Association Between Initiation, Intensity, and Cessation of Smoking and Mortality Risk in Patients With Cardiovascular Disease: A Cohort Study

Objectives: To examine the effect of smoking status, smoking intensity, duration of smoking cessation and age of smoking initiation on the risk of all-cause and cause-specific mortality among cardiovascular disease (CVD) patients.Design: A population-based prospective cohort study.Setting: The National Health Interview Survey (NHIS) in the U.S. that were linked to the National Death Index (NDI).Participants: 66,190 CVD participants ≥ 18 years of age who were interviewed between 1997 and 2013 in the NHIS linked to the NDI through December 31, 2015.Outcome Measures: The primary outcome was all-cause mortality and the secondary outcome was cause-specific mortality including CVD mortality and cancer mortality.Results: During the mean follow-up of 8.1 years, we documented 22,518 deaths (including 6,473 CVD deaths and 4,050 cancer deaths). In the overall CVD population, former and current smokers had higher risk of all-cause (Former smokers: hazard ratios (HRs), 1.26; 95% confidence interval (CI), 1.21–1.31, P < 0.001; Current smokers: HRs, 1.96; 95%CI, 1.86–2.07, P < 0.001), CVD (Former smokers: HRs, 1.12; 95%CI, 1.05–1.21, P = 0.001; Current smokers: HRs, 1.80; 95%CI, 1.64–1.97, P < 0.001) and cancer mortality (Former smokers: HRs, 1.49; 95%CI, 1.35–1.64, P < 0.001; Current smokers: HRs, 2.78; 95%CI, 2.49–3.09, P < 0.001) than never smokers. Furthermore, similar results were observed when the study subjects were stratified according to the type of CVD. Among current smokers, the risk for cancer mortality increased as the daily number of cigarettes increased, regardless of the specific type of CVD. However, the association of the risk for all-cause and CVD mortality with smoking intensity did not present a dose-response relationship. In participants with angina pectoris or stroke, smoking intensity was inversely associated with deaths from CVD. In addition, the risk for all-cause, CVD and cancer mortality declined as years of smoking cessation increased. Finally, the relative risk of all-cause mortality was not significantly different in individuals with a younger age of smoking initiation.Conclusions: CVD patients who are smokers have an increased risk of all-cause, CVD and cancer mortality, and the risk decreases significantly after quitting smoking. These data further provide strong evidence that supports the recommendation to quit smoking for the prevention of premature deaths among individuals with CVD.

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Dose–Response Relation between Tea Consumption and Risk of Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis of Population-Based Studies

Advances in Nutrition ◽

10.1093/advances/nmaa010 ◽

2020 ◽

Vol 11 (4) ◽

pp. 790-814 ◽

Cited By ~ 4

Author(s):

Mei Chung ◽

Naisi Zhao ◽

Deena Wang ◽

Marissa Shams-White ◽

Micaela Karlsen ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cohort Studies ◽

Prospective Cohort ◽

Lower Risk ◽

Meta Analysis ◽

Risk Of Bias ◽

Tea Consumption ◽

All Cause Mortality ◽

Specific Mortality ◽

Cvd Mortality

ABSTRACT Tea flavonoids have been suggested to offer potential benefits to cardiovascular health. This review synthesized the evidence on the relation between tea consumption and risks of cardiovascular disease (CVD) and all-cause mortality among generally healthy adults. PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Food Science and Technology Abstracts, and Ovid CAB Abstract databases were searched to identify English-language publications through 1 November 2019, including randomized trials, prospective cohort studies, and nested case-control (or case-cohort) studies with data on tea consumption and risk of incident cardiovascular events (cardiac or peripheral vascular events), stroke events (including mortality), CVD-specific mortality, or all-cause mortality. Data from 39 prospective cohort publications were synthesized. Linear meta-regression showed that each cup (236.6 mL) increase in daily tea consumption (estimated 280 mg and 338 mg total flavonoids/d for black and green tea, respectively) was associated with an average 4% lower risk of CVD mortality, a 2% lower risk of CVD events, a 4% lower risk of stroke, and a 1.5% lower risk of all-cause mortality. Subgroup meta-analysis results showed that the magnitude of association was larger in elderly individuals for both CVD mortality (n = 4; pooled adjusted RR: 0.89; 95% CI: 0.83, 0.96; P = 0.001), with large heterogeneity (I2 = 72.4%), and all-cause mortality (n = 3; pooled adjusted RR: 0.92; 95% CI: 0.90, 0.94; P < 0.0001; I2 = 0.3%). Generally, studies with higher risk of bias appeared to show larger magnitudes of associations than studies with lower risk of bias. Strength of evidence was rated as low and moderate (depending on study population age group) for CVD-specific mortality outcome and was rated as low for CVD events, stroke, and all-cause mortality outcomes. Daily tea intake as part of a healthy habitual dietary pattern may be associated with lower risks of CVD and all-cause mortality among adults.

