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Vitamin D insufficiency and frailty syndrome in older adults living in a Northern Taiwan community
Archives of Gerontology and Geriatrics 50 Suppl. 1 (2010) S17–S21
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Vitamin D insufficiency and frailty syndrome in older adults living in a Northern Taiwan community Ching-I Changa , Ding-Cheng (Derrick) Chanb , Ken-N Kuoc , Chao Agnes Hsiungd , Ching-Yu Chena,e, * a Division
of Geriatric Research, Institute of Population Health Sciences, National Health Research Institutes, 100 R440, 4F, No. 17 Xu-Zhou Road, Taipei, Taiwan of Geriatrics and Gerontology, National Taiwan University Hospital, 100 No. 1 ChangDe St., Taipei, Taiwan c Division of Health Policy Research and Development, Institute of Population Health Sciences, National Health Research Institutes, 350 No. 35 Keyan Road, Zhunan, Miaoli, Taiwan d Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 350 No. 35 Keyan Road, Zhunan, Miaoli, Taiwan e Department of Family Medicine, College of Medicine, National Taiwan University, 100 No. 1 Sec 1, Jen-Ai Road, Taipei, Taiwan b Department
article info
abstract
Keywords: Vitamin D insufficiency Fried Frailty Index Edmonton Frail Scale Elderly in Taiwan
This study explored the association between vitamin D insufficiency and frailty syndrome defined by the Fried Frailty Index (FFI) and the Edmonton Frail Scale (EFS) in a northern Taiwan community. Data of 215 subjects participating in an integrated interventional trial involving community-dwelling older adults with a high frailty risk were analyzed. Subjects were first screened by telephone interview and then evaluated at a local hospital with questionnaires, physical performance tests, and serum 25(OH)D measurements. Of the 215 participants, 31% had 25(OH)D insufficiency (<20 ng/ml). Frail subjects based on the FFI were older, had lower MiniMental Status Exam (MMSE) scores, Barthel Index (BI) scores, and 25(OH)D levels. Using the EFS, frailer cases were more likely to be female, have less education, higher comorbid conditions, lower MMSE scores, lower Barthel Index scores, and lower 25(OH)D levels. The associations between insufficient 25(OH)D status and both frailty scales were significant. After adjustment of variables, the odds ratio of 25(OH)D insufficiency was 10.74 (95% CI 2.60–44.31) for frail versus robust individuals. The prevalence of vitamin D insufficiency was high in this population. There was a strong association between vitamin D insufficiency and the FFI. Vitamin D measurements and supplements are suggested for high-risk older people. © 2010 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Frailty can be described as “a biological syndrome of decreased reserve (energy, physical ability, cognition, health) and resistance to stressors, resulting from cumulative declines across multiple physiological systems and causing vulnerability to adverse outcomes” (Fried et al., 2001). Older people with frailty are at increased risk for adverse health outcomes, including lost functional abilities and frequent hospitalizations (Rockwood et al., 1999; Fried et al., 2001). It is widely accepted that frailty is multidimensional, heterogeneous, and unstable, thus distinguishing it from disability or aging alone (Hogan et al., 2003). However, many instruments have been developed to measure frailty without a unifying classification system (Fried et al., 2001; Rockwood et al., 2005; Rolfson et al., 2006; Abellan van Kan et al., 2008). The instrument proposed by Fried et al. (2001), the FFI, following the Cardiovascular Health Study, classified subjects into three * Corresponding author. Division of Geriatric Research, Institute of Population Health Sciences, National Health Research Institutes, 100 R440, 4F, No. 17 Xu-Zhou Road, Taipei, Taiwan. Tel.: +(886-2)-3393-2198; fax: +(886-2)-2356-3260. E-mail address: [email protected] (C-Y. Chen). 0167-4943 /$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.
categories based on five indicators. It is one of the most widely used instruments in the research setting with emphasis on the physical domain (Abellan van Kan et al., 2008). Other instruments measure deficiencies in other areas such as cognition, burden of medical illness, and quality of life. For example, the EFS classifies subjects into five categories based on 10 domains (11 indicators) (Rolfson et al., 2006; Abellan van Kan et al., 2008) . Vitamin D, hydroxylated in the liver into 25-hydroxyvitamin D [25(OH)D], increases the absorption of calcium and phosphate needed for mineralization of the skeleton (Lips, 2001). Low 25(OH)D increases the risk of falls (Bischoff-Ferrari et al., 2004, 2005; Snijder et al., 2006), fractures (Bischoff-Ferrari et al., 2005), bone pain (Atherton et al., 2009; Lips, 2001; Mascarenhas and Mobarhan, 2004; Bischoff-Ferrari et al., 2005), muscle weakness (Bischoff-Ferrari et al., 2004; Gerdhem et al., 2005), sarcopenia (Visser et al., 2003), and disability (Lips, 2001). Recent studies have suggested that vitamin D may play some role in immunomodulation, infectious disease prevention, and psychiatric disorders (particularly depression) (Adams and Hewison, 2008; Hoogendijk et al., 2008). Low 25(OH)D levels are common in the elderly due to decreased vitamin synthesis in the skin, insufficient sunlight exposure, and deficient dietary supplementation (Holick
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65–79-year-old people in Tofun (n = 6828) Random sampling n = 2900 1st step screening
Eligible, N = 548 Category 3 n = 236 Category 4 n = 224 Category 5 n = 69 Category 6 n = 19
Chinese CSHA_CFS telephone interview version screening
Excluded, N = 2352 Non-eligible (Category 1, n = 206; Category 2, n = 86; Category 7, n = 5) Refusal, n = 998 Communication barrier, n = 43 Cannot reach after 3 attempts, n = 1004
Second Stage Frailty syndrome evaluation Fried Frailty Index Edmonton Frail Scale N = 275
Refusal N = 273
Blood specimen collection N = 215
Refusal N = 60
Fig. 1. Patient enrolment in the study.
et al., 1989; Kinyamu et al., 1998). Though a few investigators have studied the association between low vitamin D levels and frailty, most have emphasized the physical aspect (Puts et al., 2005; Shardell et al., 2009). It is not certain whether the finding would be replicable in other studies assessing frailty differently. The association between vitamin D insufficiency and frailty using both the FFI and the EFS was explored. 2. Subjects and methods 2.1. Subjects The target population was community-dwelling older adults aged 65–79 years in the 31 census areas of Tofun town (roughly 7,000 people, 7.1% of the whole population). Details regarding design and sampling have been described elsewhere (Chan, D.C., Tsou, H.H., Chen, C.Y., Hsiung, C., Kuo, K.N. A pilot randomised controlled trial of integrated care model on geriatric frailty. Unpublished results). Briefly, 2,900 population-representative random samples were screened through a two-stage process to enroll eligible older adults into a randomized controlled trial of an integrated care model for geriatric frailty (Figure 1). Subjects were first screened with the Chinese Canadian Study of Health and Aging Clinical Frailty Scale Telephone Version (CCSHA_CFS_TV). The CCSHA_CFS_TV is a validated seven-point scale with a higher score indicating frailer status (Chan et al., 2009). The seven categories were: (7) severely frail – completely dependent on others for activities of daily living (ADLs); (6) moderately frail – help is needed for both instrumental activities of daily living (IADLs) and ADLs; (5) mildly frail – with limited dependence on others for IADL items; (4) apparently vulnerable, although not frankly dependent – these people commonly complain of being “slowed down” or have disease symptoms; (3) well, with treated comorbid disease – disease symptoms are well controlled compared with those in category 4; (2) well – without active disease, but less fit than people in category 1; (1) very fit – robust, active, energetic, well motivated, and fit (Rockwood et al., 2005). A total of 548 subjects who scored 3–6 on the CCSHA_CFS TV were invited for further evaluation at a local hospital using the FFI and the EFS. However, only 275 subjects were actually interviewed (Figure 1).
