Association between vitamin K1 intake and mortality in the Danish Diet, Cancer, and Health cohort

AbstractReported associations between vitamin K1 and both all-cause and cause-specific mortality are conflicting. The 56,048 participants from the Danish Diet, Cancer, and Health prospective cohort study, with a median [IQR] age of 56 [52–60] years at entry and of whom 47.6% male, were followed for 23 years, with 14,083 reported deaths. Of these, 5015 deaths were CVD-related, and 6342 deaths were cancer-related. Intake of vitamin K1 (phylloquinone) was estimated from a food-frequency questionnaire (FFQ), and its relationship with mortality outcomes was investigated using Cox proportional hazards models. A moderate to high (87–192 µg/d) intake of vitamin K1 was associated with a lower risk of all-cause [HR (95%CI) for quintile 5 vs quintile 1: 0.76 (0.72, 0.79)], cardiovascular disease (CVD)-related [quintile 5 vs quintile 1: 0.72 (0.66, 0.79)], and cancer-related mortality [quintile 5 vs quintile 1: 0.80 (0.75, 0.86)], after adjusting for demographic and lifestyle confounders. The association between vitamin K1 intake and cardiovascular disease-related mortality was present in all subpopulations (categorised according to sex, smoking status, diabetes status, and hypertension status), while the association with cancer-related mortality was only present in current/former smokers (p for interaction = 0.002). These findings suggest that promoting adequate intakes of foods rich in vitamin K1 may help to reduce all-cause, CVD-related, and cancer-related mortality at the population level.

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THE ASSOCIATION BETWEEN VITAMIN K STATUS AND CARDIOVASCULAR DISEASE IN OLDER ADULTS

Innovation in Aging ◽

10.1093/geroni/igz038.2393 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S644-S644

Author(s):

M Kyla Shea ◽

Daniel Weiner ◽

Gergory Matuszek ◽

Sarah L Booth ◽

Stephen Kritchevsky ◽

...

Keyword(s):

Cardiovascular Disease ◽

Older Adults ◽

Vitamin K ◽

Proportional Hazards ◽

Vascular Tissue ◽

Cox Proportional Hazards ◽

Body Composition Study ◽

Cox Proportional Hazards Models ◽

Health Aging

Abstract A role for vitamin K in cardiovascular disease (CVD) has been proposed because vitamin K-dependent proteins are present in vascular tissue. We evaluated the association between vitamin K status and incident CVD and mortality in older adults from the Health, Aging, and Body Composition Study (Health ABC), and conducted a replication analysis using the Multi-ethnic Study of Atherosclerosis (MESA). In both cohorts circulating phylloquinone (vitamin K1), measured from baseline fasting blood samples, was categorized as ≤0.5nM, >0.5-≤1.0nM, and >1.0nM. Multivariable Cox proportional hazards models assessed the association between circulating phylloquinone and risk of a composite of CVD and mortality. In Health ABC (n=1246, mean age 74 years, 57% female, 58% Caucasian), over a median 11.5 follow-up years, participants with ≤0.5 nM plasma phylloquinone (n=351) had a 27% higher risk for CVD and mortality compared to those with >1.0nM (n=457) [adjusted hazard ratio (95% confidence interval) (HR(95%CI)): 1.27(1.06-1.52)]. However, the risk for CVD and mortality did not differ between those with >0.5-≤1.0nM (n=438) and with >1.0nM plasma phylloquinone [HR(95%CI): 1.03(0.87-1.52)]. Serum phylloquinone was similarly associated with CVD and mortality in MESA, over a median 12.1 follow-up years (n=764, mean age 62 years, 54% female, 35% Caucasian) [HR(95%CI), compared to those with >1.0nM (n=368): <0.5nM (n=253): 1.54(1.03-2.32); 0.5-≤1.0nM (n=153): 1.23(0.76, 1.98)]. Lower circulating phylloquinone was associated with a higher CVD and mortality risk in two independent cohorts. Additional studies are needed to corroborate our findings and clarify if certain segments of the population can derive cardiovascular benefit from improving vitamin K status.

