Context Dietary patterns and lifestyle factors are associated with mortality
from all causes, coronary heart disease, cardiovascular diseases, and cancer,
but few studies have investigated these factors in combination.
Objective To investigate the single and combined effect of Mediterranean diet,
being physically active, moderate alcohol use, and nonsmoking on all-cause
and cause-specific mortality in European elderly individuals.
Design, Setting, and Participants The Healthy Ageing: a Longitudinal study in Europe (HALE) population,
comprising individuals enrolled in the Survey in Europe on Nutrition and the
Elderly: a Concerned Action (SENECA) and the Finland, Italy, the Netherlands,
Elderly (FINE) studies, includes 1507 apparently healthy men and 832 women,
aged 70 to 90 years in 11 European countries. This cohort study was conducted
between 1988 and 2000.
Main Outcome Measures Ten-year mortality from all causes, coronary heart disease, cardiovascular
diseases, and cancer.
Results During follow-up, 935 participants died: 371 from cardiovascular diseases,
233 from cancer, and 145 from other causes; for 186, the cause of death was
unknown. Adhering to a Mediterranean diet (hazard ratio [HR], 0.77; 95% confidence
interval [CI], 0.68-0.88), moderate alcohol use (HR, 0.78; 95% CI, 0.67-0.91),
physical activity (HR, 0.63; 95% CI, 0.55-0.72), and nonsmoking (HR, 0.65;
95% CI, 0.57-0.75) were associated with a lower risk of all-cause mortality
(HRs controlled for age, sex, years of education, body mass index, study,
and other factors). Similar results were observed for mortality from coronary
heart disease, cardiovascular diseases, and cancer. The combination of 4 low
risk factors lowered the all-cause mortality rate to 0.35 (95% CI, 0.28-0.44).
In total, lack of adherence to this low-risk pattern was associated with a
population attributable risk of 60% of all deaths, 64% of deaths from coronary
heart disease, 61% from cardiovascular diseases, and 60% from cancer.
Conclusion Among individuals aged 70 to 90 years, adherence to a Mediterranean
diet and healthful lifestyle is associated with a more than 50% lower rate
of all-causes and cause-specific mortality.
The number of older people is growing rapidly worldwide. More than 580
million people are older than 60 years, and the number is projected to rise
to 1000 million by 2020.1 With the increase
in life expectancy, the leading causes of death have shifted dramatically
from infectious diseases to noncommunicable diseases and from younger to older
individuals. In industrialized countries, about 75% of deaths in persons older
than the age of 65 are now from cardiovascular diseases and cancer.2
Regardless of predisposing factors, diet and lifestyle influence morbidity
and mortality during the course of life.2 Because
of the cumulative effect of adverse factors throughout life, it is particularly
important for older persons to adopt diet and lifestyle practices that minimize
their risk of death from morbidity and maximize their prospects for healthful
aging.2
Dietary patterns and other modifiable lifestyle factors are associated
with mortality from all causes, coronary heart disease (CHD), cardiovascular
diseases (CVD), and cancer.3-8 As
yet, few studies have investigated the combined effect of diet and other lifestyle
factors.7,9
In the current study, we investigated the association of individual
and combined dietary patterns and lifestyle factors (alcohol use, smoking
status, and physical activity) with mortality from all causes, CHD, CVD, and
cancer in elderly men and women from 11 European countries in the Healthy
Ageing: a Longitudinal study in Europe (HALE) population.
The HALE project included participants of the Survey in Europe on Nutrition
and the Elderly: a Concerned Action (SENECA) and Finland, Italy, the Netherlands,
Elderly (FINE) studies who were examined in 1988-1991 and were followed up
for 10 years. Details about the SENECA and FINE studies have been described
elsewhere10,11 and are briefly
summarized herein.
