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Combined impact of lifestyle factors on mortality: Prospective cohort study in

US women

Article in The BMJ · February 2008

DOI: 10.1136/bmj.a1440 · Source: PubMed

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 RESEARCH

Combined impact of lifestyle factors on mortality:

prospective cohort study in US women
Rob M van Dam, assistant professor of medicine,1,2 Tricia Li, research fellow,1 Donna Spiegelman, professor
of epidemiology and biostatistics,3,4 Oscar H Franco, researcher,5 Frank B Hu, professor of nutrition and
epidemiology1,2,3

1
Department of Nutrition, Harvard ABSTRACT The proportion of deaths that is attributable to
School of Public Health, 665 Objective To evaluate the impact of combinations of lifestyle factors has been estimated by Mokdad and
Huntington Ave, Boston, MA
02115, USA lifestyle factors on mortality in middle aged women. colleagues and in the global burden of disease study,
2
Channing Laboratory, Design Prospective cohort study. using data on relative risks and the prevalence of risk
Department of Medicine, Brigham Setting Nurses’ health study, United States. factors from multiple sources.8 9 As a result of this broad
and Women’s Hospital, and
Harvard Medical School, Boston
Participants 77 782 women aged 34 to 59 years and free approach, the imprecision and potential biases affect-
MA 02115 from cardiovascular disease and cancer in 1980. ing the results were less transparent and the analysis of
3
Department of Epidemiology, Main outcome measure Relative risk of mortality during lifestyle factors was less detailed than can be achieved
Harvard School of Public Health 24 years of follow-up in relation to five lifestyle factors in a well characterised prospective cohort study. In a
4
Department of Biostatistics, (cigarette smoking, being overweight, taking little cohort study in 11 European countries, an estimated
Harvard School of Public Health
5 moderate to vigorous physical activity, no light to 60% of deaths from all causes during 10 years of follow-
Unilever Corporate Research,
Sharnbrook, Bedfordshire moderate alcohol intake, and low diet quality score). up could be attributed to lack of adherence to non-
MK44 1LQ Results 8882 deaths were documented, including 1790 smoking, a healthy diet, regular physical activity, and
Correspondence to: R van Dam from cardiovascular disease and 4527 from cancer. Each moderate alcohol intake.10 However, this study
[email protected] included only 2339 participants, who were elderly
lifestyle factor independently and significantly predicted
Cite this as: BMJ 2008;337:a1440 mortality. Relative risks for five compared with zero and mostly male, and whether the findings apply to
doi:10.1136/bmj.a1440 lifestyle risk factors were 3.26 (95% confidence interval younger populations and women thus remains unclear.
2.45 to 4.34) for cancer mortality, 8.17 (4.96 to 13.47) for We therefore examined combinations of lifestyle
cardiovascular mortality, and 4.31 (3.51 to 5.31) for all factors in relation to cancer, cardiovascular, and all
cause mortality. A total of 28% (25% to 31%) of deaths cause mortality during 24 years of follow-up among
during follow-up could be attributed to smoking and 55% middle aged women who participated in the nurses’
(47% to 62%) to the combination of smoking, being health study. We also estimated population attributa-
overweight, lack of physical activity, and a low diet quality. ble risks, the proportion of deaths during follow-up that
Additionally considering alcohol intake did not could potentially have been avoided by adherence to
substantially change this estimate. lifestyle guidelines.
Conclusions These results indicate that adherence to
lifestyle guidelines is associated with markedly lower METHODS
mortality in middle aged women. Both efforts to eradicate Study population
cigarette smoking and those to stimulate regular physical The nurses’ health study is a prospective cohort study
activity and a healthy diet should be intensified. that was established in 1976 when 121 700 female
registered US nurses, aged 30 to 55 years, completed a
INTRODUCTION mailed questionnaire on known and suspected risk
Diet, physical activity, adiposity, alcohol consumption, factors for chronic diseases. Since then, participants
and cigarette smoking have been associated with risk of have been sent biennial follow-up questionnaires to
chronic diseases including type 2 diabetes,1 2 cardio- update information on lifestyle and health conditions.
vascular diseases,3-5 and various cancers.6 7 However, For the current analysis, we began follow-up in 1980,
to identify priorities for clinical and public health because this was the first year when diet was assessed.
efforts, understanding the magnitude of effects of risk In 1980, 98 462 women, aged 34 to 59 years, completed
factors, individually and in combination, on overall the questionnaire. We excluded women with pre-
health is fundamental. One way to assess the impact of viously diagnosed cancer (except non-melanoma skin
lifestyle factors on overall health is to evaluate the cancer) or cardiovascular disease (n=8527). We also
effects on mortality, which allows comparison of the excluded alcohol abstainers who reported on the 1980
magnitude of effects of individual factors as well as questionnaire a great decrease in alcohol consumption
estimation of combined effects. during the previous decade (n=2797), because this
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 RESEARCH

