Migraine in Young Stroke Patients—Better Outcomes Despite Distinct Risk Profiles: Insights From the STROKE‐CARD‐Study

ABSTRACT

Introduction

Migraine is a common neurological disorder and a non‐traditional risk factor for ischaemic stroke. Its relationship with specific stroke subtypes and post‐stroke outcomes remains unclear. We evaluated the association between migraine (with and without aura), stroke aetiology, functional outcomes, and cardiovascular risk profiles in young patients with ischaemic stroke or TIA.

Methods

Patients aged ≤ 55 years enrolled in the STROKE‐CARD long‐term follow‐up study underwent structured face‐to‐face headache interviews by headache specialists using ICHD‐3 criteria. A predefined protocol collected demographic, clinical, neuroimaging, aetiological, and cardiovascular risk data.

Results

Among 289 young stroke patients (median age 48.0 [41–52] years; 36.3% women), 92 (31.8%) had a history of migraine (51.1% with aura). Migraine was more common in women, associated with younger age at stroke onset and more frequent headache at stroke onset, but not with traditional vascular risk factors. PFO was more prevalent in patients with migraine with aura (68.9% vs. 36.9% no migraine, p < 0.001). No significant differences were observed in stroke territory or stroke pattern. Stroke severity (NIHSS) and functional outcome (mRS) at discharge were more favourable in migraineurs (p ≤ 0.001). In multivariable analysis, migraine without aura was independently associated with good functional outcome (OR 7.21, 95% CI 1.93–26.93, p = 0.003).

Conclusion

In young adults with ischaemic stroke, migraine—particularly with aura—was associated with younger age at stroke onset and a higher prevalence of PFO, while traditional vascular risk factors and stroke characteristics were similar across groups. Despite comparable stroke patterns, patients with migraine experienced more favourable short‐term outcomes.

Trial Registration

Post‐Stroke Disease Management—Stroke Card: NCT02156778; Stroke Card Long‐term Follow‐Up NCT04205006

Among young adults with ischaemic stroke, migraine—particularly with aura—was associated with younger stroke onset and a higher prevalence of PFO. Vascular risk profiles and stroke characteristics were similar across groups. Migraine patients showed more favourable short‐term outcomes.

1. Introduction

Migraine is the second most prevalent primary headache entity and a leading neurological disorder, predominantly occurring in women. Approximately 15% of the general population—more than one billion individuals worldwide—are affected [1]. Beyond the burden of recurrent headache attacks and impaired quality of life, migraine has been consistently identified as an independent, non‐traditional risk factor for ischaemic stroke [2, 3, 4, 5, 6, 7]. The risk is particularly elevated among young women, especially among those with migraine with aura, frequent attacks, concomitant smoking, or hormonal contraceptive use [8]. Several shared pathophysiological mechanisms—such as vascular dysfunction, endothelial activation, cortical spreading depression, and neuroinflammation—have been proposed, though the exact pathways remain incompletely understood [9, 10].

This issue has gained urgency given the rising incidence of ischaemic stroke among young adults and the increasing use of CGRP‐modifying therapies in migraine patients and their proposed vascular risk [10, 11, 12, 13]. For this vulnerable population, identifying non‐traditional risk factors such as migraine may be critical to improve prevention and risk stratification. However, despite growing evidence for a migraine‐stroke link, the relationship between migraine and specific stroke subtypes or post‐stroke outcomes remains poorly understood, especially in systematically characterised young cohorts.

To address these gaps, we analysed data from the STROKE‐CARD trial, focusing on patients ≤ 55 years of age with ischaemic stroke and transient ischaemic attack. Migraine status (with aura, without aura, or no migraine) was determined via structured headache interviews by specialists. We then examined whether migraine was associated with (i) stroke aetiology, (ii) functional outcome after stroke, and (iii) traditional cardiovascular risk factors.

