As prevalence and incidence rates of falls in older people living in the community are
important, so too is an understanding of the risk factors which contribute to an older person’s risk of falling. A large volume of research has now been collected over the past 4 decades adding to the evidence of which factors contribute to a first or further falls. Several meta- analyses have also been performed in an effort to pool the data from individual studies. (12, 38) The objectives of these studies have been to determine the risk factors for falls, and in the case of Ganz et al., to identify the prognostic value of risk factors for further falls. (38)
As described above, Deandrea et al. sought to expand on the evidence contained within the 2003 National Institute of Clinical Excellence (NICE) guidelines on the assessment and prevention of falls in older people. (12) The NICE guidelines included meta-analyses of prospective studies published from 1988 to 2002. Deandrea et al. expanded the search to include prospective cohort studies published from 2002 to December 2008, with inclusion criteria as described previously. The meta-analysis was restricted to look at potential risk factors that had been assessed for their association with falls in at least 5 studies. The outcome data was analysed in 3 stages: first using data from all studies identified, then from the subgroup of studies that had conducted multivariate analyses and finally only the subgroup of studies for which the quality of falls ascertainment was described as “high”. Tables 1.1 and 1.2 show details on the combined odds ratios (OR) and 95% confidence intervals (95% C.I.), and heterogeneity tests for risk factors where a significant association with one or more falls and recurrent falls was demonstrated in the meta-analysis. The meta- analyses for those studies which included a multivariate analysis and those with high
32
frequency falls outcome ascertainment are shown in these tables, as this is the more robust evidence.
Examining the risk factors associated with one or more falls, the meta-analysis of studies that had reported a multivariate analysis reported the following associations (Table 1.1). The strongest associations with one or more falls were seen with a prior history of falls (OR 2.92; 95% C.I. 2.50 – 3.40), the use of a walking aid (OR 2.50; 95% C.I. 1.80 – 3.47), cognitive impairment (OR 2.24; 95% C.I. 1.25 – 4.03), dizziness and vertigo (OR 2.30; 95% C.I. 1.35 – 3.93), Parkinson’s disease (OR 2.73; 95% C.I. 1.00 – 7.45) and gait problems (OR 2.06; 95% C.I. 1.76 – 2.41). For those studies with high frequency falls ascertainment, the meta-analysis reported a strong association between the following factors and having one or more falls: prior history of falls (OR 2.79; 95% C.I. 2.43 – 3.20), physical disability (OR 2.30; 95% C.I. 1.55 – 3.43), use of a walking aid (OR 2.46; 95% C.I. 1.91 – 3.15), cognitive impairment (OR 2.21; 95% C.I. 1.18 – 4.14), Parkinson’s disease (OR 3.89; 95% C.I. 3.88 – 3.90), and gait problems (OR 2.02; 95% C.I. 1.39 – 2.93). A range of other socio-demographic, medical and psychological, medication and mobility and sensory risk factors had a more modest
association with increased risk of falling in both analyses.
Table 1.2 shows the combined odds ratios (OR), 95% confidence intervals and heterogeneity tests for risk factors with a significant association with recurrent falls in the meta-analysis. In studies which reported multivariate analyses the risk factors strongly associated with
recurrent falls were as follows: history of falls (OR 3.07; 95% C.I. 2.31 – 4.08), physical disability (OR 2.63; 95% C.I. 1.06 – 6.51), use of a walking aid (OR 3.20; 95% C.I. 1.70 – 6.01), cognitive impairment (OR 3.65; 95% C.I. 1.71 – 7.79), history of stroke (OR 2.94; 95% C.I. 1.77 – 4.87), dizziness and vertigo (OR 2.14; 95% C.I. 1.54 – 2.99), Parkinson’s
33
disease (OR 3.79; 95% C.I. 1.00 – 14.30), use of antiepileptics (OR 2.52; 95% C.I. 1.61 – 3.93) and gait problems (OR 3.68; 95% C.I. 1.87– 7.22). The magnitude of association between risk factors and the outcome of recurrent falls was higher than when the outcome was one or more falls. History of falls, use of a walking aid, cognitive impairment, Parkinson’s disease and gait problems were all associated with a 3-fold increased risk of recurrent falls. Physical disability, history of stroke and use of antiepileptics had a 2-fold increased risk of recurrent falls, compared with a modest association for history of stroke with one or more fall, and no significant association between these other risk factors and one or more falls. In the studies with high frequency of falls assessment the following factors were strongly associated with recurrent falls: history of falls (OR 3.09; 95% C.I. 2.63 – 3.63), physical disability (OR 2.24; 95% C.I. 1.81 – 2.77), use of a walking aid (OR 3.05; 95% C.I. 1.87 – 4.95), history of Parkinson’s disease (OR 6.57; 95% C.I. 2.11 – 20.44) and gait problems (OR 2.58; 1.79 – 3.74). The risk of having recurrent falls in the 12 months after follow-up was increased by between 2-fold and 6-fold in the presence of these risk factors and this list of factors is similar to what was found for the outcome of at least one fall. Additional risk factors for recurrent falls were history of stroke (OR 2.35; 95% C.I. 1.51 – 3.66), dizziness and vertigo (OR 2.18; 95% C.I. 1.77 – 2.68) and fear of falling (OR 2.21; 95% C.I. 1.55 – 3.15).