The FFI has five indicators (Fried et al., 2001): “Weight loss” was defined as self-reported unintentional weight loss more than 3 kg (instead of 5 kg), or greater than 5% of body weight in the previous year. “Exhaustion” was indicated by self-response as “a moderate amount of the time” or “most of the time” to either of the following two statements: “I felt everything I did was an effort” or “I could not get going” from the Center for Epidemiological Studies-Depression Scale (Radloff, 1977). “Low physical activity” was defined by sex-specific low weekly energy expenditure measured by the Taiwan IPAQ-SF (International Physical Activity Questionnaire-Short Form (Liu, 2004) instead of the Minnesota Leisure Time Physical Activity Questionnaire (Taylor et al., 1978). “Slow walking speed” was defined as usual walking speed below certain sex- and height-specific cut-points. “Weakness” was defined as the mean grip strength of the dominant hand measured by three times below certain sex- and body mass index (BMI)-specific cut-points. The subjects were classified as “robust”, “pre-frail”, or “frail” respectively when 0, 1–2, or at least 3 indicators screened positive (Fried et al., 2001). Subjects were also evaluated using the EFS, consisting of 10 domains with 11 items including cognition (the clock drawing test, 2 points), general health status (times of hospitalization in the past year, 2 points and self-reported health status, 2 points), functional dependence (from eight IADLs, 2 points), social support (count on someone who is willing and able to meet the subject’s needs when the subject needs help, 2 points), medication use (use of at least five prescription medications, 1 point and forgetfulness for taking medications, 1 point), nutrition (weight loss, 1 point), mood (depression, 1 point), incontinence (1 point), and functional performance (the Timed Up-and-Go (TUG) test, 2 points) (Lawton and Brody, 1969; Podsiadlo and Richardson, 1991; Brody et al., 1997; Rolfson et al., 2006). The maximum total score is 17. Rolfson et al., (2006) proposed a five-level categorization (robust 0–4, apparently vulnerable, 5–6, mildly frail, 7–8, moderately frail, 9–10, severely frail, 11–17). In the present study, the final three categories were categorized into a single frail category due to small numbers. Other data collected included demographics, BMI, history of smoking and drinking, history of falls, and pain affecting daily life and sleep. The self-reported chronic co-morbidities included
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Table 1 Characteristics of study participants, mean ± S.D. or n(%) Characteristics
Number
Total
215
EFS
FFI Robust
Pre-frail
Frail
75
119
21
p<
Robust
Apparently vulnerable
Frail
137
52
26
p<
Age (years)
71.1±3.9
70.3±3.7
71.4±3.8
72.1±4.4
0.071
70.8±4.0
71.5±3.6
71.9±3.7
0.254
Gender (female %)
128 (59.5)
43 (57.3)
70 (58.8)
15 (71.4)
0.494
71 (51.8)
38 (73.1)
19 (73.1)
0.009
BMI (kg/m2 )
25.4±3.5
25.5±3.1
25.4±3.7
24.9±3.8
0.767
25.3±3.2
25.3±4.1
26.0±3.5
0.623
0
76 (35.3)
20 (26.7)
48 (40.3)
8 (38.1)
0.166
36 (26.3)
25 (48.1)
15 (57.7)
0.001
<7
89 (41.4)
35 (46.7)
43 (36.1)
11 (52.4)
60 (43.8)
23 (44.2)
6 (23.1)
Education (years)
Smoking history (Yes)
38 (17.8)
12 (16.0)
23 (19.3)
3 (15.0)
0.793
28 (20.4)
7 (13.7)
3 (11.5)
Alcohol history (Yes)
42 (19.5)
16 (21.3)
21 (17.6)
5 (23.8)
0.716
29 (21.2)
11 (21.2)
2 (7.7)
0.267
History of fall in 1 year
58 (27.2)
20 (26.7)
29 (24.8)
9 (42.9)
0.228
31 (22.8)
14 (27.5)
13 (50.0)
0.017
Pain history
66 (31.0)
19 (25.3)
37 (31.6)
10 (47.6)
0.145
32 (23.5)
21 (41.2)
13 (50.0)
0.005
Number of comorbidities
3.4±2.0
3.2±1.8
3.3±2.0
4.1±2.5
0.196
3.2±1.9
3.2±1.9
4.7±2.3
0.004
MMSE score
25.1±3.7
26.3±3.0
24.7±3.8
23.1±4.1
0.001
26.3±2.9
23.4±3.9
22.2±4.1
0.001
BI score
98.5±4.3
99.3±2.2
99.0±2.9
92.6±9.3
0.001
99.2±3.0
98.2±4.2
95.4±7.6
0.001
25 (OH)D (ng/ml)
39.9 (25.9)
47.0 (26.1)
37.2 (24.2)
30.8 (30.2)
0.009
43.6 (26.6)
32.7 (19.9)
34.3 (29.4)
0.004
2 (1.5)
3 (5.9)
3 (11.5)
32 (23.5)
21 (41.2)
13 (50.0)
25 (OH)D (ng/ml) <10
8 (3.7)
0 (0)
6 (5.0)
2 (9.5)
25 (OH)D (ng/ml) <20
66 (31.0)
12 (16.4)
41 (34.5)
13 (61.9)
p indicates ANOVA-test for continuous variables, and the
c2 -test
0.001
0.381
0.005
test for categorical variables.
hypertension, diabetes mellitus, heart disease (defined as a history of coronary heart disease, myocardial infarction, congestive heart failure, or arrhythmia), stroke, hyperlipidemia, gout and arthritis, chronic lung disease, gastric ulcer, chronic kidney or liver or thyroid disease, prostatomegaly, Parkinson’s disease, dementia, depression, cataracts, glaucoma, anemia, osteoporosis, and fractures. The MMSE (Folstein et al., 1975) and the Barthel Index (BI) were also evaluated (Mahoney and Barthel, 1965).
3. Results 3.1. Baseline characteristics The distributions of baseline characteristics for the entire study population (n = 215) are listed in Table 1. The mean age was 71.1±3.9 years, with 128 (59.5%) female. The study cohort had an average of 3.4±2.0 comorbid conditions. The mean MMSE score was 25.1±3.7, and the mean BI score was 98.5±4.3. The mean 25(OH)D level was 39.9±25.9 ng/ml, with 66 (31%) under 20 ng/ml (vitamin D insufficiency).