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P5495Sex differences in marital status and risk of cardiovascular disease, cancer, and all-cause mortality: a systematic review and meta-analysis of 7,881,040 individuals

European Heart Journal ◽

10.1093/eurheartj/ehz746.0446 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J Nie ◽

Y Wang

Keyword(s):

Cardiovascular Disease ◽

Sex Differences ◽

Marital Status ◽

Cancer Mortality ◽

Meta Analysis ◽

Excess Risk ◽

Stroke Mortality ◽

Never Married ◽

All Cause Mortality ◽

Cvd Mortality

Abstract Background Marital status has been identified as an important social factor associated with mortality. In current epidemiologic research, being unmarried was observed to be a suboptimal health status in the global population. The growing number of unmarried people has health implications, in light of evidence suggesting that it is associated with an increase in the incidence of various diseases and high mortality. Few attempts have been made to produce an overall estimate and sufficiently clarified of the sex difference between unmarried status and mortality risks, this is still a matter of debate. Purpose To ascertain whether sex differences exist in the relationship between marital status and cardiovascular disease (CVD), cancer, all-cause mortality in the general population and to explore the potential effect of age, location, the duration of follow-up and publication years on these outcomes. Methods A systematic search was performed in PubMed and EMBASE from inception through to April 2018 and review of references. We used the sex-specific RRs (relative risk) to derive the women-to-men ratio of RRs (RRR) and 95% CIs from each study. Subsequently, the RRR for each outcome was pooled with random effects meta-analysis weighted by the inverse of the variances of the log RRRs. Results Twenty-one studies with 7,881,040 individuals were included for meta-analysis. Compared with married individuals, being unmarried was significantly associated with all-cause mortality, cancer mortality, CVD mortality and coronary heart disease (CHD) mortality, especially for singles, for both sexes (Figure 1). However, the association with death from all-cause and CVD was significantly stronger in men. Compared with women who were divorced/separated, divorced/separated men had significantly higher risk of all-cause mortality, cancer mortality and CVD mortality. Moreover, never married men had 31% and 9% higher excess risk of stroke mortality and all-cause mortality, respectively, compared with never married women. No sex differences were observed concerning the impact of any unmarried status on CHD mortality. Conclusions Being unmarried (widowed, divorced/separated or never married) conferred higher excess risk of stroke mortality and all-cause mortality for men than women. Moreover, divorced/separated men had significantly higher risk of cancer mortality and CVD mortality. Further studies are warranted to clarify the biological, behavioral, and/or social mechanisms involved in sex differences driving these associations.

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Adiposity change and mortality in middle-aged to older Chinese: an 8-year follow-up of the Guangzhou Biobank Cohort Study

BMJ Open ◽

10.1136/bmjopen-2020-039239 ◽

2020 ◽

Vol 10 (12) ◽

pp. e039239

Author(s):

Ying Yue Huang ◽

Chao Qiang Jiang ◽

Lin Xu ◽

Wei Sen Zhang ◽

Feng Zhu ◽

...

Keyword(s):

