Cigarette Smoking and Risk of Different Pathologic Types of Stroke: A Systematic Review and Dose-Response Meta-Analysis

Abstract

Objectives: To quantify the association of cigarette smoking, including cigarettes per day and quitting duration, with the risk of different types of stroke morbidity and mortality in the general population, and to clarify the shape of the dose-response relations.

Study selection: Prospective cohort studies and reported on the association between smoking, quitting and the incidence or mortality of stroke were included.

Data extraction and synthesis: All available data were converted uniformly to odds ratios (ORs) and were pooled using random-effects meta-analysis with inverse variance weighting. A dose-response meta-analysis was performed to explore the quantitative relationship between different smoking characteristics and the risk of different pathologic types of stroke incidence.

Results: Twenty-five studies with 3,734,216 individuals were included. Compared to never smokers, the pooled ORs of stroke morbidity and mortality were 1.45 (1.24-1.70) and 1.44 (1.23-1.67) among ever smokers and 1.90 (1.55-2.34) and 1.70 (1.45-1.98) among current smokers. The risk of different pathologic types of stroke was also increased among ever and current smokers. There was a significant non-linear dose-response association between the number of cigarette smoking and the risk of stroke incidence. Comparing no smoking, the ORs for smoking five and 35 cigarettes per day were 1.44 (1.35-1.53) and 1.86 (1.71-2.02). Other pathologic types of stroke have a similar dose-response relationship. There was also non-linear dose-response association between the length of time since quitting and risk of stroke. The risk of stroke decreased significantly after quitting for 3 years [OR = 0.56 (0.42-0.74)].

Conclusion: The risk of different types of stroke among smokers is remarkably high. Our findings revealed a more detailed dose-response relationship and have important implications for developing smoking control strategies for stroke prevention.

Systematic review registration: https://inplasy.com/inplasy-2020-6-0062/, identifier: INPLASY202060062.

Keywords: cigarette smoking; dose-response; meta-analysis; quantitative relationship; stroke.

Figure 1

Flow diagram of the literature search.

Figure 2

Forest plot of the primary outcome. CL, confidence interval.

Figure 3

Non-linear dose-response analyses of smoking/quitting and risk of stroke in meta-analysis. (A) Association between CPD and risk of stroke incidence restricted cubic splines with four knots (0, 5, 15.5, 35 CPD) and 0 CPD as a reference. P non-linearity = 0.0000. (B) Association between the length of time since quitting and the risk of stroke incidence restricted cubic splines with four knots (0, 1, 6, 22.5 years) and quitting 0 years as a reference. P non-linearity = 0.0022. The solid line represents the estimated OR, and the dashed lines represent the 95% CI.

Figure 4

Non-linear dose-response analyses of smoking/quitting and risk of IS/HS/SAH in meta-analysis. (A) Association between dose of cigarette consumption and risk of Ischemic stroke incidence restricted cubic splines with 4 knots (0, 5, 15, 37.5 CPD) and 0 CPD as reference. P non-linearity = 0.0000. Solid line represents the estimated OR and the dashed lines represent the 95% CI. OR = 1.73, 95% CI 1.59–1.90, for 10 CPD; OR = 1.88, 95% CI 1.74–2.04, for 30 CPD. (B) Association between dose of cigarette consumption and risk of Hemorrhagic stroke incidence restricted cubic splines with 4 knots (0, 5, 19.5, 37.5 CPD) and 0 CPD as reference. P non-linearity = 0.0447. Solid line represents the estimated OR and the dashed lines represent the 95% CI. OR = 1.53, 95% CI 1.23–1.91, for 10 CPD; OR = 2.34, 95% CI 1.83–2.97, for 30 CPD. (C) Association between dose of cigarette consumption and risk of Subarachnoid Hemorrhage incidence restricted cubic splines with 4 knots (0, 6.5, 21, 49.5 CPD) and 0 CPD as reference. P non-linearity = 0.0002. Solid line represents the estimated OR and the dashed lines represent the 95% CI. OR = 2.24, 95% CI 1.90–2.64, for 10 CPD; OR = 2.55, 95% CI 2.16–3.01, for 30 CPD. (D) Association between the length of time since quitting and risk of Ischemic stroke incidence restricted cubic splines with 4 knots (0, 1, 5.5, 22.5 year) and quitting 0 year as reference. P non-linearity = 0.0022. Solid line represents the estimated OR and the dashed lines represent the 95% CI. OR = 0.59, 95% CI 0.48–0.73, for 3 year; OR = 0.51, 95% CI 0.44–0.60, for 15 year; OR = 0.32, 95% CI 0.17–0.59, for 22.5 year.