Stroke

Epidemiology and Pathology

Christopher Moran, Velandai K. Srikanth, Amanda G. Thrift

Stroke Epidemiology

This chapter is concerned with the study of patterns and risk factors associated with stroke and the pathologic changes observed in stroke. The major types of stroke are ischemic stroke (due to cerebral vessel occlusion) and hemorrhagic stroke (due to bleeding from cerebral vessel). In epidemiologic tradition, stroke has been defined as “rapidly developing clinical signs of focal disturbance of cerebral function lasting more than 24 hours (unless interrupted by surgery or death) with no apparent cause other than of vascular origin.”¹ However, this definition has since evolved with the use of modern radiologic techniques (e.g., diffusion-weighted magnetic resonance imaging [DW-MRI]) that are more sensitive to early infarction in patients suffering transient symptoms lasting less than 24 hours. The American Heart Association has recently adopted a position defining ischemic stroke—or central nervous system (CNS) infarction—as “brain, spinal cord, or retinal cell death attributable to ischemia, based on either pathological, imaging, or other objective evidence of focal ischemic injury in a defined vascular distribution, or clinical evidence of focal ischemic injury based on symptoms persisting ≥24 hours or until death, and other etiologies [are] excluded.”² Those who suffer transient sudden focal neurologic symptoms less than 24 hours of presumed vascular origin, but without demonstrable infarction on sensitive brain imaging, are considered as having a transient ischemic attack (TIA). The impact of the these revisions to stroke and TIA definitions on prior and future estimates of prevalence, incidence, mortality, and risk factors have yet to be fully understood.

In the following sections, we summarize the current knowledge about the epidemiology and pathology of stroke, with implications particularly for older adults with frailty.

Burden of Stroke

From a population level, the burden of stroke can be measured in three different ways—by measuring mortality, prevalence, or incidence. Each method has its advantages and limitations.

Stroke mortality figures usually include all individuals with stroke recorded as the primary cause of death on their death certificates. Systematic and long-term collection of these data allows assessment of trends over time and comparisons among countries. Mortality figures are subject to limitations, including imprecision in death certification and incomplete assessment of the overall burden of stroke; between 45% and 60% of people with stroke survive beyond 5 years.³^–⁵

Stroke prevalence studies can be used to assess health in survivors and assist with the planning of community health care resources, but may not provide an accurate reflection of the population burden of stroke because of issues such as selection and survival bias. Carefully conducted stroke incidence studies provide the best source of information on the burden of stroke, allowing a better understanding of the empirical relation among incidence, mortality, and survival. For example, changes in stroke mortality may attributable to changes in stroke incidence, case fatality (reflecting changes to stroke severity or poststroke management), or a combination of both.

Comparison between identically conducted stroke incidence studies in the same population will help determine where the changes have occurred. Such repeat incidence studies are expensive and labor-intensive because of the strict ideal criteria required for their conduct.⁶^–⁹ Because of this, most stroke incidence studies in the past decade were undertaken in high-income countries, but there are several now being carried out in low and middle-income countries. Recent comprehensive reviews of the global burden of stroke summarizes many of these studies and shows some marked differences in stroke burden between high-income and low- and middle-income countries.¹⁰^–¹²

Stroke Mortality

According to the Global Burden of Diseases Study, stroke and ischemic heart disease collectively contributed to 1279 million deaths in 2010, or one in four deaths worldwide, compared with one in five in 1990.¹³ According to the World Health Organization (WHO), stroke is the second most common single cause of death in the world after ischemic heart disease.¹⁴ In 2012, an estimated 6.7 million deaths from stroke occurred worldwide; these deaths comprised approximately 11.9% of all deaths.¹⁴ The contribution of stroke to mortality varies by income level of countries. In 2012, approximately 43% of these deaths occurred in low- to middle-income countries, 55% in upper middle-income countries, and only 22% in high-income countries.¹⁴ The greater number of strokes deaths occurring in low- and middle-income countries than in high-income countries is attributable to their larger population (≈fourfold that of the population in high-income countries).¹⁵