Cohort Study ◽

Outcome Measures ◽

Mortality Risk ◽

Cancer Mortality ◽

Secondary Outcome ◽

Middle Aged ◽

All Cause Mortality ◽

Older Chinese ◽

Cvd Mortality

ObjectiveTo examine the associations of change in body mass index (BMI) and waist circumference (WC) over an average of 4 years with subsequent mortality risk in middle-aged to older Chinese.DesignProspective cohort study based on the Guangzhou Biobank Cohort Study.SettingCommunity-based sample.Participants17 773 participants (12 956 women and 4817 men) aged 50+ years.Primary and secondary outcome measuresPrimary outcome measure was all-cause mortality. Secondary outcome measures were cardiovascular disease (CVD) and cancer mortality. Causes of death were obtained via record linkage, and coded according to the International Classification of Diseases (tenth revision).Results1424 deaths (53.4% women) occurred in the 17 773 participants (mean age 61.2, SD 6.8 years) during an average follow-up of 7.8 (SD=1.5) years, and 97.7% of participants did not have an intention of weight loss . Compared with participants with stable BMI, participants with BMI loss (>5%), but not gain, had a higher risk of all-cause mortality (HR=1.49, 95% CI 1.31 to 1.71), which was greatest in those who were underweight (HR=2.45, 95% CI 1.31 to 4.59). Similar patterns were found for WC. In contrast, for participants with a BMI of ≥27.5 kg/m2, BMI gain, versus stable BMI, was associated with 89% higher risk of all-cause mortality (HR=1.89, 95% CI 1.25 to 2.88), 72% higher risk of CVD mortality (HR=1.72, 95% CI 0.80 to 3.72) and 2.27-fold risk of cancer mortality (HR=2.27, 95% CI 1.26 to 4.10).ConclusionIn older people, unintentional BMI/WC loss, especially in those who were underweight was associated with higher mortality risk. However, BMI gain in those with obesity showed excess risks of all-cause and cancer mortality, but not CVD mortality. Frequent monitoring of changes in body size can be used as an early warning for timely clinical investigations and interventions and is important to inform appropriate health management in older Chinese.

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Unhealthy Lifestyle, Genetics and Risk of Cardiovascular Disease and Mortality in 76,958 Individuals from the UK Biobank Cohort Study

Nutrients ◽

10.3390/nu13124283 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4283

Author(s):

Katherine M. Livingstone ◽

Gavin Abbott ◽

Joey Ward ◽

Steven J. Bowe

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Polygenic Risk Score ◽

Nucleotide Polymorphisms ◽

Uk Biobank ◽

Unhealthy Lifestyle ◽

Hazard Ratios ◽

All Cause Mortality ◽

The Uk ◽

Cvd Mortality

To examine associations of unhealthy lifestyle and genetics with risk of all-cause mortality, cardiovascular disease (CVD) mortality, myocardial infarction (MI) and stroke. We used data on 76,958 adults from the UK Biobank prospective cohort study. Favourable lifestyle included no overweight/obesity, not smoking, physical activity, not sedentary, healthy diet and adequate sleep. A Polygenic Risk Score (PRS) was derived using 300 CVD-related single nucleotide polymorphisms. Cox proportional hazard ratios (HR) were used to model effects of lifestyle and PRS on risk of CVD and all-cause mortality, stroke and MI. New CVD (n = 364) and all-cause (n = 2408) deaths, and stroke (n = 748) and MI (n = 1140) events were observed during a 7.8 year mean follow-up. An unfavourable lifestyle (0–1 healthy behaviours) was associated with higher risk of all-cause mortality (HR: 2.06; 95% CI: 1.73, 2.45), CVD mortality (HR: 2.48; 95% CI: 1.64, 3.76), MI (HR: 2.12; 95% CI: 1.65, 2.72) and stroke (HR:1.74; 95% CI: 1.25, 2.43) compared to a favourable lifestyle (≥4 healthy behaviours). PRS was associated with MI (HR: 1.35; 95% CI: 1.27, 1.43). There was evidence of a lifestyle-genetics interaction for stroke (p = 0.017). Unfavourable lifestyle behaviours predicted higher risk of all-cause mortality, CVD mortality, MI and stroke, independent of genetic risk.

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Long working hours and mortality in Central and Eastern Europe: the HAPIEE study

European Journal of Public Health ◽

10.1093/eurpub/ckz185.365 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

H Pikhart ◽

Q Liu ◽

A Pajak ◽

S Malyutina ◽

R Kubinova ◽

...

Keyword(s):