our validation study, the correlation between self

Deaths per 100 000 person years

1000
All causes
Cancer
reported and technician measured weight was 0.97.16
800 Father’s occupation when the participant was 16 years
Cardiovascular disease
of age was assessed on the 1976 questionnaire. In 1992,
600
we also asked about the degrees the participant had
400 received (registered nurse, bachelors, masters, docto-
rate) and, for women who were married or widowed,
200 the highest level of education that their husband
completed (less than high school, some high school,
0
0 1 2 3 4 5 high school graduate, college graduate, graduate
school).
No of risk factors

Age standardised all cause, cancer, and cardiovascular Classification of low risk categories
mortality during 24 years of follow-up by number of lifestyle risk or adiposity, we defined low risk as a body mass index
factors. Lifestyle risk factors included cigarette smoking (ever), between 18.5 and 25.0.17 For physical activity, we
lack of physical activity (<30 min/day moderate to vigorous defined low risk as an average of at least 30 minutes a
intensity activity), low diet quality (lowest three fifths of healthy
day of activity of at least moderate intensity (requiring
diet score), alcohol intake of 0 or ≥15 g/day, and overweight
(body mass index ≥25) ≥3 metabolic equivalents an hour, including brisk
walking), consistent with existing guidelines.18 For
cigarette smoking, we defined low risk as never smoking.
could be subsequent to alcoholism or disease. Simi- For alcohol consumption, we defined low risk as light to
larly, we excluded women with a body mass index moderate consumption (≥1 and <15 g/day—that is, up to
below 18.5 (n=1848), because this may be due to weight approximately one drink a day).
loss secondary to preclinical diseases.11 Finally, we To quantify the healthiness of the diet, we used the
excluded participants who left 10 or more items blank previously designed alternative healthy eating score.19
on the 1980 diet questionnaire, those with implausibly For this analysis, we decided a priori to use only seven
high or low reported energy intakes (below 2.09 or of the nine original items: we did not include multi-
above 14.63 MJ/day), those with ages outside the vitamin intake, because this has become less relevant as
eligible range, and those with missing information for a folate source as a result of widespread fortification of
smoking or body mass index (n=7562). After exclu- foods, and we did not include alcohol intake, because
sions, a total of 77 782 women remained for the current we wanted to present results on alcohol intake
analysis. Completion of the questionnaire was con- separately. For each of the remaining seven items, we
sidered to imply informed consent. assigned a score between 0 (least healthy) and 10
(recommended intake). We then added the scores for
Assessment of risk factors the individual items, resulting in a minimum healthy
Diet was assessed with a 61 item food frequency diet score of 0 and a maximum healthy diet score of 70.
questionnaire in 1980.12 An expanded questionnaire The seven included items were vegetables (recom-
including approximately 120 food items was used to mended: at least five servings a day), fruit (at least four
update information about diet every two to four years. servings a day), nuts and soya (at least one serving a
Participants were asked how often, on average, during day), ratio of fish and poultry to red meat (ratio at least
the previous year they had consumed a specified four or red meat less than twice a month), cereal fibre
common unit or portion size of a specific type of food. (≥15 g/day), trans-fat (≤0.5% of total energy), and the
The participants could choose from nine response polyunsaturated to saturated fatty acid ratio (ratio at
