Background: Uncertainties persist regarding the precise shape of the smoking-outcome curves across various cardiovascular and mortality endpoints. This study aims to elucidate the relationships among smoking burden, intensity, and cessation duration across multiple cardiovascular outcomes. Methods and findings: Cox proportional hazard models were constructed to evaluate the association between pack-years, cigarettes per day (CPD), and years since cessation with cardiovascular outcomes in participants from 22 prospective cohort studies within the Cross-Cohort Collaboration Tobacco Working Group. We evaluated myocardial infarction (MI), stroke, coronary heart disease (CHD; MI, coronary revascularization, or coronary death), cardiovascular disease (CVD; stroke or cardiovascular death), heart failure (HF), atrial fibrillation (AFib), CHD mortality, CVD mortality, and all-cause mortality. Median follow-up varied across outcomes, with 14.4 years for MI (17,570 events), 19.3 years for CHD (30,625 events), 18.6 years for CVD (54,078 events), and approximately 19.4–19.9 years for mortality outcomes (CHD mortality: 17,429 events; CVD mortality: 33,120 events; all-cause mortality: 125,044 events). Spline terms were used to investigate the nonlinear association of continuous smoking/cessation measures with the examined outcomes. Models were adjusted for demographic, socioeconomic, and other cardiovascular risk factors. The study included 323,826 adults (148,635 non-mortality and 176,396 mortality outcomes with 25 and 16 million person-years at risk, respectively). Compared to never-smokers, current smokers had significantly increased risks for CVD (hazard ratio (HR) 1.74, 95% confidence intervals (CIs) [1.66,1.83] in men; HR 2.07, 95% CI [2.00,2.14] in women) and all-cause mortality (HR 2.17, 95% CI [2.09,2.25] in men; HR 2.43, 95% CI [2.38,2.48] in women; all p < 0.001). Compared with never-smokers, participants with 2–5 CPD demonstrated substantially elevated cardiovascular risks, with HR ranging from 1.26 (95% CI [1.09,1.45], p = 0.002) for AFib to 1.57 (95% CI [1.39,1.78], p < 0.001) for HF. Smoking 2–5 CPD was associated with increased CVD mortality (HR 1.57, 95% CI [1.41,1.75]), and all-cause mortality (HR 1.60, 95% CI [1.52,1.69]; both p < 0.001). Smoking 11–15 CPD conferred a higher risk of CVD (HR 1.87, 95% CI [1.69,2.06]) and all-cause mortality (HR 2.30, 95% CI [2.14,2.47]; both p < 0.001). The increased risk associated with the evaluated outcomes was steeper for the initial 20 pack-years and 20 CPD, respectively, compared to further smoking exposure. The most substantial reduction in risk across all outcomes was observed within the first 10 years after smoking cessation. However, the progressive risk reduction continues over extended time periods, with former smokers demonstrating over 80% lower relative risk than those of current smokers within 20 years of cessation. Limitations include potential exposure misclassification due to reliance on single baseline self-reported smoking measurements with extended follow-up periods, which may underestimate true risk associations, and lack of data on other tobacco products and electronic nicotine delivery systems, preventing analysis of dual- and poly-use patterns. Conclusion: Lower-intensity smoking is associated with cardiovascular risk and the primary public health message for current smokers should be early cessation, rather than reducing the amount of smoking. Cessation provides substantial immediate risk reduction, although risk continues to decrease significantly for the following two decades.

BACKGROUND: Understanding the associations of tobacco product use with subclinical markers is essential in evaluating health effects to inform regulatory policy. This is particularly relevant for noncigarette products (eg, cigars, pipes, and smokeless tobacco), which have been understudied because of their low prevalence in individual cohorts. METHODS: This cross-sectional study included 98 450 participants from the Cross-Cohort Collaboration–Tobacco data set. Associations between the use of tobacco products and subclinical markers (high-sensitivity C-reactive protein, interleukin-6, fibrinogen, D-dimer, coronary artery calcium, carotid intima-media thickness, carotid plaque, and ankle-brachial index) were evaluated. The analyses used multivariable linear and logistic regression models to examine current use status for each product, with additional analyses of “sole” and “exclusive” noncigarette use (versus never use of either cigarettes or specific noncigarette tobacco). Sole use was defined as the current use of a given noncigarette tobacco without concurrent combustible cigarette use, whereas exclusive use was defined as current noncigarette tobacco use without any history of combustible cigarette use. RESULTS: A total of 20.0%, 3.0%, 0.8%, and 1.5% of participants were current cigarette, cigar, pipe, or smokeless tobacco users, respectively. Current cigarette use was linked to higher levels of all markers compared with never cigarette use. Compared with respective reference groups, current, sole, and exclusive cigar use was associated with 10% (95% CI, 1–20), 19% (95% CI, 12–26), and 11% (95% CI, 2–21) higher high-sensitivity C-reactive protein levels on the geometric mean scale. Similar associations were noted for pipe and smokeless tobacco use. For interleukin-6, we observed that sole cigar use was associated with a 15% (95% CI, 6–24) higher level, whereas current, sole, and exclusive pipe use were associated with 22% to 32% (all P values <0.05) higher levels compared with their respective reference groups. Fibrinogen levels were 2% to 6% higher (all P values <0.05) among sole users of cigars, pipes, and smokeless tobacco, compared with their respective reference groups. Additionally, noncigarette tobacco use was moderately associated with carotid plaque and carotid intima-media thickness. CONCLUSIONS: Use of noncigarette tobacco products is linked to subclinical markers related to cardiovascular harm. Inflammatory markers, such as high-sensitivity C-reactive protein and interleukin-6, have the potential for assessing early cardiovascular harm from using these products and aiding regulatory authorities in evaluating their associated risks.