1.2.1 Stroke Prevalence

The worldwide prevalence in 2013 was an estimated 25.7 million, with approximately 10.3 million people having a first stroke in that year. ² Most were ischemic in nature, and about 30% occurred in those younger than 65 years of age. ³ Due to the problems with reporting in different health systems and countries, it is likely that these findings are an underestimation of the real prevalence of stroke. There are, however, large sample studies available, mainly from developed countries, that provide essential information in this area.

Even though some findings suggest that age-adjusted mortality rates for ischemic and hemorrhagic stroke decreased between 1990 and 2013, the total number of strokes, related deaths and disability- adjusted life- years lost, increased. ⁴ In our opinion, it is very likely that this trend continues today, given the increase in life expectancy in recent years and that stroke prevalence increases with age. ⁴ Supporting this fact are findings from studies arising from the Behavioral Risk Factor Surveillance System (BRFSS) in the US, which shows that between 2006 to 2010, overall self-reported stroke prevalence did not change. ⁵

Furthermore, in a US study of general population without prior diagnosis of stroke or TIA involving 18462 participants, the presence of least one neurologic symptom in those over 45 years old was 17.8%. ⁶ These findings strongly suggest that the true prevalence of stroke is even higher than estimated, with many undiagnosed or unreported events. These were more frequent in African Americans, those with lower education and income, and those with poor perceived health status, ⁶ which represent the more vulnerable populations in that country. Limitations in access to healthcare may also play a role in this population segment.

Finally, following worldwide trends, the prevalence of stroke in the US is expected to increase by 20.5% by 2030, compared to 2012. ⁷ In addition, prevalence of stroke survivors in the ageing population is expected to increase, ⁸ which will represent an increased challenge to healthcare systems and society as a whole. An optimization of prevention strategies and effective treatments will likely mitigate this expected increase, and might even prove predictions wrong. It is our responsibility as healthcare professionals to advocate for these changes to take place.

1.2.2 Stroke Incidence

Obtaining a global incidence statistic for stroke is a complex endeavor. The actual incidence varies greatly among different geographical regions, populations, and even across time. ¹

Worldwide, in 2010, there were an estimated 11.6 million ischemic strokes and 5.3 million hemorrhagic strokes, with increased incidence in low and middle-income countries. ⁹ This represents an incidence estimate of 258/100,000 people-year. ¹⁰ Between 1990 and 2010 the incidence of ischemic stroke fell by 13% in high income countries, but not in low or middle-income ones. ⁹ Furthermore, the incidence of hemorrhagic stroke decreased by 19% in high income countries, but increased by 22% in the rest with a higher burden on those 75 years old or younger. ⁹

While socioeconomic status and an aging population clearly play a role, we believe that this also reflects the commitment of different countries to prevention and treatment of stroke, and to challenges in global healthcare, which must be addressed in following years to revert this situation.

The worldwide variations in incidence are far reaching across different populations, ranging from 130 to 410/100000 person-years. ¹ There are also variations according to stroke subtypes, with the incidence of hemorrhagic stroke being significantly higher in Asian countries than in the Western world. This has been linked to a higher prevalence of hypertension in these populations, although other factors cannot be ruled out. ¹

In the US, about 795 000 people per year experience a new or recurrent stroke, of which approximately 610 000 are first attacks. ⁴ Of these, 87% are ischemic, 10% are ICH, and the remainder 3% are SAH strokes. ⁴

Stroke incidence seems to be higher in those of African descent, with a lower incidence of cerebral infarction in women under 75, irrespective of ethnicity. ⁴ Among those aged 75 or older, African American women showed a higher incidence of cerebral infarction than men of the same ethnicity, while no difference was observed between white men and women aged 75 to 84. ⁴

Women seem to have a higher incidence of stroke than men with a higher lifetime risk than men. ¹¹ In the Framingham heart study, the lifetime risk was about 20% for women between 55 and 75 years of age, while it was approximately 15% for men of the same group. This seems to be at the expense of an increased incidence in older age groups and longer life span, since age adjusted incidence is lower for females in middle age or younger. ⁴

Findings from both the BASIC Project between 2000 and 2010, the Framingham Heart Study, and Medicare recipients in the US show a reduction in incidence of global stroke over time ⁴ consistent with global findings of decreased incidence in high income countries. ¹² Although incidence seems to be decreasing, the total burden of the disease has not changed, and is likely to increase, ¹ especially with an aging population ¹² and the increased prevalence of risk factors, ¹³ which we will discuss later in this chapter.