2. Material and Methods

2.1. Trial Design

Between 2014 and 2018, the STROKE‐CARD trial was conducted to assess the efficacy and feasibility of a structured post‐stroke disease management program. The study design and results have been published previously [14, 15]. In this prospective study, > 2000 patients with acute ischaemic stroke or transient ischaemic attack (ABCD₂ score ≥ 3) were enrolled at two study sites (Innsbruck and Vienna). Exclusion criteria included modified Rankin Scale (mRS) score of 5, a life expectancy < 1 year, drug addiction or alcohol abuse. Baseline data, including a wide range of demographic, clinical, and laboratory parameters, were systematically collected to evaluate individual cardiovascular risk profiles and disease‐related biomarkers.

A prospective observational follow‐up study extended the observation period to 3–6 years [16]. In addition to recurrent vascular events and the assessment of health‐related quality of life, a structured face‐to‐face or telephone headache interview was performed. All headache diagnoses were established according to the latest International Classification of Headache Disorders (ICHD‐3) criteria [17].

All participants provided written informed consent. Both studies were approved by the local ethics committee of the Medical University of Innsbruck. The trials were conducted in accordance with the Declaration of Helsinki and have been registered at clinicaltrials.gov (NCT02156778; NCT04205006).

2.2. Study Population

This analysis focused on patients aged ≤ 55 years; the age cut‐off was chosen in accordance with recent literature [18, 19, 20, 21, 22].

A detailed headache history was obtained only from patients who were treated at the study centre in Innsbruck, Austria. Of 2149 originally screened, 1730 were enrolled in Innsbruck, 1667 participated in the follow‐up, and 289 were ≤ 55 years at the index event (Figure 1).

FIGURE 1.

Flow‐chart of the patient selection.

2.3. Demographic Data, Cardiovascular Risk Factors and Assessments

Baseline characteristics were collected at admission and included demographic data, cardiovascular risk factors (smoking status, dyslipidaemia [total cholesterol > 200 mg/dL, low‐density lipoprotein (LDL) cholesterol > 100 mg/dL, triglycerides > 150 mg/dL, or high‐density lipoprotein (HDL) cholesterol < 40 mg/dL [23]], obesity [BMI ≥ 30 kg/m² [24]], arterial hypertension [treatment with antihypertensive medication prior to stroke or blood pressure value exceeding 140/90 mmHg on at least two separate measurements], diabetes [previous diagnosis of type 1 or type 2 diabetes, fasting plasma glucose ≥ 126 mg/dL (≥ 7.0 mmol/L), or HbA1c ≥ 6.5% (≥ 48 mmol/mol)], and history of cardiovascular disease) as well as pre‐existing comorbidities.

To assess functional outcomes and stroke severity, the National Institutes of Health Stroke Scale (NIHSS) [25] and the mRS [26] were documented at admission and discharge. A TIA was defined as a transient neurological deficit lasting < 24 h in the absence of diffusion‐weighted imaging (DWI) positive lesions on MRI. The stroke pattern was categorised into two groups based on imaging findings: lacunar (small (< 2 cm) ischaemic lesions located in non‐cortical regions) and embolic (cortical lesions, and/or involving multiple vascular territories). The localisation of stroke—referring to the affected vascular territory—was classified into anterior and posterior circulation strokes. Transoesophageal echocardiography (TEE) was performed to detect patent foramen ovale (PFO). However, this diagnostic assessment was not performed in all patients (depending on suspected stroke aetiology). The available data did not allow allocation of PFO size or high‐risk features.

Ischaemic stroke aetiology was categorised according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria [27].

2.4. Headache Characteristics

In 192 patients (66.4%), headache specialists conducted direct face‐to‐face assessments during outpatient visits. For the remaining 97 patients (33.6%), clinical information was obtained, where available, through telephone interviews with patients or relatives and/or review of electronic medical records, physician correspondence, and other medical documentation. Electronic medical records were reviewed for all patients [17].

