Effects of metabolic syndrome on the correlation between the most common groups of prescribed medications and the risk of fall in Brazilian elderly people

Aging is an irreversible process of all living beings and one of the great challenges we have to face is learning how to live healthier. Several health conditions, such as cardiovascular disease, diabetes, stroke, depression, hypertension, metabolic disorders, and falls, are related to senescence and can directly affect quality of life around the world. In addition to these physiological disorders, the use of medications can directly affect the quality of life of the elderly, and some studies have already reported the correlation between metabolic syndrome, prescription medications, and injury caused by falling. This study was conducted with a group of 102 adults over 60 years of age, including volunteers in the city of Viçosa - Minas Gerais, Brazil. The instruments of analysis were performed using three types of tests: The Timed Up and Go (TUG) test, the Functional Reach Test, and the Tandem Test. Two questionnaires were used - the Falls Ecacy Scale-International (FES-I) and quality of life questionnaire (the Short Form [SF]-36) - in order to establish a connection between the intake of prescription of medication and the quality of life of this population. The statistical analysis was performed using R software version 3.2.2.


Results
The analysis of factors indicated that risk of fall was directly related to the amount of medications used by patients. The medicines associated with the risk of falls were grouped into nine categories: 28%, antihypertensive; 17%, anti-cholesterolemic; 8%, cardiovascular agents; 2%, musculoskeletal pain; 2%, hormones; 14%, central nervous system agents;6%, vitamins, 8%,anti-diabetic; and 15%, other target action medication. When the risk of fall was compared according to each category, the most signi cant difference in proportion was observed when related to central nervous system.

Conclusion
The data analysis showed that type of medications prescribed should be considered to better understand how some are related to the risk of fall in elderly people. The knowledge of how some prescribed medications can affect the way of life in the elderly community helps to guide some clinicians' orientations to prevent possible injuries.

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Aging is an irreversible process of all living beings. 1,2 One of the great challenges we face is to learn how to live in a healthy way with a high quality of life. 3,4 Bad habits acquired in youth such as sedentarism and poor diet increase susceptibility to chronic diseases in adulthood. [5][6][7] Among the chronic diseases that affect the aging process are Alzheimer's disease, depression, diabetes, systemic arterial hypertension, and heart disease. 8 In the people of this age group, several ill-de ned factors predispose them to unintentional falls that subsequently lead to impaired activities of daily living and an increase in mortality. 5,8,9 Recent studies have demonstrated the possibility of the relationship between metabolic syndrome (MetS) and the risk of falling in the elderly population. [8][9][10][11][12][13] The World Health Organization (WHO) created the rst criterion for MetS, 13,14,19,43 and shortly thereafter, the de nition of MetS was improved by the European Resistance Insulin Study Group (EGIR), followed by the National Cholesterol Education Program -Adult Treatment Panel III (NCEP -ATPIII) [15][16] and nally by the International Diabetes Federation (IDF). The latter organization has created a more accessible tool for research needs and improved clinical use. 15,20 According to the IDF and other organizations, the central components of MetS are central obesity, increased triglyceride levels, low HDL cholesterol, increased blood pressure, and elevated fasting plasma glucose. 13,16−20 Due to the central components of MetS, it is believed that the individual will become more dependent on certain medications. 21,22 Additionally, the side effects generated by medications and the common alterations in aging increase the risk of the elderly suffering injury due to falls. 10,21−26 The objective of this study was to perform an analysis of the medications used by the Brazilian elderly population. We also sought to investigate the relationship between MetS and the groups of medications prescribed, their interactions and concentrations, and this population's risk of suffering some type of fall.

