Prognosis After Stroke - Clinical Tree

Key Points

Stroke is the second most common cause of death in the world and a leading cause of long-term disability.
In the United States, stroke has declined from the third leading cause of death to the fifth cause of death. Despite this encouraging trend, there is a substantial ongoing race-ethnic and geographic disparity in stroke mortality and other outcomes.
Strokes recur in 6%–13% of patients within the first year; most recurrences will occur within the first 90 days.
Our ability to accurately identify patients at high risk is modest, and most recurrent strokes cannot be explained by traditional risk factors. However, the stroke prediction scales that combine neuroimaging with stroke severity and other clinical information hold promise of being reliable tools in predicting outcomes after stroke and therefore useful in clinical practice.
Early hospital readmissions post stoke are high. Up to 25% of hospital readmissions post stroke occur within 30 days after discharge to home, predominately for recurrent stroke and preventable infections. This fact is an indication of fragmented transition of stroke care after hospitalization and poor coordination of systems of stroke care.
Stroke patients are faced with a great risk of other conditions such as cardiac events, disability and handicap, poor quality of life, depression, cognitive decline, and dementia.
With the population aging, the need for timely and effective secondary prevention strategies is more pressing than ever.

Introduction

Despite tremendous advances in the management of cerebrovascular diseases, stroke continues to be a common and debilitating disease with a great impact on the public health as the second most common cause of death worldwide and a leading cause of long-term disability, as summarized in Chapter 14 .

The global burden of stroke is likely to be substantially underestimated given the consequences of stroke that substantially affect well-being. Overt and occult cerebrovascular disease contributes to the risk of depression, vascular cognitive impairment, and dementia, including Alzheimer disease. Other stroke-related outcomes may be less recognized, including gait disorders and oropharyngeal dysphagia, which all lead to poor quality of life (QOL). The importance of recurrent stroke, functional disability, QOL, depression, and dementia after stroke will increase as more patients experience and survive a first stroke. The success of secondary stroke prevention programs relies on understanding the frequency and timing of outcomes after stroke, factors associated with increased risks for these outcomes, and implementation of evidence-based preventive interventions and strategies as part of a comprehensive public health approach.

This chapter focuses on the prognosis after ischemic stroke, the most frequent type of stroke, and reviews evidence on ischemic stroke mortality, recurrence, functional disability, QOL, and depression after stroke. Cognitive impairment and dementia after stroke are discussed in Chapter 18 .

Mortality After Ischemic Stroke

There has been a decline in stroke mortality over the past decades. Globally, the age-standardized stroke death rate decreased by 36.2% from 1990 to 2016. Similarly, in the United States, stroke has declined from the third to the fifth leading cause of death, and it is behind diseases of the heart, cancer, chronic lower respiratory disease, and unintentional injuries or accidents. From 2006 to 2016, the age-adjusted stroke death rate decreased by 16.7%, whereas the actual number of stroke deaths increased 3.7% (from 137,119 deaths to 142,142 deaths). Stroke death rates have declined most among people aged 65–74 years (−19.9%), 75–84 years (−20.5%), and 85 years or older (−14%), when compared with those aged 25–34 years (0%), 35–44 years (−9.8%), 45–54 years (−14.4%), and 55–64 years (−9.7%). However, despite the improvements noted since 2006, there has been a recent flattening or increase in death rates among all age groups in the United States. ^, In the United Kingdom, stroke mortality decreased by 55% between 2001 and 2010. The mortality reduction in people younger than 55 years was mainly due to a decrease in case fatality, while in the elderly, reduction in case fatality and decreased event rates contribute equally. A decline in case-fatality rates has been observed in other countries as well. This relative improvement has resulted from implementation of proven therapies such as thrombolysis, endovascular thrombectomy, antiplatelet agents within 48 hours, admission to a stroke unit care, and better control of cerebrovascular risk factors. ^,

Early Mortality After Ischemic Stroke

Risk of death is especially high early after stroke. The 30-day case fatality of stroke varies considerable among countries and ranges between 10% and 37%. ^, ^, In large cohort studies from the United States and Canada, the 7-day case fatality is about 7% ^, and 30-day case fatality ranges from 8% to 15%. In the Northern Manhattan Study (NOMAS), the 30-day mortality decreased from 7.7% in the 1980s (1983–1988) to 5.0% in the 1990s (1990–1997). The 30-day cumulative mortality risk of 5% in NOMAS was lower than reported in other cohorts, likely due to exclusion of prior strokes, a higher proportion of lacunar infarcts, and less severe strokes at onset ( Table 17.1 ). In the Florida–Puerto Rico Registry, 62 hospitals participating in the Get With the Guidelines quality improvement program, a 30-day mortality ranged from 9% to 15% among 44,013 patients admitted with ischemic stroke between 2010 and 2013. In more recent randomized controlled trials assessing the value of antithrombotic therapy with two antiplatelet agents in patients with minor stroke or high-risk transient ischemic attack (TIA), the 90-day mortality ranged from 0.4% to 0.7%. ^, However, randomized controlled trials of mechanical thrombectomy that included patients with more severe neurologic deficits and large vessel occlusion reported 90-day mortality was from 15% to 26%.