The SENECA study started in 1988 and consisted of a random age- and
sex-stratified sample of inhabitants, born between 1913 and 1918, of 19 European
towns. In the HALE project, 13 centers that carried out mortality follow-up
were included. The original participation rate in the centers varied from
37% to 81%.12 Surveys were repeated in 1993
and 1999. The response rates for SENECA were 68% in 1993 and 55% in 1999,
and for FINE they were 86% in 1993 and 85% in 1993. All men and women of the
following towns were included: Hamme, Belgium; Roskilde, Denmark; Strasbourg,
France; Valence, France; Iraklion, Greece; Monor, Hungary; Padua, Italy; Culemborg,
the Netherlands; Vila Franca de Xira, Portugal; Betanzos, Spain; and Yverdon,
Burgdorf, and Bellinzona, Switzerland.10
The FINE study consists of the survivors of 5 cohorts of the Seven Countries
Study: Ilomantsi, East Finland; Pöytyä, and Mellilä, West Finland;
Crevalcore and Montegiorgio, Italy; and Zutphen, the Netherlands. The FINE
study, which started in 1984 and continued to 2000, recruited men who were
born between 1900 and 1920. For our study, we used the 1989-1991 baseline
measurements of men aged 70 to 90 years.11 Surveys
were repeated in the years 1994-1995 and 1999-2000. The response rates in
1989-1991 were 92% for the Finnish cohorts, 74% for the Dutch cohort, and
76% for the Italian cohorts.13
Because CHD, CVD, cancer, and diabetes increase the risk of mortality
and can induce changes in diet and lifestyle, participants who had these diseases
were excluded at baseline. The average follow-up time was 10 years in both
SENECA and FINE.
In both studies, food consumption data were collected by trained dietitians
using a dietary history method.10,11 This
method provides information about the usual food consumption of the participants
from the month before the interview in SENECA and from 2 to 4 weeks before
the interview in FINE. The central part of the dietary history was the same
for both studies. The coding was based on frequency tables, which were the
same in both studies, but the start of the dietary interview about usual food
consumption patterns was based on a food record and by an oral interview in
FINE. Both dietary histories were validated.10,13
Information on smoking status; physical activity level; educational
achievement (number of years); the prevalence of CHD, stroke, diabetes, and
cancer; the use of antihypertensive medication (only in FINE); and occupation
(only in FINE) was collected using questionnaires. The prevalence of chronic
diseases was confirmed by general practitioners, hospital registrants, or
both in the FINE study only.
Information on physical habitual activity was obtained using the Voorrips
questionnaire in SENECA and the Morris questionnaire in FINE.14,15 Both
questionnaires were developed for retired elderly individuals and focus on
leisure-time activities, such as walking, cycling, and gardening. SENECA also
included household activities.14,15
Weight, height, and waist circumference (SENECA only) measurements have
been described in detail elsewhere.10,11 Body
mass index (BMI) was calculated as weight in kilograms divided by height in
meters squared. In the analyses, BMI was dichotomized as 25 or less vs greater
than 25. The HALE study comprised 98.6% of individuals who lived independently.
Definition of Low-Risk Groups
To assess the association of diet and the lifestyle factors with mortality,
a low-risk group was defined for diet and lifestyle factors. For dietary intake,
the low-risk group was defined as those who had a score of at least 4 on a
modified version of the Mediterranean diet score proposed by Trichopoulou
et al.4
The modified Mediterranean diet score comprised 8 components: ratio
of monounsaturated to saturated fat; legumes, nuts, and seeds; grains; fruit;
vegetables and potatoes; meat and meat products; dairy products; and fish.
Intake of each component was adjusted to daily intakes of 2500 kcal (10.5
MJ) for men and 2000 kcal (8.5 MJ) for women. The sex-specific median intake
values were taken as cutoff points. The diet score varied from 0 (low-quality
diet) to 8 (high-quality diet). For the components monounsaturated fatty acids
to saturated fatty acids (MUFA to SAFA) ratio; fruits and fruit products;
vegetables and potatoes; legumes, nuts, and seeds; fish; and grains, a value
of 1 was assigned to persons whose consumption was at least as high as the
sex-specific median value, and 0 to the others. The vegetables group of the
original Mediterranean diet score was replaced by the vegetables and potatoes
group because the European classification system (EUROCODE) was used when
the 2 food groups were assessed together.16 For
meat and meat products and dairy products, a value of 1 was assigned to persons
whose consumption was less than the sex-specific median and 0 to the others.