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Pre-diagnosis neutrophil-to-lymphocyte ratio and mortality in individuals who develop lung cancer

Cancer Causes & Control ◽

10.1007/s10552-021-01469-3 ◽

2021 ◽

Author(s):

Laurie Grieshober ◽

Stefan Graw ◽

Matt J. Barnett ◽

Gary E. Goodman ◽

Chu Chen ◽

...

Keyword(s):

Lung Cancer ◽

Proportional Hazards ◽

Smoking Status ◽

Cox Proportional Hazards ◽

Neutrophil To Lymphocyte Ratio ◽

Blood Draw ◽

Lymphocyte Ratio ◽

Cox Proportional Hazards Models ◽

Inflammatory Profile ◽

Heavy Smokers

Abstract Purpose The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. Methods We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the β-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. Results Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22–23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. Conclusion Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.

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Added value of cardiovascular calcifications for prediction of recurrent cardiovascular events and cardiovascular interventions in patients with established cardiovascular disease

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-021-02164-9 ◽

2021 ◽

Author(s):

Cilie C. van ’t Klooster ◽

◽

Yolanda van der Graaf ◽

Hendrik M. Nathoe ◽

Michiel L. Bots ◽

...

Keyword(s):

Cardiovascular Disease ◽

Heart Valve ◽

Cardiovascular Events ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Added Value ◽

Cvd Risk ◽

Major Cardiovascular Events ◽

Cox Proportional Hazards Models ◽

Cardiovascular Interventions

AbstractThe purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28–4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59–0.72). Calibration for models II–V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59–29.39)) and model V (NRI 20.00% (95%CI 5.59–34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+ . Addition of the TAC or heart valve score did not improve risk predictions.

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Dietary Omega-3 Fatty Acid Intake and Mortality in CKD Population: A 1999–2014 NHANES Analysis

American Journal of Nephrology ◽

10.1159/000520027 ◽

2021 ◽

pp. 1-10

Author(s):

Wei-Lan Li ◽

Nan-Hui Zhang ◽

Shu-Wang Ge ◽

Gang Xu

Keyword(s):

Cardiovascular Disease ◽

Fatty Acid ◽

Proportional Hazards ◽

Early Death ◽

Cox Proportional Hazards ◽

Omega 3 ◽

Pufa Intake ◽

Dietary Recall ◽

Cox Proportional Hazards Models ◽

All Cause Mortality

Introduction: High risk of early death, especially contributed to cardiovascular disease, exists in patients who have chronic kidney disease (CKD). And the burden of cardiovascular disease is able to be lightened by an increase in omega-3 polyunsaturated fatty acid (omega-3 PUFA). A diet high in omega-3 PUFA in the general population is protective, although it is inconclusive about its beneficial role in the CKD population. Methods: From the 1999 to 2014 National Health and Nutrition Examination Surveys (NHANES), we can collect 2,990 participants who suffered from CKD, who were classified into 4 groups: <0.86, 0.87–1.30, 1.31–1.92, and 1.93–9.65 g/day based on NHANES 24-h dietary recall questionnaire dietary omega-3 PUFA. Moreover, their mortality details were available to be obtained by linking NHANES to the National Death Index. The associations between dietary omega-3 PUFA and mortality were evaluated by constructing multivariable Cox proportional hazards models. Results: Over 8 years of a median follow-up, 864 deaths were recorded. The adjusted hazard ratios (95% confidence interval) for all-cause mortality of the diseased people with CKD in the 2nd (0.87–1.30 g/day), 3rd (0.87–1.30 g/day), and 4th (1.93–9.65 g/day) quartiles of dietary omega-3 PUFA were 0.94 (0.72, 1.23), 0.74 (0.54, 1.02), and 0.67 (0.48, 0.93), respectively, versus those with the lowest quartile of dietary omega-3 PUFA intake (<0.86 g/day) (p for trend = 0.011). Conclusion: There may be a inverse relation of dietary omega-3 PUFA intake and all-cause mortality in patients with CKD. Therefore, an increase of dietary omega-3 PUFA may be encouraged to be used clinically in patients with CKD.

