Journals of Gerontology: Medical Sciences
cite as: J Gerontol A Biol Sci Med Sci, 2016, Vol. 71, No. 7, 923–928
doi:10.1093/gerona/glv311
Advance Access publication January 16, 2016
Research Article
Association of Self-Rated Health in Midlife With Mortality
and Old Age Frailty: A 26-Year Follow-Up of Initially Healthy
Men
Emmi Huohvanainen,1 Arto Y. Strandberg,2 Sari Stenholm,3,4,5 Kaisu H. Pitkälä,6
Reijo S. Tilvis,2 and Timo E. Strandberg1,2
Center for Life Course Health Research, University of Oulu, Finland. 2Geriatrics, Helsinki University Central Hospital, University of Helsinki,
Finland. 3School of Health Sciences, University of Tampere, Finland. 4Gerontology Research Center, University of Tampere and University
of Jyväskylä, Finland. 5Department of Public Health, University of Turku, Finland. 6Department of General Practice, Unit of Primary Health
Care, Helsinki University Central Hospital, University of Helsinki, Finland.
1
Address correspondence to Timo E. Strandberg, MD, PhD, University of Helsinki, PO Box 340, FIN-00029, Helsinki, Finland. E-mail: [email protected]
Received June 22, 2015; Accepted December 18, 2015
Decision Editor: Stephen Kritchevsky, PhD
Abstract
Background: The aim was to investigate the relationship between self-rated health (SRH) in healthy midlife, mortality, and frailty in old age.
Methods: In 1974, male volunteers for a primary prevention trial in the Helsinki Businessmen Study (mean age 47 years, n = 1,753) reported
SRH using a five-step scale (1 = “very good,” n = 124; 2 = “fairly good,” n = 862; 3 = “average,” n = 706; 4 = “fairly poor,” or 5 = “very poor”;
in the analyses, 4 and 5 were combined as “poor”, n = 61). In 2000 (mean age 73 years), the survivors were assessed using a questionnaire
including the RAND-36/SF-36 health-related quality of life instrument. Simplified self-reported criteria were used to define phenotypic
prefrailty and frailty. Mortality was retrieved from national registers.
Results: During the 26-year follow-up, 410 men had died. Frailty status was assessed in 81.0% (n = 1,088) of survivors: 434 (39.9%), 552
(50.7%), and 102 (9.4%) were classified as not frail, prefrail, and frail, respectively. With fairly good SRH as reference, and adjusted for
cardiovascular risk in midlife and comorbidity in old age, midlife SRH was related to mortality in a J-shaped fashion: significant increase with
both very good and poor SRH. In similar analyses, average SRH in midlife (n = 425) was related to prefrailty (odds ratio: 1.52, 95% confidence
interval: 1.14–2.04) and poor SRH (n = 31) both to prefrailty (odds ratio: 3.56, 95% confidence interval: 1.16–10.9) and frailty (odds ratio:
8.38, 95% confidence interval: 2.32–30.3) in old age.
Conclusions: SRH in clinically healthy midlife among volunteers of a primary prevention trial was related to the development of both
prefrailty and frailty in old age, independent of baseline cardiovascular risk and later comorbidity.
Keywords: Aged—Comorbidity—Frailty—RAND-36—Self-rated health
Self-rated health (SRH or “self-perceived health”) is considered to
represent a global perception of one’s current state of health, which
is not necessarily identical with objective health status (1–7). SRH is
usually defined by asking individuals to evaluate their health status
on a three- to five-point scale (with response options ranging from
excellent to very poor) or to compare their health status with their
age peers. As a person may be intuitively aware of pathologic processes far before they become measurable, SRH could be a valuable
instrument for identifying persons at risk (1,5). A wide body of literature has risen around SRH with attempts to conceptualize it (7).
Dimensions of SRH are numerous, but physical ones are probably
very important (2). SRH has been associated with follow-up mortality in many relatively short-term studies (3,6,8), but decades-long
studies are scarce (4,5,9).
Frailty is a geriatric syndrome characterized by excess vulnerability to stress, loss of resiliency, and multisystem decline, leading
© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.
For permissions, please e-mail: [email protected].
