Prevalence of Anemia and Its Association with Handgrip Strength in Indonesian Elderly Population: A Cross-Sectional Study Using Indonesian Family Life Survey Data Year 2014-2015

This study aimed to elucidate the prevalence of anemia in Indonesian elderly population aged ≥ 60 years old and to analyze its association with handgrip strength in the elderly. Method This was a cross-sectional study using data from Indonesian Family Life Survey-5 (IFLS-5). All participants aged ≥ 60 years old were included in this study. Exclusion criteria were: (1) respondents who refused to take health measurements (hemoglobin level, handgrip strength, weight, stature, and waist circumference); (2) respondents with incomplete or missing data; (3) respondents with history of stroke; and (4) respondents with history of pain, swelling, inammation, injury, and surgery on one or both hands within the last 6 months. The dependent variable for this study was handgrip strength. The independent variables were hemoglobin level, gender, age, body mass index (BMI), waist circumference, smoking history, comorbidities, and current use of drug therapies. Statistical analyses included correlation, bivariable, and multivariable analyses.


Introduction
Indonesia as the fourth most populous country is experiencing an increase in life expectancy. 1,2 While this is a well-received improvement for Indonesia, there are several concerning consequences that may impact the country negatively if not promptly solved. One of the these is the growth of Indonesian elderly population. 3 By the year 2050, it is predicted that the Indonesian aging population will be around 25% This study was a multicenter, non-interventional, cross-sectional study using data from IFLS5 that was conducted in late 2014 and early 2015 at 13 provinces in Indonesia. Despite IFLS consisted of ve waves, only the most recent wave, the fth IFLS (IFLS5) was used for this study.
The dependent variable for this study was handgrip strength. The independent variables were hemoglobin level, gender, age, body mass index (BMI), waist circumference, smoking history, comorbidities, and current use of drug therapies.
The inclusion criteria used in this study was respondents aged ≥60 years old as in Indonesia, the elderly is de ned by age 60 years and above. 25 Exclusion criteria were: (1) respondents who refused to take health measurements (hemoglobin level, handgrip strength, weight, stature, and waist circumference); (2) respondents with incomplete or missing data; (3) respondents with history of stroke; and (4) respondents with a history of pain, swelling, in ammation, injury, and surgery on one or both hands within the last 6 months.

Variable Classi cations and Measurements
Hemoglobin Level Hemoglobin test was performed using capillary blood drawn from a nger prick. The measurement was performed using a Hemocue handheld meter (model Hb201+) together with its respective HB201 microcuvettes. The nger sticks lancets manufactured by Hospital and Home Care were used. Meanwhile, the dried blood spot cards used were Whatman ® 903 Protein Saver Cards containing ve half-inch circles with each circle capable of holding 75 to 80 μL of sample. 26 Based on WHO standard, male and female participants with Hb less than 13 g/dL and 12 g/dL, respectively, were de ned as anemic. 27 Handgrip Strength Handgrip strength on each hand was measured twice using a Baseline Smedley Spring type dynamometer. The dynamometer was calibrated daily.
Trained personals instructed the study participants to hold and squeeze the handle of the dynamometer as rmly as they could. The measurement begins with the dominant hand and continues with alternating hand, with a resting period in between measurements.
The value for handgrip strength used for this study was the average of both left and right hands, each measured twice. Subjects were classi ed as weak if the handgrip strength <28 kg for men and <18 kg for women based on classi cation from Asian Working Group for Sarcopenia (AWGS) 2019. 19 Confounders Confounders included in this study were age, sex, BMI, waist circumference, history of smoking, comorbidities, history of taking anemia medicine, history of taking hypertension medicine, history of taking diabetes medicine, and history of taking cholesterol medicine.
The stature of subjects was recorded to the nearest millimeter using a Seca plastic height board (model 213). Meanwhile, weights of subjects were measured using Camry model EB1003 scale to the nearest tenth of a kilogram. Subsequently, body mass index (BMI) was calculated as weight in kg divided by stature in meter square. The BMI was classi ed based on Western Paci c Region of World Health Organization criteria which are: (1) <18.5 kg/m 2 as underweight; (2) 18.5 to 22.9 kg/m 2 as normal weight; (3) 23.0 to 24.9 kg/m 2 as overweight; and (4) ≥25 kg/m 2 as obese. 28 Waist circumference was based on cut-offs of ≥80 cm for women and ≥90 cm for men.
The comorbidities were heart disease, diabetes, hypercholesterolemia, hypertension, kidney disease, and tuberculosis. Comorbidities were assessed using the question "Have a doctor/paramedic/nurse/midwife ever told you had…. (Comorbidities mention above)".
This study also investigated whether the participant had been taking drug therapies for anemia, hypertension, diabetes, and hypercholesterolemia. Participants were categorized into yes and no groups based on whether they take the medicine or not.