Eastern Europe ◽

Cancer Mortality ◽

Central And Eastern Europe ◽

Working Hours ◽

Long Working Hours ◽

Risk Of Mortality ◽

All Cause Mortality ◽

Specific Mortality ◽

Mortality Analysis ◽

Cvd Mortality

Abstract Background Long working hours are common in countries of Central and Eastern Europe (CEE). A wide range of epidemiological studies have showed that long working hours had an adverse effect on health but the evidence mostly comes from Western Europe, East Asia and North America. This study aimed to assess the relationship between long working hours and the risk of mortality in employed people in three Eastern European countries. Methods Participants, aged 45-69 years at baseline, were from the Health, Alcohol and Psychosocial Indicators in Eastern Europe (HAPIEE) cohort study conducted in Russia, Poland and the Czech Republic. Baseline survey included a structured questionnaire and examination in the clinic during 2002-2005. Working hours were assessed by a self-reported questionnaire at baseline. Participants have been followed-up for all-cause mortality and cause-specific mortality for an average of 11 years. Impact of long working hours on mortality was analysed by Cox proportional hazards regression. In all-cause mortality analysis, a total of 10878 men and women were included, and 10399 participants were included in cause-specific mortality analysis. Results During the follow-up, there were 1187 deaths from all causes, 288 from CVD, and 251 from cancer. Those who worked 61 hours or more in a week showed higher risk of mortality compared to those working 36-45 hours per week: HR 1.32 (95%CI 1.01 to 1.74) for all-cause mortality and 1.73 (95% CI 1.03-2.93) for CVD mortality. There was no significant increase in risk of cancer mortality associated with working long hours. There was no significant association between working 46-60 hours a week and risk of mortality, including all-cause mortality and cause-specific mortality. Conclusions The risk of all-cause and CVD mortality in three CEE was significantly higher among employees working extensive hours. These findings suggest that more attention should be paid to shortening working hours for those who work extensively. Key messages Long working hours increase risk of all cause and CVD mortality. Cancer mortality is not related to long working hours.

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The Japanese food score and risk of all-cause, CVD and cancer mortality: the Japan Collaborative Cohort Study

British Journal Of Nutrition ◽

10.1017/s000711451800154x ◽

2018 ◽

Vol 120 (4) ◽

pp. 464-471 ◽

Cited By ~ 16

Author(s):

Emiko Okada ◽

Koshi Nakamura ◽

Shigekazu Ukawa ◽

Kenji Wakai ◽

Chigusa Date ◽

...

Keyword(s):

Cohort Study ◽

Cancer Mortality ◽

Food Groups ◽

Hazard Ratios ◽

All Cause Mortality ◽

Japanese Diet ◽

Cvd Mortality

AbstractFew studies have reported the association between the Japanese diet as food score and mortality. This study aimed to investigate adherence to the Japanese food score associated with all-cause, CVD and cancer mortality. A total of 58 767 (23 162 men and 34 232 women) Japanese participants aged 40–79 years, who enrolled in the Japan Collaborative Cohort Study between 1988 and 1990, were included. The Japanese food score was derived from the components of seven food groups (beans and bean products, fresh fishes, vegetables, Japanese pickles, fungi, seaweeds and fruits) based on the FFQ. The total score ranged from 0 to 7, and participants were divided into five categories based on scores (0–2, 3, 4, 5 and 6–7). Hazard ratios (HR) and 95 % CI for all-cause, CVD and cancer mortality based on sex were estimated using Cox proportional models. During the follow-up period until 2009, 11 692 participants with all-cause, 3408 with CVD and 4247 with cancer died. The multivariable HR in the 6–7 and 0–2 Japanese food score groups were 0·93 (95 % CI 0·86, 1·01) in men and 0·82 (95 % CI 0·75, 0·90) in women for all-cause mortality and 0·89 (95 % CI 0·76, 1·04) in men and 0·66 (95 % CI 0·56, 0·77) in women for CVD mortality. Our findings suggest that adherence to the Japanese food score consisting of food combinations characterised by a Japanese diet may help in preventing all-cause and CVD mortality, especially in women.

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Association of soy and fermented soy product intake with total and cause specific mortality: prospective cohort study

BMJ ◽

10.1136/bmj.m34 ◽

2020 ◽

pp. m34 ◽

Cited By ~ 7

Author(s):

Ryoko Katagiri ◽

Norie Sawada ◽

Atsushi Goto ◽

Taiki Yamaji ◽

Motoki Iwasaki ◽

...

Keyword(s):