2.2. Serum 25(OH)D levels Serum 25(OH)D, which represents vitamin D storage, was measured by the DiaSorin 25-Hydroxyvitamin D 125I RIA (DiaSorin, Vercelli, Italy). Fasting serum blood specimens were stored at −80°C for further analysis. Serum 25(OH)D under 10 ng/ml was previously defined as vitamin D deficiency, and between 10 and 20 ng/ml was defined as vitamin D insufficiency (Lips, 2001). In the present study, vitamin D deficiency was defined as a serum 25(OH)D level under 20 ng/ml without further classification, since only 4% of the sample had a serum 25(OH)D level below 10 ng/ml. The study included only the 215 subjects with available vitamin D blood samples (Figure 1).
3.2. Distribution of baseline characteristics among subjects with different frailty statuses Using the FFI, 75 (34.9%) subjects were classified as robust, 119 (55.3%) as pre-frail, and 21 (9.8%) as frail. With the EFS, 137 (63.7%) were classified as robust, 52 (24.2%) as apparently vulnerable, and 26 (12.1%) as frail. (Table 1). Older age, a lower MMSE score, a lower BI score, and a lower 25(OH)D level were significantly associated with frailer status using the FFI. Characteristics that distributed differently among the three frailty categories of the EFS included sex, education, history of falls, history of chronic pain, number of comorbid conditions, MMSE score, BI score, and 25(OH)D level (Table 1).
2.3. Statistical analysis 3.3. Association between 25(OH)D level and frailty Differences in characteristics among the categories of the two frailty scales were compared by ANOVA test (continuous variables) or c2 -test (categorical variables). To examine the association of 25(OH)D and frailty, bivariate and multivariate multinomial logistic regressions were performed. Adjusted variables, including age, sex, educational status, BMI, smoking and drinking behaviors, comorbidity conditions, the MMSE scores, and the BI scores were added in the multivariate models. Data management and analysis were performed using SPSS 17.0 software (SPSS Corporation, Chicago, Illinois, USA).
There was a graded association between vitamin D insufficiency (below 20 ng/ml) and frailty levels on bivariate analysis (Table 2). Using the FFI, the odds ratio (OR) of vitamin D insufficiency was 2.67 (95% confidence interval = 95% CI = 1.29–5.52) for pre-frail versus robust individuals and 8.26 (95% CI = 2.82–24.24) for frail versus robust individuals (Table 2). Similarly, using the EFS, the odds ratio of apparently vulnerable versus robust was 2.28 (95% CI = 1.15–4.51), and that of frail versus robust was 3.25 (95% CI =1.37–7.72). The association did not change when the 25(OH)D level was treated as a continuous variable in both models (Table 2).
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Table 2 Association between 25(OH)D insufficiency and frailty by simple multinomial logistic regression EFS
FFI Frail vs. robust
Apparently vulnerable vs. robust
Frail vs. robust
OR (95% CI)
p<
OR (95% CI)
p<
OR (95% CI)
p<
OR (95% CI)
p<
Vitamin D (low vs. high)
2.67 (1.294–5.519)
0.008
8.26 (2.815–24.238)
0.001
2.275 (1.148–4.509)
0.019
3.250 (1.369–7.718)
0.008
Vitamin D (continuous)
0.984 (0.972–0.997)
0.013
0.97 (0.946–0.995)
0.018
0.979 (0.963–0.995)
0.009
0.984 (0.965–1.003)
0.107
Pre-frail vs. robust
Vitamin D insufficiency = 25-hydroxyvitamin D <20 ng/ml
Table 3 Multivariate-adjusted association between 25(OH)D insufficiency and the frailty scale EFS
FFI Frail vs. robust
Apparently vulnerable vs. robust
Frail vs. robust
OR (95% CI)
p<
OR (95% CI)
p<
OR (95% CI)
p<
OR (95% CI)
p<
Vitamin D (low vs. high)
3.139 (1.426–6.908)
0.004
10.739 (2.602–44.312)
0.002
2.377 (1.006–5.300)
0.034
2.023 (0.678–6.032)
0.206
Vitamin D (continuous)
0.982 (0.969–0.995)
0.008
0.972 (0.945–0.999)
0.039
0.981 (0.964–0.998)
0.026
0.995 (0.973–1.016)
0.616
Pre-frail vs. robust
(kg/m2 ,
Adjusted-variates: age (years), gender, body mass index education status (years), smoke and drink history, co-morbidity condition (hypertension, diabetes mellitus, heart disease [defined as a history of coronary heart disease, myocardial infarction, congestive heart failure, or arrhythmia], stroke, hyperlipidemia, gout and arthritis, chronic lung disease, gastric ulcer, chronic kidney or liver or thyroid disease, prostatomegaly, Parkinson’s disease, dementia, depression, cataracts, glaucoma, anemia, osteoporosis and fracture), MMSE (Mini-Mental State Examination) scores and Barthel Index scores.
After adjusting for age, sex, BMI, educational status, smoking and drinking history, co-morbidity conditions, MMSE scores, and BI scores, the odds ratio of vitamin D insufficiency comparing subjects with pre-frailty and frailty to those with robust was 3.14 (95% CI = 1.43–6.91) and 10.74 (95% CI = 2.60–44.31), respectively, using the FFI (Table 3). With the EFS, however, the association after model adjustment was only significant between the apparently vulnerable versus robust individuals (odds ratio = 2.38, 95% CI = 1.07–5.30), but not between the frail versus robust individuals (odds ratio = 2.02, 95% CI = 0.68–6.03) (Table 3). The results did not differ when the 25(OH)D level was treated as a continuous variable. 4. Discussion The present study found that there was a strong dose-response relationship between vitamin D insufficiency and frailty using the FFI. The association may be attenuated using the EFS assessment. To the best of our knowledge, this is the first report to examine the association between vitamin D insufficiency and frailty using different frailty assessment instruments. In the present study, the mean serum 25(OH)D level was 39.9 ng/ml, which was in the normal range (Lips, 2001). Studies by Lee and Tsai et al. have reported similar results in rural Southern Taiwan and the urban Northern Taiwan area (Tsai et al., 1997; Lips, 2001; Lee et al., 2002). First of all, subjects were recruited during June to August when the sunshine was sufficient compared with other seasons. Secondly, Tofun Town is located in a subtropical region with good sunlight exposure (latitude 24°68 N). Thirdly, data from the Nutrition and Health Surveys in Taiwan (NAHSIT) by Lee et al. (2008) showed that vitamin D intakes of Taiwanese people were generally adequate, and supplemental sources of vitamin D increased in the elderly population. These factors may explain the normal range mean 25(OH)D level in the present study population. Overall, 31% of the study population had vitamin D insufficiency. However, this number cannot be interpreted as a population-based prevalence estimate since not all participants enrolled in the trial had vitamin D data available, and the trial was not designed to provide the prevalence data. The physiological functions of vitamin D related to bone, muscle, and inflammation have been well established (Lips, 2001;
Bischoff-Ferrari et al., 2004, 2005; Gerdhem et al., 2005; Adams and Hewison, 2008). Serum 25(OH)D, the hydroxylated form of vitamin D, is the major circulating metabolite. A low 25(OH)D level is associated with decreased absorption of calcium and phosphate from the gut, leading to increased bone turnover, bone mass loss, osteoporosis, and eventually fracture and disability (Lips, 2001). In the present study, an insufficient 25(OH)D status was strongly and independently associated with the frailty classification using the FFI, a measure of physical domain performance that was likely to be influenced by the vitamin D level. Vitamin D plays an important role in protein synthesis and the regulation of calcium transport that affects muscle strength, as well as the balance between neurons and muscles (Lips, 2001; Kochupillai, 2008). A low vitamin D level is associated with sarcopenia, weak muscle strength, poor physical performance, balance problems, and falls (Lips, 2001; Visser et al., 2003; BischoffFerrari et al., 2004, 2005; Gerdhem et al., 2005; Snijder et al., 2006). Several indicators in the FFI, such as weak grip strength, slow walking speed, and weight loss, could be manifestations of sarcopenia that might explain the observed association between vitamin D insufficiency and the FFI classification. Compared with the FFI with its focus on physical frailty, the EFS included many other domains, such as cognition, depression, incontinence, general health, polypharmacy, and social support. There is growing evidence showing that low vitamin D may be associated with reduced protection against infectious disease, increasing susceptibility to autoimmune diseases such as type 1 diabetes mellitus, and neuropsychiatric disorders such as depression (Adams and Hewison, 2008). These diseases may, in turn, lead to frequent hospitalizations, poor self-rated health, polypharmacy, and some other indicators measured in the EFS. However, a direct link between the above mentioned factors and vitamin D may not be obvious. A weaker association between the EFS classification and vitamin D insufficiency is expected. The other possibility is that a larger sample size is needed to confirm the relationship. With the cross-sectional design, causality between vitamin D deficiency and frailty could not be established. More prospective data are needed to explore the existence of a causal relationship between vitamin D and frailty syndrome.