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Coffee consumption and mortality in three Eastern European countries: results from the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study

Public Health Nutrition ◽

10.1017/s1368980016001749 ◽

2016 ◽

Vol 20 (1) ◽

pp. 82-91 ◽

Cited By ~ 14

Author(s):

Giuseppe Grosso ◽

Urszula Stepaniak ◽

Agnieszka Micek ◽

Denes Stefler ◽

Martin Bobak ◽

...

Keyword(s):

Cancer Mortality ◽

Alcohol Intake ◽

Proportional Hazards ◽

Smoking Status ◽

Coffee Consumption ◽

Cox Proportional Hazards ◽

Similar Amount ◽

Cox Proportional Hazards Models ◽

Eastern European Countries ◽

Moderate Alcohol Intake

AbstractObjectiveTo test the association between coffee consumption and risk of all-cause, CVD and cancer death in a European cohort.DesignProspective cohort study. Cox proportional hazards models with adjustment for potential confounders to estimate multivariable hazard ratios (HR) and 95 % CI were used.SettingCzech Republic, Russia and Poland.SubjectsA total of 28561 individuals followed for 6·1 years.ResultsA total of 2121 deaths (43·1 % CVD and 35·7 % cancer mortality) occurred during the follow-up. Consumption of 3–4 cups coffee/d was associated with lower mortality risk in men (HR=0·83; 95 % CI 0·71, 0·99) and women (HR=0·63; 95 % CI 0·47, 0·84), while further intake showed non-significant reduced risk estimates (HR=0·71; 95 % CI 0·49, 1·04 and HR=0·51; 95 % CI 0·24, 1·10 in men and women, respectively). Decreased risk of CVD mortality was also found in men (HR=0·71; 95 % CI 0·54, 0·93) for consumption of 3–4 cups coffee/d. Stratified analysis revealed that consumption of a similar amount of coffee was associated with decreased risk of all-cause (HR=0·61; 95 % CI 0·43, 0·87) and cancer mortality (HR=0·59; 95 % CI 0·35, 0·99) in non-smoking women and decreased risk of all-cause mortality for >4 cups coffee/d in men with no/moderate alcohol intake.ConclusionsCoffee consumption was associated with decreased risk of mortality. The protective effect was even stronger when stratification by smoking status and alcohol intake was performed.

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Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality

RMD Open ◽

10.1136/rmdopen-2019-001015 ◽

2019 ◽

Vol 5 (2) ◽

pp. e001015 ◽

Cited By ~ 10

Author(s):

Fernando Pérez Ruiz ◽

Pascal Richette ◽

Austin G Stack ◽

Ravichandra Karra Gurunath ◽

Ma Jesus García de Yébenes ◽

...

Keyword(s):

Uric Acid ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

First Year ◽

Cox Proportional Hazards Models ◽

Crude Mortality ◽

Risk Patients ◽

The Impact ◽

Related Mortality

ObjectiveTo determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout.MethodsProspective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs.ResultsOf 1193 patients, 92% were men with a mean age of 60 years, 6.8 years’ disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45).ConclusionsFailure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival.