categories ranging from “never or less than once a least one).19 We considered participants with a healthy
month” to “six or more times a day.” Nutrient intakes diet score in the upper two fifths (highest 40%) to be in
were calculated by summing the nutrient content of a the low risk category for diet.
unit of each food multiplied by a weight proportional to
the frequency of its use. Validation studies in this Ascertainment of mortality
cohort using biochemical markers and diet records as Deaths were reported by next of kin, the postal
references indicated that the food frequency question- authorities, or both or were ascertained through
naire estimated dietary intakes with reasonably good searching for non-responders in the National Death
accuracy.12-14 Index. Follow-up for deaths in the National Death
Information on disease history and cigarette smok- Index has been estimated to be 98% complete for this
ing was assessed on each biennial questionnaire. cohort.20 Information on the cause of death was
Frequency of physical activity during the previous obtained from the next of kin (for external deaths
year was assessed in 1980, and this information was such as those due to traffic accidents), death certificates,
updated every two to four years.15 Height (in inches) or medical records. We requested permission from the
was assessed in the 1976 questionnaire, weight (in next of kin to review medical records for suspected
pounds) was assessed on the 1980 questionnaire, and deaths due to cancer or cardiovascular diseases if we
the body mass index was calculated as weight in did not yet have these records for follow-up of disease
kilograms divided by the square of height in metres. In incidence. The cause of death was determined after
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review by physicians and primarily based on medical the intervals is small,22 conditions that were satisfied for
records if both medical records and death certificates this analysis.
were available. We used ICD-8 (international classifi- We calculated population attributable risks, which
cation of diseases, 8th revision) codes to distinguish are estimates of the percentage of deaths during follow-
deaths due to cancer (140-207) and cardiovascular
up that would not have occurred if all women had been
diseases (390-459 and 795).
in the low risk category for lifestyle factors, assuming
that the observed associations represent causal effects.
Statistical analysis
For these analyses, we compared women in the low risk
Women contributed follow-up time from the date of
category for each of the component risk factors with all
return of the baseline questionnaire to the date of death
other women.23 We calculated population attributable
or 1 June 2004, whichever came first. We used pooled
logistic regression analysis stratified by two year risks by using previously described formulas that were
calendar time periods to estimate multivariate relative elaborated for this specific study design and are
risks and corresponding 95% confidence intervals. We appropriate for use with multivariate adjusted relative
chose this method because it obtains all information risks (SAS macro: www.hsph.harvard.edu/faculty/
needed for the calculation of partially adjusted spiegelman/software.html).21 24 25 Because of the large
population attributable risk estimates, including esti- computational computer capacity needed for this
mation of the relative risks for age.21 Pooled logistic calculation, we reduced the number of categories for
regression analysis is asymptotically equivalent to Cox the covariable calendar time by combining 12 two year
proportional hazards regression if time intervals are time periods into four periods. We estimated preva-
relatively short and the probability of the outcome in lence of exposures for 1990, because this year is