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5. Conclusion The prevalence of vitamin D insufficiency was high among this population. There was a strong association between vitamin D insufficiency and frailty index. Vitamin D insufficiency is easily treated with adequate supplements. Future clinical trials may consider the treatment of vitamin D insufficiency to improve frailty syndrome in older adults in order to prevent the progression to functional disability and worse outcomes. Conflict of interest statement None. Acknowledgements This study was supported by the 97_HDSP08_020 grant “Interventional study of Geriatric Frailty, Osteoporosis, and Depression in a Community Based Randomized Trial” from the National Health Research Institutes, Zhunan, Taiwan. References Abellan van Kan, G., Rolland, Y., Bergman, H., Morley, J.E., Kritchevsky, S.B., Vellas, B., 2008. The I.A.N.A Task Force on frailty assessment of older people in clinical practice. J. Nutr. Health Aging 12, 29–37. Adams, J.S., Hewison, M., 2008. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat. Clin. Pract. Endocrinol. Metab. 4, 80–90. Atherton, K., Berry, D.J., Parsons, T., Macfarlane, G.J., Power, C., Hypponen, E., 2009. Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from a cross-sectional population survey. Ann. Rheum. Dis. 68, 817–822. Bischoff-Ferrari, H.A., Dietrich, T., Orav, E.J., Hu, F.B., Zhang, Y., Karlson, E.W., DawsonHughes, B., 2004. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y. Am. J. Clin. Nutr. 80, 752–758. Bischoff-Ferrari, H.A., Willett, W.C., Wong, J.B., Giovannucci, E., Dietrich, T., DawsonHughes, B., 2005. Fracture prevention with vitamin D supplementation: a metaanalysis of randomized controlled trials. J. Am. Med. Assoc. 293, 2257–2264. Brody, K.K., Johnson, R.E., Douglas Ried, L., 1997. Evaluation of a self-report screening instrument to predict frailty outcomes in aging populations. Gerontologist 37, 182– 191. Chan, D.C., Tsou, H.H., Chen, C.Y., Chen, C.Y., 2009. Validation of the Chinese Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS) Telephone Version. Arch. Gerontol. Geriatr. (Epub ahead of print: doi: 10.1016/j.archger. 2009.06.004). Chan, D.C., Tsou, H.H., Chen, C.Y., Hsiung, C., Kuo, K.N., Unpublished. A pilot randomised controlled trial of integrated care model on geriatric frailty. Folstein, M.F., Folstein, S.E., McHugh, P.R., 1975. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189–198. Fried, L.P., Tangen, C.M., Walston, J., Newman, A.B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W.J., Burke, G., McBurnie, M.A., 2001. Frailty in older adults: evidence for a phenotype. J. Gerontol. A: Biol. Sci. Med. Sci. 56, M146– M156. Gerdhem, P., Ringsberg, K.A., Obrant, K.J., Akesson, K., 2005. Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporos. Int. 16, 1425–1431.
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Hogan, D.B., MacKnight, C., Bergman, H., 2003. Models, definitions, and criteria of frailty. Aging Clin. Exp. Res. 15, 1–29. Holick, M.F., Matsuoka, L.Y., Wortsman, J., 1989. Age, vitamin D, and solar ultraviolet. Lancet 2, 1104–1105. Hoogendijk, W.J., Lips, P., Dik, M.G., Deeg, D.J., Beekman, A.T., Penninx, B.W., 2008. Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch. Gen. Psychiatry 65, 508–512. Kinyamu, H.K., Gallagher, J.C., Rafferty, K.A., Balhorn, K.E., 1998. Dietary calcium and vitamin D intake in elderly women: effect on serum parathyroid hormone and vitamin D metabolites. Am. J. Clin. Nutr. 67, 342–348. Kochupillai, N., 2008. The physiology of vitamin D : current concepts. Indian J. Med. Res. 127, 256–262. Lawton, M.P., Brody, E.M., 1969. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 9, 179–186. Lee, M.S., Li, H.L., Hung, T.H., Chang, H.Y., Yang, F.L., Wahlqvist, M.L., 2008. Vitamin D intake and its food sources in Taiwanese. Asia Pac. J. Clin. Nutr. 17, 397–407. Lee, W.P., Lin, L.W., Yeh, S.H., Liu, R.H., Tseng, C.F., 2002. Correlations among serum calcium, vitamin D and parathyroid hormone levels in the elderly in southern Taiwan. J. Nurs. Res. 10, 65–72. Lips, P., 2001. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr. Rev. 22, 477–501. Liu, Y.-M., 2004. Validation of the Taiwan International Physical Activity Questionnaire-Short Form (Doctoral Dissertation in Chinese). Institute of Nursing. Taipei, National Taiwan University. Mahoney, F.I., Barthel, D.W., 1965. Functional evaluation: The Barthel index. Md. State Med. J. 14, 61–65. Mascarenhas, R., Mobarhan, S., 2004. Hypovitaminosis D-induced pain. Nutr. Rev. 62, 354–359. Podsiadlo, D., Richardson, S. 1991. The timed “Up & Go”: a test of basic functional mobility for frail elderly persons. J. Am. Geriatr. Soc. 39, 142–148. Puts, M.T., Visser, M., Twisk, J.W., Deeg, D.J., Lips, P., 2005. Endocrine and inflammatory markers as predictors of frailty. Clin. Endocrinol. (Oxf.) 63, 403– 411. Radloff, L., 1977. The CES-D scale: a self-report depression scale for research in the general population. Appl. Psychol. Meas. 1, 385–401. Rockwood, K., Stadnyk, K., MacKnight, C., McDowell, I., Hebert, R., Hogan, D.B., 1999. A brief clinical instrument to classify frailty in elderly people. Lancet 353, 205– 206. Rockwood, K., Song, X., MacKnight, C., Bergman, H., Hogan, D.B., McDowell, I., Mitnitski, A., 2005. A global clinical measure of fitness and frailty in elderly people. Can. Med. Assoc. J. 173, 489–495. Rolfson, D.B., Majumdar, S.R., Tsuyuki, R.T., Tahir, A., Rockwood, K., 2006. Validity and reliability of the Edmonton Frail Scale. Age Ageing 35, 526–529. Shardell, M., Hicks, G.E., Miller, R.R., Kritchevsky, S., Andersen, D., Bandinelli, S., Cherubini, A., Ferrucci, L., 2009. Association of low vitamin D levels with the frailty syndrome in men and women. J. Gerontol. A: Biol. Sci. Med. Sci. 64, M69– M75. Snijder, M.B., Van Schoor, N.M., Pluijm, S.M., Van Dam, R.M., Visser, M., Lips, P., 2006. Vitamin D status in relation to one-year risk of recurrent falling in older men and women. J. Clin. Endocrinol. Metab. 91, 2980–2985. Taylor, H.L., Jacobs, D.R.Jr., Schucker, B., Knudsen, J., Leon, A.S., Debacker, G., 1978. A questionnaire for the assessment of leisure time physical activities. J. Chronic. Dis. 31, 741–755. Tsai, K.S., Hsu, S.H., Cheng, J.P., Yang, R.S., 1997. Vitamin D stores of urban women in Taipei: effect on bone density and bone turnover, and seasonal variation. Bone 20, 371–374. Visser, M., Deeg, D.J., Lips, P., 2003. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J. Clin. Endocrinol. Metab. 88, 5766– 5772.