34
Table 1.1: Meta-analysis of risk factors associated with at least one fall in community dwelling older people*
Studies with a multivariate analysis Studies with high frequency of falls assessment Characteristic No. Studies Heterogeneity P OR (95% C.I.) No. Studies Heterogeneity P OR (95% C.I.) Sociodemographic risk factors
Age (5-year increase) 8 0.0002 1.12 (1.05 – 1.19) 8 0.007 1.11 (1.05 – 1.17)
Sex (women vs men) 7 0.003 1.28 (1.06 – 1.54) 12 0.22 1.37 (1.21 – 1.55)
Living situation (alone vs not alone) 1 NS 3 0.52 1.26 (1.04 – 1.53)
History of falls (yes vs no) 12 0.002 2.92 (2.50 – 3.40) 9 0.35 2.79 (2.43 – 3.20)
Physical activity (limitation vs no limitation) 1 NS 7 0.008 1.22 (1.00 – 1.50)
Physical disability (yes vs no) 4 NS 4 0.20 2.30 (1.55 – 3.43)
Instrumental disability (yes vs no) 2 0.70 1.25 (1.02 – 1.53) 1 NS
Walking aid use (yes vs no) 3 0.80 2.50 (1.80 – 3.47) 6 0.12 2.46 (1.91 – 3.15)
Medical and psychological risk factors
Cognitive impairment (yes vs no) 4 0.07 2.24 (1.25 – 4.03) 4 0.07 2.21 (1.18 – 4.14)
Depression (yes vs no) 6 <0.0001 1.44 (1.11 – 1.86) 8 0.88 1.70 (1.46 – 1.97)
History of stroke (yes vs no) 2 0.7 1.65 (1.22 – 2.22) 4 0.81 1.59 (1.28 – 1.98)
Urinary incontinence (yes vs no) 6 0.001 1.33 (1.11 – 1.61) 3 0.17 1.74 (1.32 – 2.28)
Rheumatic disease (yes vs no) 4 0.03 1.41 (1.09 – 1.81) 4 0.24 1.76 (1.44 – 2.16)
Dizziness and vertigo (yes vs no) 1 NA 2.30 (1.35 – 3.93) 4 0.26 1.50 (1.23 – 1.82)
Diabetes (yes vs no) 3 0.99 1.36 (1.15 – 1.61) 2 NS
Comorbidity (increment of 1 condition) 2 NS 3 0.54 1.18 (1.13 – 1.23)
Self-perceived health status (poor vs good) 1 NS 2 0.94 1.32 (1.08 – 1.61)
Fear of falling (yes vs no) 3 NS 5 <0.0001 1.57 (1.03 – 2.40)
Parkinson disease (yes vs no) 4 0.0001 2.73 (1.00 – 7.45) 2 0.79 3.89 (3.88 – 3.90)
Medication risk factors
Number of medications (for 1-drug increase) 4 1.00 1.05 (1.01 – 1.09) 2 0.80 1.05 (1.00 – 1.10)
Use of sedatives (yes vs no) 6 0.30 1.38 (1.18 – 1.62) 5 0.05 1.65 (1.06 – 2.57)
Use of antihypertensives (use vs no use) 4 0.11 1.25 (1.02 – 1.54) 3 NS
Mobility and sensory risk factors
Gait problems (yes vs no) 3 0.32 2.06 (1.76 – 2.41) 2 0.17 2.02 (1.39 – 2.93)
Vision impairment (yes vs no) 6 NS 7 0.61 1.51 (1.29 – 1.78)
Hearing impairment (yes vs no) 0 … … 4 0.15 1.25 (1.03 – 1.51)
35
Table 1.2: Meta-analysis of risk factors associated with recurrent falls in community dwelling older people *
Studies with a multivariate analysis Studies with high frequency of falls assessment Characteristic No. Studies Heterogeneity P OR (95% C.I.) No. Studies Heterogeneity P OR (95% C.I.) Sociodemographic risk factors
Age (5-year increase) 6 0.0007 1.15 (1.00 – 1.32) 9 0.10 1.12 (1.07 – 1.18)
Sex (women vs men) 6 NS 12 0.0002 1.34(1.08 – 1.68)