Statistical Analysis
All statistical analyses were performed using SPSS Statistical software version 21.0 (IBM Corp, Armonk, NY, USA) with statistical signi cance de ned as p < 0.05.
In this study, categorical variables reported as percentages were used for characteristics of our study population. Prevalence of anemia and weak handgrip strength were calculated as percentages. Sexspeci c and age-speci c anemia prevalence were also calculated. Differences in prevalence of anemia between participants aged ≥80 years old with those aged <80 years old were assessed using Chi-square (χ 2 ) test.
Correlation analysis was conducted using Pearson's correlation test for data with normal distribution. If the data has non-parametric distribution, Spearman correlation was used instead. Normality of data was assessed using Kolmogorov-Smirnov test and Shapiro-Wilk test.
Logistic regression was conducted for bivariable and multivariable analysis of risk factors associated with weak handgrip strength. Subsequently, Hosmer and Lemeshow test was used to determine goodness of t for the multivariable model. Multicollinearity test was also conducted with multicollinearity de ned as variable in ation factor (VIF) >5. The multivariable analysis in this study employed a backward elimination model-building process.
Subgroup analysis was then conducted to explore the association between anemia and weak handgrip strength based on gender and age (60-69 years, 70-79 years, and ≥ 80 years)

Result Eligible Participants
In total, 52587 unique individuals were obtained after combining from multiple datasets of IFLS5. Of these, 3742 participants aged ≥60 years old were selected. Subsequently, 86 individuals without hemoglobin measurement and 172 individuals with a history of pain, swelling, in ammation, injury, and surgery on one or both hands within the last 6 months were excluded. Another 174 individuals were excluded due to missing data in handgrip, waist circumference, and weight or stature measurements. Additionally, 111 individuals with stroke were excluded. Finally, 7 individuals that did not know whether they have comorbidities were excluded. Hence, a total of 3192 individuals were selected for analysis ( Figure 1).

Characteristics of the Study Participants
Characteristics of participants are summarized in Table 1.

Prevalence of Anemia
The prevalence of anemia can be seen in Table 2. Overall, 38.8% of participants aged ≥60 years had anemia based on the de nition of anemia by WHO. 27 When adjusted by age, the prevalence of anemia is lowest on age 60-64 (28.8%), but it slowly increases with age, resulting in participants aged ≥80 years old having the highest prevalence of anemia (56.3%). The differences in anemia prevalence between participants aged ≥80 years old and participants aged <80 years old were signi cant statistically (Table  1. Supplementary).

Prevalence of Weak Handgrip
The prevalence of weak handgrip can be seen on Table 3. Using handgrip criteria from Asian Working Group for Sarcopenia (AWGS), a total of 68.7% participants had weak handgrip. 19 The prevalence of weak handgrip also increased with age.  Figure 2, and Figure 3. test of the variables used for multivariable analysis showed no presence of multicollinearity. The multicollinearity test and complete regression parameters of the multivariable analysis can be seen on Table 3 Supplementary and Table 4 Supplementary.
We conducted subgroup analysis based on age (Table 6). Based on the analysis, the odds ratios for weak handgrip strength were highest in participants aged ≥ 80 years. Additionally, participants with male gender had higher odds ratios for weak handgrip strength

Prevalence of Anemia in Indonesian Elderly
Anemia is often perceived as a benign condition due to aging process. Recently, this paradigm is challenged by studies showing that even mild anemia is a risk factor for adverse clinical outcomes in the elderly. [7][8][9][10] This current study is the rst Indonesian study with large sample that assesses the prevalence of anemia in the elderly. We observed that 38.8% of participants aged ≥60 years had anemia based on the de nition of anemia by WHO (less than 12g/dL in women and less than 13 g/d in men). This is similar to the study by Hidayat et al. using 118 elderly participants living in nursing home. 29 According to a systematic review by Gaskell et al. which used 45 studies, the mean prevalence of anemia in older adults was 17% (3-50%). 5 Therefore, our results con rm that anemia is common in Indonesian elderly population and is within the range of the systematic review by Gaskell et al. 5 Furthermore, the anemia prevalence is similar to the prevalence of Malaysia, a neighbouring country that has similar ethnicities, with anemia prevalence of 35.3%. 30 Other studies on north-eastern Thailand, Philippines, and India showed anemia prevalence of 48%, 21.6%, and 68.7% respectively in the elderly. [31][32][33] However, Indonesia and all of these countries are in contrast with Singapore and Taiwan that had a lower anemia prevalence of 15.2% and 18.8% respectively. 34,35 The difference in prevalence between countries may be caused by heterogeneity in living conditions, elderly healthcare, health problems, and socioeconomic factors.
The age-associated increase of anemia in our study appears to be more pronounced in males than females. By the age of ≥65 years old, male have higher prevalence of anemia than females in our study.
This observation is similar with data from Third National Health and Nutrition Examination Survey (NHANES III) from USA. 36 Other studies also observe this phenomenon. 5,[37][38][39][40] The difference is that in the data by NHANES III, anemia became more common in males starting from age 75 while the anemia in our study started to become more common from age 65 years old.
We believe that the prevalence of anemia in Indonesian elderly may be indirectly caused by economic status and poverty since a signi cant number of Indonesians are living below poverty line. Poverty may impact the ability to access necessary animal-based food which contain iron to maintain hemoglobin. Data from NHANES III shown that around one third of anemic elderly had de ciencies in iron, folate, and cobalamin. 36,41 Additionally, a study speci c for Indonesian elderly in East Java found that anemia in elderly is related to lower consumption of folic acid and higher consumption of coffee and tea due to the role of tannins as iron absorption inhibitor. 42 Other possible causes of anemia in the elderly include chronic kidney disease (CKD), chronic in ammation, and myelodysplastic syndrome. 41 Unfortunately, the datasets we obtained for this study did not have kidney function, marker of in ammations, and bone marrow examinations which made analyses of these causes impossible. Furthermore, there are currently no published studies in Indonesia on elderly Indonesian population that analyze the role of CKD, chronic in ammation, and myelodysplastic syndrome in anemia.