There are now substantial data on time trends in stroke mortality rates from low-, middle-, and high-income countries. In a comprehensive systematic review, Krishnamurthi and Feigin and colleagues have summarized trends in annual mortality rates by age and country income status from 1990 to 2010.¹⁰^,¹¹ They showed that overall, stroke mortality rates declined over this period, irrespective of a country’s income status. The age-adjusted annual mortality rate/100,000 population for ischemic stroke fell significantly from 63.8 (95% confidence interval [CI], 56.5 to 66.0) to 40.3 (95% CI, 38.2 to 43.1) in high-income countries and from 50.1 (95% CI, 42.0 to 64.1) to 43.1 (95% CI, 38.3 to 51.9) in low-income countries. Mortality rates for hemorrhagic stroke also fell from 32.7 (95% CI, 29.9 to 35.7) to 20.3 (95% CI, 18.6 to 22.9) in high-income countries and from 80.4 (95% CI, 63.7 to 96.9) to 61.9 (95% CI, 52.5 to 72.3) in low-income countries.

These declines were observed for all age categories, but were more pronounced in those aged 75 years and older, with up to a 40% reduction in rates in these older age groups (Table 60-1). However, mortality overall from stroke was much greater in those 75 years and older than in those younger than 75 years. In the WHO Monitoring Trends and Determinants in Cardiovascular Disease (WHO MONICA) project, Sarti and associates have provided evidence to suggest that declining case fatality rates may underlie the observed changes in mortality.¹⁶ These observations have been supported by reductions in the mortality incidence rates observed by Krishnamurthi and coworkers from 1990 to 2010 in most countries.¹⁰ The reasons underlying reduced case fatality rates are most likely to be improvements in stroke care, with earlier and more appropriate diagnoses, rapid acute treatments, and increasing presence of organized stroke units. However, it is not yet clear if case fatality rates are higher among those with prestroke frailty, which is common in older adults. In preliminary analyses, a frailty index derived from a combination of prestroke health conditions, function, walking ability, and blood test results was associated with a 16% increased risk of dying in hospital after an acute stroke.¹⁷ These results, although intuitive, need to be supported by more substantive evidence.

TABLE 60-1

Global Trends in Age-Adjusted Annual Stroke Incidence and Mortality *

Age Group, Stroke Type, and Effect Measure	High-Income Countries		Low- and Middle-Income Countries
Age Group, Stroke Type, and Effect Measure	1990	2010	1990	2010
AGE < 75 YR
Ischemic Stroke
Incidence	110.8 (95% CI, 103.1-118.5)	100.5 (95% CI, 94.0-107.2)	101.88 (95% CI, 89.20-116.42)	106.90 (95% CI, 93.62-121.41)
Mortality	18.57 (95% CI, 16.07-19.49)	11.86 (95% CI, 10.47-12.69)	18.08 (95% CI, 14.57-24.39)	14.71 (95% CI, 12.90-18.75)
Hemorrhagic Stroke
Incidence	41.9 (95% CI, 38.9-45.2)	38.5 (95% CI, 35.6-41.2)	61.64 (95% CI, 52.84-71.54)	75.68 (95% CI, 64.93-88.74)
Mortality	20.95 (95% CI, 18.82-22.83)	12.29 (95% CI, 11.12-13.74)	49.36 (95% CI, 39.54-59.56)	36.53 (95% CI, 31.01-42.71)
Total Stroke
Incidence	152.7 (95% CI, 142.3-163.2)	138.9 (95% CI, 130.6-148.2)	163.5 (95% CI, 142.4-187.2)	182.5 (95% CI, 158.9-209.6)
Mortality	39.5 (95% CI, 35.8-42.4)	24.2 (95% CI, 22,3-26.3)	67.4 (95% CI, 63.5-77.0)	51.2 (95% CI, 44.4-55.0)
AGE ≥ 75 YR
Ischemic Stroke
Incidence	2824.4 (95% CI, 2627.6-3018.4)	2344.0 (95% CI, 2197.0-2503.8)	2367.5 (95% CI, 2026.7-2735.5)	2575.4 (95% CI, 2240.7-2850.2)
Mortality	1511.4 (95% CI, 1353.6-1565.1)	950.1 (95% CI, 905.5-1030.6)	1075.7 (95% CI, 915.7-1336.5)	949.9 (95% CI, 838.6-1128.4)
Hemorrhagic Stroke
Incidence	417.5 (95% CI, 385.9-450.8)	380.1 (95% CI, 351.4-409.6)	713.8 (95% CI, 603.3-847.4)	859.4 (95% CI, 729.2-1012.6)
Mortality	407.1 (95% CI, 380.5-462.1)	275.1 (95% CI, 253.8-320.3)	1072.9 (95% CI, 819.3-1329.5)	874.8 (95% CI, 736.8-1026.6)
Total Stroke
Incidence	3241.9 (95% CI, 3020.9-3458.8)	2724.1 (95% CI, 2553.9-2899.8)	3081.4 (95% CI, 2631.0-3562.0)	3434.8 (95% CI, 2979.2-3952.1)
Mortality	1918.5 (95% CI, 1746.9-2031.9)	1225.1 (95% CI, 1155.4-1393.9)	2148.6 (95% CI, 2009.7-2459.4)	1824.7 (95% CI, 1590.7-1947.8)