TABLE 17.1

Stroke Mortality and Recurrence Rates.

	Stroke Mortality	Stroke Mortality in NOMAS	Stroke Recurrence	Stroke Recurrence in NOMAS
30-day	3%–20%	5%	1%–6%	2%
1-year	20%–35%	16%	5%–25%	8%
5-year	38%–75%	41%	15%–40%	16%

NOMAS, Northern Manhattan Study.

The immediate cause of death in more than 60% of stroke cases is related to the stroke itself. Impaired consciousness on admission, posterior circulation infarcts, and transtentorial herniation are the most important neurologic causes of death during the first week after stroke onset. Thereafter, cardiac causes, pneumonia, pulmonary embolism, sepsis, and other medical complications account for the majority of deaths within the first month after stroke. In the entire stroke population, pneumonia had the highest attributable risk of death, accounting for about a third of all deaths. ^, Pneumonia has been associated with a threefold increased risk of in-hospital death in a study including 14,293 patients hospitalized for acute stroke and with a fourfold increased early stroke mortality in a systematic review and meta-analysis of 87 studies involving 137,817 patients.

Late Mortality After Ischemic Stroke

Longitudinal studies among patients with ischemic stroke have demonstrated that the risk of death at 5-year risk ranged from 40% to 60, including early fatalities. ^, ^, ^, ^, In NOMAS the lifetable cumulative risk of ischemic stroke mortality was 5% at 30 days, 16% at 1 year, and 41% at 5 years after stroke (see Table 17.1 ). The average annual mortality rate in 30-day stroke survivors ranges from 8% to 9%, and the risk of death is two to three times higher than that of the age- and sex-matched general population. ^, A study in Auckland, New Zealand, showed that stroke reduced the life expectancy during 21 years of follow-up, with 70% greater risk of dying than the general population. Similarly, in the Framingham study, stroke survivors for 20 years or more had a greater mortality rate than age- and sex-matched control subjects.

In patients who survive the first few months after stroke, cardiovascular disease increasingly becomes the major cause of death, reflecting the generalized nature of atherosclerosis. ^, ^, ^, In the Copenhagen Stroke Study, stroke was the dominant cause of death during first year, with an absolute risk of 20% versus 5% for cardiovascular disease and 6.5% for nonvascular disease. The subsequent absolute risk of death per year was 2.8% for stroke, 4.5% for cardiovascular disease, and 5.2% for nonvascular disease. Among 30-day survivors from the Oxfordshire Community Stroke Project, 17% died of their first stroke, 16% died as a result of recurrent stroke, 35% died of cardiovascular cause, and 30% died of nonvascular causes. Excess mortality related to cardiovascular disease has also been described among young adults. In the Helsinki Young Stroke Registry, the cause of death was stroke in 21%, cardioaortic and other vascular causes in 36%, malignancies in 12%, and infections in 9% of patients.

Predictors of Death After Ischemic Stroke

For early and late mortality, predictors of death after ischemic stroke may differ ( Table 17.2 ). However, most of them affect both early and late mortality, and there is no a clear distinction between them. Early recognition of predictors of death after stroke onset is of special importance when relevant clinical variables are accounted for within the first 72 hours after a stroke. Although the prediction of stroke outcome could probably be improved by including variables that are assessed later, the practical value would be limited, as the prediction cannot be given as early. In addition, a development of early prediction models taking into account only variables that are evaluated within the first 24 hours after onset would be important for acute stroke interventional clinical trials. Furthermore, now that the management approach for acute stroke is very active, knowledge about predictors of early fatality is essential for optimizing stroke survival strategies.

TABLE 17.2

Definite and Potential Predictors of Death and Poor Outcome After Ischemic Stroke.

	Definite Predictors	Potential Predictors
Demographics	Age	Sex Race-ethnicity Socioeconomic status Region, country
Clinical parameters	Initial severity of stroke (NIHSS) Decreased consciousness Infarct size Large hemispheric or basilar syndrome Ischemic stroke subtype Fever Hypertension Atrial fibrillation Diabetes Congestive heart failure	Other cardiac disease Previous stroke Prestroke disability Prestroke depression Prestroke dementia Obstructive sleep apnea
Lifestyle parameters	Smoking Alcohol Obesity/diet
Biochemical biomarkers	Hyperglycemia C-reactive protein	Cholesterol Erythrocyte sedimentation rate Fibrinogen White blood cell count Uric acid/creatinine Microalbuminuria/albumin–globulin ratio LpPLA2 Homocysteine
Neuroimaging markers		White matter disease Silent brain infarcts Microbleeds
Systems of health care		Access to care Emergency response Telemedicine

LpPLA2, Lipoprotein-associated phospholipase A2; NIHSS, National Institutes of Health Stroke Scale.

