BMJ No 7115 Volume 315 Education and debate Saturday 25 October 1997
Healthy aging
Kay-Tee Khaw
|
Summary points | | Healthy life expectancy is influenced by a relatively limited
number of chronic disabling conditions | | A substantial proportion of these chronic disabling conditions can be
prevented or postponed | | A greater focus is needed on prevention and health maintenance - much is
already known about the impact of modifiable influences such as diet,
physical activity, smoking, infection, pollution, and housing | | The social framework and policies that enable individuals to fulfil
their potential and attain optimal health are crucial |
A major challenge facing society is how we can maintain
health and quality of life in an aging population. Maximum life
expectancy has not changed substantially, but average life
expectancy has increased greatly in the past century. This reflects
profound improvements in mortality in infancy and young adulthood,
resulting in a much greater proportion of people surviving to older
ages (tables 1, 2, and 3).
| Table 1 - Percentage of people surviving to, and further expectation
of life from, age 55 and age 75, by year of birth, 1841-1981(1) |
| Year of birth |
Survival
|
Expectation of life
|
| To age 55
|
To age 75
|
At age 55
|
At age 75
|
| Men |
Women |
Men |
Women |
Men |
Women |
Men |
Women |
| 1,841 |
40 |
41 |
14 |
19 |
16.1 |
17.8 |
6.3 |
7.2 |
| 1,901 |
61 |
66 |
28 |
45 |
18.9 |
24.6 |
7.7 |
10.4 |
| 1,921 |
73 |
79 |
41 |
58 |
21.5 |
26.4 |
9.4 |
11.9 |
| 1,941 |
84 |
89 |
54 |
68 |
23.6 |
27.6 |
10.0 |
12.3 |
| 1,961 |
89 |
93 |
59 |
72 |
24.0 |
27.8 |
10.1 |
12.4 |
| 1,981 |
93 |
95 |
61 |
74 |
24.1 |
27.9 |
10.1 |
12.4. |
| Table 2 - Estimated number (percentage) in the population aged
60 years over in UK(2) |
| Year |
60-74 years |
75 years |
| 1994 |
8,031 (14) |
3,963 (7) |
| 2001 |
7,712 (13) |
4,383 (7) |
| 2011 |
9,212 (15) |
4,517 (7) |
| 2021 |
10,543 (17) |
5,186 (8) |
| 2031 |
11,925 (20) |
6,427 (11). |
| Table 3 - Expectation of life for people of various ages, according
to death rates assumed for remainder of their lifetimes, United
Kingdom(2) |
| Age (years) |
Men
|
Women
|
| 1994 |
2001 |
2031 |
1994 |
2001 |
2031 |
| 0 |
78.4 |
78.7 |
79.0 |
83.5 |
83.6 |
84.0 |
| 15 |
63.9 |
64.0 |
64.3 |
68.9 |
69.0 |
69.2 |
| 60 |
19.7 |
20.4 |
21.7 |
23.6 |
24.4 |
25.6 |
| 65 |
15.4 |
16.2 |
17.6 |
19.0 |
19.8 |
21.2 |
| 75 |
9.0 |
9.4 |
10.7 |
11.5 |
11.8 |
13.3 |
| 85 |
4.9 |
5.0 |
5.9 |
6.3 |
6.4 |
7.3. |
Aging and disability
The rise in numbers and proportion of older people has led to much
concern about societal consequences, not least health consequences.
Increasing age is associated with increasing disability and loss of
independence, with functional impairments such as loss of mobility,
sight, and hearing. In Britain in 1984-5, the estimated prevalence of
those with severe disability was less than 1% in those aged 50-59
years but 13% in those aged over 80 years.(3) Murray and
Lopez have estimated that at age 60, we might expect to live about a
quarter of our remaining years with some disability.(4-5)
If the average age of onset of ill health is unchanged, increased life
span would mean more years of ill health before death for an individual
and a greater proportion of people with disability. Much current
discussion thus revolves around how best to support and care for large
numbers of older people with disability. According to Fries, the
age of onset of ill health might, however, rise more quickly than our
life span increases, resulting in "compression of morbidity" (a
shorter period of disability and ill health before
death).(6-7) So how far can we reduce, or postpone the
onset of, disability that is associated with age?