Public Health ◽

Cardiovascular Disease ◽

Cohort Study ◽

Health Centre ◽

Total Mortality ◽

Population Based ◽

Public Health Centre ◽

Hazard Ratios ◽

All Cause Mortality ◽

Specific Mortality

Abstract Objective To investigate the association between several types of soy products and all cause and cause specific mortality. Design Population based cohort study. Setting Japan Public Health Centre-based Prospective Study, which includes 11 public health centre areas in Japan. Participants 92 915 participants (42 750 men and 50 165 women) aged 45 to 74 years. Exposures Intake of total soy products, fermented soy products (natto and miso), non-fermented soy products, and tofu from a five year survey questionnaire. Main outcome measures All cause and cause specific mortality (cancer, total cardiovascular disease, heart disease, cerebrovascular disease, respiratory disease, and injury) obtained from residential registries and death certificates. Results During 14.8 years of follow-up, 13 303 deaths were identified. In the multivariable adjusted models, intake of total soy products was not significantly associated with total mortality. Compared with the lowest fifth of total soy product intake, the hazard ratios in the highest fifth were 0.98 (95% confidence interval 0.91 to 1.06, P trend =0.43) in men and 0.98 (0.89 to 1.08, P trend =0.46) in women. Intake of fermented soy products was inversely associated with all cause mortality in both sexes (highest versus lowest fifth: 0.90 (0.83 to 0.97), P trend =0.05 in men, and 0.89 (0.80 to 0.98), P trend =0.01 in women). Natto showed significant and inverse associations with total cardiovascular disease related mortality in both sexes. Conclusions In this study a higher intake of fermented soy was associated with a lower risk of mortality. A significant association between intake of total soy products and all cause mortality was not, however, observed. The findings should be interpreted with caution because the significant association of fermented soy products might be attenuated by unadjusted residual confounding.

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Impact of Combined Lifestyle Factors on All-Cause and Cause-Specific Mortality and Life Expectancy in Chinese: The Singapore Chinese Health Study

The Journals of Gerontology Series A ◽

10.1093/gerona/glz271 ◽

2019 ◽

Vol 75 (11) ◽

pp. 2193-2199

Author(s):

Xiong-Fei Pan ◽

Yanping Li ◽

Oscar H Franco ◽

Jian-Min Yuan ◽

An Pan ◽

...

Keyword(s):

Life Expectancy ◽

Cancer Mortality ◽

Healthy Lifestyle ◽

Lifestyle Factors ◽

Health Study ◽

Chinese Adults ◽

All Cause Mortality ◽

Specific Mortality ◽

Singapore Chinese ◽

Cvd Mortality

Abstract Background To examine the impact of combined lifestyle factors on premature mortality and life expectancy in Chinese adults. Methods A total of 44,052 Chinese adults aged 45–74 years free of cardiovascular disease (CVD), cancer, and diabetes were followed from recruitment (1993–1998) to the end of 2016 in the Singapore Chinese Health Study. A composite score (0–5 scale) was calculated based on five baseline healthy lifestyle factors including healthy diet, nonsmoking status, light to moderate alcohol drinking, being physically active and optimal body mass index. Mortality cases were identified through linkage with the nationwide death registry. Results Adopting five healthy versus none was associated with a lower risk of all-cause and cause-specific mortality, and the hazard ratio (95% confidence interval [CI]) was 0.38 (0.29, 0.51) for all-cause mortality, 0.26 (0.13, 0.52) for CVD mortality, and 0.59 (0.37, 0.92) for cancer mortality. Nonadherence to 4–5 healthy lifestyle factors accounted for 34.9% (95% CI = 29.2, 40.2) in population attributable fraction for all-cause mortality, 35.1% (23.7, 44.9) for CVD mortality, and 18.0% (6.5, 28.0) for cancer mortality. Conversely, adherence to 4–5 healthy lifestyle factors versus none could achieve a gain of 8.1 years in women and 6.6 years in men for the life expectancy at 50 years. Conclusions A healthier lifestyle is associated with a substantially reduced risk of mortality and a longer life expectancy in the Chinese population. Our findings highlight the necessity of coordinated actions targeting combined lifestyle factors in reducing the overall burden of diseases and premature deaths.

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A nonlinear association of total cholesterol with all-cause and cause-specific mortality

Nutrition & Metabolism ◽

10.1186/s12986-021-00548-1 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Guo-dong He ◽

Xiao-cong Liu ◽

Lin Liu ◽

Yu-ling Yu ◽

Chao-lei Chen ◽

...