Living situation (alone vs not alone) 1 NA 1.59 (1.00 – 2.52) 4 NS
History of falls (yes vs no) 7 0.04 3.07 (2.31 – 4.08) 9 0.54 3.09 (2.63 – 3.63)
Physical disability (yes vs no) 2 0.02 2.63 (1.06 – 6.51) 6 0.22 2.24 (1.81 – 2.77)
Instrumental disability (yes vs no) 0 … … 1 NA 2.00 (1.35 – 2.96)
Walking aid use (yes vs no) 1 NA 3.20 (1.70 – 6.01) 4 0.01 3.05 (1.87 – 4.95)
Medical and psychological risk factors
Cognitive impairment (yes vs no) 2 0.40 3.65 (1.71 – 7.79) 12 0.02 1.56 (1.26 – 1.94)
Depression (yes vs no) 3 NS 8 0.98 1.79 (1.53 – 2.09)
History of stroke (yes vs no) 2 0.60 2.94 (1.77 – 4.87) 2 0.72 2.35 (1.51 – 3.66)
Urinary incontinence (yes vs no) 4 0.009 1.71(1.17 – 2.49) 7 0.34 1.75 (1.53 – 2.01)
Rheumatic disease (yes vs no) 4 0.12 1.91 (1.43 – 2.56) 6 0.58 1.54 (1.34 – 1.77)
Dizziness and vertigo (yes vs no) 2 0.94 2.14 (1.54 – 2.99) 6 0.18 2.18 (1.77 – 2.68)
Diabetes (yes vs no) 2 0.88 1.43 (1.15 – 1.77) 2 0.31 1.48 (1.06 – 2.07)
Comorbidity (increment of 1 condition) 0 … … 3 0.52 1.25 (1.12 – 1.40)
Pain (yes vs no) 3 0.64 1.55 (1.38 – 1.75) 3 0.94 1.78 (1.49 – 2.13)
Fear of falling (yes vs no) 3 0.12 1.88 (1.24 – 2.85) 5 0.02 2.21 (1.55 – 3.15)
Parkinson disease (yes vs no) 2 0.12 3.79 (1.00 – 14.30) 2 0.55 6.57 (2.11 – 20.44)
Medication risk factors
Number of medications (for 1-drug increase) 3 0.62 1.04 (1.01 – 1.07) 5 0.37 1.05 (1.03 – 1.07)
Use of sedatives (yes vs no) 3 0.65 1.44 (1.16 – 1.78) 4 0.58 1.53 (1.21 – 1.93)
Use of antihypertensives (use vs no use) 3 NS 4 0.15 1.32 (1.07 – 1.64)
Use of antiepileptics (use vs no use) 3 0.38 2.52 (1.61 – 3.93) 2 0.84 3.19 (1.53 – 6.66)
Mobility and sensory risk factors
Gait problems (yes vs no) 2 0.11 3.68 (1.87– 7.22) 4 0.04 2.58 (1.79 – 3.74)
Vision impairment (yes vs no) 4 NS 8 0.50 1.81 (1.58 – 2.08)
Hearing impairment (yes vs no) 0 … … 5 0.28 1.50 (1.27 – 1.78)
36
Ganz et al. approached the assessment of risk of having falls from the perspective of how a falls risk at baseline predicted the likelihood of developing a fall in the following 12 months. (38) The objective of the study was to more closely mimic the clinical scenario that is faced in the real world. Data was extracted from prospective cohort studies that published the results of multivariate analyses that looked at common risk factors associated with falls, including studies which had high falls ascertainment only. Individual risk factors were examined, and where the data permitted, likelihood ratios for further falls were calculated for these risk factors. The risk factors examined were age, prior history of falls, orthostatic hypotension, visual impairment, impaired gait or balance, medications, impairment in activities of daily living (ADLs) and cognitive impairment.
