Abstract
Stroke represents a major public health problem, ranking as a leading cause of death and long-term disability worldwide (1–3). The goal of prevention strategies is to avoid the occurrence of stroke by educating both healthcare professionals and patients about the reduction of risk factors. Despite increasing improvements in acute revascularization therapies, preventive measures remain more effective in decreasing the burden of stroke, as evidenced by the fact that over 75 % of strokes are first events (2). This paper attempts to provide a comprehensive approach by outlining risk factors and new therapeutic approaches. Understanding these is essential for healthcare providers and the general public to develop effective prevention strategies and ultimately reduce the overall incidence of stroke.
Keywords: Stroke, Prevention, Risk factors, Cardiovascular disease, Lifestyle modifications, Public health
Highlights
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Over 75 % of strokes are first events, emphasizing the need for early risk factor management.
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Non-modifiable factors help identify individuals at high risk for stroke, while modifiable factors offer targets for stroke prevention.
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Therapies like RNA-based treatments, GLP-1Ras, Colchicine and Factor XI inhibitors demonstrate potential in reducing cardiovascular risk.
1. Non-modifiable risk factors
Non-modifiable risk factors are inherent characteristics over which an individual has no control. Recognizing them helps healthcare providers identify high-risk individuals for targeted management of modifiable factors. Scoring systems can help detect these high-risk individuals. The SCORE2 and SCORE2-OP established by the European Society of Cardiology estimate the 10-year cardiovascular risk based on sex, age, blood pressure, cholesterol, and smoking status in those without prior cardiovascular disease or diabetes [4].
Advancing age increases the likelihood of stroke by 9 % in men and 10 % in women each year. Gender, genetic predisposition and ethnicity also appear to play an important role. While women have a higher cumulative lifetime prevalence of stroke, men have a higher age-adjusted incidence. A positive family history increases the risk of stroke by approximately 30 %. Epidemiological studies show that African Americans, Hispanics, and South Asians have disproportionately high rates of stroke [2].
| Risk Factor | Description |
|---|---|
| Age | Stroke risk increases with age, rising by 9 % per year in men and 10 % per year in women. |
| Sex | Men have a higher age-adjusted incidence, while women have a higher lifetime prevalence of stroke. |
| Genetic Predisposition | A family history of stroke increases individual risk by approximately 30 %. |
| Ethnicity | Certain ethnic groups, including African Americans, Hispanics, and South Asians, have higher stroke rates. |
2. Modifiable risk factors
Approximately 90 % of the population attributable likelihood of stroke can be explained by 10 modifiable risk factors. These include hypertension, smoking, dyslipidemia, poor diet, physical inactivity, obesity, diabetes, heart disease, excessive alcohol consumption and psychosocial factors [3].
Of these, hypertension is probably the most important modifiable risk factor, as the likelihood of a stroke increases progressively with rising blood pressure levels. Reducing systolic blood pressure by 5 mmHg lowers stroke risk by 10 %. In general the target blood pressure is <130/80 mmHg. However, a meta-analysis showed a 22 % reduction of recurrent stroke in patients with targeted systolic blood pressure levels as low as 120 mmHg [2,4].
In patients with pre-existing heart disease, such as atrial fibrillation or coronary artery disease, it is particularly important to prevent further cardiovascular events. Atrial fibrillation causes turbulent flow in the left atrium with ineffective contraction, which may lead to thrombus formation and ultimately to an increased risk of thromboembolism. The CHA₂DS₂-VASc score helps identify patients at high risk for stroke who are candidates for anticoagulation. In particular, non-vitamin K dependent oral anticoagulants (NOACs), which have been shown to be safer and more convenient than vitamin K antagonists, can help patients and their healthcare providers effectively reduce the risk of cardioembolic stroke [2].
Epidemiologic studies have linked elevated cholesterol levels to an increased likelihood of stroke, underscored by a meta-analysis of more than 90,000 patients that found statins reduced the risk of stroke by approximately 21 % [2].
Another important risk factor is diabetes, which accelerates atherosclerosis and damages blood vessels. Target HbA1c levels should be <7 %, with lifestyle modifications playing a critical role in achieving this goal [2,5].
Lifestyle changes, including regular physical activity, a healthy diet, smoking and alcohol cessation and maintaining a healthy weight, are critical to preventing both first and recurrent strokes. Heavy smoking, probably due to its short-term effect of promoting thrombus formation in atherosclerotic arteries and its long-term role in the progression of atherosclerosis, increases the likelihood of stroke by two to four times and the prevalence of cardiovascular events. Physical inactivity is associated with higher cardiovascular morbidity and mortality, while regular exercise can reduce the risk of stroke by 25 % to 30 %. It is recommended that healthy adults get at least 40 min of moderate- to vigorous-intensity aerobic physical activity per day, 3 to 4 times a week. In addition, a balanced diet such as the Mediterranean diet and stress reduction are important modifiers [2].
3. New therapeutic approaches and future perspectives
As mentioned above, cholesterol, especially mixed hyperlipidemia, plays an important role in cardiovascular health. Ridker et al. found that singular combined measurement of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels in healthy women strongly predicted an increased cardiovascular risk over 30 years. Promising studies suggest that RNA-based therapies, such as Pelacarsen or Zodasiran, may reduce elevated levels of lipoprotein (a) and triglycerides [[6], [7], [8]].
In patients with coronary artery disease, Colchicine has shown potential in reducing stroke likelihood by suppressing inflammation and stabilizing atherosclerotic plaques, with possible roles in both primary and secondary prevention [1].
Glucagon-like peptide-1 receptor agonists (GLP-1Ras) and combination therapy with glucose-dependent insulinotropic polypeptide (GIP), such as tirzepatide, have been shown to be neuroprotective by reducing the risk of stroke and other major cardiovascular events in patients with type 2 diabetes and cardiovascular disease. Their benefits include improvements in glycemic control, weight loss and blood pressure reduction, all of which contribute to lowering overall cardiovascular risk [5].
Factor XI inhibitors may offer additional benefits in preventing recurrent strokes by inhibiting thrombin amplification. Although Phase II trials like PACIFIC-STROKE and AXIOMATIC-SPSS found no significant reduction in ischemic stroke risk with Factor XIa inhibitors, ongoing Phase III trials may provide further insights into their role in secondary stroke prevention [9].
Despite new therapeutic approaches stroke prevention requires a multifaceted approach that includes public health measures that address environmental factors such as air, water and soil pollution, urbanization and endocrine-disrupting substances, as these hazards have been shown to be associated with stroke [10].
4. Discussion and conclusion
Prevention of stroke is essential to reduce global morbidity and mortality and requires lifestyle changes, medical management and public health efforts. Controlling modifiable risk factors such as hypertension, diabetes, atrial fibrillation and smoking can significantly reduce the incidence of stroke. Non-modifiable risk factors must also be considered, as they help identify patients at high risk for cardiovascular events. Emerging therapeutic approaches such as Colchicine, Tirezaptide, RNA-based therapies for patients with mixed hyperlipidemia, and factor XIa inhibitors may further improve cardiovascular health.
CRediT authorship contribution statement
Lisa Kaindl: Writing – review & editing, Writing – original draft, Resources, Conceptualization. Julian Frederic Hotz: Writing – review & editing. Julia Ferrari: Writing – review & editing, Supervision, Resources, Conceptualization.
Declaration of competing interest
None.
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