Table 1 | Multivariate relative risk of death from any cause, cardiovascular disease, and cancer during 24 years of follow-up according to body mass index, cigarette
smoking, alcohol consumption, physical activity, and diet*
Deaths from any cause Cardiovascular deaths Cancer deaths
Person years Cases Relative risk (95% CI) Cases Relative risk (95% CI) Cases Relative risk (95% CI)
Body mass index (kg/m2)
18.5-24.9 1 174 514 5095 1.00 (1.00 to 1.00) 855 1.00 (1.00 to 1.00) 2747 1.00 (1.00 to 1.00)
25-29.9 404 856 2359 1.18 (1.12 to 1.24) 511 1.46 (1.31 to 1.63) 1195 1.14 (1.06 to 1.22)
≥30.0 180 039 1428 1.67 (1.57 to 1.78) 424 2.81 (2.49 to 3.17) 585 1.32 (1.21 to 1.45)
Cigarette smoking
Never 787 104 2998 1.00 (1.00 to 1.00) 595 1.00 (1.00 to 1.00) 1519 1.00 (1.00 to 1.00)
Past 667 250 4076 1.52 (1.44 to 1.59) 743 1.49 (1.33 to 1.66) 2079 1.47 (1.37 to 1.57)
Current 1-14/ 104 428 609 1.94 (1.77 to 2.12) 145 2.61 (2.17 to 3.14) 318 1.82 (1.61 to 2.06)
day
Current ≥15/day 200 626 1199 2.32 (2.16 to 2.49) 307 3.34 (2.88 to 3.87) 611 2.10 (1.90 to 2.32)
† (g/day)
Alcohol consumption†
0 386 395 2044 1.00 (1.00 to 1.00) 502 1.00 (1.00 to 1.00) 887 1.00 (1.00 to 1.00)
1-4 745 039 3589 0.81 (0.76 to 0.85) 712 0.69 (0.61 to 0.77) 1878 0.97 (0.90 to 1.06)
5-14 405 344 1861 0.80 (0.75 to 0.86) 324 0.63 (0.54 to 0.73) 1023 0.99 (0.90 to 1.09)
15-29 155 024 900 0.90 (0.83 to 0.98) 168 0.75 (0.62 to 0.90) 492 1.11 (0.99 to 1.24)
≥30 67 369 485 1.11 (1.00 to 1.23) 82 0.75 (0.59 to 0.96) 246 1.26 (1.09 to 1.46)
‡ (hours/week)
Physical activity‡
0-0.4 116 915 1143 1.00 (1.00 to 1.00) 231 1.00 (1.00 to 1.00) 513 1.00 (1.00 to 1.00)
0.5-1.9 596 872 3366 0.84 (0.78 to 0.90) 715 0.94 (0.81 to 1.09) 1644 0.88 (0.79 to 0.97)
2.0-3.4 370 631 1690 0.77 (0.71 to 0.83) 345 0.87 (0.73 to 1.03) 896 0.83 (0.75 to 0.93)
3.5-5.4 201 459 768 0.72 (0.65 to 0.79) 126 0.70 (0.56 to 0.87) 446 0.82 (0.72 to 0.94)
≥5.5 248 639 636 0.63 (0.57 to 0.69) 96 0.57 (0.45 to 0.73) 379 0.73 (0.64 to 0.84)
§
Healthy diet score§
Fifth 1 337 747 2122 1.00 (1.00 to 1.00) 443 1.00 (1.00 to 1.00) 1038 1.00 (1.00 to 1.00)
Fifth 2 348 559 1848 0.85 (0.79 to 0.90) 427 0.96 (0.84 to 1.10) 891 0.83 (0.76 to 0.91)
Fifth 3 355 705 1766 0.80 (0.75 to 0.85) 344 0.78 (0.67 to 0.90) 895 0.81 (0.74 to 0.89)
Fifth 4 359 442 1701 0.76 (0.71 to 0.81) 326 0.75 (0.65 to 0.87) 894 0.80 (0.73 to 0.87)
Fifth 5 357 955 1445 0.65 (0.61 to 0.70) 250 0.59 (0.51 to 0.70) 809 0.72 (0.65 to 0.79)
*Relative risks adjusted for age (5 year categories), time period (12 periods), and other risk factors included in table.
†Three deaths and 239 person years not included because of missing values.
‡Of moderate to vigorous intensity; 1279 deaths and 224 893 person years not included because of missing values.
§In 1990 healthy diet score was <22.61 (median 18.65) for fifth 1, 22.61-28.85 (median 25.89) for fifth 2, 28.86-34.57 (median 31.68) for fifth 3, 34.58-41.38 (median 37.72) for fifth 4, and
>41.39 (median 46.34) for fifth 5.