Prevalence of Weak Handgrip in Indonesian Elderly
Using criteria from AWGS 2019 that was based from 8 Asian cohorts aged ≥65 years, we observed that a total of 68.7% participants in our study had weak handgrip. 19 45 However, it should be noted that these studies differ in weak handgrip strength de nitions, economic income, and racial population.
A recent study conducted in our institution using 164 elderly patients showed a weak handgrip prevalence of 67.1%. 46 However, despite a similar prevalence of weak handgrip with this study, it may not be comparable since the study used Jamar hydraulic dynamometer. 46 Here, we used Smedley spring type dynamometer for handgrip measurement which is the commonest used device in Asia for measuring handgrip strength. 47 The second commonest used device is Jamar hydraulic dynamometer. 47 According to AWGS 2019, the handgrip measurement from Jamar hydraulic dynamometer may be higher when compared with Smedley spring type dynamometer. 19 Thus, using different dynamometer may impact the prevalence of weak handgrip strength in a study, however, there is currently no available speci c cutoffs made for these dynamometers. 19 Factors Associated with Weak Handgrip Strength Anemia causes a reduction in oxygen carrying capacity of the blood to organs, including to muscle tissue. 12,17 This impairment of oxygen delivery can result in decreased aerobic capacity, decreased physical strength, sarcopenia, and further reduce the already declined physiologic reserve in the elderly. 12,13,17,48 Additionally, both muscle strength and muscle mass appeared to be lower in anemic elderly. 12,14,49 However, it is believed that there are still unknown pathophysiological processes of anemia in the elderly. Further studies to elucidate the complete mechanisms of how anemia affects the elderly should be conducted.
The correlation tests in this study showed a positive correlation between hemoglobin level and handgrip strength in Indonesian elderly population which is consistent with other studies. 12,15,16,45,50,51 Studies on elderly population of >90 years old also demonstrated association between anemia with handgrip strength. 52,53 Similarly, we also observed that the association of anemia with weak handgrip was more pronounced in the oldest old group and in male group. Other studies have also shown the role of anemia in other medical outcomes such as cognitive declines and mortality. 10,18,54,55 Thus, anemia is clinically important in elderly due to poor medical outcomes associated with it. Further supporting this is the data showing that even low hemoglobin level in normal range cause higher risk of frailty. 56 Based on this, it may be considered that the oldest old group should be screened for anemia and given prompt treatment. We observe that participants taking medicine had low odds ratios for weak handgrip, however, the 95% CI was very wide and further information of the type of anemia medicine and the dose were unavailable. Further studies to analyze how difference anemia medicine and dosages affect the elderly should be conducted.
Another important nding in this study is that the association of anemia with weak handgrip was more pronounced in the oldest old group and in male group. Nevertheless, despite these signi cant ndings, it is very di cult to directly declare that anemia is a causal risk factor for weak handgrip due to observational nature of this study and the possibility of anemia being a marker for other medical conditions. For examples, anemia is closely related to chronic in ammation which is observed in sarcopenia, hence, may indicate a bidirectional relationship between anemia and sarcopenia. [57][58][59] Our study also found that hypertension, BMI, and age were risk factors for weak handgrip strength.

Study Limitations
Despite bridging the scienti c gap of anemia and handgrip strength in the Indonesian elderly, the current study has several limitations. First, this study is a cross-sectional study which is unable to elucidate causal relationship between the variables and weak handgrip. Secondly, this study did not analyze the impact of dietary factors among the subjects on anemia. The type of anemia also could not be identi ed because of the insu cient laboratory and lack of nutritional status data. Finally, while the handgrip criteria from AWGS 2019 used normative handgrip data from Asian countries, we believe that using normative handgrip data speci c for the Indonesian elderly population which is currently unavailable should be more appropriate.
Recommendations for Indonesia 1. We recommend future studies that analyse dietary intake of Indonesian elderly population to be conducted 2. We recommend studies that assess the prevalence of anemia in elderly based on etiologies to be conducted 3. We recommend a study to develop normative handgrip data for Indonesian population to be conducted 4. We recommend both short-term and long-term policies to be made by the Indonesian government to support health of elderly population

Conclusion
The prevalence of anemia in the Indonesian elderly population was 38.8%. Prevalence of anemia was affected by age and sex. Furthermore, anemia was signi cantly associated with weak handgrip strength in Indonesian elderly population. This association was stronger for males and elderly aged ≥80 years old.