The low-risk group for alcohol was defined as those who consumed more
than 0 g of alcohol per day. Alcohol consumption was initially divided into
3 groups: 0 g, 1 to 29 g, and 30 g or more of alcohol per day. However, the
Kaplan-Meier survival curves of the 3 alcohol groups showed no difference
in survival between participants who consumed between 1 g to 29 g of alcohol
per day and those who consumed 30 g or more alcohol per day.
For smoking, individuals were considered to be at low risk if they had
never smoked or had stopped smoking more than 15 years ago.17-19
Individuals with a score in the intermediate and the highest tertile
on the Voorrips or Morris questionnaire were considered the low-risk group
for physical activity.14,15
A lifestyle score was calculated by adding the individual scores for
diet, physical activity level, smoking status, and alcohol intake. Individuals
scored 1 point if they belonged to the low-risk group for diet or a particular
lifestyle factor and 0 if they belonged to the high-risk group. In total,
an individual could obtain 4 points: 1 point for a Mediterranean diet and
3 points for the healthful lifestyle factors.
Information on vital status and causes of death was collected every
5 years in FINE and in 1999-2000 for SENECA and was available for 99.7% of
participants. Causes of death were coded by an experienced physician and classified
according to the International Classification of Diseases, Ninth Revision (ICD-9) coding system.20 Codes
410-414 were used for defining CHD, codes 390-459 for CVD, and codes 140-240
for cancer. Causes of death were available for 92% of the participants in
FINE and 72% of the participants in SENECA. Mortality from other causes was
defined as total mortality minus the deaths from unknown causes, CHD, CVD,
and cancer.
Statistical analyses were carried out using the SAS statistical software
version 8.2 (SAS Institute, Cary, NC). Before pooling the data for SENECA
and FINE, a test for heterogeneity was performed, which was not significant
(P = .93); no significant interactions between diet,
lifestyle factors, and study were found. Cox proportional hazards models were
used to estimate the single and the combined effect of diet, smoking status,
alcohol consumption, and physical activity level on mortality.21 In
the analyses for cause-specific mortality and mortality from other causes,
individuals with a missing cause of death were excluded. For all models, the
Cox proportional hazards assumption was tested and met. Dummy variables were
created for the number of healthful dietary and lifestyle factors; a score
of 0 or 1 for the healthful dietary and lifestyle factor was used as reference
category.
All models were adjusted for the other diet and lifestyle factors, sex,
age at baseline, BMI, and study population (SENECA vs FINE). To correct the
estimates for socioeconomic status, the models were adjusted for the number
of years of education.
Region (northern or southern Europe), center, occupation, waist circumference
(continuous), marital status, and use of antihypertensive medication were
tested as potential confounders but did not affect our estimates. Because
several studies indicate that exposure to pesticides and industrialized environment
increases the risk of mortality,22 we classified
participants' occupation as farmers (an indicator of pesticide exposure) vs
nonfarmers and whether individuals were exposed or not exposed to an industrialized
environment. Occupation as farmer and exposure to an industrialized environment
also did not affect our results.
To minimize the possibility that diet or lifestyle factors had changed
in response to subclinical disease, the analyses were repeated after excluding
the first 2 years of mortality follow-up.9 Interactions
between all dietary and lifestyle factors and confounders were tested, but
none of them was statistically significant at α = .1. To ensure that
the estimates were not biased by multicollinearity, the crude hazard ratios
(HRs) for the dietary and lifestyle factors were also calculated and compared
with the adjusted HRs. The crude HRs and the adjusted HRs were similar, indicating
that the estimates were not biased by multicollinearity.