Can we prevent age related disability?
Fries has suggested that people of high socioeconomic status, with
more education, or with particular lifestyles (such as those who are
physically active) seem to experience compression of
morbidity.(7) Indeed, even in Britain, there is evidence of
secular improvement. The proportion of men unable to perform four
activities of daily living at any specified age has halved between 1976
and 1994 (fig 1).(1)(8) |
|
 | | Fig 1: Percentage by age of men unable to perform four
activities of daily living in 1976, 1985, and 1994(1)(8) |
Variation in rates of chronic disease
Healthy life expectancy is determined by a relatively limited
number of chronic conditions that become more common with increasing
age. Their exact contributions vary according to definitions of
disability, but all estimates include cardiovascular disease, such as
coronary heart disease and stroke; musculoskeletal diseases, such as
arthritis and osteoporosis leading to fractures; neurodegenerative
disorders, such as memory loss and dementia; neuropsychiatric orders,
such as depression; cancers, including lung, breast, prostate and
colorectal cancers; and other degenerative conditions, such as visual
loss from cataracts, macular degeneration and glaucoma, and hearing
loss. Reduction or postponement of these conditions may not only reduce
premature death and increase longevity but, more importantly, may also
decrease the period of illnesses so that people can remain healthy
until near
death.
The great variation in rates of chronic diseases in different
communities shows that a substantial proportion of the chronic diseases
associated with aging can be prevented, or at least postponed. Figure 2
gives examples of the relation between age and rates of some chronic
disabling conditions in different countries; mortality has been used as
a surrogate for incident morbidity data, which are often not available.
Japanese men and women show much less increase with age for these
conditions than men and women in Britain, with Spain having rates in
between.(9) Similar age related patterns can be seen for
many other conditions, including other cancers, heart disease cataracts
and glaucoma. Secular trends and changes with migration show
that
these large differences are likely to be due
to environmental rather than genetic factors. Over the past 30 years,
age specific rates for cardiovascular disease have halved in Japan and
the United States but doubled in Hungary.(10) Rates for hip
fracture have doubled in several countries, including Britain (fig
3), Hong Kong, and Sweden.(11-12) These trends have a huge
impact. In Britain, for example, about 50,000 hip fractures occur
annually. This number is projected to increase to 120,000 by 2020, but
if age specific rates could return to those of 1950, most of this
epidemic could be averted. In Britain wide regional and social class
variations exist for total mortality, which is often used as an
indicator of overall health status; throughout adult life, men in
social class V have about twice the mortality of men in social class
I.(13)(1)(8)Variation in age related physiological decline
The rate at which many physiological functions change with age,
and hence the occurrence of their clinical consequences, varies greatly
in people in different circumstances. |
|
 | | Fig 2: Mortality in United Kingdom, Spain, and Japan
1992-4 for ischaemic heart disease in men, breast cancer in women, and
prostate cancer(9)
|  | | Fig 3: Annual incidence by age for fractured proximal
femur in men in Oxford, 1954-8 and 1983 |
In communities worldwide, blood
pressure or concentrations of cholesterol or blood glucose do not
increase markedly with age; thus, rises in these factors are not
necessary concomitants of the aging process. These communities also
have low rates of cardiovascular disease even among elderly people.
