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Summary
Background In 2011, WHO member states signed up to the 2525 initiative, a plan to cut mortality due to non- Lancet 2017; 389: 122937
communicable diseases by 25% by 2025. However, socioeconomic factors influencing non-communicable diseases Published Online
have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to January 31, 2017
http://dx.doi.org/10.1016/
mortality and years-of-life-lost with that of the 2525 conventional risk factors.
S0140-6736(16)32380-7
This online publication has
Methods We did a multicohort study and meta-analysis with individual-level data from 48 independent prospective been corrected. The first
cohort studies with information about socioeconomic status, indexed by occupational position, 2525 risk factors corrected version first
(high alcohol intake, physical inactivity, current smoking, hypertension, diabetes, and obesity), and mortality, for a appeared at thelancet.com on
February 27, 2017
total population of 1751479 (54% women) from seven high-income WHO member countries. We estimated the
association of socioeconomic status and the 2525 risk factors with all-cause mortality and cause-specific mortality by See Comment page 1172
calculating minimally adjusted and mutually adjusted hazard ratios [HR] and 95% CIs. We also estimated the *These authors contributed
equally to this work
population attributable fraction and the years of life lost due to suboptimal risk factors.
Joint last authors
Members are listed at end of
Findings During 266 million person-years at risk (mean follow-up 133 years [SD 64 years]), 310277 participants
paper
died. HR for the 2525 risk factors and mortality varied between 104 (95% CI 098111) for obesity in men and
Institute of Social and
217 (206229) for current smoking in men. Participants with low socioeconomic status had greater mortality Preventive Medicine and
compared with those with high socioeconomic status (HR 142, 95% CI 138145 for men; 134, 128139 for Departments of Psychiatry and
women); this association remained significant in mutually adjusted models that included the 2525 factors (HR 126, Internal Medicine, Lausanne
University Hospital, Lausanne,
121132, men and women combined). The population attributable fraction was highest for smoking, followed by
Switzerland (S Stringhini PhD,
physical inactivity then socioeconomic status. Low socioeconomic status was associated with a 21-year reduction in C Carmeli PhD,
life expectancy between ages 40 and 85 years, the corresponding years-of-life-lost were 05 years for high alcohol Prof M Bochud PhD,
intake, 07 years for obesity, 39 years for diabetes, 16 years for hypertension, 24 years for physical inactivity, and A M Lasserre MD,
Prof M Preisig MD,
48 years for current smoking.
Prof P Vollenweider MD);
Institute of Behavioural
Interpretation Socioeconomic circumstances, in addition to the 2525 factors, should be targeted by local and global Sciences, University of Helsinki,
health strategies and health risk surveillance to reduce mortality. Helsinki, Finland
(M Jokela PhD); Department of
Global Health and Social
Funding European Commission, Swiss State Secretariat for Education, Swiss National Science Foundation, the Medicine, Kings College
Medical Research Council, NordForsk, Portuguese Foundation for Science and Technology. London, London, UK
(M Avendao PhD); Harvard T H
Chan School of Public Health,
Copyright The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license.
