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Cited by 75Coffee research and impactsAcute Ischemic Stroke ManagementAlcohol Consumption and Health Effects

Coffee and acute ischemic stroke onset: The Stroke Onset Study

Open access
Mostofsky, E., Schlaug, G., Mukamal, K.J., Rosamond, W.D., Mittleman, M.A.·2010·Neurology
DOI 10.1212/wnl.0b013e3181fb443dPMC PMC3120108
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Abstract

OBJECTIVE: Prior research suggests an acutely elevated risk of myocardial infarction and sudden cardiac death in the hour after coffee intake. However, the risk of ischemic stroke associated with transient exposure to coffee remains unclear. We hypothesized that caffeine intake is associated with a transiently increased risk of ischemic stroke. METHODS: In this multicenter case-crossover study, we interviewed 390 subjects (209 men, 181 women) between January 2001 and November 2006 a median of 3 days after acute ischemic stroke. Each subject's coffee consumption in the hour before stroke symptoms was compared with his or her usual frequency of consumption in the prior year. RESULTS: Of the 390 subjects, 304 (78%) drank coffee in the prior year, 232 within 24 hours and 35 within 1 hour of stroke onset. The relative risk (RR) of stroke in the hour after consuming coffee was 2.0 (95% confidence interval [CI], 1.4-2.8; p < 0.001). There was no apparent increase in risk in the hour following consumption of caffeinated tea (RR = 0.9, 95% CI 0.4-2.0; p = 0.85) or cola (RR = 1.0, 95% CI 0.4-2.4; p = 0.95). The association between ischemic stroke in the hour after coffee consumption was only apparent among those consuming ≤1 cup per day but not for patients who consumed coffee more regularly (p for trend = 0.002). Relative risks remained similar when the sample was restricted to those who were not simultaneously exposed to other potential triggers and the results remained significant after stratifying by time of day. CONCLUSION: Coffee consumption transiently increases the risk of ischemic stroke onset, particularly among infrequent drinkers.

AI snapshot

Written from the paper’s full text.

TL;DR

In a multicenter case-crossover study of 390 acute ischemic stroke patients, coffee consumption was associated with a transient doubled risk of ischemic stroke in the following hour (RR 2.0, 95% CI 1.4–2.8). The risk was apparent among infrequent coffee drinkers and was not seen after caffeinated tea or cola.

Key findings

  • Among 304 subjects who drank coffee in the prior year, 35 consumed coffee within 1 hour of stroke onset; the relative risk of ischemic stroke in the hour after coffee consumption was 2.0 (95% CI 1.4–2.8; p < 0.001), and risk returned to baseline thereafter.
  • No elevated risk was found in the hour after caffeinated tea (RR 0.9, 95% CI 0.4–2.0; p = 0.85) or cola (RR 1.0, 95% CI 0.4–2.4; p = 0.95).
  • The association was only apparent among those consuming ≤1 cup per day, not regular coffee drinkers (p for trend = 0.002). A sensitivity analysis assuming all past-year coffee was consumed from 6 AM–9 AM still showed increased risk (RR 3.8, 95% CI 2.0–7.0; p < 0.001).
  • RRs did not vary significantly by sex (p = 0.13), age (p = 0.56), smoking status (p = 0.22), physical activity (p = 0.44), or stroke etiology (p = 0.29).

Methods

  • Multicenter case-crossover study conducted at 3 medical centers between January 2001 and November 2006; 390 subjects (209 men, 181 women) were interviewed a median of 3 days after acute ischemic stroke, and 304 reported coffee consumption in the prior year.
  • Each subject’s coffee consumption in the hour before stroke symptoms (case period) was compared with his or her usual frequency of coffee consumption in the prior year (control period); rate ratios were calculated as relative risks, with similar analyses for caffeinated tea and cola.
  • Eligibility required neurologist-confirmed acute ischemic stroke, English-speaking status, and no dementia before the index event; exclusions included cognitive impairment, poor memory around stroke, inability to identify symptom onset, aphasia, or being too ill. Questionnaire reliability in 25 re-interviewed subjects showed intraclass correlation 0.96 for usual coffee frequency and agreement κ = 0.96 for any coffee in the past year and κ = 0.88 for coffee in the hour before stroke onset.

Limitations

  • The paper states that it did not collect information on coffee type, preparation method, or decaffeinated beverages; it also notes possible confounding by time-varying factors, possible residual confounding by time of day, and limited power to determine whether effects varied by clinical characteristics or stroke etiology.
  • The paper states that recall bias may occur if subjects systematically misreport usual exposure frequency versus exposure in the hour before stroke, potentially biasing the RR upward; participation bias could also overestimate the RR if patients whose strokes were triggered by coffee were more likely to participate or had milder strokes.
  • The paper states that patients with aphasia, memory difficulties, or severe/incapacitating strokes were excluded, so results may not be generalizable to severe or fatal stroke; the text also makes evident that exposure and timing relied on self-report from a structured interview.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1212/wnl.0b013e3181fb443d

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 29 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In a sensitivity analysis using the conservative assumption that all coffee in the past year is only consumed in the morning (6 AM-9 AM), coffee consumption was still associated with an increased risk of ischemic stroke onset (RR=3.8, 95% CI 2.0-7.0; p<0.001).