Migration studies show that the primary determinants are environmental
not genetic. Members of the Luo tribe in Kenya had low blood pressures
when living in a rural environment but higher blood pressures that
increased with age when they moved to urban Nairobi.(14)
Japanese people have much lower blood cholesterol concentrations and
lower coronary heart disease rates than white Americans, but Japanese
migrants in the United States have much higher cholesterol
concentrations and rates of heart disease.(15) White people
with diets of Buddhist monks had low blood cholesterol concentrations
similar to those of Japanese people living in Japan, but Japanese
people in the United States army with an American diet had high
cholesterol concentrations resembling those of white people in the
army.(10)(16) Dutch women living in the Antilles had high
bone mass and lower rates of fractures than Dutch women of the same age
in the Netherlands.(17)
Genes and environment
Many of the diseases that we associate with aging reflect
deterioration of physiological functions. As we age, blood pressure and
blood cholesterol concentration usually increase, leading to increased
risk of heart attacks and strokes; glucose tolerance declines and
insulin resistance increases, leading to diabetes; intraocular pressure
increases, leading to glaucoma and visual loss; and immune function
deteriorates, resulting in increased risk of infections and possibly
some cancers. Loss of bone mass increases fracture risk, neuronal
degeneration results in loss of cognitive function and dementia,
cartilage degeneration in arthritis, and muscle loss in functional
weakness.
 Numerous theories explain the aging process; most suggest that
senescence results from the accumulation of unrepaired damage. Kirkwood
and Wolff suggest that the different life spans of different species
reflect differing distributions of investment in allocation of
metabolic resources between maintenance and reproduction, which have
evolved in response to extrinsic circumstances.(18) Their
theory predicts that, rather than any single mechanism for aging, the
mechanisms responsible are those types of damage for which maintenance
and repair are metabolically costly, such as damage to and mutations of
DNA, defective mitochondria, oxidative damage by free radicals, and
accumulation of aberrant proteins. Whatever the possible mechanisms,
these seem to result in a progressive generalised impairment of
functions and loss of adaptive response to stress, a growing risk of
chronic diseases, and an increase in the probability of dying. The
biological process of aging and its clinical manifestations reflect the
interaction between our genetic inheritance and the environment.
Indeed, we know that huge variation in phenotype exists in people with
the same genes and that gene expression and function is profoundly
modified by environmental factors. Thus, while the maximum life span is
probably genetically determined, the likelihood of reaching that life
span in good health seems to be largely determined by environmental and
lifestyle factors.
Model for intervention strategies
 Evidence confirms that throughout life our chances of aging
successfully can be increased in various ways. In early life the
intrauterine and early postnatal environment may programme basic
metabolic processes and hence susceptibility to various conditions
such as cardiovascular disease and diabetes in later life, and Barker
has suggested that maternal nutrition plays a critical
role.(19) Growth and development of vital organs such as
brain, muscles, bone, and blood vessels during childhood and early
adulthood build reserves that may affect later capacity. For example,
pattern of fatty acid intake, or cognitive exposures in infancy
influence brain development, and calcium intake and physical activity
influence bone mass in youth, the consequences of which may extend well
into old age. In later life, strategies may be to reduce damage (for
example, from infections or toxins), to increase protection against
damage (for example, by increasing antioxidant defences or
strengthening immune function), or to prevent loss through lack of use
(for example, by remaining physically and mentally active) (box).
