BMJ Open. 2026 Jun 30;16(6):e116158. doi: 10.1136/bmjopen-2025-116158.
ABSTRACT
OBJECTIVES: While smoking is a well-established risk factor for various cardiovascular diseases, its association with intracerebral haemorrhage (ICH) remains controversial. Cerebral microbleeds (CMBs) are markers of haemorrhage-prone small vessel disease, but ICH can also occur without detectable CMBs. Therefore, we investigated the association between smoking and ICH according to CMB status.
DESIGN: Single-centre retrospective case-control study.
SETTING: A tertiary stroke centre in Osaka, Japan (2017-2021).
PARTICIPANTS: 487 patients with ICH as their first stroke (female sex 41.5%) and 322 controls with non-stroke neurological conditions (female sex 47.5%) were included. Patients with missing CMB evaluation or smoking status data were excluded.
PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was ICH status, analysed according to CMB status, with current smoking as the primary exposure. Secondary analyses evaluated the association between smoking cessation duration and the odds of ICH, using current smoking as the reference.
RESULTS: Patients with ICH (median age, 70.0 years; presence of CMBs, 53.6%) and controls (median age, 71.0 years; presence of CMBs, 13.4%) were analysed. Among individuals without CMBs, current smoking was more frequently observed in patients with ICH than in controls (25.7% vs 14.0%, p<0.001) and was independently associated with ICH following adjustment for potential confounders (adjusted OR (aOR) 1.84, 95% CI 1.02 to 3.31, p=0.042). Long-term smoking cessation (>10 years) was associated with lower odds of ICH than current smoking (aOR 0.31, 95% CI 0.14 to 0.67, p=0.003), whereas short-term cessation (≤10 years) showed no significant difference. Among individuals with CMBs, no significant association was observed between smoking status and ICH.
CONCLUSIONS: Current smoking was associated with higher odds of ICH among individuals without CMBs, whereas long-term cessation was associated with lower odds. These findings suggest that the absence of CMBs should not be interpreted as the absence of modifiable ICH risk, highlighting the clinical relevance of smoking history in this population.
TRIAL REGISTRATION NUMBER: NCT02251665.
PMID:42379713 | DOI:10.1136/bmjopen-2025-116158