Traditional Risk Factors and Etiologies in Early-Onset Ischemic Stroke

By: Nicolas Martinez-Majander, Department of Neurology, Helsinki University Hospital, Finland

Incidence

Incidence of early-onset ischemic stroke remains low in children and adolescents, and increases after that, being about 10/100,000 per year in people aged between 18-50 years.¹ Remarkably, early-onset ischemic stroke has become even more common in high-income countries since 1980s.² The exact reasons for this remain unknown, but better awareness of the disease, improved diagnostics, urbanization, and in particular, increasing prevalence of overweight, unhealthy diet, sedentary lifestyle, and adult-onset diabetes may underlie this observation.

Early-onset ischemic stroke should be considered separately from older age groups since the young have a wider range of potential risk factors and recognized causes underlying their strokes. Traditional risk factors can obviously affect also the younger patients, and some risk factors are exclusively specific to young age, or the association appears stronger in the young, including illicit drug use, combined oral contraceptives, and patent foramen ovale.

Traditional risk factors

The association of traditional risk factors in younger stroke patients has been assessed by a small number of studies. Overall, most of the risk factors are more prevalent among men and accumulate with age in both sexes.³

As for individual risk factors, the associations of hypertension and smoking with ischemic stroke have been consistently demonstrated, but there are only inconsistent results for diabetes.^4-6 Only few studies investigated the association between cardiac disease and ischemic stroke at younger ages, with no data available separately for atrial fibrillation. Obesity (>30 kg/m²) was associated with early-onset stroke only in a recent population-based case-control study when adjusted for demographic factors. However, this association diminished after further adjustment for smoking, hypertension, and diabetes mellitus suggesting that the effect of obesity may be mediated by some of these factors.⁷ Metabolic syndrome has also been suggested by an early study.⁵

Regarding dyslipidemia, low HDL and its major protein component, apolipoprotein A-I, has been demonstrated as risk factors for early-onset ischemic stroke, but the association with stroke was not shown for LDL or total cholesterol when adjusted for confounders.^5,8 This may point out that non-atherogenic altered functions of the lipid particles—especially those of  HDL cholesterol— may be more relevant in early-onset ischemic stroke. Such functions include modulation of platelet function, coagulation and vascular endothelium.

Interestingly, a longitudinal study including patients with obstructive sleep apnea showed a higher stroke risk for women aged ≤35 years compared to older age groups, and a relatively higher risk for women.⁹

 Etiology

The most common single etiology is cervico-cephalic arterial dissection (up to about 25% of cases). Large artery atherosclerosis accounts approximately 10-25% of early-onset strokes, but even greater proportions in certain ethnic groups, such as Asians. Small-vessel disease was reported to cause 3-17 % of early-onset ischemic strokes,^10-12yet there exists a grey sector among the younger patients with “lacunar infarcts” in whom the underlying pathology is probably not related to the classical concept of small-vessel disease or known monogenetic conditions with small-vessel disease pathology. Cardioembolism accounts for 17-34% and undetermined etiology 19-40% of young ischemic stroke in the most recent studies.^10-12

Conclusions

Ischemic stroke in the young is a devastating disease having an impact on several domains of everyday life and causing uncertainty for decades to come. Recent studies show that traditional risk factors may actually play a greater role in young-onset stroke than previously thought. Such risk factors may contribute even more at younger ages than with the elderly. Moreover, the underlying etiology differs from older patients and this should be kept in mind when planning appropriate diagnostic work-up.

 

 

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