|
Potential health interventions at different stages of life |
| Period | Process | Potential interventions |
|---|
| Intrauterine | Metabolic programming | Maternal nutrition |
| Childhood and
adolescence | Growth and development; building reserves
Reduce damage | Nutrition, physical activity, cognitive stimulation
No smoking, reduce exposure to pollution and infection |
| Adult |
Increase protection
Prevent disuse |
Nutrition
Physical and mental activity |
|
Interventions to improve health in later life |
| Intervention | Potential effects | |
| No smoking | Smoking increases risks of many cancers including lung, stomach,
larynx, colon; cardiovascular disease and thereby vascular dementia;
respiratory disease; osteoporotic fractures; stomach ulcers |
|
Diet
High fruit and vegetable intake
(5 or more servings daily) | Protective for cardiovascular disease; respiratory function; macular
degeneration and cataracts; cancers including breast, prostate,
colorectal and stomach; diverticular disease; diabetes |
| High complex carbohydrates,
non-starch polysaccharides
(eg potatoes, bread, pulses, pasta) | Protective for cardiovascular disease; cancers including breast
and colorectal |
| Reduced saturated fat (<15%
food energy intake) and total fat
(<35% food energy intake) | High saturated fat intake increases risk of coronary heart disease;
cancers including colorectal, prostate, and breast; large bowel
disease; osteoarthritis |
| Reduced sodium | High sodium intake increases risk of stroke, stomach cancer, osteoporosis,
respiratory disease |
|
| Physical activity |
Protective for cardiovascular disease; diabetes; osteoporosis;
cancers including colorectal and breast; depression |
|
The "free radical" and "immune function" theories of aging both
give clues as to possible interventions. Free radicals are reactive
molecules produced as byproducts of cell metabolism that cause
oxidative damage to cell components, including proteins, nucleic acids,
and membranes. Damage by free radicals in different tissues has been
postulated to be responsible for conditions as diverse as cancers,
respiratory disease, dementia, cardiovascular disease, and eye diseases
including macular degeneration and cataracts. Many exposures such as
infection, toxins, smoking, or high dietary saturated fat load are
associated with increased production of and damage by free radicals;
antioxidants such as vitamin C, carotenoids, vitamin E, or selenium may
mitigate such damage.
The immune theory suggests that functional capacity of the immune
system declines throughout life, with involution of the thymus gland
and deterioration of stem cells; this is associated with an increased
incidence of infections, cancer, and other immune-complex type
diseases. Exercise, smoking, and nutrition such as zinc, vitamin A, or
pyridoxine and riboflavin can affect immune function.(20)
Preventing cardiovascular disease and osteoporosis
Cardiovascular disease
Risk of cardiovascular disease rises incrementally with increasing
level of blood pressure and cholesterol
concentration.(21-23) Intervention trials have shown that
reduction of blood pressure by 6 mm Hg reduces risk of stroke by 40%
and of heart attack by 15% and that a 10% reduction in blood
cholesterol concentrations will reduce risk of coronary heart disease
by 30%.(24-25) Reducing blood pressure and cholesterol
concentrations in older people could have a substantial effect on
reducing the burden of cardiovascular disease. The exact blood pressure
or cholesterol concentration at which drug treatment is considered
warranted is still debated. Observational studies and trials, however,
have implicated high dietary saturated fat as a cause of high
cholesterol concentration and rates of coronary heart disease, and high
dietary sodium intake in the aetiology of the age related rise in blood
pressure and stroke, and have shown that relatively modest reductions
in saturated fat and salt intake may greatly affect cardiovascular
disease.(26-28) The feasibility and achievability of such
changes in diet and cardiovascular disease are well supported by the
existing large international and secular variations. Dietary changes
seem to affect risk factor levels throughout life and may have even
more impact in elderly people. For example,
reducing
dietary sodium lowers blood pressure more in elderly people than in
younger people. Many other dietary and other factors such as cigarette
smoking, physical activity, infection, and psychosocial stress also
seem to influence cardiovascular risk throughout life through various
mechanisms, such as haemostatic tendency, inflammatory processes, or
homocysteine metabolism, not all of them well understood or tested in
trials. Again, the available evidence shows that the potential impact
may be substantial: increasing fruit and vegetables by 1-2 servings
daily may decrease cardiovascular risk by 30%.(29) Fruit
and vegetables may act through various mechanisms including increasing
folic acid and lowering homocysteine levels,
increasing
vitamin C and flavonoids and thus
antioxidant defences, and increasing minerals such as potassium and
magnesium, possibly reducing blood pressure.