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to a risk of disability, immobility, and death (10–12). Although it is
a frequent and clinically important condition among older people,
frailty still lacks a universal definition, and there are both phenotypic
and frailty-index-based definitions currently in use (11). Studies on
long-term predictors of frailty are scarce, but we have reported that
in healthy men midlife clinical characteristics, such as obesity and
cardiovascular disease (CVD) risk factors (13), as well as lower
levels of leisure-time physical activity (14) were associated with the
development of phenotypic frailty 26 years later. Because these characteristics are well known to associate with mortality, we hypothesized that SRH in midlife would be independently associated with
frailty as well. To the best of our knowledge, this association has not
been tested in long-term studies.
In the Helsinki Businessmen Study (HBS) (13–15), SRH was
assessed in midlife, and mortality follow-up extends to old age when
the presence of frailty also was determined using simplified, selfreported phenotypic criteria. The purpose of the present study was
to investigate the long-term relationships between SRH, mortality,
and frailty in the HBS cohort.
Participants and Methods
Study Population
Details of the HBS have been described in detail previously (refs.
13–15; full bibliography at http://www.gernet.fi/artikkelit/1463/
helsinki-businessmen-study-hbs-summary-and-bibliography).
In
brief, 3,490 men, mostly business-executives born between 1919 and
1934, participated in volunteer health check-ups during the 1960s
and early 1970s organized by Finnish Institute of Occupational
Health. At that time, they received health education to diminish
their CVD risk. In 1974, men were evaluated by questionnaires and
clinical and laboratory examinations to find participants in a CVD
primary prevention trial. At that time, 63 men were dead, 563 men
were found to be unsuitable for a primary prevention trial due to
clinical diseases or medications, and 1,064 refused to participate
or did not respond. The volunteering 1,815 men had a mean age
of 47 years and were found to be professionally active and clinically healthy (without signs and symptoms of clinically meaningful
chronic diseases including severe hypertension, drug-treated diabetes, CVD, cancer, metabolic, renal, and psychiatric diseases, and
without regular medications). However, the majority of them had
various untreated CVD risk factors.
Because preliminary analyses showed that participation in the
primary prevention trial during the 1970s did not affect the present
analyses 26 years later, all 1,815 men were included in the analysis
in order to improve statistical power. Data of SRH were available of
1,753 healthy men (96.6%), and they form the population of the present study. The follow-up of the HBS has been approved by the ethical committee of the Department of Medicine, Helsinki University
Central Hospital, and the study is registered as ClinicalTrials.gov
identifier: NCT02526082.
Baseline Risk Factors
In 1974, the following CVD risk factors were assessed: body mass
index (BMI) was calculated from measured weight and height as
weight (kilograms) divided by height (meters) squared. Additionally,
participants were asked to recall their weight at 25 years of age.
Weight status was defined as normal weight (BMI < 25 kg/m2), overweight (≥25 to <30 kg/m2), and obese (≥30 kg/m2). Systolic and diastolic blood pressure (mmHg) was registered after a 10-minute rest
Journals of Gerontology: MEDICAL SCIENCES, 2016, Vol. 71, No. 7
with the participant in a sitting position and using a mercury sphygmomanometer. Fasting serum, total cholesterol and triglyceride, and
fasting blood glucose levels were measured using standard methods.
Smoking (cigarettes per day) and alcohol consumption (grams per
week) were assessed with questionnaires. Glucose tolerance was
measured as blood glucose after 1 hour of a glucose load (1 g per kg)
administered orally. In 1974, the composite risk score for coronary
artery disease (CAD) was calculated according to the contemporary
Keys’ risk equation (16). It takes into account age, systolic blood
pressure, cholesterol, smoking, and BMI and estimates the 5-year
risk (%) of CAD among European men aged 40–59 years. CAD or
CVD risk could not be assessed according to the Framingham risk
equation because serum high-density lipoprotein cholesterol was not
available.
Assessment of SRH
The way SRH is inquired has varied in studies. In our study in 1974,
global SRH was assessed by asking “What do you think about your
present state of health; is it ‘very good’, ‘fairly good’, ‘average’,
‘fairly poor’ or ‘very poor’.” Because there were very few men perceiving their status as “very poor,” they were combined with “fairly
poor” as “poor.” This wording of SRH was similar to that used in
the Whitehall II study (17). Perhaps the most widely used wording
of SRH in the United States (and also used in SF-36/RAND-36) is
excellent, very good, good, fair, or poor (18). In our study, this version was used in 2000 as part of the RAND-36 questionnaire (see
below).