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Vitamin D insufficiency and frailty syndrome in older adults living in a Northern Taiwan community Ching-I Changa , Ding-Cheng (Derrick) Chanb , Ken-N Kuoc , Chao Agnes Hsiungd , Ching-Yu Chena,e, * a Division
of Geriatric Research, Institute of Population Health Sciences, National Health Research Institutes, 100 R440, 4F, No. 17 Xu-Zhou Road, Taipei, Taiwan of Geriatrics and Gerontology, National Taiwan University Hospital, 100 No. 1 ChangDe St., Taipei, Taiwan c Division of Health Policy Research and Development, Institute of Population Health Sciences, National Health Research Institutes, 350 No. 35 Keyan Road, Zhunan, Miaoli, Taiwan d Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 350 No. 35 Keyan Road, Zhunan, Miaoli, Taiwan e Department of Family Medicine, College of Medicine, National Taiwan University, 100 No. 1 Sec 1, Jen-Ai Road, Taipei, Taiwan b Department
article info
abstract
Keywords: Vitamin D insufficiency Fried Frailty Index Edmonton Frail Scale Elderly in Taiwan
This study explored the association between vitamin D insufficiency and frailty syndrome defined by the Fried Frailty Index (FFI) and the Edmonton Frail Scale (EFS) in a northern Taiwan community. Data of 215 subjects participating in an integrated interventional trial involving community-dwelling older adults with a high frailty risk were analyzed. Subjects were first screened by telephone interview and then evaluated at a local hospital with questionnaires, physical performance tests, and serum 25(OH)D measurements. Of the 215 participants, 31% had 25(OH)D insufficiency (<20 ng/ml). Frail subjects based on the FFI were older, had lower MiniMental Status Exam (MMSE) scores, Barthel Index (BI) scores, and 25(OH)D levels. Using the EFS, frailer cases were more likely to be female, have less education, higher comorbid conditions, lower MMSE scores, lower Barthel Index scores, and lower 25(OH)D levels. The associations between insufficient 25(OH)D status and both frailty scales were significant. After adjustment of variables, the odds ratio of 25(OH)D insufficiency was 10.74 (95% CI 2.60–44.31) for frail versus robust individuals. The prevalence of vitamin D insufficiency was high in this population. There was a strong association between vitamin D insufficiency and the FFI. Vitamin D measurements and supplements are suggested for high-risk older people. © 2010 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Frailty can be described as “a biological syndrome of decreased reserve (energy, physical ability, cognition, health) and resistance to stressors, resulting from cumulative declines across multiple physiological systems and causing vulnerability to adverse outcomes” (Fried et al., 2001). Older people with frailty are at increased risk for adverse health outcomes, including lost functional abilities and frequent hospitalizations (Rockwood et al., 1999; Fried et al., 2001). It is widely accepted that frailty is multidimensional, heterogeneous, and unstable, thus distinguishing it from disability or aging alone (Hogan et al., 2003). However, many instruments have been developed to measure frailty without a unifying classification system (Fried et al., 2001; Rockwood et al., 2005; Rolfson et al., 2006; Abellan van Kan et al., 2008). The instrument proposed by Fried et al. (2001), the FFI, following the Cardiovascular Health Study, classified subjects into three * Corresponding author. Division of Geriatric Research, Institute of Population Health Sciences, National Health Research Institutes, 100 R440, 4F, No. 17 Xu-Zhou Road, Taipei, Taiwan. Tel.: +(886-2)-3393-2198; fax: +(886-2)-2356-3260. E-mail address: [email protected] (C-Y. Chen). 0167-4943 /$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.
categories based on five indicators. It is one of the most widely used instruments in the research setting with emphasis on the physical domain (Abellan van Kan et al., 2008). Other instruments measure deficiencies in other areas such as cognition, burden of medical illness, and quality of life. For example, the EFS classifies subjects into five categories based on 10 domains (11 indicators) (Rolfson et al., 2006; Abellan van Kan et al., 2008) . Vitamin D, hydroxylated in the liver into 25-hydroxyvitamin D [25(OH)D], increases the absorption of calcium and phosphate needed for mineralization of the skeleton (Lips, 2001). Low 25(OH)D increases the risk of falls (Bischoff-Ferrari et al., 2004, 2005; Snijder et al., 2006), fractures (Bischoff-Ferrari et al., 2005), bone pain (Atherton et al., 2009; Lips, 2001; Mascarenhas and Mobarhan, 2004; Bischoff-Ferrari et al., 2005), muscle weakness (Bischoff-Ferrari et al., 2004; Gerdhem et al., 2005), sarcopenia (Visser et al., 2003), and disability (Lips, 2001). Recent studies have suggested that vitamin D may play some role in immunomodulation, infectious disease prevention, and psychiatric disorders (particularly depression) (Adams and Hewison, 2008; Hoogendijk et al., 2008). Low 25(OH)D levels are common in the elderly due to decreased vitamin synthesis in the skin, insufficient sunlight exposure, and deficient dietary supplementation (Holick
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65–79-year-old people in Tofun (n = 6828) Random sampling n = 2900 1st step screening
Eligible, N = 548 Category 3 n = 236 Category 4 n = 224 Category 5 n = 69 Category 6 n = 19
Chinese CSHA_CFS telephone interview version screening
Excluded, N = 2352 Non-eligible (Category 1, n = 206; Category 2, n = 86; Category 7, n = 5) Refusal, n = 998 Communication barrier, n = 43 Cannot reach after 3 attempts, n = 1004
Second Stage Frailty syndrome evaluation Fried Frailty Index Edmonton Frail Scale N = 275
Refusal N = 273
Blood specimen collection N = 215
Refusal N = 60
Fig. 1. Patient enrolment in the study.