Prevalence and Incidence of Stroke and Subtypes

A number of stroke prevalence studies have been conducted around the world. Stroke prevalence (per 100,000 population, standardized to the world population older than 65 years) appears least in rural South Africa (1,539/100,000), United States (4,536/100,000) and New Zealand (4,872/100,000), whereas a greater prevalence was evident in L’Aquila, Italy (6,812/100,000), Newcastle, England (>7,000/100,000), and Singapore (7,337/100,000).¹⁸^–²¹ Interestingly in Singapore, prevalence rates among Malays (5,396/100,000) appeared less than those of Chinese (7,829/100,000) or Indian (6,871/100,000) descent, although this difference was not statistically different.²¹ Differences in environmental or genetic risk factor profiles, poststroke care, or both may influence these geographic variations in prevalence.

Stroke is a heterogeneous condition with two main subtypes, ischemic and hemorrhagic stroke. Depending on the study region, the more common ischemic stroke (IS) accounts for 63% to 84% of all strokes, whereas intracerebral hemorrhage (ICH) accounts for 7% and 20% of all strokes.¹⁸ The proportion of hemorrhagic strokes appears to be greater in nonwhite populations and among those living in low- and middle-income countries compared with white populations in high-income countries.²²^–²⁵ Within the category of ischemic stroke, there are further subtypes that are classified based on clinical signs alone or on actual stroke mechanisms (e.g., large vessel disease, cardioembolism, small vessel disease).²⁶^,²⁷ The most frequently used classification system in large-scale, population-based epidemiologic studies is based on clinical features alone, as devised by the investigators of the Oxfordshire Community Stroke Project, which differentiates stroke into total or partial anterior infarction, posterior infarction, and lacunar infarction.²⁷ The advantage of this classification system is that it does not require expensive investigations ,which may be unavailable in low-income countries or less freely available in middle-income countries. The disadvantage of such a system is that the actual subtype of ischemic stroke may be erroneous because at least 10% of those classified as “lacunar” infarctions (implying small vessel disease) will have a proximal source of embolus from large vessels or the heart.²⁸

Prevalence studies also provide a measure of the impact of stroke on survivors and the consequent health burden on patients, caregivers, and society at large. Declining stroke case fatality and mortality rates translate into an increased prevalence, resulting in an increased burden of stroke to those communities affected. Importantly, about 50% of stroke survivors are likely to require assistance in everyday activities. Frail older adults who suffer strokes are most at risk of poststroke functional decline, with one preliminary report suggesting an 8% increased risk of major physical disability in those with a higher prestroke score on a frailty index.¹⁷ Stroke²⁹ and frailty³⁰ are each also associated with a greater prevalence of cognitive impairment, and hence it is likely that the burden of cognitive impairment will be greater among frail older adults suffering strokes than among others. Thus, frailty may be an important marker of particularly vulnerable stroke patients who are likely to require enhanced health care, rehabilitation, and support systems to maintain their functional status.