Secondary prevention trials may be more generalisable to elderly
people, many of whom may have established diseases. A secondary
prevention trial of advice to eat fatty fish twice a week reduced
cardiovascular death by 30%(30); another secondary
prevention trial of Mediterranean diet (essentially substituting foods
rich in |ga linolenic acid for dairy and animal fats and increasing
intake of bread, fruit, and vegetables) reduced mortality by 70% after
four years.(31)
Osteoporosis
Low bone mass increases risk of fracture,(32) but bone
loss and subsequent risk of fractures including vertebral and hip
fractures in elderly women or in those with existing fractures can be
reduced by 30-50% by various treatments including vitamin D and
calcium supplementation or bisphosphonates.(33-34) As with
cardiovascular disease, preventive drug treatment in the whole older
population is debatable because of risk-benefit issues, but risk of
fracture can be reduced by ensuring that older people have adequate
dietary intake of calcium and vitamin D.
Interventions to improve health in later life
Cardiovascular disease and osteoporosis are examples of conditions
for which substantial trial evidence exists of the effectiveness and
magnitude of impact of preventive interventions in later life; however,
since many conditions coexist in elderly people, the impact of
interventions on overall health is also crucial.
For most other chronic diseases, a wealth of evidence implicates the
substantial role of environmental (including lifestyle) factors, though
for most, data from trials are not available. The box summarises some
of these factors. Tobacco smoking must be the single most preventable
cause of ill health and disability(35); the benefits of not
smoking in terms of respiratory function and cardiovascular disease are
apparent even at older ages.
Nutrition clearly has a key role in health throughout life - from
maternal nutrition and fetal metabolic programming, to childhood
nutrition affecting growth and development, to diet in later life
influencing maintenance of health. Caloric restriction is often
believed to delay aging, because of experiments reporting that severe
food restriction increased longevity in surviving rats. However,
findings from studies of rats in strictly controlled and protected
experimental conditions are not easily generalisable to
humans,(36) and prospective population studies have shown an
inverse relation between mortality and caloric intake.(37)
Higher caloric intake associated with better health outcome in humans
may reflect higher levels of physical activity (which may be
beneficial) or higher intake of protective
nutrients.(38-39) Indeed, aging may be associated with less
efficient processing of essential nutrients - for example, poorer
ability to synthesise vitamin D in the skin, and poorer ability of the
gut to absorb nutrients - so older people may need higher intakes of
particular nutrients.
Numerous other nutrients have been the focus of interest, including the
B vitamins such as B-12 and pyridoxine (which have been implicated in
neurological function) and folate and possibly riboflavin (involved in
homocysteine metabolism). Unfortunately, trials of antioxidant vitamin
supplementation have been largely discouraging; several |gb carotene
supplementation trials show no effect or adverse effects on
cardiovascular disease, cancer, or total mortality(40, 41);
and a trial of vitamin E in secondary prevention of coronary heart
disease which reduced non-fatal events by 70% had no, or possibly, an
adverse, effect on mortality.(42) Nevertheless, high fruit
and vegetable intakes have been most consistently associated with
protective benefits in several conditions, including macular
degeneration, visual loss, cataracts, respiratory disease, and cancers
such as breast, stomach, and colorectal.(43-45) The
discrepancy between foods and isolated supplementation may be that many
other nutrients in food or their interactions are responsible for the
clinical effects.
Although we may not know precisely which nutrients are responsible for
which particular actions, the evidence is overwhelming that particular
dietary patterns do seem to relate to good health.(46-49)
The 1994 recommendations of the Committee on Medical Aspects of Food
Policy emphasise the importance of adequate intake of nutrients such as
vitamins and minerals and of -3 fatty acids, which can be achieved by
diets high in fruit, vegetables, and complex carbohydrates or plant
polysaccharides such as rice, bread, and pulses.(49)
Conversely, reduction in dietary sodium and saturated fat or transfatty
acid intake can be achieved by reductions in intakes of certain
processed foods (their major source in Western diets) or replacement
with low fat foods or oils rich in unsaturated fatty acids. These are
diets characteristic of Japan and Crete, which now have greatest
average life expectancies.
