The Association between heart diseases, social factors, and physical frailty in community-dwelling older populations: SONIC study

Objectives Physical frailty is geriatric syndrome and can increase the risk of adverse outcome in the older population. Heart diseases are associated with physical frailty but a few studies in community-dwelling old population. Therefore the aim of this study was to examine the association between heart diseases, social factors, and physical frailty in community-dwelling older populations including the oldest old people. Methods The cross-sectional study included 1882 participants in community-dwelling older and oldest-old people in three age groups: 73 (±1), 83 (±1), and 93(±1) from both urban and rural areas of Japan. Questionnaires on medical history, psycho-social factors, blood samples, physical examinations, the hand grip strength test, and gait speed were measured at the venue. Physical frailty was dened based on a slow gait speed or weak grip strength. Heart diseases were assessed by self-reported questionnaires. Social interaction was based on the frequency of going outdoors and direct social contact. Analyses were conducted mainly using multiple logistic regression with adjustments for physical frailty risk factors. Results Heart disease subjects had a higher prevalence of physical frailty than those without heart disease (slow gait speed: 69.6 vs. 56.2%, p<.001; slow gait speed or weak grip strength: 80 vs. 69.6%, p=.002). After adjusting the covariate factors, heart diseases were associated with a slow gait speed (OR=1.5; 95%CI: 1.03-2.20, p=.035). Social interaction was associated with a slow gait speed (frequency of going outdoors: OR=0.87, 95%CI 0.79-0.9, p=.008; frequency of direct social contact: OR=0.88, 95%CI 0.82-0.95, p=.001), a weak grip strength (frequency of going outdoors: OR=0.86, 95%CI 0.77-0.96, p=.005), and with physical frailty (frequency of going outdoors: OR=0.84, 95%CI 0.75-0.94, p=.002; frequency of direct social contact: OR=0.89, 95%CI 0.82-0.97,


Background
Physical frailty is a geriatric syndrome that results from a multi-system reduction in reserve capacity and leads to a negative outcome in older populations [1][2][3]. Older people with physical frailty need more institutional care and show increased vulnerability, a higher risk of falls, repeated hospitalization, and premature mortality [4,5]. Physical frailty in older people requires high expenditure and skilled nursing facilities [6,7]. Heart diseases have a very high prevalence and are leading causes of death in older populations word wide [8]. Recently, medical technology had been advancing. This might reduce premature death from heart disease if patients get appropriate treatment and they can return to the community. Frailty is more common in the old population, which is about 3 times more prevalent among persons with heart disease compared to older people in the community. The prevalence of frailty in older with heart diseases was presented up to 10-60 percent [9]. A few studies examined the associations among physical frailty and heart diseases in the community-dwelling old population, mainly with a focus on speci c types of heart diseases and frailty, especially heart failure [10], myocardial infarction [11], and atrial brillation [12] or cardiovascular diseases (including stroke). However, many patients do not have a single type of heart disease. For example, they may have symptoms of many speci c types of heart diseases that occur in about the same period, such as arrhythmia, chest pain from myocardial ischemia, and angina pectoris, or the condition may worsen and develop into heart failure. Therefore, studying multiple or combined heart diseases and frailty in older population would be an important issue.
Social factors are elements of society that can in uence to older population's health such as education, economic status, social interaction and so on. To date, several studies have shown a strong correlation between social factors, and health, and well-being among older people and have suggested that social isolation may have signi cant adverse effects on older populations [13,14] but few studies have focused on social factors and physical frailty in older populations and older people with heart disease.
The purpose of this study was to examine the association between heart diseases, social factors, and physical frailty in community-dwelling old populations.