Boston MA, USA (M Avendao,
Prof I Kawachi PhD); Global
Introduction disease and injury attributable to 67 risk factors in Research Analytics for
The 201320 World Health Organization (WHO) Global 21 world-regions.2 Despite the fact that low socioeconomic Population Health, Health
Policy and Management,
Action Plan for the Prevention and Control of Non- status is one of the strongest predictors of morbidity and Columbia University, New
Communicable Diseases (NCDs) targets seven major premature mortality worldwide,36 poor socioeconomic York, NY, USA
risk factors, comprising the harmful use of alcohol, circumstances are not considered modifiable risk factors (Prof P Muennig MD); MRC-PHE
insufficient physical activity, current tobacco use, raised in these important global health strategies. Centre for Environment and
Health, School of Public Health,
blood pressure, intake of salt or sodium, diabetes, and Socioeconomic circumstances and their consequences Department of Epidemiology
obesity (referred to as the 2525 risk factors), with the are modifiable by policies at the local, national, and and Biostatistics, Imperial
overall aim of reducing premature mortality from non- international levels,79 as are risk factors targeted by College London, London, UK
communicable diseases by 25% by 2025.1 Similarly, the existing global health strategies. Evidence also suggests (F Guida PhD,
M Chadeau-Hyam PhD,
Global Burden of Disease (GBD) Collaboration, the that the burden of most 2525 risk factors is concentrated Prof P Vineis PhD);
largest study monitoring health changes globally, in lower socioeconomic groups worldwide.10,11 Inter Epidemiology Unit, ASL TO3
performs an annual risk assessment of the burden of ventions to reduce premature mortality attributable to Piedmont Region, Grugliasco,
men, 114 per week for women), or heavy (>21 units per model the baseline hazard using age as the timescale. For more on the Lifepath
week for men, >14 per week for women) drinkers. Separate models were fitted for men and women and project see http://www.
lifepathproject.eu/
Although physical activity was measured with different included marital status and race or ethnicity (minimally
For more on ESEC see https://
questions in each study, a dichotomised variable adjusted models). To check for the proportional hazard
www.iser.essex.ac.uk/archives/
indicating the presence or absence of physical activity assumption, we performed tests based on Schoenfeld esec/user-guide
was defined (appendix). Body-mass index (BMI) was residuals and inspected log-log plots of Kaplan-Meier
categorised as normal (185<25 kg/m), overweight curves. Age stratification in 5-year intervals was
(25<30 kg/m), or obese (30 kg/m). Hypertension conducted in all cohorts as a sensitivity analysis to adjust
was defined as the presence of at least one of the for age calendar effects (results not shown).
following conditions: systolic blood pressure more than In further analyses combining men and women, we
140 mm Hg, diastolic blood pressure more than examined the association of socioeconomic status with
90 mm Hg, current intake of anti-hypertensive cause-specific mortality before and after adjustment for
medication, or self-reported hypertension. Diabetes was the 2525 risk factors. The mutually adjusted models
defined as the presence of at least one of the following included age, sex, race or ethnicity, marital status,
conditions: fasting glucose more than 7 mmol/L, 2 h socioeconomic status, and all 2525 risk factors as
post-load glucose above 111 mmol/L, glycated independent variables with total mortality and deaths
haemoglobin A1c more than 65%, or self-reported from cardiovascular disease, cancer, and other causes as
diabetes. Data for salt intake were only available from outcomes. To enable balanced comparisons between
less than a third of the cohort studies; we therefore socioeconomic status and 25 25 risk factors as
omitted this risk factor from our analysis. predictors of cause-specific mortality, these analyses
We considered age, sex, race or ethnicity, and marital were restricted to a subgroup of participants with
status as potential confounders. Race or ethnicity was complete data for socioeconomic status and the
categorised as white and non-white individuals. Marital 2525 risk factors.
status was categorised as married or cohabiting versus To examine whether the association between socio
living alone. economic status and mortality is attributable to the
Participants were linked to national mortality registries higher prevalence of the 2525 risk factors among low
that provided information about vital status with the socioeconomic status individuals, we repeated the
exception of the COLAUS study in which vital status was analyses in a subgroup of participants without any
ascertained through active follow-up. Mean follow-up for 25
25 risk factors. Analyses were also repeated
mortality ranged between 32 years in the National specifically focusing on premature mortality (<70 years)
Health Interview Survey 2009, and 270 years in men and and by restricting the population to cohorts in which
295 years in women of the Alameda County Study 1965, height and weight as well as blood pressure were
with a mean across cohorts of 133 years [SD 64 years]. measured objectively using standard procedures.