    “In a sensitivity analysis using the conservative assumption that all coffee in the past year is only consumed in the morning (6 AM-9 AM), coffee consumption was still associated with an increased risk of ischemic stroke onset (RR ϭ 3.8, 95% CI 2.0 -7.0; p Ͻ 0.001).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: All coffee consumed in the past year was consumed only in the morning (6 AM-9 AM).
  • Findingown data

    When the analysis excluded the 75 people exposed to any potential stroke trigger in the hour preceding stroke onset, the results remained similar.

    “When we conducted an analysis excluding the 75 people exposed to any potential stroke trigger in the hour preceding stroke onset, the results remained similar.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Within 1 hour after coffee consumption, the risk of stroke onset was 2.0-fold higher (95% CI 1.4-2.8; p<0.001) compared with periods of nonuse.

    “We found that within 1 hour after coffee consumption, the risk of stroke onset was 2.0fold higher (95% confidence interval [CI] 1.4 -2.8; p Ͻ 0.001) compared with periods of nonuse”
    Quote in the paperSubstantial claim
  • Findingown data

    Among the 304 subjects who drank coffee in the prior year, 35 subjects consumed at least 1 serving of coffee within 1 hour of the onset of stroke symptoms.

    “Among the 304 subjects who drank coffee in the prior year, 35 subjects consumed at least 1 serving of coffee within 1 hour of the onset of stroke symptoms (the case period).”
    Quote in the paperSubstantial claim
  • Findingown data

    The risk of ischemic stroke rapidly returned to baseline after the first hour following coffee consumption.

    “and it rapidly returned to baseline thereafter.”
    Quote in the paperSubstantial claim
  • May combine two claims. 16
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Findingown data

    On average, subjects reported almost identical levels of coffee consumption in the week preceding the stroke and in the prior year, so the RR did not change when using each subject's reported frequency of consumption in the past week to estimate control periods.

    “On average, subjects reported almost identical levels of coffee consumption in the week preceding the stroke and in the prior year, so the RR did not change when we used each subject's reported frequency of consumption in the past week to estimate control periods.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among the 304 subjects who drank coffee in the prior year, the median frequency of consumption was 7 times per week.

    “the median frequency of consumption was 7 times per week.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Compared to nondrinkers, subjects who reported coffee consumption within the past year were more likely to be current smokers and less likely to have a history of atrial fibrillation.

    “Compared to nondrinkers, subjects who reported coffee consumption within the past year were more likely to be current smokers and they were less likely to have a history of atrial fibrillation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    When stratified by daily intake of caffeinated coffee in the past week, the association between ischemic stroke in the hour after coffee consumption was only apparent among those consuming 1 or fewer cups per day but not for patients who consumed coffee more regularly (p for trend=0.002).

    “When we stratified by daily intake of caffeinated coffee in the past week, the association between ischemic stroke in the hour after coffee consumption was only apparent among those consuming 1 or fewer cups per day but not for patients who consumed coffee more regularly ( p for trend ϭ 0.002; figure 2).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The average amount of person-time exposed to coffee in the prior year (control period) was 364 hours per subject.

    “Thus, the average amount of persontime exposed to coffee in the prior year (the control period) was 364 hours per subject.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The risks of ischemic stroke in the hour following consumption of caffeinated tea (RR=0.9, 95% CI 0.4-2.0; p=0.85) or cola (RR=1.0, 95% CI 0.4-2.4; p=0.95) were not elevated.

    “The risks of ischemic stroke in the hour following consumption of caffeinated tea (RR ϭ 0.9, 95% CI 0.4 -2.0; p ϭ 0.85) or cola (RR ϭ 1.0, 95% CI 0.4 -2.4; p ϭ 0.95) were not elevated (figure 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The RRs for coffee consumption did not vary by sex, age, smoking status, physical activity, or stroke etiology.

    “The RRs for coffee consumption did not vary by sex ( p ϭ 0.13), age ( p ϭ 0.56), smoking status ( p ϭ 0.22), physical activity ( p ϭ 0.44), or stroke etiology ( p ϭ 0.29).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Prior research suggests an acutely elevated risk of myocardial infarction and sudden cardiac death in the hour after coffee intake.