Study populations
This was a cross-sectional study, we analyzed data from the SONIC study, a longitudinal cohort study in Japan. The SONIC term stands for the Septuagenarians, Octogenarians, Nonagenarians, and Investigation with Centenarians. The study began in 2010 in the older population aged 69-71-year-old group, with tracking data every 3 years in 4 cities from the west and east areas of Japan cover in the urban and rural [15]. This study recruited 1,882 randomly selected from the participants that enrolled in 2013, 2014, and 2015 in community-dwelling 899 individuals aged 72-74 years (419 males, 480 females), 854 individuals aged 82-84 years (430 males, 424 females), 129 individuals aged 92-94 years (52 males, 77 females), respectively. Severe paralysis Stroke and Parkinson patients were not included in this study [11].
De nition of frailty Physical frailty was measured using slowness and weakness. Weakness was assessed using the hand grip strength measured two times of the dominant hand and the mean grip strength was used for analysis. A weak grip strength was de ned as <26 kg in males and <18 kg in females [16]. Slowness was assessed base on two measurements of gait speed over a 2.44-meter course, and the mean gait speed was used for analysis. A slow gait speed was de ned as<1.0 m/s [17]. Participants were classi ed as physical frailty if they had a slow gait speed or weak grip strength.

Measurement
Heart diseases were de ned based on a positive self-reported history according to diagnosis by a doctor and patients were asked about the speci c type of heart disease. In the event of those have more than 1 speci c type of heart disease, the type was classi ed based on dominant type or a type of heart disease that was found a signi cant correlation with frailty in the previous study [10,11,[18][19][20][21][22]. The heart disease group in this study included those with angina pectoris, myocardial infarction, atrial brillation, heart failure, and other types or unknown types, and participants who had only a history of arrhythmia symptoms were excluded from the heart disease group.
Social factors in this study were cover for economic status, education level, living status, and social interaction which based on 2 factors: frequency of going outdoors and frequency of direct social contact. Frequency of going outdoors was assessed by the question, "how often do you usually go outdoors?" (e.g. going shopping, walking, going to the hospital or participating in social activities), assigned as (0) for less than once a week, (1) once or twice a week, (2) three or four times a week, (3) ve or six times a day, and (4) every day. Frequency of direct social contact was assessed by asking about the frequency of direct interaction with relatives, neighbors, or friends. The answer was then assigned as (0) not at all, (1) less than once a month, (2) about once a month, (3) two or three times a month, (4) once a week, and (5) more than twice a week. Regarding their economic status, the participants were asked about their level of satisfaction with household income and this was rated on a ve-point scale ranging from "not satis ed" (score 1) to "extremely satis ed" (score 5).
Other measurements. Information on demographic data, medications, and medical history was recorded. Physical examination and blood samples were tested by a physician or registered nurses.
Serum albumin, Hemoglobin A1c (National Glycohemiglobin Standardization Program (NGSP)), blood glucose, low-density lipoprotein cholesterol (LDL), High-Density Lipoprotein cholesterol (HDL), and triglycerides were determined by biochemical examinations. Hypertension was de ned by systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg or being on antihypertensive treatment according to the Japanese Society of Hypertension guideline 2019 (JSH2019) [23]; diabetes mellitus (DM) was de ned by fasting blood glucose ≥ 126 mg/dL or random blood glucose testing ≥ 200 mg/dL, HbA1c (NGSP) ≥ 6.5%, or taking medication for diabetes according to the Japanese Clinical Practice Guideline for Diabetes 2016 [24]. Dyslipidemia was de ned based on low-density lipoprotein cholesterol ≥ 140 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL, triglycerides ≥150 mg/dL, or taking medication for dyslipidemia according to the Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2017 [25]. Smoking experience was assessed based on a questionnaire and classi ed into three categories: never, current, and ex-smoker experience. Alcohol consumption behavior was classi ed into three categories: do not drink or drink only occasionally (less than one day a week), habitually drinking but not excessive (1 -3 days a week or, 3 units of Japanese sake, 3 bottles of beer, less than 180 mL of whiskey), and habitually excessive drinking (more than 3 days a week, and the average daily amount is three go of sake, three or more bottles of beer, or more with whiskey of 180 mL). The cognitive function was assessed based on the Japanese version of

Statistical analyses
Clinical and demographic data are summarized using the mean ± SD for continuous variables and percentages for categorical variables. The Kolmogorov-Smirnov test was used to assess the normality of continuous variables. The chi-square test was used for categorical variables, and t-test was used for continuous variables. We used multiple logistic regression to examine the association between heart diseases, social factors, and physical frailty. Covariates were selected according to the scienti c literature [27][28][29][30]. Associations were considered signi cant at a 2-tailed p-value <.05. All data were analyzed using SPSS version 24. Table 1 presents the characteristics of total participants (N=1,882). Most were female (52.1%), 224 had heart disease, and 1,658 were without heart disease. The highest prevalence of heart disease was in the 82-84-year-old group (44.2%), followed by the 72-74year-old group (40.6%). There were specific types of heart disease including angina pectoris (4.0%), atrial fibrillation (2.5%), myocardial infarction (1.8%), and heart failure (0.7%) (Fig. 1).

