PDF: INTERSTROKE
(2024)Objective
To examine the associations between tea and coffee consumption and risk of acute stroke using a large, multicenter, matched case-control study.
Study Summary
• High coffee intake (>4/day) was associated with higher stroke odds (OR 1.37), lower coffee consumption had no effect on stroke.• Tea intake linked to reduced stroke odds
Intervention
Observational exposure comparison: none vs. low/moderate vs. high consumption of coffee and various teas.
Inclusion Criteria
Cases: First-ever stroke within 5 days of symptom onset. Controls: age-, sex-, and region-matched individuals without stroke.
Study Design
Arms: Tea only vs. Coffee only vs. Both vs. None
Patients per Arm: Tea only: 12,666; Coffee only: 4024; Both: 5021; None: 5239
Outcome
• High coffee intake (>4/day) associated with higher stroke odds (OR 1.37). <br>• Tea intake linked to reduced stroke odds (OR 0.81 for highest intake). <br>• Black and green tea both showed protective effects..
Bottom Line
High coffee intake (>4 cups/day) was associated with increased odds of all stroke and ischemic stroke, while tea consumption (including black, green, and other tea types) was associated with reduced odds of stroke.
Major Points
- INTERSTROKE is a large, international case–control study of 26,950 participants (13,462 cases, 13,488 controls) from 32 countries across 142 centers — the largest study of tea/coffee and stroke risk to date.
- High coffee consumption (>4 cups/day) was associated with increased odds of all stroke (OR 1.37, 95% CI 1.06–1.77) and ischemic stroke (OR 1.32, 95% CI 1.00–1.74), contrasting with prospective cohort studies that mostly show coffee as protective — likely reflecting case-control design limitations.
- Low-to-moderate coffee intake (1–4 cups/day) showed no significant association with stroke risk, suggesting a threshold effect rather than linear dose-response.
- Tea consumption (any type, ≥4 cups/day) was associated with reduced odds of all stroke (OR 0.81) and ischemic stroke, with the strongest effect at 3–4 cups/day — consistent with polyphenol/catechin-mediated endothelial protection.
- Black tea intake (3–4 cups/day) showed a striking protective effect against ICH (OR 0.41, 95% CI 0.22–0.78), though based on relatively few ICH events and requiring confirmation.
- Green tea (≥4 cups/day) was associated with reduced odds of all stroke (OR 0.70, 95% CI 0.52–0.94), consistent with prior Asian cohort data from the JPHC and Shanghai Women's Health studies.
- Marked regional heterogeneity: tea was protective in China and South America but paradoxically increased stroke risk in South Asia — likely reflecting confounding by preparation method, additives (sugar, milk), and co-consumed foods.
- Milk addition modified the tea-stroke association: tea without milk was protective, while tea with milk showed attenuated benefit, possibly through casein binding of catechins.
- The study is a subanalysis of the landmark INTERSTROKE study (O'Donnell et al., Lancet 2010/2016) which identified 10 modifiable risk factors accounting for 90% of stroke risk globally.
- Hypertension modified the coffee-stroke association: the harmful effect of high coffee consumption was more pronounced in hypertensive individuals, consistent with the acute pressor effect of caffeine.
Study Design
- Study Type
- International matched case–control study
- Randomization
- No
- Sample Size
- 26950
- Centers
- 142
- Countries
- Canada, Ireland, Australia, UK, Poland, Sweden, India, USA, China, Colombia, Ecuador, Mozambique, Denmark, Chile, and others
Primary Outcome
Definition: Association of tea and coffee consumption with risk of all stroke and ischemic stroke
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| No coffee: Reference group | High coffee: OR 1.37 for all stroke, OR 1.32 for ischemic stroke | - (1.06–1.77 (all stroke); 1.00–1.74 (ischemic stroke)) |
Limitations & Criticisms
- Case-control design is inherently susceptible to recall bias — stroke patients may recall dietary habits differently from controls, and hospitalized cases may have altered intake patterns preceding the event.
- Self-reported intake measured at a single time point may not reflect long-term cumulative exposure or recent changes in consumption patterns before stroke.
- No data on coffee preparation method (filtered vs unfiltered/boiled), roast type, or decaffeination — diterpenes in unfiltered coffee have different cardiovascular effects than filtered.
- Limited power for ICH subgroup analyses — the striking black tea OR 0.41 for ICH was based on few events and had wide confidence intervals (0.22–0.78).
- Potential for residual confounding despite multivariable adjustment — tea and coffee consumption correlates with socioeconomic status, diet quality, exercise, and healthcare access differently across regions.
- Cup size was not standardized across 32 countries — a 'cup' in Scandinavia (~250 mL) differs substantially from espresso cultures (~30–60 mL), introducing measurement heterogeneity.
- Contradicts large prospective cohort studies (Nurses' Health Study, Health Professionals Follow-up Study) showing coffee as protective — case-control design and reverse causation may explain this discrepancy.
- Regional heterogeneity in tea-stroke associations (protective in China, harmful in South Asia) likely reflects unmeasured confounding by preparation method and additives rather than a true biological interaction.
- No biomarker validation of self-reported intake — caffeine metabolites or polyphenol biomarkers would strengthen causal inference but were not measured.
Citation
Int J Stroke. 2024;19(9):1053–1063. doi:10.1177/17474930241264685