All-cause mortality, cancer mortality, cardio vascular To further evaluate the effects of socioeconomic status
disease mortality, and mortality from other causes of and the 2525 risk factors on mortality, we computed the
death were examined separately. We focus on cancer and population attributable fraction. The population
cardiovascular disease as these diseases are the most attributable fraction is based on the HR and the
common causes of death in our samples. We used codes proportion of participants exposed assuming the
from the International Classification of Diseases, 10th association between exposure and outcome is causal.14
Revision (ICD-10) to define cancer (C00C97) and The variance of population attributable fraction was
cardiovascular disease (I00I99) mortality. Other causes estimated via bootstrapping using 1000 independent
of death include all remaining deaths not classified as replications. The proportion of participants exposed
cancer or cardiovascular disease. (prevalence) was calculated as the mean prevalence
across all cohorts for each risk factor.
Statistical analysis YLLs were calculated as the difference of the areas
Analyses were first performed separately in each study; under the survival curves (from age 40 years to 85 years)
estimates were subsequently combined in a meta- comparing the population exposed to a given risk factor
analytical framework. In study-specific analyses, we with the reference population with no exposure. Area
considered the maximum number of participants under the curve was computed via numerical integration
without missing values for each exposure. To estimate with a spline-based method. Life expectancies were
the association between risk factors and mortality, hazard estimated conditional on survival to age 40 years. In view
ratios (HR) and 95% CIs were generated using flexible of the truncation at age 85 years, the theoretical maximal
parametric survival models on the cumulative hazards life expectancy at 40 years old is 45 years. Variance
scale,13 which, in addition to the HRs, allow direct of YLLs was estimated via bootstrapping using
estimation of the conditional cumulative hazard function. 1000 independent replications.
Within these models, we used restricted cubic splines Study-specific HRs, PAF, and YLLs estimates were
with 0 to 4 (depending on the cohort) internal knots to meta-analysed using the Hartung-Knapp random-effects
Men
datasets. SS, PV, and MK had final responsibility for the
Deaths Mean HR (95% CI) Weight decision to submit for publication.
follow-up (years)
COLAUS
NHIS 2009
55
86
616
322
208 (098438)
123 (072211)
01%
02%
Results
NHIS 2008 111 418 125 (078200) 02% 48 studies were included (appendix). After excluding
MIDUS 133 1161 121 (081181) 03% 27392 (15%) of 1778871 participants who had missing
EPIPORTO 144 688 164 (094286) 02%
NHIS 2007 148 513 130 (085199) 03% data for the covariates or mortality, 1751479 participants
NCDS 159 745 174 (115264) 03% were included in the analysis (appendix). Mean age at
NHIS 2006 183 609 182 (129258) 04%
NHANES 2007 190 386 121 (085173) 04% study entry was 478 years (SD 148) and 54% of
NHANES 2005 234 573 117 (085160) 05% participants were women. The proportion of par
NHIS 2005 290 700 109 (080148) 05%
NHIS 2003 291 910 114 (086150) 06%
ticipants with low occupational position ranged from
WLSS 360 1272 131 (104165) 09% 69% to 669% across studies (mean 414% [SD 125]
NHIS 2002 372 1005 190 (147247) 07% for men and 271% [SD 149] for women). The
NHANES 2003 381 739 119 (094149) 09%
NHIS 2001 463 1101 189 (149239) 09% proportion of people with a high occupational position
NHANES 1999 479 1051 133 (107166) 10% varied between 59% and 848% (mean 325% [SD
NHANES 2001 483 912 146 (119180) 11%
WLSG 502 1495 149 (123182) 12%
117] men and 261% [SD 123] women). Age
NHANES II 528 1374 132 (105164) 10% stratification revealed no age calendar effects (data not
NHIS 2000 530 1194 147 (119181) 11% shown).