et al., 1989; Kinyamu et al., 1998). Though a few investigators have studied the association between low vitamin D levels and frailty, most have emphasized the physical aspect (Puts et al., 2005; Shardell et al., 2009). It is not certain whether the finding would be replicable in other studies assessing frailty differently. The association between vitamin D insufficiency and frailty using both the FFI and the EFS was explored. 2. Subjects and methods 2.1. Subjects The target population was community-dwelling older adults aged 65–79 years in the 31 census areas of Tofun town (roughly 7,000 people, 7.1% of the whole population). Details regarding design and sampling have been described elsewhere (Chan, D.C., Tsou, H.H., Chen, C.Y., Hsiung, C., Kuo, K.N. A pilot randomised controlled trial of integrated care model on geriatric frailty. Unpublished results). Briefly, 2,900 population-representative random samples were screened through a two-stage process to enroll eligible older adults into a randomized controlled trial of an integrated care model for geriatric frailty (Figure 1). Subjects were first screened with the Chinese Canadian Study of Health and Aging Clinical Frailty Scale Telephone Version (CCSHA_CFS_TV). The CCSHA_CFS_TV is a validated seven-point scale with a higher score indicating frailer status (Chan et al., 2009). The seven categories were: (7) severely frail – completely dependent on others for activities of daily living (ADLs); (6) moderately frail – help is needed for both instrumental activities of daily living (IADLs) and ADLs; (5) mildly frail – with limited dependence on others for IADL items; (4) apparently vulnerable, although not frankly dependent – these people commonly complain of being “slowed down” or have disease symptoms; (3) well, with treated comorbid disease – disease symptoms are well controlled compared with those in category 4; (2) well – without active disease, but less fit than people in category 1; (1) very fit – robust, active, energetic, well motivated, and fit (Rockwood et al., 2005). A total of 548 subjects who scored 3–6 on the CCSHA_CFS TV were invited for further evaluation at a local hospital using the FFI and the EFS. However, only 275 subjects were actually interviewed (Figure 1).
The FFI has five indicators (Fried et al., 2001): “Weight loss” was defined as self-reported unintentional weight loss more than 3 kg (instead of 5 kg), or greater than 5% of body weight in the previous year. “Exhaustion” was indicated by self-response as “a moderate amount of the time” or “most of the time” to either of the following two statements: “I felt everything I did was an effort” or “I could not get going” from the Center for Epidemiological Studies-Depression Scale (Radloff, 1977). “Low physical activity” was defined by sex-specific low weekly energy expenditure measured by the Taiwan IPAQ-SF (International Physical Activity Questionnaire-Short Form (Liu, 2004) instead of the Minnesota Leisure Time Physical Activity Questionnaire (Taylor et al., 1978). “Slow walking speed” was defined as usual walking speed below certain sex- and height-specific cut-points. “Weakness” was defined as the mean grip strength of the dominant hand measured by three times below certain sex- and body mass index (BMI)-specific cut-points. The subjects were classified as “robust”, “pre-frail”, or “frail” respectively when 0, 1–2, or at least 3 indicators screened positive (Fried et al., 2001). Subjects were also evaluated using the EFS, consisting of 10 domains with 11 items including cognition (the clock drawing test, 2 points), general health status (times of hospitalization in the past year, 2 points and self-reported health status, 2 points), functional dependence (from eight IADLs, 2 points), social support (count on someone who is willing and able to meet the subject’s needs when the subject needs help, 2 points), medication use (use of at least five prescription medications, 1 point and forgetfulness for taking medications, 1 point), nutrition (weight loss, 1 point), mood (depression, 1 point), incontinence (1 point), and functional performance (the Timed Up-and-Go (TUG) test, 2 points) (Lawton and Brody, 1969; Podsiadlo and Richardson, 1991; Brody et al., 1997; Rolfson et al., 2006). The maximum total score is 17. Rolfson et al., (2006) proposed a five-level categorization (robust 0–4, apparently vulnerable, 5–6, mildly frail, 7–8, moderately frail, 9–10, severely frail, 11–17). In the present study, the final three categories were categorized into a single frail category due to small numbers. Other data collected included demographics, BMI, history of smoking and drinking, history of falls, and pain affecting daily life and sleep. The self-reported chronic co-morbidities included
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Table 1 Characteristics of study participants, mean ± S.D. or n(%) Characteristics
Number
Total
215
EFS
FFI Robust
Pre-frail
Frail
75
119
21
p<
Robust
Apparently vulnerable
Frail
137
52
26
p<
Age (years)
71.1±3.9
70.3±3.7
71.4±3.8
72.1±4.4
0.071
70.8±4.0
71.5±3.6
71.9±3.7
0.254
Gender (female %)
128 (59.5)
43 (57.3)
70 (58.8)
15 (71.4)
0.494
71 (51.8)
38 (73.1)
19 (73.1)
0.009
BMI (kg/m2 )
25.4±3.5
25.5±3.1
25.4±3.7
24.9±3.8
0.767
25.3±3.2
25.3±4.1
26.0±3.5
0.623
0
76 (35.3)
20 (26.7)
48 (40.3)
8 (38.1)
0.166
36 (26.3)
25 (48.1)
15 (57.7)
0.001
<7
89 (41.4)
35 (46.7)
43 (36.1)
11 (52.4)
60 (43.8)
23 (44.2)
6 (23.1)
Education (years)
Smoking history (Yes)
38 (17.8)
12 (16.0)
23 (19.3)
3 (15.0)
0.793
28 (20.4)
7 (13.7)
3 (11.5)
Alcohol history (Yes)
42 (19.5)
16 (21.3)
21 (17.6)
5 (23.8)
0.716
29 (21.2)
11 (21.2)
2 (7.7)
0.267
History of fall in 1 year
58 (27.2)
20 (26.7)
29 (24.8)
9 (42.9)
0.228
31 (22.8)
14 (27.5)
13 (50.0)
0.017
Pain history
66 (31.0)
19 (25.3)
37 (31.6)
10 (47.6)
0.145
32 (23.5)
21 (41.2)
13 (50.0)
0.005
Number of comorbidities
3.4±2.0
3.2±1.8
3.3±2.0
4.1±2.5
0.196
3.2±1.9
3.2±1.9
4.7±2.3
0.004
MMSE score
25.1±3.7
26.3±3.0
24.7±3.8
23.1±4.1
0.001
26.3±2.9
23.4±3.9
22.2±4.1
0.001
BI score
98.5±4.3
99.3±2.2
99.0±2.9
92.6±9.3
0.001
99.2±3.0
98.2±4.2
95.4±7.6
0.001
25 (OH)D (ng/ml)
39.9 (25.9)
47.0 (26.1)
37.2 (24.2)
30.8 (30.2)
0.009
43.6 (26.6)
32.7 (19.9)
34.3 (29.4)
0.004
2 (1.5)
3 (5.9)
3 (11.5)
32 (23.5)
21 (41.2)
13 (50.0)
25 (OH)D (ng/ml) <10
8 (3.7)
0 (0)
6 (5.0)
2 (9.5)
25 (OH)D (ng/ml) <20
66 (31.0)
12 (16.4)
41 (34.5)
13 (61.9)
p indicates ANOVA-test for continuous variables, and the
c2 -test
0.001
0.381
0.005
test for categorical variables.