2.5. Statistics

All statistical analyses were performed using SPSS Version 30.0.0.0 (IBM SPSS Statistics, Armonk, NY). Descriptive statistics were reported using median and interquartile range [IQR] or percentages. Normality was assessed with the Kolmogorov–Smirnov test. Group differences were analysed using the Mann–Whitney U test, Chi‐square, Fisher's Exact or Kruskal–Wallis tests. Missing data are indicated per variable. Statistical significance was set at p < 0.05. To account for multiple comparisons, Bonferroni correction was applied where appropriate; p‐values reported in the tables are unadjusted. To explore predictors of stroke at very young age, a binary logistic regression was performed with ‘≤ 30 years’ vs. ‘> 30 years’ as the dependent variable; sex, migraine status (MWoA/MWA), PFO, obesity, hypertension, dyslipidaemia, smoking, and headache at stroke onset were covariates. Good functional outcome was defined as mRS < 2 at discharge. Binary logistic regression was performed to identify predictors of favourable outcome, adjusting for age, sex, and cardiovascular risk factors, baseline stroke severity (NIHSS at admission), baseline disability (mRS at admission) as well as recanalisation therapy (intravenous thrombolysis and/or mechanical thrombectomy). Variables with very low event numbers (diabetes, atrial fibrillation, prior myocardial infarction) were excluded from the regression models.

3. Results

3.1. Demographics and Cardiovascular Risk Factors

Table 1 presents the baseline demographic and clinical characteristics of young stroke patients stratified by migraine status. A total of 289 patients were ≤ 55 years of age at the time of the index stroke, with a median age of 48.0 [41–52]. Overall, 105 (36.3%) individuals were female. Among the young stroke patients, 92 (31.8%) had a history of migraine prior to the index stroke. Among them, 45 (48.9%) were classified as MWoA and 47 (51.1%) as MWA. Patients with migraine were more frequently female than non‐migraineurs (48.9% vs. 30.5%; p = 0.002).

TABLE 1.

Characteristics and traditional cardiovascular risk factors of the study population at index stroke.

	No migraine (n = 197)	All migraine (n = 92)	p	MWoA (n = 45)	p	MWA (n = 47)	p
Female	60 (30.5%)	45 (48.9%)	0.002	23 (51.1%)	0.008	22 (46.8%)	0.033
Age	50 [43–53]	46 [38–50]	< 0.001	46 [41–50]	0.019	45 [37–50]	< 0.001
Headache at stroke a	43 (23.5%)	43 (48.9%)	< 0.001	22 (52.4%)	< 0.001	21 (45.7%)	0.004
Smoker	87 (44.2%)	31 (33.7%)	0.092	17 (37.8%)	0.435	14 (29.8%)	0.072
Diabetes b	15 (7.7%)	6 (6.5%)	0.731	3 (6.7%)	0.999	3 (6.4%)	0.999
Obesity b	107 (54.9%)	49 (53.3%)	0.798	29 (64.4%)	0.243	20 (42.6%)	0.129
Arterial hypertension	87 (44.2%)	35 (38.0%)	0.327	22 (48.9%)	0.565	13 (27.7%)	0.039
Dyslipidaemia	158 (80.2%)	63 (68.5%)	0.029	34 (75.6%)	0.487	29 (61.7%)	0.007
Patent foramen ovale c	62 (36.9%)	43 (53.1%)	0.042	12 (33.3%)	0.629	31 (68.9%)	< 0.001
Cerebrovascular history	22 (11.2%)	14 (15.2%)	0.331	5 (11.1%)	0.991	9 (19.1%)	0.140
Atrial fibrillation	7 (3.6%)	2 (2.2%)	0.724	1 (2.2%)	0.999	1 (2.1%)	0.999
History of myocardial infarction	12 (6.1%)	3 (3.3%)	0.402	0 (0.0%)	0.130	3 (6.4%)	0.999

Note: p‐Values shown are unadjusted values. To account for multiple comparisons, Bonferroni correction was applied; accordingly, statistical significance was defined as p ≤ 0.004. Values are given as n (%) or median [IQR], p‐values are given for migraine, MWoA and MWA versus no migraine. The bold values present statistical significance.