Follow-Up
Mortality was comprehensively followed up using national central
registers (Population Information System). About 425 men out of
1,815 had died by the year 2000. Their frailty status (see below) at
death was not known. The survivors (n = 1,390, mean age 73 years)
were sent a mailed questionnaire 26 years later. The questionnaire
was resent once for nonrespondents, and in all 1,207 (86.8%) men
responded. The questionnaire included items about anthropometric
measures, living conditions, medication, and lifestyle factors (eg,
alcohol consumption, smoking). History or presence of the following conditions were asked: hypertension, memory disturbances,
stroke, coronary heart disease, heart failure, chronic pulmonary disease, claudication, diabetes, cancer, musculoskeletal disorder, psychiatric disease, any other long-term condition, or trauma. In addition,
the Finnish version of the RAND-36-Item Health Survey 1.0 (practically identical to SF-36 and validated in the Finnish population)
was embedded into the questionnaire (19). From the responses, a
comorbidity index was calculated, taking into account the number
and severity of comorbid conditions (20).
Frailty Assessment
In this study, phenotypic frailty status at follow-up in 2000 was
defined by simplified self-reported criteria as a modification of the
method initially described in the Cardiovascular Health Study and
included shrinking, subjective exhaustion, physical inactivity, slow
walking speed, and physical weakness (10). Because walking speed
was not measured in our study in 2000, we used four criteria as follows: (i) shrinking was defined as weight loss of ≥5% from midlife or
having current BMI < 21 kg/m2; (ii) evaluation of physical weakness
was based on self-reported difficulty in carrying or lifting a grocery
bag (an item in the physical functioning scale of RAND-36); (iii)
assessment of exhaustion was based on reported low energy most of
Journals of Gerontology: MEDICAL SCIENCES, 2016, Vol. 71, No. 7
the time during the preceding 4 weeks (an item in the vitality scale of
RAND-36); and (iv) evaluation of physical inactivity was based on
the question “Do you exercise regularly weekly?” The answer “No”
was taken to denote physical inactivity. The participant was classified to be frail or prefrail if (iii)–(iv) or (i)–(ii) of the aforementioned
criteria were met, respectively, and not frail if zero criteria were present. This frailty definition prospectively predicted important clinical
end points (walking speed, mobility disability, and mortality) in our
cohort (15).
Statistical Analysis
T-tests, nonparametric tests, and analyses of covariance were used
where appropriate to compare continuous variables (mean with
standard error [SE], logarithmic transformation where appropriate)
across baseline SRH status. Chi-square and trend tests were used
to compare proportions. Logistic regression was used to assess the
relationship between SRH and mortality during follow-up and multinominal logistic regression (with forward stepping) was used to
assess the relationship between midlife SRH and old age prefrailty
and frailty. The largest SRH group (“Fairly good”) was taken as reference category. The results are presented as odds ratios (OR) with
their 95% confidence intervals (CI). We report results as (i) unadjusted, (ii) adjusted for age, (iii) adjusted for the log Keys’ equation
in midlife (includes age), and (iv) log Keys’ equation plus comorbidity in old age. The last one may actually be an over adjustment
because comorbidities contribute to frailty. In statistical analyses,
two-sided p values <.05 were taken as significant. The statistical
software NCSS (version 2004, www.ncss.com, Kaysville, UT) was
used for the statistical analyses.
Results
In 1974, when all men were clinically healthy without chronic
diseases or regular medications, 124 (7.1%), 862 (49.2%), 706
(40.3%), and 61 (3.5%) rated their health as very good, fairly good,
average, and poor, respectively. Table 1 shows clinical and laboratory
characteristics according to SRH status in 1974. Poorer SRH was
associated with higher BMI, systolic and diastolic blood pressure,
triglycerides, and blood glucose, as well as with smoking.