Obesity is a risk factor for many chronic diseases. Although studies
give varying values for ideal weights in older people, extremes of
weight (very high (>30) or very low (18) body mass indices
(kg/m2) are adversely associated with health in most
populations; to maintain adequate nutrition while keeping body mass
index within the (wide) desirable range implies regular physical
activity.
Indeed, physical activity seems to protect against many diseases, such
as cardiovascular disease, osteoporosis and fractures, diabetes,
and breast and colon cancer.(50-51) Exactly how much and
what sort of physical activity at different ages has particular effects
is still unclear, but even moderate activities such as walking,
gardening, and keeping generally mobile seem to promote physical and
mental functioning and wellbeing.
Prevention of cognitive loss or dementia poses a particular challenge
in elderly people. Some deterioration can be attributed to
atherosclerotic disease, and thus interventions such as aspirin or
particular dietary patterns that reduce cardiovascular risk may also
prevent dementia. High educational status early in life and,
intriguingly, continued mental stimulation, also seem protective.
Many other extraneous factors offer future possibilities for
interventions. For example, chronic infections such as chlamydia and
helicobacter have been implicated as risk factors for cardiovascular
disease and cancer of the stomach, and air pollution is now believed to
affect cardiovascular health. Thus, general public health measures in
other, not hitherto directly related, areas may have additional
benefits for age related chronic diseases.
Conclusion
For many diseases we do not yet have sufficient evidence to make
highly specific recommendations for prevention, but we know the general
environmental and lifestyle patterns that can help. However,
individuals' ability to make changes to improve their health is
determined by the social and cultural context and circumstances
including choice, access, availability, information, and income.
Environmental determinants such as adequate housing and clean air and
water, fundamentals for health, cannot always be taken for granted. The
large inequalities in health experienced by social class and region in
Britain reflect these varying circumstances.
Successful aging of course encompasses social as well as physical
and psychological wellbeing. The social framework and policies that may
enable individuals to fulfil their potential and attain optimal health
are crucial.
Clinical Gerontology Unit Box 110,
University of Cambridge School of Clinical Medicine,
Addenbrooke's
Hospital,
Cambridge CB2 2QQ
Kay-Tee
Khaw, professor of clinical
gerontology
cthl@medschl.cam.ac.uk
References
1 Grundy E. The health and health care of older adults in
England and Wales, 1941-1994. In: Charlton J, Murphy M. The
Health of Adult Britain 1941-1994. London: Office for National
Statistics, 1997:182-203.
2 Office for National Statistics. National population
projections. London: Office for National Statistics, 1996.
(Series PP2, No 20.)
3 Martin J, Meltzer H, Elliot D. OPCS surveys of
disability in Great Britain. Report 1. The prevalence of disability
among adults. London: HMSO, 1988.
4 Murray C J L, Lopez A D. Regional patterns of disability-free
life expectancy and disability-adjusted life expectancy: global burden
of disease study. Lancet 1997;349:1347-52.
5 Murray C J L, Lopez A D. Alternative projections of mortality and
disability by cause 1990-2020: global burden of disease study.
Lancet 1997;349:1498-1504.
6 Fries J F. Ageing, natural death, and the compression of
morbidity. New Engl J Med 1980;313:407-28.
7 Fries J F. Physical activity, the compression of morbidity and
the health of the elderly. J R Soc Med 1996;89:64-8.
8 Bone M, Bebbington A, Jagger C, Morgan K, Nicholaas C.
Calculations of trends in health expectancies 1976-1992. In:
Health expectancy and its uses. London: HMSO, London
1996.
9 World health statistics annual. Geneva: World
Health Organisation, 1995.
10 Kesteloot H. Changing trends in mortality. In: Yamori Y,
Strasser T, eds. New horizons in preventing cardiovascular
diseases. Amsterdam: Elsevier, 1989.
11 Boyce W J, Vessey M P. Rising incidence of fracture of the
proximal femur. Lancet 1985;i:150-1.