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Non-Vitamin K Oral Anticoagulants in Comparison to Phenprocoumon in Geriatric and Non-Geriatric Patients with Non-Valvular Atrial Fibrillation

Thrombosis and Haemostasis ◽

10.1055/s-0039-1683422 ◽

2019 ◽

Vol 119 (06) ◽

pp. 971-980 ◽

Cited By ~ 9

Author(s):

Christopher Hohmann ◽

Stefan H. Hohnloser ◽

Josephine Jacob ◽

Jochen Walker ◽

Stephan Baldus ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Geriatric Patients ◽

Proportional Hazards ◽

Oral Anticoagulants ◽

Cox Proportional Hazards ◽

Intracranial Bleeding ◽

P Values ◽

Interaction Terms ◽

Cox Proportional Hazards Models

AbstractGeriatric characteristics such as high age, multi-morbidity, polypharmacy and frailty are common in patients with atrial fibrillation (AF). In a retrospective study using a German claims database, effectiveness (ischaemic stroke/systemic embolism) and safety (intracerebral, gastrointestinal and major extracranial bleeding) were compared in patients with non-valvular AF starting non-vitamin K oral antagonists (NOACs) (apixaban, dabigatran and rivaroxaban) and phenprocoumon. Cox proportional hazards models were used to calculate adjusted hazard ratios, and interaction terms of the treatment group and geriatric status (defined by age ≥75 years, frailty, ≥ 4 co-morbidities and polypharmacy) were entered into the model. A total of 42,562 and 27,939 patients initiated NOAC and phenprocoumon treatment (mean age 74 years ± 11, 51% male) with a follow-up time of 147,785 person-years. Note that 52.9% of patients were elderly, 50.8% were frail, 37.0% were co-morbid and 46.5% had polypharmacy. NOAC use was not associated with effectiveness and gastrointestinal bleeding, neither in geriatric nor in non-geriatric patients. The hazard of major extracranial and intracranial bleeding was significantly decreased for NOAC use, with similar risk reduction in geriatric and non-geriatric patients: major extracranial bleeding 0.70 (95% confidence interval [CI], 0.56–0.87) to 0.73 (95% CI, 0.60–0.89) for the geriatric groups and 0.71 (95% CI, 0.56–0.93) to 0.76 (0.59–0.98) for the non-geriatric groups (p-values for interaction > 0.6); and intracranial bleeding 0.52 (95% CI, 0.39–0.69) to 0.59 (95% CI, 0.47–0.73) for the geriatric groups and 0.54 (95% CI, 0.37–0.79) to 0.65 (95% CI, 0.49–0.86) for the non-geriatric groups (p-values for interaction > 0.2). Hence, NOACs showed similar effectiveness and superior safety in geriatric and non-geriatric patients.

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Comparative analysis of treatments, utilization, and survival benefit in HCC patients: A real-world analysis of SEER Medicare.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.214 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 214-214

Author(s):

Fadia T. Shaya ◽

Ian Michael Breunig ◽

C. Daniel Mullins ◽

Naimish B. Pandya ◽

Viktor Chirikov ◽

...

Keyword(s):

Radiation Therapy ◽

Health Status ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

External Beam Radiation ◽

Beam Radiation ◽

Cox Proportional Hazards Models ◽

Severe Liver Dysfunction ◽

Related Mortality ◽

Overall Mortality

214 Background: We explore various treatments at all stages of Hepatocellular Carcinoma (HCC), in a SEER (Surveillance, Epidemiology and End-Results Program) Medicare population and assess their impact on HCC-specific and overall survival. Methods: Medicare enrollees, older than 65, with an initial diagnosis of a primary HCC between 2000-07 were followed up through end of 2009. Data are from the SEER and linked Medicare databases, with claims generated from Medicare parts A and B. Using multivariate Cox-proportional hazards models, we assessed overall and HCC-related mortality in relation to receipt of treatment/no treatment, adjusting for demographics, general health status (CCI), cancer stage and liver conditions. Results: Out of the 9054 HCC patients, older than 65, who did not get a liver transplant, 76% were Caucasian, 8% African American (AA), 63% male, and 37% got treatment [12% transarterial chemoembolization (TACE), 12% systemic chemotherapy, 1.5% selective internal radiation therapy (SIRT), 9% external beam radiation therapy (EBRT), 8% surgical resection and 9% ablative therapy]. Treatment was associated with a reduction of overall (HR=0.35, P= <0.001) and HCC-related (0.33, <0.001) mortality. HCC-related mortality was significantly reduced in those getting resection (0.38, <0.001), ablation (0.59, <0.001), TACE (0.76, <0.001), EBRT (0.85, 0.017), or chemotherapy (0.85, 0.013). Significant reduction in overall mortality was seen with resection, ablation and TACE but not with chemotherapy, EBRT or SIRT. No particular treatment was associated with greater mortality reduction in early vs advanced stages. Patients with poor underlying health status (CCI>1) had higher mortality (1.27, <0.001). Alcohol related disease, Hep C, and moderate/severe liver dysfunction were not significantly associated with overall or HCC related mortality. Caucasians and non-African Americans had lower overall mortality (0.87, <0.001). Conclusions: In HCC SEER Medicare patients, all treatments except SIRT were associated with a significant reduction in HCC related mortality. A limitation of this study is that, through the data, we cannot accurately depict the severity of the disease.