During the follow-up through 2000 (at the mean age of 73 years),
410 men out of 1,753 (23.4%) had died. Of the deceased men, 32
(7.8%) rated their health very good in midlife, 183 (44.6%) fairly
good, 174 (42.4%) average, and 21 (5.1%) poor. With fairly good
SRH as reference and fully adjusted (log Keys’ equation reflecting
combined CAD risk in midlife), SRH was related to mortality in
a J-shaped fashion: OR: 1.65, 95% CI: 1.04–2.62 for very good;
OR: 1.17, 95% CI: 0.91–1.50 for average; and OR: 2.15, 95% CI:
1.19–3.88 for poor SRH (Table 2). In 2000, SRH and comorbidity
status could be assessed in 1,180 (84.9% of survivors) and 1,184
men (85.2%), respectively. Among survivors, SRH in 1974 and
2000 were significantly associated (data not shown). Age-adjusted
comorbidity index was 0.82 (SE 0.15), 1.28 (0.05), 1.50 (0.06),
and 1.84 (0.2) among men with very good, fairly good, average and
poor midlife SRH, respectively (p < .001). Frailty status could be
assessed in 1,088 men (81.0% of survivors with SRH in 1974) and
of those 434 (39.9%) were classified as not frail, 552 (50.7%) prefrail, and 102 (9.4%) frail. Among men without frailty assessment,
the distribution of SRH in 1974 resembled that of men found to be
prefrail in 2000, but as a whole, there was no significant difference
in 1974 SRH between men with and without frailty assessment in
2000 (p = 0.29).
925
Midlife SRH was related to both to prefrailty and frailty in old
age. With fairly good SRH as reference and fully adjusted (combined
CAD risk in midlife plus comorbidity in old age), average SRH in
midlife was associated with a 1.5-fold increased risk of prefrailty
(OR: 1.52, 95% CI: 1.14–2.04), and poor SRH with a 3.6-fold risk
of prefrailty (OR: 3.56, 95% CI: 1.16–10.9), and 8.4-fold increased
risk of frailty (OR: 8.38, 95% CI: 2.32–30.3) (Table 2). The relationship between poor SRH and frailty was significant irrespective of
adjustments, but it is of note that the analysis was based on only 31
individuals. As compared to fairly good SRH, the point estimates of
very good SRH for prefrailty and frailty were below unity, but they
were not statistically significant (Table 2).
Discussion
Our results indicate that poorer SRH in clinically healthy midlife
was related to phenotypic prefrailty and frailty status in old age.
Although this association was independent of midlife CVD risk
factor status, as well as of comorbidities in old age, the relationship can also be explained by unmeasured health attributes such as
depression or subclinical disease at baseline. The results nevertheless
suggest that the development of frailty is a long-term pathophysiological process. In contrast to frailty, the association between midlife
SRH and subsequent mortality was not linear in our study.
Frailty and SRH have been associated in cross-sectional studies
(21), but this is the first observation—to the best of our knowledge—
of a long-term association between SRH and frailty.
There are several mechanisms that could mediate the long-term
relationship. Inflammation and psychoneuroendocrine dysregulation
seem to be involved in the development of frailty and sarcopenia
(22–24), and low-grade inflammation may also be associated with
poor SRH (25,26).
Depression is related to inflammation, immunology (22,27,28),
and SRH (1,29–32), but the association between depression and
frailty is complex (27,28,33–35). In our study, depression was not
assessed at baseline, but the association between SRH in midlife and
frailty in old age prevailed after adjustment for the mental health
scale (reflecting depression) of RAND-36 in old age (data not shown).
Also, other psychosocial processes, including individual constitution
(optimism, pessimism), mood (anxiety), resources (coping, social
support, meaning), and various stressors may affect vulnerability
to illness via biopsychosocial model (21,36) and be associated with
SRH (36,37). However, the effect of, for example, social support on
frailty may be minor (36,38,39). Finally, one link between SRH and
frailty could be the feeling of physical fitness. In a subcohort of the
HBS, lower physical activity in midlife was strongly associated with
frailty in old age (14), but in this subgroup, a significant association
between SRH and frailty prevailed after midlife physical activity was
adjusted for (T. Strandberg, MD, unpublished data, 2015).
Our study has not only several strengths but also limitations.