Age is commonly included in multivariate analyses of risk factors for falls. Ganz et al. reported that of 11 studies which included age in their multivariate analyses, only 4 studies reported a significant association between age and falls in their original analyses. Three studies provided data that could be used to calculate a likelihood ratio. (16, 39-41) Only one study demonstrated a significant association between age and one or more falls in terms of the calculated likelihood ratio. (41) A prior history of falls was a strong predictor of future falls and all 11 studies within the Ganz analysis, found a significant association between prior falls and future falls. The likelihood ratio (LR) ranged from LR 2.8 (95% C.I. 2.1 – 3.8) for one or more falls in the next year after experiencing one or more fall in the preceding year (16), to LR 3.8 (95% C.I. 2.2 – 6.4) if there was a history of one fall in the previous month (41). Impaired gait and/or balance also had a strong association with future falls. Four studies provided data for calculation of likelihood ratios as follows: accumulation of gait
abnormalities (6 of 7 abnormalities) (LR 1.9; 95% C.I. 1.4 – 2.6), lower extremity disability (sensory loss, weakness or impaired balance) (LR 1.8; 95% C.I. 1.5 – 2.2) and an inability to
37
tandem stand (LR 2.0; 95% C.I. 1.7 – 2.4) were all associated with increased likelihood of having one or more falls in the following 12 months. (13, 16) Self perceived mobility issues were associated with both increased likelihood of one or more falls (LR 1.7; 95% C.I. 1.5 – 1.9) and recurrent falls, defined as 2 or more falls (LR 2.0; 95% C.I. 1.7 – 2.4). (16) More than 2 falls in one year was also associated with inability to tandem walk (LR 2.4; 95% C.I. 2.0 – 2.9) and slow 10m walking speed (LR 2.0; 95% C.I. 1.5 – 2.7). (16, 42) Medications, both specific classes of medications and polypharmacy were significantly associated with increased risk of falls. Psychotropic medications were associated with increased risk of one or more falls in the next year (LR 1.7; 95% C.I. 1.3 – 2.2) (39), with a further study specifying benzodiazepines, phenothiazine and antidepressants (LR 27; 95% C.I. 3.6 – 207). (13) Polypharmacy, defined as taking 4 or more medications, was associated with increased likelihood of falls in women only (LR 1.9; 95% C.I. 1.4 – 2.5). (39) The authors of this study postulated that the lack of association in males may have been due to the smaller cohort of male subjects within the study population. Cognitive impairment also had a strong
association with one or more falls in 2 studies with extractable data, either as demonstrated by a history of dementia (LR 13; 95% C.I. 2.3 – 79) (16), or 5 or more errors on the Short Portable Mental Status Questionnaire (SPMSQ) (LR 4.2; 95% C.I. 1.9 – 9.6). (13)
The associations between impairment in activities of daily living, visual impairment and orthostatic hypotension and one or more falls in the following 12 months, were weaker than for the previous risk factors discussed. Ganz et al. calculated the likelihood of falling in those with impairment in activities of daily living, based on 2 studies. An inability to rise from a chair without using upper limbs had a significant association with further falls in men (LR 4.3; 95% C.I. 2.3 – 7.9), but not in women. (39) The accumulation of 5 or more of 11 physical impairments was associated with increased risk of one or more falls (LR 1.9; 95%
38
C.I. 1.4 – 2.6). (43) Although there were no extractable data to perform further analysis, Ganz et al. also reported on the association between falls and visual impairment, with poor vision as demonstrated by an inability to recognise a face at 4m or inability to read a newspaper, associated with an increased risk of fall of between 60% and 100%. (15, 44) Another study demonstrated that for each additional letter recognised on a Bailey-Lovie chart there was an associated lower rate of falling (OR 0.96). (45) Orthostatic hypotension did not have a strong association with the risk of further falls in the next year when adjusted for other known risk factors. (15, 39, 40, 46)
In this study a pre-test probability of having falls could be calculated using the incidence rates for each of 18 included studies. The pre-test probability of having one or more falls was 27% (95% C.I. 19 – 36%) and of having 2 or more falls was 10% (95% C.I. 7 – 15%). Ganz et al. went on to discuss how pre-test odds of having a further fall at baseline for older patients ranges from 1:4 to 1:2, and with the addition of a risk factor with a positive
likelihood of 2 to 4 that risk of having one or more fall in the next year could be increased to 50%. Risk factors which would increase the annual risk to 50% would include prior history of falls in the past year or month, and a clinically detected abnormality of gait or balance, such as the inability to tandem walk. (38)
Medications have also been associated with increasing the risk of falling. Three additional meta-analyses looked at the effect of medications on this risk. (47-49) Studies spanning from 1966 to 1996 (47, 48) and 1996 to 2007 (49) were selected based on the quality of the falls and medication ascertainment to examine the pooled effects of a variety of medications on falls. The results of these 3 meta-analyses including a Bayesian pooled odds ratio from
39
Woolcott et al. combining all the information from the studies identified from 1966 to 2007, are included in Table 1.3. (49, 50)
Table 1.3: Summary of the pooled Odds Ratios from Leipzig et al. and Woolcott et al.: meta- analyses of the effect of drugs on risk of falling.