12 Melton L J III, O'Fallon W M, Riggs B L. Secular trends in the
incidence of hip fractures. Calcif Tiss Int
1987;41:57-64.
13 Health of the nation. Variations in health: report of the
variations subgroup of the chief medical officer's Health of the
Nation Working Group. London: Department of Health, 1995.
14 Poulter N R, Khaw K T, Hopwood B E C, Mugambi M, Peart W S, Rose G,
et al. The Kenyan Luo migration study: observations on the initiation
of a rise in blood pressure. BMJ 1990;300:967-72.
15 Worth R M, Kato H, Rhoads G G, Kagan A, Syme S L. Epidemiologic
studies of coronary heart disease and stroke in Japanese men living in
Japan, Hawaii and California: mortality. Am J Epidemiol
1975;102:481-90.
16 Kita T, Ishii K, Kume N, Nagano Y, Kawai C. The level of serum
cholesterol in Caucasian and Japanese Zen monks.
Circulation 1986;74(suppl II):131.
17 Dubbelman R, Jonxis J H P, Muskiet F A J, Saleh A E C. Age-dependent
vitamin D status and vertebral condition of white women living in
Curacao (the Netherlands Antilles) as compared with their counterparts
in the Netherlands. Am J Clin Nutrit 1993;58:106-9.
18 Kirkwood T B L, Wolff S P. The biological basis of ageing.
Age Ageing 1995;24:167-71.
19 Barker D J P. Maternal and fetal origins of coronary heart
disease. J R Coll Phys London 1994;28:544-51.
20 Tuormaa T E. A brief review of the immune system and its
function in relation to PVFS, non-antibody mediated allergy,
autoimmunity, and immune deficiency. Nutr Health
1988;6:53-62.
21 Neaton J D, Wentworth D. Serum cholesterol, blood pressure,
cigarette smoking, and death from coronary heart disease. Arch
Int Med 1992;152:56-64.
22 Kannel W B, Doyle J T, Shephard R J, Stamler J, Vokonas P S.
Prevention of cardiovascular disease in the elderly. J Am Coll
Cardiol 1987;10:25-8A.
23 Qizilbash N, Lewington S, Duffy S, Peto R, Smith T,
Spiegelhalter D. Cholesterol, diastolic blood pressure, and stroke:
13,000 strokes in 450,000 people in 45 prospective cohorts.
Lancet 1995;346:1647-53.
24 Collins R, Peto R, MacMahon S, Hebert P, Fiebach N H, Eberlein
K A, et al. Blood pressure, stroke, and coronary heart disease. Part 2.
Short-term reductions in blood pressure: overview of randomised drug
trials in their epidemiological context. Lancet
1990;335:827-38.
25 Scandinavian Simvastatin Survival Study Group. Randomised trial
of cholesterol lowering in 4,444 patients with coronary heart disease:
the Scandinavian simvastatin survival study (4S). Lancet
1994;344:1383-9.
26 Law M R, Frost C D, Wald N J. By how much does dietary salt
reduction lower blood pressure? I - Analysis of observational data among
populations. BMJ 1991;302:811-5.
27 Law M R, Frost C D, Wald N J. By how much does dietary salt
reduction lower blood pressure? III - Analysis of data from trials of
salt reduction. BMJ 1991;302:819-24.
28 Clarke R, Frost C, Collins R, Appleby P, Peto R. Dietary lipids
and blood cholesterol: quantitative meta-analysis of metabolic ward
studies. BMJ 1997;314:112-7.
29 Gillman M W, Cupples L A, Gagnon D, Posner B M, Ellison R C,
Castelli W P, et al. Protective effect of fruits and vegetables on
development of stroke in men. JAMA 1995;273:1113-7.
30 Burr M L, Fehily A M, Gilbert J F, Rogers S, Holliday R M, Sweetnam
P M, et al. Effects of changes in fat, fish and fibre intakes on death
and myocardial infarction. Lancet 1989;ii:757-61.