Obvious strengths include the exceptionally long follow-up from the
clinically healthy midlife up to old age, and the homogenous population in which socioeconomic confounders have been minimized. On
the other hand, homogeneity is also a limitation, and generalization
to other groups, for example women, should be done cautiously. The
men were obviously not free of every possible disease (cf, Methods
section) in 1974, but they were nevertheless considered suitable for
a primary prevention trial. Frailty status was not formally assessed
in 1974, but all men were professionally active at that time, and
they did not have clinical diseases including CVD or diabetes, or
regular medications. We did not evaluate the participants clinically
Journals of Gerontology: MEDICAL SCIENCES, 2016, Vol. 71, No. 7
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in 2000, and self-report on prevalent diseases in 2000 was used
to assess comorbidity. Also, the definition of frailty was based on
questionnaire data, specifically from the RAND-36 health survey.
However, there is no strict consensus for defining frailty, and various
definitions may be used, also based on simplified, self-reported questionnaire data (11). Our criteria recognized about 10% of older men
as frail, a figure quite similar to large epidemiological surveys using
Fried criteria (12,40). But most importantly, the frailty criteria used
in this study have been shown to be associated with future development of slower walking speed and disability and powerfully predict
mortality (15). We believe that our definition can be taken to satisfactorily reflect phenotypic frailty. We could not assess the frailty status of those who died before 2000, and because frailty and mortality
share common risk factors (eg, cardiovascular [24]), the long-term
Table 1. Age-Adjusted Characteristics According to Self-Rated Health in 1974
SRH
Variable in 1974*
Very Good, n = 124
Fairly Good, n = 862
Average, n = 706
Poor, n = 61
p Value for Difference
Between SRH Groups
Age, y
BMI at 25 y of age, kg/m2 (n = 1,683)
Weight gain from 25 y to 1974, kg
BMI, kg/m2
Smokers, n (%)
Alcohol consumption, g/week
Blood pressure, mmHg
Systolic
Diastolic
Resting heart rate, beats/min
(n = 1,683)
Serum lipids, mmol/L
Cholesterol
Triglycerides
Blood glucose, mmol/L
Fasting (n = 1,322)
1h
Keys’ risk equation† (%)
47.4 (0.4)
22.6 (0.2)
8.3 (0.8)
25.2 (0.3)
24 (19.4)
164.9 (13.7)
47.4 (0.1)
22.7 (0.07)
9.2 (0.3)
25.7 (0.09)
235 (27.3)
157.2 (5.2)
48.1 (0.2)
22.8 (0.08)
10.5 (0.3)
26.1 (0.1)
251 (35.6)
159.8 (5.8)
47.9 (0.5)
22.6 (0.3)
11.1 (1.1)
26.2 (0.4)
26 (42.6)
150.7 (19.7)
.006
.87
.002
.0008
<.001
.94
137 (2)
89 (1)
61.6 (1.0)
143 (1)
91 (0.4)
63.2 (0.4)
144 (1)
92 (0.4)
65.0 (0.4)
141 (2)
92 (1)
67.3 (1.4)
.003
.02
.0001
6.1 (0.09)
1.41 (0.08)
6.2 (0.04)
1.60 (0.03)
6.2 (0.04)
1.65 (0.03)
6.1 (0.1)
1.79 (0.1)
.49
.006 (log)
4.6 (0.07)
6.7 (0.2)
1.7 (0.2)
4.7 (0.03)
6.9 (0.007)
2.02 (0.06)
4.8 (0.03)
7.2 (0.08)
2.1 (0.06)
4.7 (0.1)
7.7 (0.3)
1.8 (0.2)
.04
.0005 (log)
.03 (log)
Notes: BMI = body mass index; SRH = self-rated health.
*Age-adjusted, continuous variables are mean (SE). Log-transformed values were used as indicated.
†
Includes age, smoking, cholesterol, systolic blood pressure, and BMI and is a composite risk score for coronary artery disease (16).