NHIS 1999 540 1288 166 (134204) 11%
NHANES III 656 1447 139 (114169) 12% During 12 025208 person-years at risk for men,
WHITEHALL II 708 2040 157 (121204) 07% 161524 men died; during 14580862 person-years at risk
NHIS 1998 719 1378 147 (123175) 15%
EPIC Italy 758 1604 140 (105188) 06%
for women, a total of 148753 women died (mean follow-
NHIS 1997 829 1473 145 (123170) 17% up for men and women 133 years [SD 34]). In men,
ELSA 840 730 146 (122174) 15% 43765 (152% of total) with low occupational position
NHIS 2004 1115 815 153 (132177) 21%
NHANES I 1147 1858 148 (127172) 19% died and 17160 (115%) with high occupational position
NHIS 1996 1247 1545 155 (136178) 24% died. In women, 11 835 (94% of total) with low
HRS 1279 1728 150 (131171) 24%
HALS 1359 2023 145 (125168) 20% occupational position died and 8292 (68%) with high
Alameda County 1547 2696 129 (112147) 24% occupational position died. Participants with low
GAZEL 1935 2534 168 (148190) 28% occupational position had a higher mortality risk than
NHIS 1995 2293 1631 138 (125152) 39%
NHIS 1994 3029 1718 146 (134159) 48% did those with high occupational position, in both men
NHIS 1993 3090 1808 144 (132157) 49% (HR 142, 95% CI 138145; figure 1) and women
NHIS 1986 3331 2369 141 (129153) 51%
NHIS 1992 3898 1983 136 (126147) 57% (134, 128139; figure 2). Participants with inter
NHIS 1991 4152 1975 132 (122142) 60% mediate occupational position had a higher mortality
NHIS 1990 4590 2059 137 (128148) 63%
NHIS 1989 4848 2141 140 (131150) 66%
risk compared with participants with high occupational
NHIS 1988 5564 2221 137 (129146) 71% position (meta-analytic HR 121, 95% CI 118124 for
NHIS 1987 6018 2293 138 (129146) 74% men and 117, 112122 for women). A graded
WHIP 21 049 1160 147 (136160) 50%
association between occupational position and mortality
Pooled HR 142 (138145) 100% was observed in both men and women (HR for one unit
Prediction interval 133151
I=145%, =00008
decrease in SES 119, 95% CI 117120 in men and
05 10 25
115, 113118 in women, p<00001 for both).
Figure 1: Mortality for low versus high occupational position in men in 46 cohort studies Heterogeneity in study-specific estimates was low for
HRs are adjusted for age, marital status, and race or ethnicity. Pooled HR is represented with a grey diamond and men (I=145% [041%], p=02034, =00008) and
the 95% prediction interval with a black bar. I statistic is the percentage of between study heterogeneity;
moderate for women (I=298% [0512%], p=00309,
statistic measures the inter-study variance. The prediction interval provides a predicted range for the true
association between occupational position and mortality. HR=hazard ratio. =00048).