1.2.3 Transient Ischemic Attacks (TIA)

The knowledge of TIA epidemiology has a relevant role in stroke planning and prevention, since it is known that approximately 15% of all strokes are heralded by a TIA. ¹⁴ This means that appropriate evaluation, treatment and secondary prevention are mandatory for these patients. Failure to do so exposes them to potentially severe and life-threatening complications, and worsens their prognosis. In the US, it is estimated that that the prevalence of TIA was 2.3% overall, and increased with age. The real number is likely higher though, due to the same caveats of stroke research. ¹⁵

A patient with a TIA is at a significant risk of short term complications, both neurologic and cardiovascular, and has an increased mortality risk. In one study of 1707 TIA patients evaluated in the emergency department in a northern California hospital, 5% had a stroke in the first 48 hours and 11% presented with stroke during the following 3 months. Risk factors for progression to stroke were age over 60 years old, diabetes, and duration over 10 minutes. ¹⁶

Meta-analyses of cohorts of patients with TIA have shown that the risk of stroke in the first 48 hours is between 3% to 10%, and is 9% to 17% for the first three months. ^{17 ,​ 18} Stroke risk at 10 years is approximately 19%. ⁴ Furthermore, the Oxford Vascular Study has shown that TIAs are a significant predictor of disability at 5 years. ¹⁹

1.2.4 Recurrent Stroke

Recurrent stroke is a major complication in stroke survivors, with a major increase in morbidity and mortality. Several studies have assessed its prevalence and incidence, with results up to 18% recurrence rate at 4 years. ⁴

Actual recurrence rates vary among different studies. A study in Northern Sweden, which followed 6700 patients who survived an ischemic stroke or had an intracranial hemorrhage between 1995 and 2008, showed that in this population recurrence rates were 6% at 1 year, 16% at year 5, and 25% at year 10 ²⁰ . Another study which followed 10399 patients with a primary stroke in 2002 in the US, showed rates of 1.8% at 1 month, 5% at 6 months, 8% at 1 year, and 18.1% at 4 years. ²¹

Recurrence rates vary according to etiology, stroke subtypes, and between studies. For hemorrhagic stroke, recurrence rates have been estimated at 2.4% per year, with a fourfold increase for lobar hematoma. ¹ Most recurrences after both hemorrhagic and ischemic stroke are ischemic. ²⁰ For ischemic strokes, rates were higher for those caused by large artery disease followed by small vessel disease and stroke of cardioembolic origin. ⁴ Also, a larger number of risk factors present is associated with higher recurrence rates. ⁴ Both diabetes and age at stroke are risk factors associated with increased risk of recurrence, ²⁰ although all comorbidities play a role.

With minor variations, these findings are consistent across multiple studies in multiple populations of first world countries. ⁴

In recent years, a decline in recurrence rates has been observed, probably due to better secondary prevention and etiologic treatment. ^{22 ,​ 23} This should only strengthen our focus to improve on primary prevention, effective timely treatments and follow up, to reduce stroke’s burden and improve outcomes.

1.2.5 Mortality

A recent report on global stroke statistics by Thrift et al ¹² surveying all countries associated to the WHO has revealed an astonishing lack of accurate and recent data in over half of them, which makes evaluating true mortality difficult. This report also highlights significant differences between high income countries and low-middle income ones, where mortality adjusted by age seems to be higher, despite being probably underreported.