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midway during follow-up and approximates average attributable risks were higher for cardiovascular
exposure during follow-up. mortality than for cancer mortality. Among never
To estimate relative risks for cigarette smoking and smokers, the relative risk of mortality for being
diet, we updated information during follow-up by overweight was higher than that for the whole study
using the most recently available information. For population (1.55, 95% confidence interval 1.44 to
physical activity and alcohol intake, we used the 1.66), resulting in a higher population attributable risk
cumulative average from all available questionnaires (22%, 18% to 27%).
up to the start of each two year follow-up.26 To We also evaluated combinations of lifestyle risk
minimise bias owing to the effects of poor health factors in relation to mortality. As shown in the figure,
before death leading to weight loss,11 we used the cardiovascular, cancer, and all cause mortality
baseline (1980) body mass index in our analysis. increased with an increasing number of risk factors.
In a sensitivity analysis, we examined potential The relative risk for combining cigarette smoking,
confounding by measures of socioeconomic status being overweight, lack of physical activity, and a low
by adding father’s occupation, education degree healthy diet score compared with none of the risk
received by the participant, and education level of factors was 6.91 (4.50 to 10.63) for cardiovascular
the husband to the multivariate model. Because mortality, 2.65 (2.14 to 3.28) for cancer mortality, and
education level was only assessed in 1992, we did 3.41 (2.90 to 4.00) for all cause mortality (table 3). The
this analysis for follow-up from 1992 until 2004. population attributable risk for having any of these four
We considered two tailed P values lower than 0.05 to risk factors was 72% for cardiovascular mortality, 44%
be statistically significant. We used SAS software, for cancer mortality, and 55% for all cause mortality.
version 9.1 for all analyses. When we also considered alcohol consumption, the
population attributable risks for having any of the five
RESULTS lifestyle risk factors were modestly greater than for the
During 1 759 408 person years of follow-up we four risk factors (table 3).
documented 8882 deaths, including 1790 from cardio- Results among never smokers were consistent with
vascular disease and 4527 from cancer. Table 1 shows those for the whole study population (table 4). We also
the multivariate adjusted relative risks for lifestyle examined whether results differed for younger
factors and death during follow-up. Cigarette smoking, (<60 years) and older (≥60 years) participants by
higher body mass index, less physical activity, and a recalculating the relative risks for these subgroups and
lower healthy diet score were all associated with using the prevalence of risk factor specific for these
increased cardiovascular, cancer, and all cause mortal- subgroups. The population attributable risk for all cause
ity. Alcohol consumption was associated with a lower mortality for the five risk factors combined (smoking,
risk of cardiovascular mortality than alcohol absti- diet, physical activity, overweight, alcohol consumption)
nence. However, heavy alcohol consumption was was 51% (30% to 67%) for younger women and 63%
associated with an increased risk of cancer mortality. (52% to 72%) for older women. Finally, we examined
As a result, light to moderate alcohol consumption was potential confounding by measures of socioeconomic
associated with the lowest all cause mortality. status (father’s occupation, education level of participant
Table 2 shows the multivariate adjusted relative risks and husband). Adjustment for these variables did not
and population attributable risks of mortality for the materially alter the association between any of the
high risk compared with the low risk category of lifestyle factors and mortality during follow-up (data not
lifestyle factors. The estimated population attributable shown).
risks were 28% for cigarette smoking, 14% for being
overweight, 17% for lack of physical activity, 13% DISCUSSION
for low diet quality, and 7% for not having light In this study of 77 782 middle aged US women, never
to moderate alcohol consumption. Population smoking, engaging in regular physical activity, eating a

Table 2 | Relative riskand population attributable risk (PAR) (95% confidenceintervals) of all cause,cardiovascular, and cancer mortality during 24 years of follow-up*

Women in high risk Death from any cause Cardiovascular death Cancer death
Variable category (%)† Relative risk PAR (%) Relative risk PAR (%) Relative risk PAR (%)
Ever v never smoking 56 1.66 (1.59 to 1.74) 27.9 (24.6 to 31.2) 1.83 (1.65 to 2.02) 32.7 (25.7 to 39.4) 1.59 (1.49 to 1.70) 26.8 (21.3 to 31.3)
Body mass index ≥25 v 18.5-24.9 48 1.32 (1.27 to 1.38) 14.2 (11.6 to 16.9) 1.85 (1.68 to 2.04) 30.6 (25.5 to 35.4) 1.19 (1.12 to 1.27) 8.3 (4.4 to 12.2)
Physical activity <30 min/day v 75 1.25 (1.17 to 1.32) 16.5 (11.7 to 21.1) 1.47 (1.27 to 1.69) 27.7 (17.2 to 37.5) 1.13 (1.05 to 1.22) 9.3 (2.7 to 15.9)
≥30 min/day
Healthy diet score in lower three 59 1.25 (1.19 to 1.30) 12.9 (9.6 to 16.2) 1.35 (1.22 to 1.50) 17.7 (10.3 to 25) 1.16 (1.09 to 1.24) 8.8 (4.1 to 13.4)
fifths v upper two fifths
Heavier drinking or abstaining‡ v 34 1.18 (1.13 to 1.24) 7.4 (4.6 to 10.2) 1.31 (1.19 to 1.44) 11.3 (4.9 to 17.5) 1.06 (1.00 to 1.12) 3.1 (0.8 to 5.3)
light to moderate alcohol intake
*Relative risks and population attributable risks adjusted for age (5 year categories), time period (four periods), and other risk factors included in table.
†Based on prevalence in 1990.
‡0 or ≥15 g/day alcohol.