Abbreviations: IQR, interquartile range; MWA, migraine with aura; MWoA, migraine without aura.

^a n = 271 (missing data in 18 patients).

^b n = 287 (missing data in 2 patients).

^c n = 249 (missing data in 40 patients).

Compared with non‐migraineurs, patients with migraine were younger at stroke onset (46 [38–50] vs. 50 [43–53] years, p < 0.001). The association remained significant for MWA (45 [37–50] vs. 50 [43–53] years, p < 0.001) but not for MWoA after Bonferroni correction (46 [41–50] vs. 50 [43–53] years, p = 0.019).

Headache at the time of stroke onset was substantially more common among patients with a history of migraine (48.9% vs. 23.5%, p < 0.001). This finding was consistent in both MWoA (52.4%, p < 0.001) and MWA (45.7%, p = 0.004) subgroups.

No significant differences were observed between migraineurs and non‐migraineurs regarding smoking status, obesity, diabetes, arterial hypertension, dyslipidaemia, atrial fibrillation, history of myocardial infarction or prior cerebrovascular events after correction for multiple comparisons. However, a patent foramen ovale (PFO) was markedly more frequent in patients with MWA (68.9% vs. 36.9%; p < 0.001), whereas no significant difference was seen in MWoA patients (33.3% vs. 36.9%; p = 0.629).

3.2. Stroke Characteristics and Clinical Outcome

The stroke characteristics of the study population are shown in Table 2. NIHSS scores at admission were low across all groups and did not differ significantly between migraine patients and non‐migraineurs. At discharge, NIHSS scores were lower in migraine patients than in non‐migraineurs, both overall and in MWoA and MWA subgroup analyses respectively (all p ≤ 0.007).

TABLE 2.

Stroke characteristics of the study population.

	No migraine (n = 197)	All migraine (n = 92)	p	MWoA (n = 45)	p	MWA (n = 47)	p
Length of hospital stay (days)	9 [7–12]	9 [7–12]	0.880	9 [7–12.5]	0.847	9 [7–12]	0.676
Stroke pattern a			0.327		0.209		0.800
Embolic stroke	90 (73.8%)	38 (66.7%)		18 (62.1%)		20 (71.4%)
Lacunar stroke	32 (26.2.%)	19 (33.3%)		11 (37.9%)		8 (28.6%)
Cervical artery dissection	23 (11.7%)	10 (10.9%)	0.841	9 (20.0%)	0.137	1 (2.1%)	0.048
Stroke territory			0.467		0.065		0.404
Anterior circulation stroke	111 (56.3%)	47 (51.1%)		25 (55.6%)		22 (46.8%)
Posterior circulation stroke	67 (34.0%)	38 (41.3%)		20 (44.4%)		18 (38.3%)
Both anterior and posterior circulation stroke	19 (9.6%)	7 (7.6%)		0 (0.0%)		7 (14.9%)
TOAST classification of stroke
Large artery atherosclerosis (LAA)	32 (16.2%)	7 (7.6%)	0.045	3 (6.7%)	0.156	4 (8.5%)	0.252
Cardioembolism (CE)	24 (12.2%)	10 (10.9%)	0.747	2 (4.4%)	0.183	8 (17.0%)	0.377
Small artery occlusion (SAO)	22 (11.2%)	16 (17.4%)	0.145	12 (26.7%)	0.007	4 (8.5%)	0.794
Stroke of other determined cause (SOC)	26 (13.2%)	13 (14.1%)	0.829	11 (24.4%)	0.059	2 (4.3%)	0.124
Stroke of undetermined cause (SUC)	93 (47.2%)	46 (50.0%)	0.658	17 (37.8%)	0.252	29 (61.7%)	0.074
NIHSS at admission	2 [0–5]	1 [0–3]	0.093	1 [0–3.5]	0.296	1 [0–3]	0.124
NIHSS at discharge	0 [0–2]	0 [0–1]	0.001	0 [0–1]	0.002	0 [0–1]	0.007
mRS at admission	2 [1–3]	2 [1–3]	0.167	2 [1–3]	0.368	2 [1–3]	0.220
mRS at discharge	1 [0–2]	0 [0–1]	< 0.001	0 [0–1]	< 0.001	0 [0–1]	0.008

