Smoking confers no benefit on functional outcomes post-intracerebral haemorrhage
Nicotine may not have a neuroprotective effect on intracerebral haemorrhage (ICH) as previously suggested in animal studies, with former or current smokers demonstrating no difference in post-ICH functional outcomes compared with non-smokers, according to findings from the US-based ERICH* study.
“Our analysis of a large, multicentre cohort of ICH patients found no difference in the primary outcome [ie, modified Rankin scale (mRS) at 90 days] between ever-smokers and non-smokers,” said the researchers.
The study population comprised 1,509 non-smokers (54 percent male) and 1,423 ever-smokers (64 percent male), the latter categorized as former smokers (>30 days prior to ICH; n=841) or current smokers (≤30 days prior to ICH; n=577), with the remaining five ever-smokers having unknown timing of smoking status. The rate of comorbidities at baseline was higher among ever-smokers than non-smokers including history of ischaemic stroke (12 percent vs 8 percent) or myocardial infarction (11 percent vs 6 percent), hyperlipidaemia (48 percent vs 42 percent), and coronary artery disease (19 percent vs 14 percent; p<0.001 for all).
At 90 days post-ICH, functional outcomes, assessed through mRS score, were comparable between non-smokers and ever-smokers (adjusted odds ratio [adjOR], 1.041, 95 percent confidence interval [CI], 0.904–1.199; p=0.577), and this lack of difference persisted when ever-smokers were differentiated according to time of smoking (former or current smokers). [ISC 2019, abstract TP438; Stroke 2019;doi:10.1161/STROKEAHA.118.023580]
The rate of in-hospital mortality was lower among ever-smokers than non-smokers (adjOR, 0.744, 95 percent CI, 0.564–0.982; p=0.037), specifically former smokers (adjOR, 0.695, 95 percent CI, 0.500–0.968; p=0.031), though the benefit did not appear to persist beyond 90 days.
There were no between-group differences with regard to overall mortality at 90 days (adjOR, 0.997; p=0.978), Barthel index at 90 days (adjOR, 0.159; p=0.907), EuroQoL Group 5-Dimension (EQ-5D) score at 90 days (adjOR, -0.016; p=0.193), or EQ-5D visual analog scale score at 90 days (adjOR, -0.824; p=0.465), though current smokers had a lower EQ-5D score at 90 days (p=0.011), signifying worse health-related quality of life (HRQoL).
“Despite its many detrimental consequences, including potential associations with increased ICH risk, cigarette smoking may have paradoxical neuroprotective effects in patients presenting with ICH via the cholinergic anti-inflammatory pathway mediated by the nicotine content found in cigarettes,” said the researchers, referring to previous animal studies that have suggested this neuroprotective effect of nicotine. [J Neurosci Res 2017;95:1838-1849; Neuroscience 2012;222:10-19]
“[O]ur findings do not support the hypothesis of smoker’s paradox,” they highlighted, pointing out that the potential benefits of nicotine for ICH as suggested in the previous studies were outweighed by the “many detrimental systemic consequences of cigarette smoking”.
“Therefore, the combination of reduced in-hospital mortality and better functional outcomes in former smokers and worse HRQoL in current smokers after ICH underscores the importance of smoking cessation,” they said.
Study limitations included self-reporting of smoking history which may have led to bias, while nicotine exposure may have been inconsistent, varying by cigarette brands, number of cigarettes smoked, and, among former smokers, time between last cigarette smoked and ICH incidence.