Table 2. Multivariate-Adjusted Odds Ratios of Mortality, Prefrailty, and Frailty in Old Age According to Self-Rated Health in Midlife in 1974
OR (95% CI)*
SRH
Very good, n = 70
Unadjusted
Adjusted for age
adjusted for midlife CAD risk‡
Above plus comorbidity in old age
Fairly good, n = 562
Reference
Average, n = 425
Unadjusted
Adjusted for age
Adjusted for midlife CAD risk‡
Above plus comorbidity in old age
Poor, n = 31
Unadjusted
Adjusted for age
Adjusted for midlife CAD risk‡
Above plus comorbidity in old age
Dead, n = 410
Prefrail†, n = 552
Frail†, n = 102
1.29 (0.83–1.99)
1.30 (0.83–2.02)
1.65 (1.04–2.62)
—
0.82 (0.49–1.37)
0.78 (0.46–1.30)
0.84 (0.48–1.46)
0.89 (0.50–1.55)
0.29 (0.07–1.26)
0.26 (0.06–1.11)
0.34 (0.08–1.46)
0.39 (0.09–1.74)
1.0
1.0
1.21 (0.96–1.54)
1.13 (0.89–1.44)
1.17 (0.91–1.50)
—
1.74 (1.33–2.28)
1.66 (1.21–2.18)
1.59 (1.19–2.13)
1.52 (1.14–2.04)
1.78 (1.13–2.82)
1.61 (1.01–2.56)
1.45 (0.90–2.35)
1.33 (0.81–2.17)
1.95 (1.12–3.39)
1.90 (1.08–3.33)
2.15 (1.19–3.88)
—
3.53 (1.29–9.65)
3.41 (1.24–9.38)
3.91 (1.28–11.9)
3.56 (1.16–10.9)
8.68 (2.72–27.7)
8.19 (2.52–26.6)
10.3 (2.95–36.3)
8.38 (2.32–30.3)
Notes: CAD = coronary artery disease; CI = confidence interval; OR = odds ratio; SRH = self-rated health.
*Calculated using multinominal logistic regression.
†
Not frail (n = 434) as reference group.
‡
Log Keys’ risk equation including age, smoking, body mass index, cholesterol, and systolic blood pressure.
1.0
Journals of Gerontology: MEDICAL SCIENCES, 2016, Vol. 71, No. 7
association between SRH and frailty may be underestimated, that is,
drive the association between SRH and frailty toward null.
In conclusion, SRH in midlife is an important risk marker of phenotypic frailty in old age. Mechanisms behind this association clearly
call for further research in order to better understand the long-term
origins and better methods to predict and prevent frailty.
Funding
This work was supported by the Jahnsson Foundation, the University Central
Hospitals of Oulu and Helsinki (EVO funding), the Konung Gustaf V:s och
Drottning Victorias Frimurarestiftelse, a grant from the Academy of Finland
(138730), and Paulon Säätiö. The funding sources had no role in the design
and conduct of the study; in the collection, analysis, and interpretation of the
data; or in the preparation, review, or approval of the manuscript.
Conflict of interest
The authors have no direct conflicts of interest related to this manuscript.
References
1. Wu S, Wang R, Zhao Y, et al. The relationship between self-rated health
and objective health status: a population-based study. BMC Public Health.
2013;13:320. doi:10.1186/1471-2458-13-320
2. Mavaddat N, Kinmonth AL, Sanderson S, Surtees P, Bingham S, Khaw
KT. What determines Self-Rated Health (SRH)? A cross-sectional study
of SF-36 health domains in the EPIC-Norfolk cohort. J Epidemiol Community Health. 2011;65:800–806. doi:10.1136/jech.2009.090845
3. Sargent-Cox KA, Anstey KJ, Luszcz MA. The choice of self-rated health
measures matter when predicting mortality: evidence from 10 years followup of the Australian longitudinal study of ageing. BMC Geriatr. 2010;10:18.
doi:10.1186/1471-2318-10-18
4. Bopp M, Braun J, Gutzwiller F, Faeh D. Health risk or resource? Gradual and
independent association between self-rated health and mortality persists over
30 years. PLoS One. 2012;7:e30795. doi:10.1371/journal.pone.0030795
5. Idler EL, Benyamini Y. Self-rated health and mortality: a review of twentyseven community studies. J Health Soc Behav. 1997;38:21–37.