Note: p‐Values shown are unadjusted values. To account for multiple comparisons, Bonferroni correction was applied; accordingly, statistical significance was defined as p ≤ 0.008. Values are given as n (%) or median [IQR], p‐values are given for migraine, MWoA and MWA versus no migraine. The bold values present statistical significance.

Abbreviations: IQR, interquartile range; mRS, modified Rankin‐scale; MWA, migraine with aura; MWoA, migraine without aura; NIHSS, National Institutes of Health Stroke Scale; TOAST, Trial of ORG 10172 in Acute Stroke Treatment.

^a n = 179 (missing data in 110 patients).

Similarly, the mRS score at admission did not differ between groups. By discharge, however, migraine patients showed a significantly better functional outcome, with lower mRS scores compared with non‐migraineurs (0 [1] vs. 1 [2], p < 0.001). The effect remained significant when analysing MWoA (p < 0.001) and MWA (p = 0.008) separately.

No significant differences were found between migraineurs and non‐migraineurs in terms of stroke territory or stroke pattern. A trend toward more posterior circulation strokes was observed in MWoA patients (p = 0.065), but this did not reach statistical significance. Cervical artery dissection tended to occur more frequently in MWoA compared with non‐migraineurs (20.0% vs. 11.7%, p = 0.137), whereas MWA patients showed a lower frequency of cervical artery dissection (2.1% vs. 11.7%, p = 0.048); the latter association did not remain significant after Bonferroni correction.

Analysis of stroke aetiology according to the TOAST classification revealed that small artery occlusion (SAO) was more frequent in MWoA patients compared with non‐migraineurs (26.7% vs. 11.2%, p = 0.007). Patients with MWA showed a trend toward strokes of undetermined cause (SUC; 61.7% vs. 47.2% in non‐migraineurs, p = 0.074). Other TOAST subtypes occurred at comparable frequencies across groups.

3.3. Regression Analyses

A history of MWoA was independently associated with favourable functional outcome at discharge (mRS < 2; OR 7.21, 95% CI 1.93–26.93, p = 0.003), whereas higher baseline disability was associated with reduced odds of favourable outcome (OR 0.33, 95% CI 0.21–0.53, p < 0.001). No other variables were significantly associated with outcome (Table 3).

TABLE 3.

Multivariable binary logistic regression for predictors of good functional outcome (mRS < 2) at discharge in young stroke patients.

	OR	95% CI	Sig.
Persistent foramen ovale	1.036	0.634–1.691	0.889
Headache at stroke	0.809	0.446–1.467	0.484
Obesity	0.751	0.365–1.543	0.436
Smoking	0.893	0.430–1.855	0.761
Dyslipidemia	0.634	0.272–1.481	0.292
Hypertension	0.614	0.290–1.301	0.203
Recanalisation therapy	0.649	0.221–1.909	0.432
Female sex	0.584	0.282–1.208	0.147
NIHSS at admisison	0.894	0.766–1.043	0.153
mRS at admission	0.332	0.209–0.527	< 0.001
Migraine without aura	7.205	1.927–26.931	0.003
Migraine with aura	1.419	0.528–3.818	0.488

Note: Recanalisation therapy: intravenous thrombolysis and/or mechanical thrombectomy. The bold values present statistical significance.

Abbreviations: mRS, modified Rankin‐scale; NIHSS, National Institutes of Health Stroke Scale.