31 de Lorgeril M, Renaud S, Mamelle S, Salen P, Martin J L, Monjaud
I, et al. Mediterranean alphalinolenic acid rich diet in secondary
prevention of coronary heart disease. Lancet
1994;343:1454-9.
32 Cummings S R, Black D. Bone mass measurements and risk of
fracture in caucasian women: a review of findings from prospective
studies. Am J Med 1995;98(supp 2A), 24-28S.
33 Chapuy M C, Arlot M E, Duboeuf F, Brun J, Crouzet B, Arnaud S, et
al. Vitamin D3 and calcium to prevent hip fractures in elderly women.
New Engl J Med 1992;32:1637-42.
34 Black D M, Cummings S R, Karpf D B, Cauley J A, Thompson D E, Nevitt
M C, et al. Randomised trial of effect of alendronate on risk of
fracture in women with existing vertebral fractures.
Lancet 1996;348:1535-41.
35 Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality in
relation to smoking: 40 years' observations on male British doctors.
BMJ 1994;309:901-11.
36 Widdowson E M. Physiological processes of aging: are there
special nutritional requirements for elderly people? Do McCay's
findings apply to humans? Am J Clin Nutrit
1992;55:1246-9.
37 Kromhout D, de Lezenne Coulander C. Diet, prevalence and 10
year mortality from coronary heart disease in 871 middle aged men.
Am J Epidemiol 1984;119:733-41.
38 Magni E, Bianchetti A, Rozzini R, Trabucchi M. Influence of
nutritional intake on 6 year mortality in an Italian elderly
population. J Nutr Elder 1994;13:25-34.
39 Farchi G, Fidanza F, Grossi P, Mariotti S, Menotti A.
Relationship between eating patterns meeting recommendations and
subsequent mortality in 20 years. Eur J Clin Nutr
1995;49:408-19.
40 Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group.
The effect of vitamin E and beta carotene on the incidence of lung
cancer and other cancers in male smokers. New Engl J Med
1994;330:1029-35.
41 Gaziano J M. Randomized trials of dietary antioxidants in
cardiovascular disease prevention and treatment. J Cardiovasc
Risk 1996;3:368-71.
42 Stephens N G, Parsons A, Schofield P M, Kelly F, Cheeseman K,
Mitchinson M J, et al. Randomised controlled trial of vitamin E in
patients with coronary disease: Cambridge heart antioxidant study
(CHAOS). Lancet 1996;347:781-6.
43 Seddon J M, Ajani U A, Sperduto R D, Hiller R, Blair N, Turton T C,
et al. Dietary carotenoids, vitamins A,C, and E, and advanced
age-related macular degeneration. JAMA 1994;272:1413-20.
44 Steinmetz K A, Potter J D. Vegetables, fruit and cancer. I.
Epidemiology. Cancer Causes and Control 1991;2:325-57.
45 Sridhar M K. Nutrition and lung function. BMJ
1995;310:75-6.
46 World Health Organisation Study Group. Diet, nutrition and the
prevention of chronic diseases. WHO Tech Rep Ser
1990;797.
47 US Department of Health and Human Services. The surgeon
general's report on nutrition and health. Washington: USDHHS
(PHS), 1988. (Publication No 88-50210.)
48 Khaw K T. Nutritional status. In: Ebrahim S, Kalache A, eds.
Epidemiology in old age. London: BMJ Publishing,
1996:171-83.
49 Department of Health. Nutritional aspects of
cardiovascular disease. Report of the Cardiovascular Review Group
committee on medical aspects of food policy. London: HMSO,
1994.
50 Curfman G D. The health benefits of exercise. New Engl J
Med 1993;328:574-6.
51 Young A. Exercise. In: Ebrahim S, Kalache A, eds.
Epidemiology in old age. London: BMJ Publishing,
1996:190-200.
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