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Table 3 | Risk of mortality during 24 years of follow-up according to combinations of lifestyle risk factors*
Death from any cause Cardiovascular death Cancer death
†
Four risk factors: smoking, overweight, low diet quality, low physical activity†
Relative risk (95% CI):
No risk factors (3.4%)‡ 1.00 1.00 1.00
One risk factor (16%) 1.30 (1.10 to 1.53) 1.43 (0.91 to 2.24) 1.32 (1.06 to 1.63)
Two risk factors (33%) 1.75 (1.49 to 2.05) 2.42 (1.58 to 3.71) 1.61 (1.231 to 1.98)
Three risk factors (34%) 2.52 (2.15 to 2.95) 3.98 (2.60 to 6.08) 2.12 (1.73 to 2.60)
Four risk factors (13%) 3.41 (2.90 to 4.00) 6.91 (4.50 to 10.63) 2.65 (2.14 to 3.28)
Population attributable risk (%) for 54.8 (46.7 to 61.9) 72.0 (58.6 to 81.6) 44.3 (31.2 to 55.8)
having any of the four risk factors (95%
CI)
§
Five risk factors: above four and alcohol abstinence or heavy drinking§
Relative risk (95% CI):
No risk factors (2.4%)‡ 1.00 1.00 1.00
One risk factor (12%) 1.34 (1.09 to 1.64) 1.13 (0.67 to 1.89) 1.55 (1.18 to 2.02)
Two risk factors (27%) 1.70 (1.40 to 2.07) 1.88 (1.15 to 3.05) 1.71 (1.32 to 2.22)
Three risk factors (34%) 2.25 (1.85 to 2.72) 2.80 (1.73 to 4.54) 2.07 (1.60 to 2.68)
Four risk factors (21%) 3.27 (2.70 to 3.97) 4.77 (2.94 to 7.72) 2.79 (2.15 to 3.62)
Five risk factors (4.2%) 4.31 (3.51 to 5.31) 8.17 (4.96 to 13.47) 3.26 (2.45 to 4.34)
Population attributable risk (%) for 58.1 (49.3 to 65.7) 75.2 (60.9 to 84.7) 46.0 (31.7 to 58.3)
having any of the five risk factors (95%
CI)
*Relative risks and population attributable risks adjusted for age (5 year age categories) and time period (four periods); additionally adjusted for
alcohol consumption (0, 1-4, 5-14, 15-29, ≥30 g/d) for “four risk factor” model.
†Overweight: body mass index ≥25; low diet quality: healthy diet score in lower three fifths; low physical activity: <30 min/day.
‡Prevalence in 1990.
§0 or ≥15 g/day alcohol.