Figure 3 shows mortality associated with the 2525 risk
factors (minimally adjusted models). The greatest
method.15 To assess heterogeneity between cohorts, we increases in mortality associated with the 2525 risk
computed I and statistics; I to assess heterogeneity factors were for current smoking and diabetes, although
attributable to variation in the true association and to physical inactivity, high alcohol intake, and hypertension
measure the inter-cohort variance. To account for in were also associated (figure 3). The effect of low
the uncertainty around the pooled estimates, we further occupational position appeared greater than that of
calculated 95% prediction intervals for hazard ratios.16 hypertension or obesity (figure 3); the effect of low
occupational position on mortality was greater than that
Role of the funding source of obesity even when the obesity analysis was restricted
The funding sources had no role in the study design; in to cohorts with a mean follow-up more than 10 years
the collection, analysis, and interpretation of data; in the (>10 years; HR 112, 95% CI 105121 for men and 124,
writing of the report; or in the decision to submit the 118131 for women). 33 of 48 studies had complete
paper for publication. CC and MJ had full access to the data for occupational position and all 2525 risk factors
leading to weight loss and increased mortality risk Risk factor Prevalence (%) PAF (95% CI)
among lean or underweight individuals.31,32 Hetero
Low SES (intermediate/low)
geneity in study-specific estimates was generally low Men 251/424 1894 (1763 to 2024)
for occupational position, but larger for some of the Women 458/281 1533 (1276 to 1790)
Current smoking (former/current)
risk factors (appendix). This difference could be due to Men 328/271 2904 (2690 to 3118)
varying degrees of precision in the measurement of the Women 209/210 2104 (1902 to 2307)
2525 risk factors in the different cohorts, and random- Diabetes
Men 94 593 (485 to 700)
effect meta-analysis partially takes this uncertainty into Women 87 688 (576 to 800)
account for the estimation of pooled effects. Physical inactivity
Men 395 2616 (2301 to 2931)
Finally, the cohort studies participating in the Women 462 2341 (2042 to 2639)
LIFEPATH consortium were from high-income High alcohol intake
countries. Thus, our results might not be generalisable Men 100 434 (326 to 542)
Women 48 327 (234 to 420)
to other populations. Previous studies suggest that Hypertension
socioeconomic factors and the 2525 risk factors are Men 380 976 (792 to 1160)
Women 314 821 (622 to 1020)
also strong predictors of premature mortality in low Obesity (overweight/obese)
and middle income countries.33 Further research should Men 439/194 557 (884 to 231)
Women 289/220 355 (135 to 574)
assess socioeconomic status and 2525 risk factors in
predicting mortality in different economic settings. 10 0 10 20 20 40
Population attributable fraction (%)
Despite these limitations, our study has important
implications. Our findings suggest that existing global Figure 5: Population attributable fraction for socioeconomic status and 2525 risk factors
strategies and actions defined in the 2525 health plan Calculations assume risk in the population at the level of the least exposed group. SES=socioeconomic status.
PAF=population attributable fraction.
and the Global Burden of Diseases surveillance
programme potentially exclude a major determinant of
health from the agenda. A lack of consideration of the Men
Years of life lost (95% CI)
interrelation between social circumstances and health is 45 26 (28 to 24) 56 (61 to 52) 41 (47 to 34) 28 (34 to 22) 06 (11 to 01) 19 (23 to 16) 04 (08 to 01)
also evident in the Sustainable Development Goals
(SDGs): SDG 3 focuses on health but it makes no 40
Life expectancy (years)
Cu r
No
No
No
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e
ve
at
Ye
Ye
Ye
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Hi
Hi
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31 Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass 35 WHO. Rio Political Declaration on Social Determinants of Health.
index and mortality among 146 million white adults. N Engl J Med Rio de Janeiro, Brazil: World Health Organization, 2011.
2010; 363: 221119. 36 Levin H, Belfield C, Muennig P, Rouse C. The costs and benefits of
32 Whitlock G, Lewington S, Sherliker P, et al, for the Prospective an excellent education for Americas children. New York, NY:
Studies Collaboration. Body-mass index and cause-specific mortality Teachers College, 2006.
in 900000 adults: collaborative analyses of 57 prospective studies. 37 Elesh D, Lefcowitz MJ. The effects of the New Jersey-Pennsylvania
Lancet 2009; 373: 108396. Negative Income Tax Experiment on health and health care
33 Di Cesare M, Khang YH, Asaria P, et al. Inequalities in utilization. J Health Soc Behav 1977; 18: 391405.
non-communicable diseases and effective responses. Lancet 2013; 38 Muennig PA, Mohit B, Wu J, Jia H, Rosen Z. Cost effectiveness of
381: 58597. the earned income tax credit as a health policy investment.
34 Marmot MG, Atkinson T, Bell J, et al. Fair society, healthy lives: Am J Prev Med 2016; published online Aug 26. DOI:10.1016/
a strategic review of health inequalities in England post-2010: j.amepre.2016.07.001.
The Marmot Review. London: UCL Institute, 2010.