In a binary multivariable logistic regression model, hypertension (OR 0.19, 95% CI 0.04–0.91, p = 0.037) and dyslipidaemia (OR 0.25, 95% CI 0.09–0.72, p = 0.010) were inversely associated with younger age (< 30 years) at stroke onset. A patent foramen ovale showed a trend toward increased odds of young stroke (OR 2.10, 95% CI 0.99–4.45, p = 0.053). Migraine with aura also tended to be associated with stroke at a younger age, though this association did not reach statistical significance (OR 2.64, 95% CI 0.86–8.10, p = 0.090). Other variables, including sex, obesity, smoking, migraine without aura, and headache at stroke onset, were not significantly associated with younger age at stroke.

4. Discussion

Migraine is associated with an elevated cerebrovascular risk beyond conventional vascular factors, but its implications in young stroke patients—the primary focus of our study—remain incompletely understood. In our cohort, traditional vascular risk factors (diabetes, hypertension, smoking, dyslipidaemia) did not differ between migraineurs and non‐migraineurs. Migraineurs were younger at stroke onset in unadjusted analyses, but this association was attenuated after adjustment for conventional risk factors. Although this finding may partly reflect the limited sample size of our cohort, it is consistent with previous reports [28, 29].

Regarding stroke aetiology, SAO was significantly more frequent in patients with MWoA, whereas MWA was more often associated with SUC. Although this association did not reach statistical significance in our cohort, it is consistent with findings from the prospective study by Martinez‐Majander et al., who reported a strong association between migraine with aura and SUC in young patients, independent of vascular risk factors and PFO [30].

We observed a markedly higher prevalence of PFO among patients with MWA (68.9%), consistent with previous reports [31, 32]. While PFO is present in approximately 25% of the general population, prevalences of up to 79%–93% have been reported in young patients with SUC and migraine with aura [33, 34]. The mere presence of a PFO does not, by itself, establish a causal relationship with the index ischaemic event. Given that detailed information on high‐risk PFO morphological and functional features was incomplete in our cohort, we were unable to ascertain whether the identified PFOs constituted a plausible stroke mechanism via paradoxical embolism in individual patients or rather represented incidental findings. Cervical artery dissection was numerically higher in MWoA, aligning with prior studies [35, 36], though statistical significance was not reached—possibly reflecting limited statistical power. Stroke territory and pattern did not differ significantly between groups, though a non‐significant trend toward posterior circulation events was observed in MWoA. This phenomenon has been described predominantly in MWA [37, 38]. Existing literature suggests that migrainous infarctions are predominantly located in the posterior circulation [3]. However, only a single stroke in our cohort fulfilled criteria for a possible migrainous infarction.

In our study, headache at stroke onset was significantly more frequent in migraine patients (48.9% vs. 23.5%; p < 0.001). This phenomenon is recognised in ICHD‐3 as ‘Headache attributed to cerebral ischaemic event’ [17]. Such headaches typically represent new‐onset pain in close temporal relationship to the vascular event and occur in 6%–44% of patients [39, 40]. As we did not collect systematic headache phenotyping at the index event, we could not determine whether the onset headache resembled the patient's known migraine phenotype. Nevertheless, any change in headache characteristics should be regarded as a red flag and warrants exclusion of secondary causes [41].

Median NIHSS at admission in this cohort was low overall, partly reflecting exclusion of patients with severe stroke (mRS = 5) and the inclusion of a substantial proportion of TIA patients (1 in 10). Migraine patients had significantly lower NIHSS and mRS at discharge, which aligns with literature indicating that functional outcomes in patients with both migraine and stroke tend to be generally favourable [42, 43, 44, 45]. Younger age at stroke onset and lower baseline vascular burden among migraineurs may have contributed to these findings. Importantly, in multivariable analysis, MWoA remained independently associated with favourable functional outcome even after adjustment for demographic characteristics, vascular risk factors, recanalisation therapy, baseline stroke severity, and baseline disability.

