Causes of death by level of dependency after ischemic stroke

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By Douglas J Lanska MD MS MSPH

Article under review: Slot KB, Berge E, Sandercock P, Lewis SC, Dorman P, Dennis M; Oxfordshire Community Stroke Project; Lothian Stroke Register; International Stroke Trial (UK). Causes of death by level of dependency at 6 months after ischemic stroke in 3 large cohorts. Stroke 2009;40(5):1585-9.

Background: Although functional status 6 months after a stroke impacts on long-term survival (Slot et al 2008), there is little information on how a person's degree of disability impacts on causes of death after a stroke.

Purpose: To assess the impact of functional status 6 months after an ischemic stroke on the cause of death.

Methods: The authors used data from 3 large cohorts of patients with ischemic stroke from the United Kingdom: the Oxfordshire Community Stroke Project, the Lothian Stroke Register, and patients from the United Kingdom enrolled in the First International Stroke Trial. Ischemic stroke was diagnosed using a combination of clinical criteria and brain imaging to exclude intracerebral hemorrhages and conditions mimicking stroke. Level of dependency was determined with a modified Rankin scale score or "2 simple questions." Patients were considered functionally dependent if their modified Rankin scale score was at least 3 (ie, at least moderate disability, requiring some help but able to walk unassisted) or if they reported needing help performing daily activities within the previous 2-week period. Patients who survived at least 6 months were flagged at the National Health Service Office for National Statistics, and upon the death of a patient in these cohorts a copy of the death certificate was forwarded to the investigators. The authors categorized causes of death into 2 groups: "stroke-related" causes of death and "other" causes of death.

Results: During the study period in the 3 cohorts, 5961 of 7710 patients (78%) with ischemic stroke survived for at least 6 months. The primary cause of death in patients who were categorized as having died from stroke-related causes was (not surprisingly) most often stroke (67%), with pneumonia (12%), and cardiac causes (9%) being the other diagnoses with significant numbers of cases. Compared to independent patients, functionally dependent patients were statistically significantly more likely to die of stroke (relative risk 1.7) or pneumonia (relative risk 1.7) but, somewhat paradoxically, were less likely to die of pulmonary embolism (relative risk 0.5) and were also less likely to die of cancer (relative risk 0.6). [Although there was a statistically significantly lower risk of pulmonary embolism in dependent patients, this curious result was based on only a small number of cases attributed to pulmonary embolism (n=11), and it is not clear whether there was a bias in the classification of such cases]. Stroke-related causes of death were considered present in half (49%) of the functionally dependent patients, but in less than one third (29%) of the functionally independent patients; compared to independent patients, functionally dependent patients had a relative risk of 1.7 of dying from a stroke-related cause. Multivariate regression analyses confirmed that dependent patients were significantly more likely to die of stroke-related causes than independent patients.

Conclusions and commentary: Patients who are functionally dependent 6 months after an ischemic stroke are more likely to die of "stroke-related" causes than are those who are functionally independent 6 months after an ischemic stroke.

The authors relied on death certificates to assess the causes of death. In the absence of guidelines, neurologists vary considerably in how they classify causes of death in patients who die after a stroke, but with precise rules the interrater agreement in causes of death improved significantly (Halkes et al 2006). Apparently, because of these issues, the authors utilized a simplified 2-category classification scheme: "stroke-related" causes of death and "other" causes of death. Still, there is likely to be even more variation in the reporting of causes of death in the regular medical care setting where multiple individuals including neurologists, internists, family practitioners, surgeons, and coroners are responsible for completion of death certificates on such patients. It is also not clear whether there may be a systematic bias toward recording stroke-related causes of death more often for patients who were functionally dependent after a stroke than for those who were functionally independent because the stroke-induced dependency is a constant reminder of the prior stroke event.

Finally, the authors did not give values for the survival times of the patients who were dependent and independent at 6 months, nor did they consider survival time in their statistical analyses. It seems likely that the cause of death is less likely to be indicated as "stroke-related" on a death certificate or elsewhere the longer the patient survives from the onset of the stroke. Because the dependent and independent patients are known to have different survival times, the difference measured in stroke-related causes of death as a function of dependency at 6 months may in fact be a crude surrogate for relative survival time.