hypertension, diabetes mellitus, heart disease (defined as a history of coronary heart disease, myocardial infarction, congestive heart failure, or arrhythmia), stroke, hyperlipidemia, gout and arthritis, chronic lung disease, gastric ulcer, chronic kidney or liver or thyroid disease, prostatomegaly, Parkinson’s disease, dementia, depression, cataracts, glaucoma, anemia, osteoporosis, and fractures. The MMSE (Folstein et al., 1975) and the Barthel Index (BI) were also evaluated (Mahoney and Barthel, 1965).
3. Results 3.1. Baseline characteristics The distributions of baseline characteristics for the entire study population (n = 215) are listed in Table 1. The mean age was 71.1±3.9 years, with 128 (59.5%) female. The study cohort had an average of 3.4±2.0 comorbid conditions. The mean MMSE score was 25.1±3.7, and the mean BI score was 98.5±4.3. The mean 25(OH)D level was 39.9±25.9 ng/ml, with 66 (31%) under 20 ng/ml (vitamin D insufficiency).
2.2. Serum 25(OH)D levels Serum 25(OH)D, which represents vitamin D storage, was measured by the DiaSorin 25-Hydroxyvitamin D 125I RIA (DiaSorin, Vercelli, Italy). Fasting serum blood specimens were stored at −80°C for further analysis. Serum 25(OH)D under 10 ng/ml was previously defined as vitamin D deficiency, and between 10 and 20 ng/ml was defined as vitamin D insufficiency (Lips, 2001). In the present study, vitamin D deficiency was defined as a serum 25(OH)D level under 20 ng/ml without further classification, since only 4% of the sample had a serum 25(OH)D level below 10 ng/ml. The study included only the 215 subjects with available vitamin D blood samples (Figure 1).
3.2. Distribution of baseline characteristics among subjects with different frailty statuses Using the FFI, 75 (34.9%) subjects were classified as robust, 119 (55.3%) as pre-frail, and 21 (9.8%) as frail. With the EFS, 137 (63.7%) were classified as robust, 52 (24.2%) as apparently vulnerable, and 26 (12.1%) as frail. (Table 1). Older age, a lower MMSE score, a lower BI score, and a lower 25(OH)D level were significantly associated with frailer status using the FFI. Characteristics that distributed differently among the three frailty categories of the EFS included sex, education, history of falls, history of chronic pain, number of comorbid conditions, MMSE score, BI score, and 25(OH)D level (Table 1).
2.3. Statistical analysis 3.3. Association between 25(OH)D level and frailty Differences in characteristics among the categories of the two frailty scales were compared by ANOVA test (continuous variables) or c2 -test (categorical variables). To examine the association of 25(OH)D and frailty, bivariate and multivariate multinomial logistic regressions were performed. Adjusted variables, including age, sex, educational status, BMI, smoking and drinking behaviors, comorbidity conditions, the MMSE scores, and the BI scores were added in the multivariate models. Data management and analysis were performed using SPSS 17.0 software (SPSS Corporation, Chicago, Illinois, USA).
There was a graded association between vitamin D insufficiency (below 20 ng/ml) and frailty levels on bivariate analysis (Table 2). Using the FFI, the odds ratio (OR) of vitamin D insufficiency was 2.67 (95% confidence interval = 95% CI = 1.29–5.52) for pre-frail versus robust individuals and 8.26 (95% CI = 2.82–24.24) for frail versus robust individuals (Table 2). Similarly, using the EFS, the odds ratio of apparently vulnerable versus robust was 2.28 (95% CI = 1.15–4.51), and that of frail versus robust was 3.25 (95% CI =1.37–7.72). The association did not change when the 25(OH)D level was treated as a continuous variable in both models (Table 2).
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Table 2 Association between 25(OH)D insufficiency and frailty by simple multinomial logistic regression EFS
FFI Frail vs. robust
Apparently vulnerable vs. robust
Frail vs. robust
OR (95% CI)
p<
OR (95% CI)
p<
OR (95% CI)
p<
OR (95% CI)
p<
Vitamin D (low vs. high)
2.67 (1.294–5.519)
0.008
8.26 (2.815–24.238)
0.001
2.275 (1.148–4.509)
0.019
3.250 (1.369–7.718)
0.008
Vitamin D (continuous)
0.984 (0.972–0.997)
0.013
0.97 (0.946–0.995)
0.018
0.979 (0.963–0.995)
0.009
0.984 (0.965–1.003)
0.107
Pre-frail vs. robust
Vitamin D insufficiency = 25-hydroxyvitamin D <20 ng/ml
Table 3 Multivariate-adjusted association between 25(OH)D insufficiency and the frailty scale EFS
FFI Frail vs. robust
Apparently vulnerable vs. robust
Frail vs. robust
OR (95% CI)
p<
OR (95% CI)
p<
OR (95% CI)
p<
OR (95% CI)
p<
Vitamin D (low vs. high)
3.139 (1.426–6.908)
0.004
10.739 (2.602–44.312)
0.002
2.377 (1.006–5.300)
0.034
2.023 (0.678–6.032)
0.206
Vitamin D (continuous)
0.982 (0.969–0.995)
0.008
0.972 (0.945–0.999)
0.039
0.981 (0.964–0.998)
0.026
0.995 (0.973–1.016)
0.616
Pre-frail vs. robust
(kg/m2 ,
Adjusted-variates: age (years), gender, body mass index education status (years), smoke and drink history, co-morbidity condition (hypertension, diabetes mellitus, heart disease [defined as a history of coronary heart disease, myocardial infarction, congestive heart failure, or arrhythmia], stroke, hyperlipidemia, gout and arthritis, chronic lung disease, gastric ulcer, chronic kidney or liver or thyroid disease, prostatomegaly, Parkinson’s disease, dementia, depression, cataracts, glaucoma, anemia, osteoporosis and fracture), MMSE (Mini-Mental State Examination) scores and Barthel Index scores.