Mortality in stroke is substantial, both short-term and long-term. It varies significantly according to stroke subtype, being significantly higher for hemorrhagic subtypes in most studies, especially within the first month. ⁴ Further variances are observed across different populations, where age-adjusted mortality ranges from 41/100 000 people-years in Nigeria to 316/100 000 person-years in urban Dar-es-Salaam (Tanzania). ¹² This large variation in mortality probably responds not only to intrinsic factors of each population, but also to differences in registry keeping and reporting between different countries. These large differences cast doubt on the actual available information. Another unexpected factor is the large difference between incidence and mortality rates in some low and middle-income countries, which are not concordant. There is probably a need for international organizations to directly take representative samples in different healthcare-challenged countries in order to properly assess stroke statistics.

The Atherosclerosis Risk in Communities Study (ARIC) study, which involved US patients from 4 different cities for a period of 24 years, showed a cumulative global mortality after index stroke of 10.5% at 1 month, 21.2% at 1 year, 39.8% at 5 years, and 58.4% at the end of follow up. ⁴ In the aforementioned Swedish study, a combined endpoint of recurrence and death was 28% at 5 years, and 45% at 10 years. ²⁰ Furthermore, In the US, in 2014, stroke ranked 5^th among leading causes of death, with a rate of 36.5/10000. These findings show the importance of secondary prevention and the dreadful long-term outcome a significant number of patients have after stroke.

Global trends suggest a decrease in mortality over the last 30 years of around 25%-30%. ⁴ This decline in mortality was more noteworthy in those over 65 years old, compared to younger age groups, although some studies show conflicting results in this regard. ^{24 ,​ 25} Although the role of primary prevention cannot be discarded, the decrease in mortality has been attributed to improvements in pre-hospital and in hospital emergent care, ¹ which we agree wholeheartedly with.

1.3.1 Non-Modifiable Risk Factors

Age is the most important non-modifiable risk factor. It has been estimated that stroke risk doubles every decade after 55 years of age. ¹ The increase with age has been consistently demonstrated across all studies to date.

Male sex is a risk factor for ischemic stroke in patients younger than 75 years of age, but not in those older. ⁴ This is probably due to the increased proportion on women in said age group, which leads to a higher number of cases. ¹ For this reason, women also seem to have a higher total lifetime stroke risk. ²⁷ Male sex has also been associated with intracerebral hematoma, whereas female sex is a risk factor for subarachnoid hemorrage. ¹

Those of African ancestry have an increased stroke risk. In the US, the Northern Manhattan Study (NOMAS) has shown an age adjusted incidence of stroke of 1.91/1000 people in blacks versus 0.88/1000 in whites. ²⁸ In addition, in the US, both the NOMAS study and the BASIC project have shown an increased incidence in Mexican Americans. ^{28 ,​ 29} Even though those of black race have an increased prevalence of some risk factors which could explain this association, such as hypertension, direct interpretation is difficult since separating race from socioeconomic status is not possible. ¹

A stroke before age 65 in either parent was associated with a threefold risk increase in offspring in the Framingham Heart Study. ²⁹ This shows that there is a hereditary predisposition in some families. Recent studies suggest that the lower the age at the moment of stroke, female sex, large vessel disease and cardioembolic stroke for ischemic subtypes may have a stronger association. ⁴ The presence of a stroke on either parent increases the risk by a factor of approximately 2 ¹ .

Some genetic mutations also confer a predisposition to stroke. For ischemic stroke, mutations in HDAC, ABO, and TSPAN2 genes have been implicated in large vessel origin. ⁴ Other genes, such as PTX2 and ZFHX3 have been related to cardioembolic ischemic stroke. ⁴ FOXF2 mutations have been strongly related to small vessel disease. ⁴ Regarding hemorrhagic stroke, genes in the PMF1/BGLAP region have been linked to non-lobar ICH, and changes in Apolipoprotein E with lobar hematoma. ⁴ Even though these mutations, as well as others that are not currently known, increase stroke risk, familial risk cannot be attributed entirely to it. Other modifiable risk factors that can have an inherited component, such as hypertension or diabetes, as well as dietary habits in the family, certainly have interactions with the genetic component and affect the risk they confer. ¹