearls for Practice

• Patients with SSNHL vs control patients had a 1.64-fold greater hazard of stroke during the 5-year follow-up period, after adjustment for other variables. This association was totally independent of initial comorbid hypertension, diabetes, hyperlipidemia, renal disease, and demographic factors.
• Approximately half of the strokes occurred 2 years after onset of SSNHL. Only 12.2% of strokes occurred within 3 months after SSNHL onset, 31.4% occurred in the first year, and 50.6% occurred in the first 2 years.

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