Incidence of Stroke and Transient Ischemic Attack

Until a few years ago, most incidence studies of stroke conducted according to so-called ideal criteria had been undertaken in high-income regions, such as Europe, Australia, and the Americas,¹⁸^,²⁴^,³¹^–³⁹ with Barbados being an exception.⁴⁰ More recently, stroke incidence estimates have been generated for low-, middle-, and high-income countries (see Table 60-1).¹⁰^,¹¹ It must be noted, however, that there are a large number of regions in the world where there is a lack of high-quality data from which to infer accurate estimates of incidence or mortality.¹² Bearing this in mind, data from the Global Burden of Disease Study have shown that the age-standardized incidence/100,000 person-years for ischemic stroke is estimated to range from as low as 51.9 (Qatar) to as high as 433.9 (Lithuania; estimates for hemorrhagic stroke ranged from as low as 14.6 (Qatar) to as high as 159.8 (China).¹⁰ There also appears to be substantial regional variation by stroke type, with ischemic stroke incidence highest among Eastern Europe and hemorrhagic stroke incidence highest among Central and East Asia.¹⁰

Examination of trends over time has shown that overall stroke incidence declined significantly, particularly in the 1970s and 1980s, in high-income countries.³⁵^,⁴¹^–⁴⁶ This decline in high-income countries appears to have continued over the last decade (1990-2010), with a 13% and 19% overall reduction in ischemic and hemorrhagic stroke incidence, respectively¹⁰ However, in low- and middle-income countries during the same period, there was a nonsignificant increase (6%) in the incidence of ischemic stroke, but a significant increase (19%) in the incidence of hemorrhagic stroke. These upward trends in stroke incidence in low- and middle-income countries were observed among those younger than 75 years and those 75 years of age and older (see Table 60-1). The most likely explanation for the differences in trends in stroke incidence between high- and low-income countries is the epidemiologic transition occurring in the latter. Increasing life expectancy, industrialization, and urbanization have led to a shift in risk factor profiles (e.g., increasing rates of hypertension, diabetes, smoking) in low- and middle-income countries to resemble those historically observed in high-income countries. Such factors, in addition to genetic differences, may largely explain the rising incidence of hemorrhagic stroke in these regions.

The actual incidence of TIA is harder to determine accurately in a population because of the transient nature of symptoms and the presence of other conditions that may mimic a TIA, such as migraine and seizures. However, in parallel to stroke, the annual rates for TIA have also declined among those 65 years of age and older in high-income regions such as Rochester, Minnesota,⁴⁷ France,⁴⁸ Belgium,⁴⁹ and Australia.⁵⁰ In France and Australia, an increase was observed in TIA incidence among those younger than 65 years, possibly reflecting increased awareness of the risk of stroke in this age group over time or diagnostic misclassification of TIA mimics.⁴⁸^,⁵⁰ There are presently no published systematic estimates of TIA incidence in low- and middle-income populations.

Costs of Stroke

Globally, on a societal level, stroke is responsible for approximately 2% to 4% of total health care costs. The costs of stroke have been estimated by using a variety of bottom-up and top-down approaches in a number of Western countries. Using a bottom-up approach, the estimated 12-month cost of stroke in Australia in 1997 was $420 million.⁵¹ Acute hospitalization (28%) and inpatient rehabilitation (27%) comprised most of these costs. The average cost per case was $14,361during the first 12 months and $33,658 over a lifetime, with overall lifetime costs being greater for ischemic stroke than for intracerebral hemorrhage (ICH).⁵¹^,⁵² There are also significant economic costs attributable to informal caregiving. Dewey and colleagues⁵³ carried out an economic analysis to determine the total 12-month costs associated with informal care for first-ever strokes. They estimated that the total costs of informal care for first-ever strokes comprised between 4% and 7% of total stroke-related costs during the first year and between 14% and 23% of costs over a lifetime. This demonstrates the considerable burden placed on the families of people with stroke. Long-term costs associated with stroke have been recently estimated by Gloede and associates.⁵⁴ In this analysis, compared with cost estimates at 3 or 5 years after stroke, the costs for hemorrhagic stroke were substantially greater at 10 years (by 24%), whereas those for ischemic stroke remained relatively constant. The exact reasons for the increase in long-term direct costs for hemorrhagic stroke remain as yet unexplained, but may involve increasing costs of hospital care, medication use, and residential care, among others.

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