Our study has limitations—first, the sample size of 289 young stroke patients may restrict generalisability, although we consider our cohort reasonably representative of a young stroke population. Given the relatively small subgroup sizes, Bonferroni correction may have reduced statistical power and masked potentially meaningful associations. Second, patients with severely disabling stroke or limited life expectancy were excluded, which may have introduced selection bias; additionally, the inclusion of a relatively high proportion of TIA patients (10.4%) may have influenced cohort composition, as some cases may have represented stroke mimics. Third, headache interviews were conducted during long‐term follow‐up visits rather than at the index event, increasing the potential for recall bias. Owing in part to pandemic‐related constraints, clinical information was obtained using different modalities, including face‐to‐face interviews, telephone interviews, and review of medical records, which may have introduced heterogeneity in data acquisition. Fourth, transoesophageal echocardiography was unavailable in a subset of patients (13.8%), and incomplete data on high‐risk PFO features precluded assessment of whether paradoxical embolism was the most likely stroke mechanism in these patients.

Strengths include the use of standardised headache assessments performed by headache specialists from a tertiary headache centre, predominantly through direct face‐to‐face evaluation, complemented by an extensive review of patient records. Headaches were classified according to the latest ICHD‐3 diagnostic criteria [17], supporting robust headache phenotyping. Finally, a comprehensive pre‐defined stroke work‐up enabled in‐depth characterisation of cardiovascular risk factors, stroke presentation, and aetiology.

Taken together, our results highlight the clinical relevance of migraine in young patients with ischaemic stroke, particularly regarding stroke characteristics, associated conditions such as PFO, and functional outcome. Migraine with and without aura demonstrated distinct clinical associations within our cohort. While patients with migraine generally showed favourable functional outcomes, MWoA—but not MWA—was independently associated with better outcome.

Future studies are needed to explore whether tailored management strategies—including preventive migraine treatment, lifestyle interventions, and evaluation of non‐traditional mechanisms—may improve care in this population.

Author Contributions

Katharina Kaltseis: writing – original draft, investigation, visualization, methodology, conceptualization, data curation, formal analysis. Silvia Felicetti: data curation, writing – review and editing, investigation. Anel Karisik: writing – review and editing, formal analysis, data curation. Benjamin Dejakum: data curation, writing – review and editing, investigation. Kurt Moelgg: writing – review and editing, data curation. Lukas Mayer‐Suess: writing – review and editing, data curation, project administration. Lena Weber: data curation, writing – review and editing, investigation. Michael Thomas Eller: data curation, writing – review and editing. Florian Frank: writing – review and editing. Gregor Broessner: project administration, supervision, methodology, conceptualization, writing – original draft. Samuel Labrecque: writing – review and editing, formal analysis. Christian Boehme: writing – review and editing, project administration, data curation. Stefan Kiechl: writing – review and editing, project administration, supervision, funding acquisition. Michael Knoflach: writing – review and editing, conceptualization, project administration, supervision. Thomas Toell: writing – review and editing, data curation, project administration. Alois Schiefecker: writing – review and editing.

Funding

The Medical University of Innsbruck served as the sponsor of this study. The project was funded by VASCage‐C (Research Centre on Vascular Ageing and Stroke), an R&D K‐Centre of the Austrian Research Promotion Agency (COMET program—Competence Centres for Excellent Technologies) funded by the Austrian Ministry for Transport, Innovation and Technology, the Austrian Ministry for Digital and Economic Affairs, and the federal states Tyrol, Salzburg, and Vienna with the grant number FSG 868624. Facilities for conduct of the trial are provided by the local hospitals of the study centres (Tirol Kliniken GmbH and Krankenhaus der Barmherzigen Brüder Wien). The funding body had no role in the design of the study, collection, analysis, interpretation of data, or in writing the manuscript.

Ethics Statement

Both STROKE‐CARD studies were performed in accordance with the Declaration of Helsinki and received approval from the local ethics committee of the Medical University of Innsbruck.

Consent

All required written patient consents were obtained.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.