    “Prior research suggests an acutely elevated risk of myocardial infarction and sudden cardiac death in the hour after coffee intake.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [9] source

      Not checked in the free run.

    • cites [10]

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    There was high agreement for reporting of any coffee consumption during the past year (kappa=0.96) and during the hour preceding stroke onset (kappa=0.88).

    “there was high agreement for reporting of any coffee consumption during the past year ( ϭ 0.96) and during the hour preceding stroke onset ( ϭ 0.88).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Evidence from experimental studies indicates that coffee acutely increases circulating concentrations of (nor)epinephrine, raises systolic and diastolic blood pressure, increases arterial stiffness, and impairs endothelium-dependent vasodilation.

    “Evidence from experimental studies indicates that coffee acutely increases circulating concentrations of (nor)epinephrine, 2 raises systolic and diastolic blood pressure, 3 increases arterial stiffness, 5,6 and impairs endothelium-dependent vasodilation.7”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [2] source

      Not checked in the free run.

    • cites [3] source

      Not checked in the free run.

    • cites [5] source

      Not checked in the free run.

    • cites [6] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Coffee consumption transiently increases the risk of ischemic stroke onset, particularly among infrequent drinkers.

    “Coffee consumption transiently increases the risk of ischemic stroke onset, particularly among infrequent drinkers.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Some studies have shown that habitual consumption results in tolerance to the acute effects of caffeine, while others have found that some individuals continue to experience these acute effects with each drinking episode and that tolerance disappears after 12 hours of abstinence.

    “Some studies have shown that habitual consumption results in a tolerance to the acute effects of caffeine, 18,19 while others have found that some individuals continue to experience these acute effects with each drinking episode 20,21 and that the tolerance disappears after 12 hours of abstinence.22”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [18] source

      Not checked in the free run.

    • cites [19] source

      Not checked in the free run.

    • cites [20] source

      Not checked in the free run.

    • cites [21] source

      Not checked in the free run.

    • cites [22] source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    In an effort to minimize reporting bias and maintain subject confidentiality, efforts were made to ensure the subject's privacy during the interview; a standardized structured interview was used and subjects were not informed of the duration of the hypothesized case period.

    “In an effort to minimize reporting bias and to maintain subject confidentiality, efforts were made to ensure the subject's privacy during the interview.We used a standardized structured interview and subjects were not informed of the duration of the hypothesized case period.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The RR for recent coffee consumption did not vary by stroke etiology, suggesting that the role of coffee as a stroke trigger does not differ by stroke mechanism and is unlikely to vary by severity.

    “However, the RR for recent coffee consumption did not vary by stroke etiology, suggesting that the role of coffee as a stroke trigger does not differ by stroke mechanism and is unlikely to vary by severity.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Confounding by factors that change over time within individual subjects can occur if other transient risk factors occur during the case period of interest.

    “However, confounding by factors that change over time within individual subjects can occur if other transient risk factors occur during the case period of interest.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    If patients whose strokes were triggered by coffee consumption were more likely to participate or had milder strokes than those whose strokes were unrelated to coffee, the apparent RR might be overestimated.

    “If patients whose strokes were triggered by coffee consumption were more likely to participate or had milder strokes than those whose strokes were unrelated to coffee, the apparent RR might be overestimated.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A similar study reported that the RR of dying from sudden cardiac death within an hour after drinking a cup of coffee was 73% higher (95% CI 1.1-2.7) than periods with no coffee consumption.

    “A similar study 10 reported that the RR of dying from sudden cardiac death within an hour after drinking a cup of coffee was 73% higher (95% CI 1.1-2.7)than periods with no coffee consumption.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10]

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Though there may be residual confounding by time of day, the findings are not fully explained by the co-occurrence of coffee and the circadian peak in stroke onset.

    “Though there may be residual confounding by time of day, this suggests that the findings are not fully explained by the co-occurrence of coffee and the circadian peak in stroke onset.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation

    The case-crossover design uses subjects as their own controls, so there is no variability in traditional risk factors for stroke.

    “Since the casecrossover design uses subjects as their own controls, there is no variability in traditional risk factors for stroke.11”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    If subjects overestimate exposure in the period immediately before the stroke and underestimate exposure in the past year, the RR may be biased upwards.

    “If subjects overestimate exposure in the period immediately before the stroke and underestimate exposure in the past year, the RR may be biased upwards.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    These results are concordant with our finding of no increased risk among those who drink coffee regularly, suggesting that habitual consumption results in a tolerance to the acute effects of caffeine.

    “These results are concordant with our finding of no increased risk among those who drink coffee regularly, suggesting that habitual consumption results in a tolerance to the acute effects of caffeine.18,19”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [18] source

      Not checked in the free run.

    • cites [19] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There have been discrepant findings on the association between habitual coffee intake and ischemic stroke.

