Serum Cotinine–Defined Tobacco Exposure and Its Association With Stroke, Mortality, and Cognitive Outcomes: Evidence From NHANES 2003 to 2018

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-03 DOI:10.1016/j.clinthera.2026.03.009

Pengtao Qin MSc , Rongrong Chen MSc , Hongyan Zhang BS , Zhuo Li BS , Chongli Zhang MSc , Ying Wang MSc , Liujun Chang BS

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引用次数: 0

Abstract

Purpose

To examine the association between serum cotinine—an objective biomarker of recent tobacco smoke exposure from active smoking and secondhand smoke—and stroke, all-cause mortality, and cognitive outcomes among US adults using National Health and Nutrition Examination Survey (NHANES) 2003 to 2018 data.

Methods

We conducted a cross-sectional analysis of NHANES 2003 to 2018. Serum cotinine was categorized into quartiles and also evaluated per interquartile range (IQR) increase. All analyses accounted for the complex NHANES sampling design (weights, strata, and primary sampling units). Associations with stroke were examined using survey-weighted multivariable logistic regression. Mortality outcomes from NHANES-linked mortality files were evaluated using survey-weighted Cox proportional hazards models and Kaplan–Meier curves with log-rank tests; these analyses were interpreted as associational. Cognitive outcomes were dichotomized using test-specific 25th-percentile cutoffs and analyzed using survey-weighted logistic regression; ORs represent the odds of preserved cognition (≥25th percentile). Prespecified subgroup analyses (by sex, race/ethnicity, education, and Composite Dietary Antioxidant Index) were conducted, and multiplicative interaction terms were tested.

Findings

A total of 8285 participants were included, of whom 592 reported a physician diagnosis of stroke. Per IQR increase in serum cotinine, higher cotinine was associated with higher odds of stroke (OR 1.50, 95% CI 1.19–1.90). Among participants with stroke, higher cotinine was associated with higher all-cause mortality (per IQR increase: HR 1.30, 95% CI 1.08–1.56). Higher cotinine was also associated with lower odds of preserved cognition on Animal Fluency Test and CERAD (OR 0.67, 95% CI 0.62–0.73; OR 0.94, 95% CI 0.89–0.99, respectively). In exploratory subgroup analyses, associations appeared stronger in women and non-Hispanic White participants.

Implications

Higher serum cotinine levels were associated with stroke, all-cause mortality among individuals with stroke, and cognitive impairment in NHANES 2003 to 2018. These findings are observational and do not establish causality; prospective studies are warranted to clarify temporality and to evaluate the effects of tobacco exposure reduction or cessation interventions on stroke-related outcomes.

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血清可替宁定义的烟草暴露及其与中风、死亡率和认知结果的关系：来自NHANES 2003至2018的证据

目的：利用2003年至2018年美国国家健康与营养检查调查（NHANES）的数据，研究血清可替宁（一种反映主动吸烟和二手烟近期烟草烟雾暴露的客观生物标志物）与美国成年人中风、全因死亡率和认知结局之间的关系。方法：对2003年至2018年的NHANES进行横断面分析。血清可替宁被分为四分位数，并评估每四分位数范围（IQR）的增加。所有分析都考虑了复杂的NHANES抽样设计（权重、地层和主要抽样单位）。使用调查加权多变量logistic回归检验与中风的关系。使用调查加权Cox比例风险模型和Kaplan-Meier曲线进行log-rank检验，评估nhanes相关死亡档案的死亡结果；这些分析被解释为关联性。认知结果采用特定测试的第25百分位截断点进行二分类，并使用调查加权逻辑回归进行分析；ORs代表保留认知的几率（≥25百分位数）。进行了预先指定的亚组分析（按性别、种族/民族、教育程度和复合膳食抗氧化指数），并测试了乘法相互作用项。研究结果：共纳入8285名参与者，其中592人报告医生诊断为中风。血清可替宁每增加IQR，较高的可替宁与较高的卒中几率相关（OR 1.50, 95% CI 1.19-1.90）。在卒中患者中，较高的可替宁与较高的全因死亡率相关（每IQR增加：HR 1.30, 95% CI 1.08-1.56）。较高的可替宁还与动物流畅性测试和CERAD中保留认知的几率较低相关（OR分别为0.67,95% CI 0.62-0.73； OR为0.94,95% CI 0.89-0.99）。在探索性亚组分析中，女性和非西班牙裔白人参与者的关联更强。含义：在NHANES 2003 - 2018中，较高的血清可替宁水平与卒中、卒中患者的全因死亡率和认知障碍有关。这些发现是观察性的，不能建立因果关系；有必要进行前瞻性研究，以澄清其时间性，并评估减少烟草接触或戒烟干预对卒中相关结果的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical therapeutics 医学-药学

CiteScore

6.00

自引率

3.10%

发文量

154

审稿时长

9 weeks

期刊介绍： Clinical Therapeutics provides peer-reviewed, rapid publication of recent developments in drug and other therapies as well as in diagnostics, pharmacoeconomics, health policy, treatment outcomes, and innovations in drug and biologics research. In addition Clinical Therapeutics features updates on specific topics collated by expert Topic Editors. Clinical Therapeutics is read by a large international audience of scientists and clinicians in a variety of research, academic, and clinical practice settings. Articles are indexed by all major biomedical abstracting databases.