Population attributable risk, an estimate of the percentage of mortality
in this population that would not have occurred if all participants were in
the low-risk group, was calculated.9,23
The unadjusted Kaplan-Meier curves for the number of protective factors
in relation to all-cause mortality were fitted and the log-rank test was calculated. P<.05 was considered to be statistically significant
for all possible predictors in the model, but to investigate interaction between
all predictors, we considered P<.01 to be statistically
significant.
Information about diet, lifestyle factors, and vital status was available
for 1507 men (781 from the SENECA study, 726 from the FINE study) and 832
women without CHD, CVD, diabetes, and cancer at baseline (Table 1). Men in the SENECA study were 7 years younger on average
than men in the FINE study. The median of the diet score in the total population
was 4; 3 in northern Europe vs 5 in southern Europe. The mean alcohol intake
was 21 g/d for men and 6 g/d for women. In northern Europe, the mean alcohol
consumption was 17.5 g/d for men and 5.5 g/d for women compared with 31 g/d
for men and 6 g/d for women in southern Europe. The cutoff point for the lowest
percentile for activity in the FINE study was 200 min/wk, which means approximately
30 minutes of activity per day, with an intensity higher than 2.0 kcal/kg
per hour each day. In the SENECA study, there were almost 5 times as many
male smokers as there were female smokers. The mean follow-up time was 10
years, with a range of 8.9 to 10.5 years. Twice as many men died during the
10-year follow-up as did women.
Table 2 shows that a Mediterranean
diet, moderate alcohol consumption, moderate to high physical activity levels,
and nonsmoking were associated with lower mortality rates from all causes,
CHD, CVD, cancer, and other causes during the 10-year follow-up. The models
were adjusted for sex, age, years of education, study, and BMI. Individuals
with 2, 3, or 4 low-risk factors had a significantly lower risk of all-cause
and cause-specific mortality compared with individuals with 0 or 1 low-risk
factor during 10 years of follow-up (Table
3). Sixty percent of all deaths were associated with not adhering
to this low-risk pattern. For cause-specific mortality, 64% of deaths due
to CHD; 61% due to CVD; 60% due to cancer, and 61% due to other causes during
the 10-year follow-up period were associated with not adhering to this low-risk
pattern. Including individuals with CHD, CVD, cancer, or diabetes at baseline
in the analysis and adjusting for prevalence of these long-term diseases at
baseline did not change our estimates.
Similar results were found after excluding from the analysis the 140
persons who died during the first 2 years of follow-up: adhering to a Mediterranean
diet (HR, 0.77; 95% confidence interval [CI], 0.67-0.89), moderate alcohol
consumption (HR, 0.83; 95% CI, 0.71-0.91), engaging in physical activity (HR,
0.65; 95% CI, 0.56-0.76), and nonsmoking (HR, 0.67, 95% CI, 0.57-0.78) were
associated with a significantly lower risk of all-cause mortality. The combination
of 4 low-risk factors lowered the all-cause mortality rate to 0.37 (95% CI,
0.29-0.47). For cause-specific mortality, the HRs for the single and the combined
effects from dietary and lifestyle factors were also similar after excluding
the first 2 years of follow-up.
Figure 1 shows the Kaplan-Meier
curves for the number of healthful dietary and lifestyle factors. The corresponding
log-rank test statistic was 101.9, P<.001.
During the 10-year follow-up, men and women between the ages of 70 and
90 years who had adhered to a Mediterranean diet, were nonsmokers or had stopped
smoking more than 15 years ago, were physically active, and used alcohol moderately
had less than half the mortality rate from all causes, CHD, CVD, and cancer,
and mortality from other causes than those who did not.
Advantages of this Europe-wide study were its great diversity in dietary
patterns and lifestyle factors, its prospective nature, its large sample size,
and its measurements of many potential confounders. SENECA and FINE could
be pooled because the estimates of the separate models were similar and there
were no important differences in study population and measurement of risk
factors. To ensure that the relationships between diet, lifestyle factors,
and mortality could not be explained by a study effect, this variable was
included as a potential confounder in all pooled analyses.