healthy diet, and avoiding becoming overweight were Few previous studies have examined combinations
each associated with a markedly lower mortality during of lifestyle factors in relation to mortality. In the EPIC-
24 years of follow-up. We estimated that 55% of all Norfolk study, lifestyle factors were studied in relation
cause mortality, 44% of cancer mortality, and 72% of to mortality in men and women aged 45 to 79 years
cardiovascular mortality during follow-up could have during an average of 11 years of follow-up. Participants
been avoided by adherence to these four lifestyle who smoked, were physically inactive, were non-
guidelines. Light to moderate alcohol consumption (up moderate alcohol consumers, and had low fruit and
to one drink a day) was also associated with a lower risk vegetable intakes (measured by plasma vitamin C
of all cause mortality during follow-up. concentrations) had a relative risk of all cause mortality
during follow-up of 4.04 (2.95 to 5.54) compared with
Results in relation to other studies participants who met none of these criteria.27 In
another British prospective study, the estimated prob-
Smoking, overweight, physical activity, and quality of
ability of surviving 15 years free of cardiovascular
diet have consistently been associated with risk of
events and diabetes for a man aged 50 years ranged
chronic diseases and mortality in prospective cohort
from 89% in a moderately physically active man with a
studies.6 7 10 11 18 19 27 Not all of these risk factors have
body mass index between 20 and 24 who had never
been studied in randomised controlled trials with smoked to 42% in an inactive smoker with a body mass
disease incidence or mortality end points, and this may index of 30 or higher.33 In a cohort of elderly
never be done for feasibility or ethical reasons. Europeans aged 70 to 90 years, the combination of
However, findings from randomised controlled trials non-smoking, a Mediterranean-style diet, regular
support the protective effect of a prudent Mediterra- physical activity, and moderate alcohol consumption
nean-style diet and substitution of polyunsaturated for was associated with a relative risk of 10 year all cause
saturated fat for coronary heart disease3 4; of the mortality of 0.35 (0.28 to 0.44) compared with
combination of physical activity, a healthy diet, and adherence to only one or fewer of these lifestyle
moderate weight loss for type 2 diabetes2; and of factors.10 The estimated population attributable risk for
smoking cessation for premature mortality.28 In addi- the combination of lifestyle factors was 60% for all
tion, randomised controlled trials have shown bene- cause mortality, 61% for cardiovascular mortality, and
ficial effects of moderate alcohol consumption, 60% for cancer mortality. For women in high income
reduced trans-fat intake, high fruit and vegetable intake, countries in the global burden of disease study, the
and whole grain intake on biological markers of estimated population attributable risk for mortality was
cardiovascular risk.29-32 14% for smoking, 8% for overweight, 5% for physical
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inactivity, 4% for low fruit and vegetable intake, and consumption on personal health, women could use-
−3% for alcohol use.9 Mokdad and colleagues esti- fully discuss these risks and benefits with their
mated that the population attributable risks for US physician.
mortality in 2000 was 18% for tobacco, 15% for poor
diet and physical inactivity, and 3.5% for excess alcohol Strengths and limitations
consumption.8 Thus, our results are consistent with Strengths of our study include the large sample size, the
those from previous cohort studies that included prospective design with 24 years of follow-up and high
European and male participants and suggest that the response rates, and the repeated collection of detailed
population attributable risk estimates from studies information on lifestyle. Some measurement error is
using an indirect approach may be conservative for the inevitable, particularly in the assessment of diet and
demographic group that we studied. physical activity, and is likely to have weakened the
Heavy alcohol consumption was associated with associations seen. We would probably have seen a
higher cancer mortality in our study and has been lower mortality if we had used more restrictive criteria
associated with an increased risk of various cancers, for the low risk group (for example, healthy diet score
liver cirrhosis, hypertension, psychiatric disorders, in the highest fifth). However, our results indicate that
injuries, and violence in other studies.34 35 Consistent even modest differences in lifestyle can have a
with previous studies,10 36 we found that light to substantial impact on reducing mortality. Although
moderate alcohol consumption was associated with residual confounding can never be excluded in non-
lower cardiovascular mortality. However, even mod- randomised studies, evidence from prospective studies
erate alcohol consumption has been associated with a in other populations and randomised controlled trials
higher risk of breast cancer and traffic accidents.35 37 In supports our findings. Because incomplete adjustment
addition, people with moderate alcohol consumption for smoking habits can weaken the association between
may be more likely to transition to heavy consumption, overweight and mortality,11 our estimates for the
and a greater average alcohol consumption may association between overweight and mortality in
facilitate heavy consumption in communities.38 For never smokers may be more accurate than those for
individual people, the balance of risks and benefits of the total study population. Variation in socioeconomic
moderate alcohol consumption may depend on other status in our study of registered nurses was more
characteristics; possible benefits may exist for older limited than in the general population. Consistent with
women with cardiovascular risk factors,39 and a greater results from a British study,33 adjustment for various
likelihood of adverse effects may exist for women with measures of socioeconomic status did not appreciably
a personal or family history of alcoholism, alcohol affect associations between lifestyle factors and mor-
related cancers, or risk factors for these conditions.35 37 tality during follow-up. In analyses with mortality as an
Given the complexity of the effects of alcohol end point, confounding by poor health that precedes

