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Association of Aspirin Use With Mortality Risk Among Older Adult Participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Author/s: 
Loomans-Kroop, HA, Pinsky, P, Cao, Y, Chan, AT, Umar, A

IMPORTANCE:

Aspirin use has been associated with reduced risk of cancer mortality, particularly of the colorectum. However, aspirin efficacy may be influenced by biological characteristics, such as obesity and age. With the increasing prevalence of obesity and conflicting data regarding the effect of aspirin in older adults, understanding the potential association of aspirin use with cancer mortality according to body mass index (BMI) and age is imperative.

OBJECTIVES:

To investigate the association of aspirin use with risk of all-cause, any cancer, gastrointestinal (GI) cancer, and colorectal cancer (CRC) mortality among older adults and to perform an exploratory analysis of the association of aspirin use with mortality stratified by BMI.

DESIGN, SETTING, PARTICIPANTS:

This cohort study evaluated aspirin use among participants aged 65 years and older in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial at baseline (November 8, 1993, to July 2, 2001) and follow-up (2006-2008). Analysis began in late 2018 and was completed in September 2019.

MAIN OUTCOMES AND MEASURES:

All-cause, any cancer, GI cancer, or CRC mortality. Multivariable hazard ratios (HRs) and 95% CIs were calculated using time-varying Cox proportional hazards regression modeling, adjusting for additional factors.

RESULTS:

A total of 146 152 individuals (mean [SD] age at baseline, 66.3 [2.4] years; 74 742 [51.1%] women; 129 446 [88.6%] non-Hispanic white) were included in analysis. The median (interquartile range) follow-up time was 12.5 (8.7-16.4) years, encompassing 1 822 164 person-years. Compared with no use, aspirin use 1 to 3 times per month was associated with reduced risk of all-cause mortality (HR, 0.84; 95% CI, 0.80-0.88; P < .001) and cancer mortality (HR, 0.87; 95% CI, 0.81-0.94; P < .001). Aspirin use 3 or more times per week was associated with decreased risk of mortality of all causes (HR, 0.81; 95% CI, 0.80-0.83; P < .001), any cancer (HR, 0.85; 95% CI, 0.81-0.88; P < .001), GI cancer (HR, 0.75; 95% CI, 0.66-0.84; P < .001), and CRC (HR, 0.71; 95% CI, 0.61-0.84; P < .001). When stratified by BMI (calculated as weight in kilograms divided by height in meters squared), aspirin use 3 or more times per week among individuals with BMI 20 to 24.9 was associated with reduced risk of all-cause mortality (HR, 0.82; 95% CI, 0.78-0.85; P < .001) and any cancer mortality (HR, 0.86; 95% CI, 0.79-0.82; P < .001). Among individuals with BMI 25 to 29.9, aspirin use 3 or more times per week was associated with reduced risk of all-cause mortality (HR, 0.82; 95% CI, 0.79-0.85; P < .001), any cancer mortality (HR, 0.86; 95% CI, 0.81-0.91; P < .001), GI cancer mortality (HR, 0.72; 95% CI, 0.60-0.86; P < .001), and CRC mortality (HR, 0.66; 95% CI, 0.51-0.85; P = .001).

CONCLUSIONS AND RELEVANCE:

In this cohort study, aspirin use 3 or more times per week was associated with a reduction in all-cause, cancer, GI cancer and CRC mortality in older adults.

Keywords 
aspirin cancer mortality risk reduction

Association between vitamin D supplementation and mortality: systematic review and meta-analysis

Author/s: 
Zhang, Y., Fang, F., Tang, J., Jia, L., Feng, Y., Xu, P., Faramand, A.

Abstract

OBJECTIVE:

To investigate whether vitamin D supplementation is associated with lower mortality in adults.

DESIGN:

Systematic review and meta-analysis of randomised controlled trials.

DATA SOURCES:

Medline, Embase, and the Cochrane Central Register from their inception to 26 December 2018.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES:

Randomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group.

MAIN OUTCOME MEASURES:

All cause mortality.

RESULTS:

52 trials with a total of 75 454 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I2=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.84, 0.74 to 0.95, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation (P for interaction=0.04); neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality.

CONCLUSIONS:

Vitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 16%. Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality.

STUDY REGISTRATION:

PROSPERO registration number CRD42018117823.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Keywords 
cancer cancer mortality vitamin D Vitamin D3 supplimentation
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