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Sex differences in the 10-year survival of patients undergoing maintenance hemodialysis in the Q-Cohort Study

Scientific Reports ◽

10.1038/s41598-021-03551-x ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Hiroaki Tsujikawa ◽

Shunsuke Yamada ◽

Hiroto Hiyamuta ◽

Masatomo Taniguchi ◽

Kazuhiko Tsuruya ◽

...

Keyword(s):

Proportional Hazards ◽

Japanese Patients ◽

Hemodialysis Patients ◽

Cox Proportional Hazards ◽

Maintenance Hemodialysis ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Risk Of Mortality ◽

Related Mortality

AbstractWomen have a longer life expectancy than men in the general population. However, it has remained unclear whether this advantage is maintained in patients undergoing maintenance hemodialysis. The aim of this study was to compare the risk of mortality, especially infection-related mortality, between male and female hemodialysis patients. A total of 3065 Japanese hemodialysis patients aged ≥ 18 years old were followed up for 10 years. The primary outcomes were all-cause and infection-related mortality. The associations between sex and these outcomes were examined using Cox proportional hazards models. During the median follow-up of 8.8 years, 1498 patients died of any cause, 387 of whom died of infection. Compared with men, the multivariable-adjusted hazard ratios (95% confidence interval) for all-cause and infection-related mortality in women were 0.51 (0.45–0.58, P < 0.05) and 0.36 (0.27–0.47, P < 0.05), respectively. These findings remained significant even when propensity score-matching or inverse probability of treatment weighting adjustment methods were employed. Furthermore, even when the non-infection-related mortality was considered a competing risk, the infection-related mortality rate in women was still significantly lower than that in men. Regarding all-cause and infection-related deaths, women have a survival advantage compared with men among Japanese patients undergoing maintenance hemodialysis.

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Glucosamine use, smoking and risk of incident chronic obstructive pulmonary disease: A large prospective cohort study

British Journal Of Nutrition ◽

10.1017/s000711452100372x ◽

2021 ◽

pp. 1-35

Author(s):

Xi-Ru Zhang ◽

Pei-Dong Zhang ◽

Zhi-Hao Li ◽

Pei Yang ◽

Xiao-Meng Wang ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Proportional Hazards ◽

Smoking Status ◽

Cox Proportional Hazards ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Cox Proportional Hazards Models ◽

Large Prospective Cohort Study ◽

The Uk

Abstract Chronic inflammation exerts pleiotropic effects in the etiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HRs) as well as 95% confidence intervals (95% CIs) for the risk of incident COPD. During a median follow-up of 8.96 years (interquartile range 8.29 to 9.53 years), 9016 new-onset events of COPD were documented. We found that regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0.80 (95% CI, 0.75 to 0.85; P<0.001). When subgroup analyses were performed by smoking status, the adjusted HRs for the association of regular glucosamine use with incident COPD were 0.84 (0.73 to 0.96), 0.84 (0.77 to 0.92), and 0.71 (0.62 to 0.80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (P for interaction=0.078). Incident COPD could be reduced by 14% to 84% through a combination of regular glucosamine use and smoking cessation

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