    “There have been discrepant findings on the association between habitual coffee intake and ischemic stroke.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [23] source

      Not checked in the free run.

    • cites [24] source

      Not checked in the free run.

    • cites [25] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    One study found that total coffee consumption was not associated with an increased stroke risk in men.

    “One study found that total coffee consumption was not associated with an increased stroke risk in men 23”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Another study found that coffee consumption was associated with an increased risk of ischemic stroke among hypertensive men who reported no previous or current smoking.

    “and another study found that coffee consumption was associated with an increased risk of ischemic stroke among hypertensive men who reported no previous or current smoking.24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    Based on previous research, the a priori hypothesis was focused on caffeinated coffee consumption, so information on coffee type or preparation method or consumption of decaffeinated beverages was not collected.

    “Based on previous research, our a priori hypothesis was focused on caffeinated coffee consumption so we did not collect information on the coffee type or preparation method or on consumption of decaffeinated beverages.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    The patients interviewed tended to have milder strokes, as those with aphasia, memory difficulties, or severe strokes leaving them incapacitated or too ill to be interviewed were excluded from the study.

    “The patients we interviewed tended to have milder strokes, as those with aphasia, memory difficulties, or severe strokes leaving them incapacitated or too ill to be interviewed were excluded from the study.”
    Quote in the paperSubstantial claim
26 of 26

  • The authors state this as an assumption.

    All coffee consumed in the past year was consumed only in the morning (6 AM-9 AM).

    “We made the conservative assumption that all coffee in the past year is only consumed during that time of day, which should result in a conservative estimate of the RR.”

  • The paper relies on this without support.

    The risk of ischemic stroke associated with transient exposure to coffee remains unclear.

    “However, the risk of ischemic stroke associated with transient exposure to coffee remains unclear.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In the Health Examinees study, coffee consumption was not significantly associated with stroke risk among men, but higher coffee consumption was inversely associated with stroke incidence in women.

    “A survey of about 15,000 men and women between 40 and 69 years of age did not show any significant association between coffee consumption and stroke risk among men. However, in the case of young women, the inverse relationship between coffee consumption and stroke risk was prominent. In other words, higher coffee consumption was found to be inversely proportional to the incidence rate of stroke in”

    From Effect of Caffeine Consumption on the Risk for Neurological and Psychiatric Disorders: Sex Differences in Human (2020) · cites this paper as [93]

  • Results from case-crossover studies suggest that coffee consumption transiently increases the risk of nonfatal myocardial infarction, ischemic stroke onset, and sudden cardiac death.

    “Results from case crossover studies suggest that coffee consumption transiently increases risk of nonfatal myocardial infarction, ischemic stroke onset, and sudden cardiac death.44–46”

    From Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose–Response Meta-Analysis of Prospective Cohort Studies (2014) · cites this paper as [46]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Current smokers among nondrinkers are mispercentaged

    Minor

    The table reports 8 current smokers among 85 nondrinkers as 10%. That fraction is 9.41%, which rounds to 9% at the table's precision.

    Reported 10 · recomputed 9.411765

1 of 1

Cites

Flagged first, then by citations

1 of the 35 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Rothman KJ Greenland S Lash TL. Modern Epidemiology 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2008.

Cited by

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Related

Authors
Mostofsky, E., Schlaug, G., Mukamal, K. J., Rosamond, W. D., & Mittleman, M. A.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • From the Department of Medicine (E.M., K.J.M., M.A.M.), Department of Neurology (G.S.), and Division of General Medicine &amp; Primary Care (K.J.M.), Cardiovascular Epidemiology Research Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston; Department of Epidemiology (E.M., M.A.M.), Harvard School of Public Health, Boston, MA; and Department of Epidemiology (W.D.R.), University of North Carolina School of Public Health, Chapel Hill.
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2010-11-02
Volume
75
Issue
18
Pages
1583-1588
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0b013e3181fb443d
PMC
PMC3120108
OpenAlex
W2109361865
Semantic Scholar
e5299a5a774e8ce7c0ae8dcb06eb04a4efeca43d
Cited by
75
References
35
Citations by year
2026: 6 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 6 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 9 · 2012: 4
FWCI
5.63
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association
  • National Institutes of Health
  • U.S. Public Health Service (T32 A1007535-11)
  • National Institute of Allergy and Infectious Diseases
Topics
  • Health Sciences › Medicine › Pharmacology › Coffee research and impacts
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords
coffee consumption, acute ischemic stroke, caffeine, cola, case-crossover design
MeSH terms
Aged, Aged, 80 and over, Coffee, Female, Humans, Male, Middle Aged, Surveys and Questionnaires, Retrospective Studies, Risk Factors, Reproducibility of Results, Confidence Intervals, Case-Control Studies, Cross-Over Studies, Stroke

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