Keyword(s):

Cardiovascular Disease ◽

Survival Rate ◽

Total Cholesterol ◽

Cancer Mortality ◽

Cumulative Survival Rate ◽

Cumulative Survival ◽

Specific Mortality ◽

Level Group ◽

Cvd Mortality ◽

Nonlinear Association

Abstract Background The link between total cholesterol (TC) and all-cause and specific mortality has not been elucidated. Herein, we aimed to evaluate the effect of TC levels on all-cause, cardiovascular disease (CVD), and cancer mortality. Methods All data analyzed were obtained from the National Health and Nutrition Examination Survey 1999–2014. The relationship between levels of TC and mortality was determined through Cox proportional hazard regression analysis coupled with multivariable adjustments. Two-piecewise linear regression models and Cox models with penalized splines were applied to explore nonlinear and irregular shape relationships. Kaplan–Meier survival curve and subgroup analyses were conducted. Results The sample studied comprised 14,662 men and 16,025 women, categorized as 25,429 adults aged 18–65 and 5,258 adults over 65 years old. A total of 2,570 deaths were recorded. All-cause, cardiovascular, and cancer mortality showed U-curve associations after adjusting for confounding variables in the restricted cubic spline analysis. Hazard ratios (HRs) of all-cause and cancer mortality were particularly negatively related to TC levels in the lower range < 200 mg/dL, especially in the range < 120 mg/dL (HR 1.97; 95% CI 1.38, 2.83, HR 2.39; 95% CI 1.21, 4.71, respectively). However, the HRs of cardiovascular disease mortality in the range < 120 mg/dL were the lowest (HR 0.60; 95% CI 0.15, 2.42). In the upper range, a TC range of ≥ 280 mg/dL was correlated with mortality as a result of CVD and cancer (HR 1.31; 95% CI 0.87, 1.97 and HR 1.22; 95% CI 0.82, 1.79). The lowest cumulative survival rate of all-cause mortality was recorded in the lowest TC-level group, while the lowest cumulative survival rate of CVD mortality was recorded in the highest TC-level group. Conclusions A nonlinear association of TC level with all-cause, cancer, and CVD mortality in the American population was observed, suggesting that too low or too high serum total cholesterol levels might correlate with adverse outcomes.

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Smoking and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study

10.1101/2021.10.25.21265469 ◽

2021 ◽

Author(s):

Alvaro Hernaez ◽

Robyn E Wootton ◽

Christian M Page ◽

Karoline H Skara ◽

Abigail Fraser ◽

...

Keyword(s):

Smoking Cessation ◽

Cohort Study ◽

Tobacco Use ◽

Mendelian Randomization ◽

Smoking Initiation ◽

Smoking Intensity ◽

Genotype Information ◽

Multivariable Regression ◽

Multivariable Analyses ◽

Study Intervention

Objective. To investigate the association between smoking-related traits and subfertility. Design. Prospective study. Setting. Nationwide cohort in Norway. Patients. 28,606 women (average age 30) and 27,096 men (average age 33) with questionnaire and genotype information from the Norwegian Mother, Father and Child Cohort Study. Intervention. Self-reported information on smoking (having ever smoked [both sexes], age at smoking initiation [women only], smoking cessation [women only], and cigarettes smoked per week in current smokers [both sexes]) was gathered. Genetically predetermined levels or likelihood of presenting the mentioned traits were estimated for Mendelian randomization (MR) analyses. Main outcome measure. Subfertility, defined as time-to-pregnancy >=12 months. Results. A total of 10% of couples were subfertile. In multivariable regression accounting for age, years of education, body mass index, and number of previous pregnancies, having ever smoked was not linked to subfertility in women or men. A higher intensity of tobacco use in women who were current smokers was related to greater odds of subfertility (+ 1 standard deviation [SD, 48 cigarettes/week]: odds ratio [OR] 1.12, 95% confidence interval [CI] 1.03 to 1.21), also after adjusting for the partner's tobacco use. Later smoking initiation (+ 1 SD [3.2 years]: OR 0.89, 95% CI 0.84 to 0.95) and smoking cessation (relative to not quitting: OR 0.83, 95% CI 0.75 to 0.93) were linked to decreased subfertility in women who had ever smoked. Nevertheless, MR results were not directionally consistent for smoking intensity and cessation and were imprecisely estimated in two-sample MR, with wide confidence intervals that overlapped with the multivariable regression results. In men, greater smoking intensity was marginally linked to greater odds of subfertility in multivariable analyses, but this association was attenuated when adjusting for the partner's smoking intensity (+ 1 SD [54 cigarettes/week]: OR 1.05, 95% CI 0.96 to 1.15). MR estimates were directionally consistent but again imprecisely estimated. Conclusions. We did not find robust evidence of an effect of smoking on subfertility. This may be due to a true lack of effect, weak genetic instruments, or other kinds of confounding. The relevant limitations across all methods highlights the need for larger studies with information on subfertility.

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