This study also had several limitations. Despite the large number of
participants and long follow-up, few cases had no healthful diet or lifestyle
factors. Therefore, we had to combine those who had scores of 0 or 1 in the
healthful diet and lifestyle factor ranking to have a stable reference category.
The initial response rate in the SENECA centers was lower (37%-81%) than in
the FINE centers (74%-92%).12,13 In
prospective cohort studies, distributions of dietary and lifestyle factors
in the study population may have been affected by selective participation
in the different cohorts. However, we had almost 100% mortality follow-up,
so the relationships between dietary factors and mortality should not be distorted.24 Another limitation is the low number of deaths due
to cause-specific mortality; for example, only 122 deaths were from CHD. Due
to these low numbers, it is possible that the power was too low to find a
significant effect of all dietary and lifestyle factors in the cause-specific
analysis.
A Mediterranean diet score of 4 or more points was associated with a
lower risk of all-cause and cause-specific mortality; the strongest association
was observed for CHD. The Mediterranean diet scale relies on generally strong
epidemiological evidence concerning the individual dietary components.4,6 The components of the diet score have
been validated.25 In previous studies4,6,7 involving elderly persons
in which a Mediterranean diet score similar to ours was used, the reduction
in overall mortality associated with increased adherence to the Mediterranean
diet was also similar to that found in our study. Similar results were also
noted for mortality from CHD and cancer.4 Our
results are also compatible with those of 2 randomized trials of secondary
prevention of CHD through the use of variants of the Mediterranean diet.26,27
In the Mediterranean diet score proposed by Trichopoulou et al,4 alcohol was also included. In our study, alcohol was
considered as a separate lifestyle factor because many studies observed an
independent effect of alcohol on survival.28-30 When
we included alcohol in our diet score, we found that individuals scoring 4
or more points on the original Mediterranean diet score have a 14% lower risk
of mortality compared with 23% in the present study. Participants who were
physically active had a lower risk of all-cause and cause-specific mortality.
Other studies found also that a sedentary lifestyle was associated with a
significantly higher risk of all-cause and cause-specific mortality compared
with being moderately active.17,31 Davis
et al17 reported that nonrecreational physical
activity was an even better predictor of survival time in older persons (aged
65-74 years) than in middle-aged persons (aged 45-54 years).17
Nonsmoking was associated with lower risk from all-cause and cause-specific
mortality. Other studies also found that smokers had a higher mortality risk
although the relative risk was lower in older persons than in middle-aged
individuals.17,18
Although diet and lifestyle habits can change over time, generally they
are characteristic of a person's way of living and reflect lifelong health
habits.32,33 For smoking, we contrasted
persons who never smoked or stopped smoking more than 15 years ago with those
who still smoked or stopped less than 15 years ago. This definition of the
smoking variable takes a long exposure period into account. In SENECA, dietary
and lifestyle factors were measured 5 years apart. The Spearman correlation
coefficient for alcohol consumption, diet score, and physical activity between
1988-1989 and 1993 was highly significant (P<.01),
suggesting that diet and lifestyle factors were stable in older individuals.
Several other studies also found that smoking habits and activity patterns
in middle-aged and many elderly men were stable over the years.32,33
A multiplicative model was used to assess the combined effect of diet
and lifestyle factors on all-cause and cause-specific mortality. The more
healthful dietary and lifestyle factors a participant had, the lower the risk
for all-cause mortality and cause-specific mortality. In the current study,
60% to 64% of mortality was associated with lack of adherence to this low-risk
pattern. This supports the hypothesis that participants who follow a Mediterranean
type of diet and maintain a healthful lifestyle are less likely to die from
all-cause and cause-specific mortality even at ages 70 to 90 years. Establishing
a causal relationship would require an intervention study, and the number
of years an individual needs to maintain such a lifestyle to realize a benefit
is unknown. However, a Mediterranean diet, rich in plant foods in combination
with nonsmoking, moderate alcohol consumption, and at least 30 minutes of
physical activity per day is associated with a significantly lower mortality
rate, even in old age.
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