After adjusting for age, sex, BMI, educational status, smoking and drinking history, co-morbidity conditions, MMSE scores, and BI scores, the odds ratio of vitamin D insufficiency comparing subjects with pre-frailty and frailty to those with robust was 3.14 (95% CI = 1.43–6.91) and 10.74 (95% CI = 2.60–44.31), respectively, using the FFI (Table 3). With the EFS, however, the association after model adjustment was only significant between the apparently vulnerable versus robust individuals (odds ratio = 2.38, 95% CI = 1.07–5.30), but not between the frail versus robust individuals (odds ratio = 2.02, 95% CI = 0.68–6.03) (Table 3). The results did not differ when the 25(OH)D level was treated as a continuous variable. 4. Discussion The present study found that there was a strong dose-response relationship between vitamin D insufficiency and frailty using the FFI. The association may be attenuated using the EFS assessment. To the best of our knowledge, this is the first report to examine the association between vitamin D insufficiency and frailty using different frailty assessment instruments. In the present study, the mean serum 25(OH)D level was 39.9 ng/ml, which was in the normal range (Lips, 2001). Studies by Lee and Tsai et al. have reported similar results in rural Southern Taiwan and the urban Northern Taiwan area (Tsai et al., 1997; Lips, 2001; Lee et al., 2002). First of all, subjects were recruited during June to August when the sunshine was sufficient compared with other seasons. Secondly, Tofun Town is located in a subtropical region with good sunlight exposure (latitude 24°68 N). Thirdly, data from the Nutrition and Health Surveys in Taiwan (NAHSIT) by Lee et al. (2008) showed that vitamin D intakes of Taiwanese people were generally adequate, and supplemental sources of vitamin D increased in the elderly population. These factors may explain the normal range mean 25(OH)D level in the present study population. Overall, 31% of the study population had vitamin D insufficiency. However, this number cannot be interpreted as a population-based prevalence estimate since not all participants enrolled in the trial had vitamin D data available, and the trial was not designed to provide the prevalence data. The physiological functions of vitamin D related to bone, muscle, and inflammation have been well established (Lips, 2001;
Bischoff-Ferrari et al., 2004, 2005; Gerdhem et al., 2005; Adams and Hewison, 2008). Serum 25(OH)D, the hydroxylated form of vitamin D, is the major circulating metabolite. A low 25(OH)D level is associated with decreased absorption of calcium and phosphate from the gut, leading to increased bone turnover, bone mass loss, osteoporosis, and eventually fracture and disability (Lips, 2001). In the present study, an insufficient 25(OH)D status was strongly and independently associated with the frailty classification using the FFI, a measure of physical domain performance that was likely to be influenced by the vitamin D level. Vitamin D plays an important role in protein synthesis and the regulation of calcium transport that affects muscle strength, as well as the balance between neurons and muscles (Lips, 2001; Kochupillai, 2008). A low vitamin D level is associated with sarcopenia, weak muscle strength, poor physical performance, balance problems, and falls (Lips, 2001; Visser et al., 2003; BischoffFerrari et al., 2004, 2005; Gerdhem et al., 2005; Snijder et al., 2006). Several indicators in the FFI, such as weak grip strength, slow walking speed, and weight loss, could be manifestations of sarcopenia that might explain the observed association between vitamin D insufficiency and the FFI classification. Compared with the FFI with its focus on physical frailty, the EFS included many other domains, such as cognition, depression, incontinence, general health, polypharmacy, and social support. There is growing evidence showing that low vitamin D may be associated with reduced protection against infectious disease, increasing susceptibility to autoimmune diseases such as type 1 diabetes mellitus, and neuropsychiatric disorders such as depression (Adams and Hewison, 2008). These diseases may, in turn, lead to frequent hospitalizations, poor self-rated health, polypharmacy, and some other indicators measured in the EFS. However, a direct link between the above mentioned factors and vitamin D may not be obvious. A weaker association between the EFS classification and vitamin D insufficiency is expected. The other possibility is that a larger sample size is needed to confirm the relationship. With the cross-sectional design, causality between vitamin D deficiency and frailty could not be established. More prospective data are needed to explore the existence of a causal relationship between vitamin D and frailty syndrome.
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5. Conclusion The prevalence of vitamin D insufficiency was high among this population. There was a strong association between vitamin D insufficiency and frailty index. Vitamin D insufficiency is easily treated with adequate supplements. Future clinical trials may consider the treatment of vitamin D insufficiency to improve frailty syndrome in older adults in order to prevent the progression to functional disability and worse outcomes. Conflict of interest statement None. Acknowledgements This study was supported by the 97_HDSP08_020 grant “Interventional study of Geriatric Frailty, Osteoporosis, and Depression in a Community Based Randomized Trial” from the National Health Research Institutes, Zhunan, Taiwan. References Abellan van Kan, G., Rolland, Y., Bergman, H., Morley, J.E., Kritchevsky, S.B., Vellas, B., 2008. The I.A.N.A Task Force on frailty assessment of older people in clinical practice. J. Nutr. Health Aging 12, 29–37. Adams, J.S., Hewison, M., 2008. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat. Clin. Pract. Endocrinol. Metab. 4, 80–90. Atherton, K., Berry, D.J., Parsons, T., Macfarlane, G.J., Power, C., Hypponen, E., 2009. Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from a cross-sectional population survey. Ann. Rheum. Dis. 68, 817–822. Bischoff-Ferrari, H.A., Dietrich, T., Orav, E.J., Hu, F.B., Zhang, Y., Karlson, E.W., DawsonHughes, B., 2004. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y. Am. J. Clin. Nutr. 80, 752–758. Bischoff-Ferrari, H.A., Willett, W.C., Wong, J.B., Giovannucci, E., Dietrich, T., DawsonHughes, B., 2005. Fracture prevention with vitamin D supplementation: a metaanalysis of randomized controlled trials. J. Am. Med. Assoc. 293, 2257–2264. Brody, K.K., Johnson, R.E., Douglas Ried, L., 1997. Evaluation of a self-report screening instrument to predict frailty outcomes in aging populations. Gerontologist 37, 182– 191. Chan, D.C., Tsou, H.H., Chen, C.Y., Chen, C.Y., 2009. Validation of the Chinese Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS) Telephone Version. Arch. Gerontol. Geriatr. (Epub ahead of print: doi: 10.1016/j.archger. 2009.06.004). Chan, D.C., Tsou, H.H., Chen, C.Y., Hsiung, C., Kuo, K.N., Unpublished. A pilot randomised controlled trial of integrated care model on geriatric frailty. Folstein, M.F., Folstein, S.E., McHugh, P.R., 1975. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189–198. Fried, L.P., Tangen, C.M., Walston, J., Newman, A.B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W.J., Burke, G., McBurnie, M.A., 2001. Frailty in older adults: evidence for a phenotype. J. Gerontol. A: Biol. Sci. Med. Sci. 56, M146– M156. Gerdhem, P., Ringsberg, K.A., Obrant, K.J., Akesson, K., 2005. Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporos. Int. 16, 1425–1431.
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