Table 4 | Risk of mortality during 24 years of follow-up according to number of lifestyle risk factors in never smokers*
Death from any cause Cardiovascular death Cancer death
†
Three risk factors: low diet quality, low physical activity, overweight†
Relative risk (95% CI):
No risk factors (7.7%)‡ 1.00 1.00 1.00
One risk factor (27%) 1.20 (1.02 to 1.43) 1.44 (0.91 to 2.27) 1.19 (0.95 to 1.49)
Two risk factors (41%) 1.54 (1.31 to 1.81) 2.24 (1.44 to 3.46) 1.37 (1.11 to 1.70)
Three risk factors (25%) 2.17 (1.83 to 2.57) 3.58 (2.30 to 5.58) 1.75 (1.39 to 2.19)
Population attributable risk (%) for 34.3 (18.9 to 48.0) 56.1 (27.7 to 75.5) 22.8 (−0.01 to 44.3)
having any of the three risk factors (95%
CI)
§
Four risk factors: above three and alcohol abstinence or heavy drinking§
Relative risk (95% CI)
No risk factors (5.4%)‡ 1.00 1.00 1.00
One risk factor (20%) 1.25 (1.01 to 1.53) 1.18 (0.70 to 1.99) 1.39 (1.05 to 1.83)
Two risk factors (34%) 1.48 (1.22 to 1.81) 1.78 (1.08 to 2.92) 1.42 (1.08 to 1.85)
Three risk factors (30%) 1.95 (1.60 to 2.38) 2.64 (1.61 to 4.33) 1.70 (1.30 to 2.22)
Four risk factors (10%) 2.64 (2.13 to 3.26) 3.94 (2.35 to 6.60) 2.11 (1.57 to 2.83)
Population attributable risk (%) for 41.5 (24.3 to 56.2) 60.9 (28.3 to 80.9) 25.7 (−1.4 to 49.3)
having any of the four risk factors (95%
CI)
*Relative risks and population attributable risks adjusted for age (5 year age categories) and time period (four periods); additionally adjusted for
alcohol consumption (0, 1-4, 5-14, 15-29, ≥30.0 g/d) for the “three risk factor” model.
†Low diet quality: healthy diet score in lower three fifths; low physical activity: <30 min/day; overweight: body mass index ≥25.
‡Prevalence in 1990.
§0 or ≥15 g/day alcohol.

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contributed to the interpretation of the results and critical revision of the

WHAT IS ALREADY KNOWN ON THIS TOPIC manuscript for important intellectual content and approved the final
version of the manuscript. RMvD is the guarantor.
Many studies have shown that individual lifestyle factors are associated with risk of chronic
Funding: This research was supported by National Institutes of Health
diseases (NIH) grants CA87969 and HL60712. RMvD was partly supported by an
Few studies have evaluated the effects of combinations of lifestyle factors on mortality unrestricted research grant from the Peanut Foundation. The funding
sources had no role in the collection, management, analysis, or
WHAT THIS STUDY ADDS interpretation of the data and had no role in the preparation, review, or
approval of the manuscript. The content is solely the responsibility of the
Most deaths during 24 years of follow-up in middle aged women could have been avoided by a authors and does not necessarily represent the official views of the NIH.
combination of not smoking, maintaining a healthy weight, regular physical activity, and a Competing interests: None declared.
healthy diet Ethical approval: The institutional review board at Brigham and Women’s
Hospital approved this study.
These findings underscore the importance of intensifying both efforts to eradicate cigarette Provenance and peer review: Not commissioned; externally peer
smoking and those aimed at improving diet and physical activity reviewed.

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