Participant Characteristics
Individuals with heart disease were more likely to be male (p=.035), have diabetes (p=.005), hypertension (p<.001), a history of stroke (p=.021), and lower albumin (p=.011), and there was a significant correlation between heart disease and the frequency of going outdoors every day (p=.013). Participants live alone most were heart disease group (22.9%), most education levels of subjects were high school level (44.7%), living in urban areas (61.6%), satisfaction with household income were neutral (57.6%). There were higher rates of those with a slow gait speed (p<.001) and physical frailty (p=.002) in the heart disease group (Fig. 2).
Association between heart diseases, social factors, and physical frailty In the total participants, heart diseases were positively associated with slow gait speed     correlations between any types of physical frailty and the frequency of going outdoors, education level, satisfaction with household economic status, and residential area in community-dwelling old peoples with heart diseases ( Table 3).

Discussion
This study revealed that the prevalence of physical frailty among subjects with heart disease was higher than those without heart disease, consistent with a previous study [9]; the physical frailty of older people with heart disease has a high prevalence (10-60%) and varies according to the instrument used for assessment. In our study, slow gait speed showed a high prevalence in the heart disease group but a signi cant difference was not found in grip strength. This may suggest that gait speed can be a surrogate marker of physical frailty to detect heart diseases in community-dwelling older populations in order to provide intervention to delay a negative outcome of physical frailty.
Heart diseases and social interaction are associated with physical frailty based on slow gait speed independently of age, sex, and, other risk factors of physical frailty in older populations. Heart disease subjects had a 1.5-times risk of slow gait speed than those without heart disease but this was not associated with the grip strength. Social interaction was independently associated with physical frailty based on the frequency of going outdoors and was negatively associated with all types of physical frailty, and the frequency of direct social contact was negatively associated with gait speed and physical frailty but not associated with grip strength. In heart disease subjects, the results indicate that living alone and direct social contact were independently associated with physical frailty. This nding indicates that heart diseases and social interaction such as going outdoors and direct social contact in uence physical frailty in general community-dwelling older populations. For heart disease subjects, living alone and frequent direct social contact were associated with physical frailty, particularly slow gait speed. This result is in line with previous studies on the role of cardiovascular disease associated with physical frailty-related criteria, such as gait speed, grip strength, and fatigue [11,12,31,32]. Furthermore, this study has a novel that the associations between heart diseases and physical frailty that we found were interesting because this study also included the oldest old population while previous studies, a few studies speci cally enrolling the oldest age people in community-dwelling. To the best of our knowledge, this is the rst time found that in older people with heart diseases, some social factors: living alone and frequency of direct social contact signi cantly associated with physical frailty, especially slow gait speed.
The present ndings of social interaction (frequency of going outdoors and frequency of direct social contact) being associated with physical frailty in older populations also support ndings of a crosssectional study involving 1,200 Koreans aged 70-85 whereby the frequency of social contact was strongly associated with frailty [33]. However, this study generated the new nding that the frequency of direct social contact is associated with physical frailty in older people with heart disease.
The potential mechanisms that could explain the association between heart diseases and slow gait speed can be divided into three different pathways. Firstly, heart diseases represent a chronic illness and have an impact on functional decline; as a by-product of the extra energy generated by mitochondria, they produce excessive amounts of free radicals. This is the oxidative stress pathway and it leads to in ammation due to the elevated level of in ammatory cytokines causing many cellular and tissue changes, including the mobilization of amino acids from muscle tissue to other organ systems resulting in muscle loss and sarcopenia, which has also been associated with physical frailty [34,35]. Secondly, heart diseases are associated with slow gait speed occurrence due to atherosclerosis, as a state of chronic in ammation that is the major cause of heart diseases. Atherosclerosis refers to the accumulation of fatty and brous in the arterial wall, the cause of reduced blood ow at myocardial, which is an impact on end-organ reserve, and reduced physiological function, these reasons are leading cause of slow gait speed [31]. Because walking requires multiple organ functions such as heart, lung, brain function, and musculoskeletal muscles work together and require energy more than grip strength. Finally, the mechanism could explain by those with heart disease who had a low physical activity may be the result of symptoms of heart diseases such as fatigue, chest pain, dyspnea, loss of diet