6. Giltay EJ, Vollaard AM, Kromhout D. Self-rated health and physicianrated health as independent predictors of mortality in elderly men. Age
Ageing. 2012;41:165–171. doi:10.1093/ageing/afr161
7. Jylhä M. What is self-rated health and why does it predict mortality?
Towards a unified conceptual model. Soc Sci Med. 2009;69:307–316.
doi:10.1016/j.socscimed.2009.05.013
8. Stenholm S, Pentti J, Kawachi I, Westerlund H, Kivimaki M, Vahtera J.
Self-rated health in the last 12 years of life compared to matched surviving controls: the health and retirement study. PLoS One. 2014;9:e107879.
doi:10.1371/journal.pone.0107879
9. Halford C, Wallman T, Welin L, et al. Effects of self-rated health on sick leave,
disability pension, hospital admissions and mortality. A population-based longitudinal study of nearly 15,000 observations among Swedish women and
men. BMC Public Health. 2012;12:1103. doi:10.1186/1471-2458-12-1103
10.Walston J, Hadley EC, Ferrucci L, et al. Research agenda for frailty in
older adults: toward a better understanding of physiology and etiology:
summary from the American Geriatrics Society/National Institute on
Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc.
2006;54:991–1001. doi:10.1111/j.1532-5415.2006.00745.x
11.Strandberg TE, Pitkala KH, Tilvis RS. Frailty in older people. Eur Geriatr
Med. 2011;2:344–355. doi:10.1016/j.eurger.2011.08.003
12.Bandeen-Roche K, Seplaki CL, Huang J, et al. Frailty in older adults: a
nationally representative profile in the United States. J Gerontol A Biol Sci
Med Sci. 2015;70:1427–1434. doi:10.1093/gerona/glv133
13.Strandberg TE, Sirola J, Pitkälä KH, Tilvis RS, Strandberg AY, Stenholm
S. Association of midlife obesity and cardiovascular risk with old age
frailty: a 26-year follow-up of initially healthy men. Int J Obes (Lond).
2012;36:1153–1157. doi:10.1038/ijo.2012.83
927
14.Savela SL, Koistinen P, Stenholm S, et al. Leisure-time physical activ
ity in midlife is related to old age frailty. J Gerontol A Biol Sci Med Sci.
2013;68:1433–1438. doi:10.1093/gerona/glt029
15.Sirola J, Pitkala KH, Tilvis RS, Miettinen TA, Strandberg TE. Definition of
frailty in older men according to questionnaire data (RAND-36/SF-36):
the Helsinki Businessmen Study. J Nutr Health Aging. 2011;15:783–787.
doi:10.1007/s12603-011-0131-4
16.Keys A, Aravanis C, Blackburn H, et al. Probability of middle-aged men
developing coronary heart disease in five years. Circulation. 1972;45:815–
828. doi:10.1161/01.CIR.45.4.815
17.Marmot MG, Shipley MJ. Do socioeconomic differences in mortality persist after retirement? 25 year follow up of civil servants from the first Whitehall study. BMJ. 1996;313:1177–1180. doi:10.1136/bmj.313.7066.1177
18. Ware JE Jr, Gandek B. Overview of the SF-36 Health Survey and the International Quality of Life Assessment (IQOLA) Project. J Clin Epidemiol.
1998;51:903–912. doi:10.1016/S0895-4356(98)00081-X
19.Aalto AM, Aro AR, Teperi J. RAND-36 as a Measure of Health-Related
Quality of Life. Reliability, Construct Validity and Reference Values in
the Finnish General Population. Helsinki, Finland: Stakes; 1999. Research
Reports No. 101.
20. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–383. doi:10.1016/0021-9681(87)90171-8
21.Cramm JM, Twisk J, Nieboer AP. Self-management abilities and frailty are
important for healthy aging among community-dwelling older people; a crosssectional study. BMC Geriatr. 2014;14:28. doi:10.1186/1471-2318-14-28
22.Lutgendorf SK, Costanzo ES. Psychoneuroimmunology and health
psychology: an integrative model. Brain Behav Immun. 2003;17:225–
232. doi:10.1016/S0889-1591(03)00033-3
23.Chang SS, Weiss CO, Xue QL, Fried LP. Association between inflammatory-related disease burden and frailty: results from the Women’s Health
and Aging Studies (WHAS) I and II. Arch Gerontol Geriatr. 2012;54:9–
15. doi:10.1016/j.archger.2011.05.020
24.Strandberg TE, Pitkälä KH, Tilvis RS, O’Neill D, Erkinjuntti TJ. Geriatric
syndromes—vascular disorders? Ann Med. 2013;45:265–273. doi:10.3109/
07853890.2012.727022
25.Christian LM, Glaser R, Porter K, Malarkey WB, Beversdorf D, KiecoltGlaser JK. Poorer self-rated health is associated with elevated inflammatory markers among older adults. Psychoneuroendocrinology.