Drug type Leipzig
Pooled Odds Ratio (95% CI)
Woolcott
(studies from 1996 to 2007)
Random effects pooled Odds Ratio (95% CI) Woolcott (studies from 1960 to 2007) Pooled Bayesian Odds Ratio (95% CI) Antihypertensives Non-informative* 1.26 (1.01 to 1.50) † 1.24 (1.01 to 1.50) † Diuretics 1.08 (1.02 to 1.16) † 1.03 (0.84 to 1.26) 1.07 (1.01 to 1.14) † Beta blockers 0.93 (0.77 to 1.11) 1.14 (0.97 to 1.33) 1.01 (0.86 to 1.17) Sedatives/hypnotics 1.54 (1.40 to 1.70) † 1.31 (1.14 to 1.50) † 1.47 (1.35 to 1.62) † Neuroleptics/ Antipsychotics 1.50 (1.25 to 1.79) † 1.71 (1.44 to 2.04) † 1.59 (1.37 to 1.83) † Antidepressants 1.66 (1.41 to 1.95) † 1.72 (1.40 to 2.11) † 1.68 (1.47 to 1.91) † Benzodiazepines 1.48 (1.23 to 1.77) † 1.60 (1.46 to 1.75) † 1.57 (1.43 to 1.72) † Narcotics 0.97 (0.78 to 1.20) 0.89 (0.50 to 1.58) 0.96 (0.78 to 1.18) NSAIDs 1.16 (0.97 to 1.38) 1.65 (0.98 to 2.77) 1.21 (1.01 to 1.44) † Table reproduced from Boyle N, Naganathan V and Cumming RG. (50)
Data from Leipzig et al. (47, 48) and Woolcott JC et al. (49).
#NSAIDs - Non-steroidal anti-inflammatory drugs; C.I. – confidence intervals;
†Statistically significant Odds Ratio.
* The term “non-informative” relates to the Bayesian pooled estimates use of this information in further calculations of risk.
From the Table it can be seen that CNS active medications have the strongest association with falls. The meta-analysis by Leipzig et al. estimated this increased risk of falls to be 73% (OR 1.73; 95% C.I. 1.52 – 1.97). (48) Of the CNS active medications, antidepressants have consistently had the strongest association with falls as demonstrated in Table 1.3. Across the 2 meta-analyses and the Bayesian analysis, antidepressants have been associated with an increased risk of falls of between 66% and 72%. The time span of the publications included
40
suggested that the effect of antidepressants on the increased risk of falling is similar for both tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors (SSRI).
Sedative/hypnotics have consistently been demonstrated to be associated with increased risk of falling (Bayesian Odds Ratio 1.47; 95% C.I. 1.35 – 1.62). When examined separately, Benzodiazepines have a 1.57-fold increased risk of falling (Bayesian odds ratio 1.57; 95% C.I. 1.42 – 1.72). In addition, antipsychotics also have an association with falls, with an up to 59% increase in the risk of falls with any antipsychotic drug used. (49)
The associations between cardiovascular medications, and analgesic medications and falls are weaker than that seen with CNS active medications. There is difficulty in interpreting the association between these classes of medications and falls using the same methodology as for CNS active medications for several reasons. Cardiovascular medications have been
categorised in different ways (cardiovascular medications vs antihypertensives and antiarrhythmics) in various studies, and medication use has changed in the intervening decades. Opiate analgesics have been variously categorised as CNS active medications or as analgesics, without a consistent approach. The association with antihypertensives, diuretics and non-steroidal anti-inflammatories is weaker and inconsistent across the various analyses. Opiate analgesics were not significantly associated with increased risk of falling. (47, 49)
These meta-analyses allow us to examine the strength of association between risk factors and falls, and can provide a template for risk assessment in the clinical setting. Many of the studies included examined these associations in majority female cohorts, recruited from the community. If this information is to be used routinely in the clinical setting, it is important to understand if there is a variation in risk profile based on gender, and based on where the sample is derived.
41