appetite, and so on, are leading cause loss of muscle mass and strength called sarcopenia. Sarcopenia is a major component of physical frailty [36]. On the other hand, physical frailty also could be a cause of physical inactivity, which is an important risk factor of heart diseases, a recent longitudinal study with 3,896 older adults in 60-year-old during a median 14 year of follow-up, revealed that frail participants were less physically active than a robust group and adequate physical activity was associated with lower risk of allcause and CVD mortality in this population [32]. Another study found that sarcopenia was signi cantly correlated with left ventricular (LV) mass in a community-dwelling older population. Older people with sarcopenia had a lower ventricular mass and lower left atrium (LA) volume than those who without sarcopenia [37] being consistent with the Cardiovascular Health Study indicating that LV mass was associated with coronary heart disease in older participants [38].
These and our results suggest that heart diseases have linked to physical frailty by physical activity and sarcopenia. In part of social interaction, frequency of going outdoors and frequency to contact social directly were associated with physical frailty, could explain the association by those who had more often going outdoors and more often contact social directly can get bene t from increase a physical activity causal to improve muscle strength could prevent physical frailty [39]. Moreover, a recent study suggested that a lower frequency of going outdoors could be a cause of physical and mental frailty [40].
In older patients with heart diseases, social factors such as living alone associated with physical frailty could explain the association by a psychophysiology mechanism with those living alone being more likely to have lower physical activity levels than those living with others [41]. Physical inactivity is a cause of losing muscle mass and strength. Recent studies in the Japanese older population have revealed that older who live alone more likely poor social support and had a decline in dietary variety included di culty to provide a healthy diet [42] and they had poor appetite more than those who not living alone [43]. Our study found that older people with heart disease had a signi cantly lower albumin level than those without heart disease ( Table 1). These reasons may be the cause of muscle strength weakness due to malnutrition. This is the rst study to nd that living alone is signi cantly correlated with physical frailty in older patients with heart disease, but this result is in line with frailty and living alone in older populations which indicated that men living alone have a high risk of frailty [44]. The association between frequency of direct social contact and physical frailty could explain the association by those had more frequency of direct social contact have a more physical activity that will improve muscle strength.
This result supports a previous study reporting that social frailty (including social role, social network, and social activity) is an important factor that is a leading cause of physical frailty, especially in those with a slow walking speed in the cohort study [45].
According to the results of the present and previous studies in older populations, heart diseases and social interaction were associations with physical frailty. Older people with heart disease, living alone and direct social contact were signi cant associations with physical frailty.
The study has important strengths. The study was based on older populations in the community including the oldest populations and used gait speed and grip strength as surrogate markers of physical frailty, which are simple tools and powerful predictors of a negative outcome in community-dwelling older populations. In addition, the covariates that are studied were common variables covering physical factors, biological factors, lifestyle-related factors, and socio-demographic factors.
This study has limitations, this is a cross-sectional study that is di cult to determine the causal direction and there are some variables that were not measured as confounding factors such as physical activity level or psychological factors that cannot be overlooked. Our study data were collected from communitydwelling older populations that have assessed the participants that visited at the community center, therefore the subjects with a moderate or severe symptom of physical frailty may not participate that could make the prevalence of physical frailty was underestimated. There was a small sample size of heart disease group that made we could not examine the association between a speci c type of heart disease and physical frailty. The data of heart disease experience were obtained from self-report that could not be avoiding recall bias. The lack of data on cardiac examination such as echocardiography, ECGs, or other tests means that we could not con rm the diagnosis or explain the heart function.

Conclusions
Heart disease and social interaction were associated with physical frailty in community-dwelling older populations. Living alone and social contact were directly associated with physical frailty, especially slow gait speed in heart disease subjects. A further longitudinal study is required to clarify the causal relationship between heart diseases, social factors, and physical frailty to examine whether social factors can protect against physical frailty in community-dwelling older populations and heart disease patients.  Table 1 This  Figure 1 The prevalence of speci c types of heart disease in this study.