Age, Sex, and Race-Ethnicity

Nonmodifiable factors such as age, sex, and race-ethnicity are important determinants of stroke outcomes. Age is an independent prognostic factor of both early and late stroke mortality. Age has a significant role in the cause of death after a recurrent stroke, with a greater proportionate mortality attributable to recurrent stroke rather than cardiac causes of death. Elderly patients have a higher risk of subsequent in-hospital complications after stroke and therefore lower chances of recovery from stroke. In the Get With The Guidelines Stroke (GWTG-S) program, older stroke patients were 27% more likely to die in hospital for each 10-year increase in age. The proportional benefit of acute interventions such as intravenous thrombolysis and endovascular thrombectomy are similar for patients aged older than 80 years compared with younger patients; thus age should not be considered a contraindication in these settings.

Women have worse outcomes after stroke than men. Higher case-fatality in women was shown in the International Stroke Outcomes Study (INSTRUCT) with a crude mortality rate ratio of 1.35 at 1 year and 1.24 at 5 years. However, after adjustment for age, prestroke functional status, stroke severity, and presence of atrial fibrillation (AF), sex differences were reversed. Similarly, the International Stroke Trial (IST) reported a higher crude stroke case fatality in women at 14 days and 6 months, which disappear after adjustment of covariables, suggesting that baseline differences in age, stroke characteristics, and risk factors may account for much of the observed sex differences in case fatality. In the GWTG-S program among 383,318 acute ischemic stroke patients from 1139 US hospitals, women consistently received less care and had higher crude in-hospital mortality compared with men (6.0% vs. 5.2%). This sex-specific difference in stroke survival was modified by age. Younger than the age of 45 years, stroke mortality for women and men is similar, but women aged 45–74 years have about 20%–35% lower risk of stroke mortality than do men. This benefit for women declines in older age groups, such that women aged 85 years and older have 12%–14% higher mortality than men. In addition, women have significantly greater activity and functional limitations, lower health-related QOL (HRQOL), and higher incidence of depression after stroke. ^, Further studies are needed to specifically explore reasons for sex-specific differences in stroke outcomes and plan effective interventions to reduce these sex-specific disparities.

Despite a decline in age-adjusted stroke death rates among all racial-ethnic groups, age-adjusted stroke death rates have remained higher in blacks compared with whites. In the United States the age-adjusted stroke death rate for non-Hispanic blacks aged 45 and older is 30%–68% higher than other race-ethnicity groups. In the GWTG-S from 2003 to 2008, black patients had greater in-hospital stroke mortality relative to white patients and received fewer evidence-based care processes than white or Hispanic patients. In the Cardiovascular Health Study (CHS) cohort of patients 65 years of age or older, blacks had a greater risk of death after ischemic stroke than other groups. In a cohort of veterans with stroke living in the southeastern United States, non-Hispanic black patients had significantly higher mortality rates than did non-Hispanic whites 38 months after stroke. In the REasons for Geographic and Racial Differences in Stroke (REGARDS) national cohort study among 27,744 patients enrolled between 2003 and 2007, national patterns of black-white and regional disparities in stroke incidence were similar to those for stroke mortality. In NOMAS, 5-year cumulative lifetable mortality estimates after stroke differed only slightly among the three race-ethnic groups. Despite similar overall stroke mortality rates between race-ethnic groups in NOMAS, a higher incident stroke-related early mortality among Caribbean Hispanics was observed. In the GWTG-S data linked with Medicare claims set among 200,900 stroke patients, black and Hispanic patients had greater long-term mortality than white and Asian patients, even after adjustment for stroke severity, other prognostic variables, and hospital characteristics.

Disparities in the prevalence of stroke risk factors (e.g., hypertension, diabetes mellitus, and AF) and socioeconomic status between black, Hispanic, and white patients may, in part, explain the disproportionate mortality rates between different race-ethnicity groups after stroke. However, in the United States the majority of the excess burden of stroke mortality is borne by relatively young black people and by black people living in the southeastern states. ^, ^, Further studies are needed to determine how much of the race-ethnic disparities in stroke mortality may be explained by differences in stroke risk factors and ischemic stroke subtype as well as in differences in socioeconomic status, access to health care, social determinants of health, and deficiencies in the systems of stroke health care. (See Chapter 15 , Howard et al.)

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