2011;36:1495–1504. doi:10.1016/j.psyneuen.2011.04.003
26. Tanno K, Ohsawa M, Onoda T, et al. Poor self-rated health is significantly
associated with elevated C-reactive protein levels in women, but not in
men, in the Japanese general population. J Psychosom Res. 2012;73:225–
231. doi:10.1016/j.jpsychores.2012.05.013
27.Kiecolt-Glaser JK, McGuire L, Robles TF, Glaser R. Emotions, morbidity,
and mortality: new perspectives from psychoneuroimmunology. Annu Rev
Psychol. 2002;53:83–107. doi:10.1146/annurev.psych.53.100901.135217
28.Paulson D, Lichtenberg PA. Vascular depression and frailty: a compound threat to longevity among older-old women. Aging Ment Health.
2013;17:901–910. doi:10.1080/13607863.2013.799115
29. Luppa M, Luck T, König HH, Angermeyer MC, Riedel-Heller SG. Natural
course of depressive symptoms in late life. An 8-year population-based
prospective study. J Affect Disord. 2012;142:166–171. doi:10.1016/j.
jad.2012.05.009
30.Rouch I, Achour-Crawford E, Roche F, et al. Seven-year predictors of selfrated health and life satisfaction in the elderly: the PROOF study. J Nutr
Health Aging. 2014;18:840–847. doi:10.1007/s12603-014-0488-2
31.Wagner DC, Short JL. Longitudinal predictors of self-rated health and
mortality in older adults. Prev Chronic Dis. 2014;11:E93. doi:10.5888/
pcd11.13024
32.Ambresin G, Chondros P, Dowrick C, Herrman H, Gunn JM. Self-rated
health and long-term prognosis of depression. Ann Fam Med. 2014;12:57–
65. doi:10.1370/afm.1562
33.Lakey SL, LaCroix AZ, Gray SL, et al. Antidepressant use, depres
sive symptoms, and incident frailty in women aged 65 and older from
the Women’s Health Initiative Observational Study. J Am Geriatr Soc.
2012;60:854–861. doi:10.1111/j.1532-5415.2012.03940.x
928
34. Everson-Rose SA, Skarupski KA, Bienias JL, Wilson RS, Evans DA, Mendes de
Leon CF. Do depressive symptoms predict declines in physical performance in
an elderly, biracial population? Psychosom Med. 2005;67:609–615.
35.Mezuk B, Edwards L, Lohman M, Choi M, Lapane K. Depression
and frailty in later life: a synthetic review. Int J Geriatr Psychiatry.
2012;27:879–892. doi:10.1002/gps.2807
36.Peek MK, Howrey BT, Ternent RS, Ray LA, Ottenbacher KJ. Social support, stressors, and frailty among older Mexican American adults. J Gerontol B Psychol Sci Soc Sci. 2012;67:755–764. doi:10.1093/geronb/gbs081
37.Zeng Y, Hughes CL, Lewis MA, Li J, Zhang F. Interactions between life
stress factors and carrying the APOE4 allele adversely impact self-reported
health in old adults. J Gerontol A Biol Sci Med Sci. 2011;66:1054–1061.
doi:10.1093/gerona/glr106
Journals of Gerontology: MEDICAL SCIENCES, 2016, Vol. 71, No. 7
38.Kawano-Soto CA, García-Lara JM, Avila-Funes JA. A poor social network is not associated with frailty in Mexican community-dwelling
elderly adults. J Am Geriatr Soc. 2012;60:2360–2362. doi:10.1111/
jgs.12020
39.Gale CR, Syddall HE, Cooper C, Sayer AA, Bergman H, Brun
ner EJ. Close relationships and risk of frailty: the Hertfordshire
Cohort Study. J Am Geriatr Soc. 2012;60:390–392. doi:10.1111/
j.1532-5415.2011.03799.x
40.Santos-Eggimann B, Cuénoud P, Spagnoli J, Junod J. Prevalence of frailty
in middle-aged and older community-dwelling Europeans living in 10
countries. J Gerontol A Biol Sci Med Sci. 2009;64:675–681. doi:10.1093/
gerona/glp012