Methods
The study was implemented with 102 participants, aged 60 years or older. These participants included a group of volunteers who resided in the municipality of Viçosa-Minas Gerais, Brazil.
Clinical Data: Volunteers who participated in the study required a recent laboratory examination or they had completed one within the last six months. The examination included the measurement of cholesterol (HDL), glucose, and triglyceride levels.
Abdominal circumference: For all participants, abdominal circumference was measured (this measurement was performed by positioning a tape measurer along a horizontal plane between the lower rib margin and the upper border of the iliac crest).
MetS: Based on the criteria of the NCEP-ATP III group, MetS was de ned by the presence of hypertension and two or more of the following criteria: 10 used as a test for functional mobility and fall risk analysis. 27 The TUG test is a simple test that measures the likelihood that an elderly person will fall. 28 A standard chair is used, and the participant is invited to stand up, walk a line 3 meters away, and return to the seat. The timer was triggered from the point at which the patient's buttocks moved from the seat and made contact with the back of chair. The volunteers for whom it took ≥13 seconds to perform the test were identi ed as having a higher risk of falling. 27,28 The chronometer used was a mobile device model X1069 G(Motorola).
2.Gait analysis: Participants performed the Tandem test, which consists of walking in a straight line drawn on the oor and placing the non-dominant foot heel in front of the toes of the dominant foot at each step. 29 The scoring for the test was determined according to the following characteristics: The participant who completed 10 steps in the straight line was deemed as having good performance and normal balance. If the participant completed 7-9 steps, he/she was considered to have an average balance de cit, but no risk of falling was assessed. If the participant completed 4-7 steps, they demonstrated a moderate de cit in balance, which lead to some concern about the risk of falling. Finally, the participants who achieved completion of less than 4 steps were considered as having a high level of balance de cit and thus were considered to be at high risk of falling. 29,30 3.Functional Reach Test: In the Functional Reach Test, participants standing in the orthostatic position next to a wall marked with a straight tape measure were instructed to perform a trunk exion movement. During this movement, the extended arm demarcated the limit of its antero-posterior movement, without involving the movement of the legs, which must maintain their alignment from the beginning to the end of the movement. Values ≥ 15 test score indicated that there was a de cit in balance that can lead to a greater risk of falling. 30,31 Mean arterial pressure (MAP): The MAP is a term to describe an average blood pressure in an individual. It is de ned as the average arterial pressure during a single cardiac cycle. The equation for the MAP is as follows: MAP = 1/3 systolic blood pressure (SBP) + 2/3 diastolic blood pressure (DBP). 32 Falls history: The volunteers participating in the study were questioned about the occurrence of falls within a one-year period.
Falls E cacy Scale-International (FES-I): This is a questionnaire that assesses the individual's concern about suffering falls when performing their daily activities. The FES-I is a questionnaire modi ed by Chris Todd and Lucy Yardley through the Falls E cacy Scale (FES), which was developed by Tinetti. It consists of 16 questions focused on activities of daily living and social life, with answers to each item having a score from 1 to 4 (1 = not worried, 2 = worried, 3 = very worried, and 4 = extremely worried). The scoring system ranges from 16 to 64 points. A score of 16-19 points indicates the participant has little concern about falling. Values of 20-27characterize a moderate preoccupation with concern about falling, while values ranging from 28-64 points indicate the participant maintains great concern about suffering a fall. 33,34 Quality of Life Questionnaire (the Short Form [SF]-36): This is a questionnaire that measures health status. It calculates the cost-bene t ratio of a health treatment. It consists of eight scales, which are the weighted sums of questions in each section. The lower the score, the greater the degree of disability, and the higher the score, the lesser the degree of disability. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability, which is associated with a perceived excellent quality of life. 26,35 Results MetS-correlated variables such as MAP (P = 0.004185), HDL (P = 0.000726), and Triglycerides (P = 0.002466) are shown to be the most signi cant factors associated with an increased risk of falls in elderly people, according to the logistic regression results (TableS1). Another signi cant factor which also can be emphasized among MetS factors is the number of medications prescribed to correct MetS (P = 0.005742). When the principal components approach was performed to retrieve the correlation among all the studied factors, the number of medications prescribed, and the risk of falls behaved as strong components, especially in patients with a history of fall (Fig. 1). When the classes of medications were considered, the proportions among the falls risk ( Fig. 2A) and the non-falls risk group (Fig. 2B)  where we use the following scores (vitality, mental health and physical functioning). The performance of the logistic regression in the two groups, one with MetS and the other with risk of fall, showed distinct pro les. The MetS group had vitality (P = 0.000535) and mental health (P = 0.028382) as the most signi cant scores. The number of medications (P = 0.000102) was the only signi cant factor in the fall risk group.

Discussion
Our study showed that the medications used for the correction of hypertriglyceridemia and insulin resistance is another important factor to explain the occurrence of falls in the population aged greater than 60 years. In previous studies 10, 16 Seeking to better understand how MetS generates a higher occurrence of falls in the elderly 39 , we further analyzed the drug interaction and the risk of falls (assessing the individual in an orthostatic position while touching the ground with his or her hand or knee). Analysis of the medications was performed by observing the class, the side effects, the proportion ingested, and the time of consumption (TableS2).One study demonstrated that the use of psychotropic medications increases wounds and fractures of the femur. 22 Other studies reported that the use of phenothiazine, tricyclic antidepressants, barbiturates, and benzodiazepines has a high association with a risk of falls, and may lead to fractures. [21][22][23] However, in this study, there was no clear association between diuretics and antihypertensive agents and an increased risk of falls. The result of logistic regression analysis in another study showed that a fall could be a consequence of patients who have a fever, due to associated hypotension and malaise that may be present. 10 In a different study, 37 the researchers found that there is no increased risk of falls in users of antihypertensive medications compared to non-users of the medications (adjusted odds ratio = A = 1.13; con dence interval [CI] 95% = 0.88-1.46). Our data demonstrated that the highest fall rate is related to the use of central nervous system medicines and another target action, resulting in14% and 15% respectively. The relationship was also 40 who found between the use of statins and the side effect of myalgia, in addition to causing other serious pathologies in skeletal muscle. Various physiological mechanisms appear to contribute to the loss of muscular strength of the lower extremities in the elderly. 41 Results also demonstrate that balance training can be a useful strategy in balance rehabilitation and fall prevention, especially in the population studied. This can lead to an improvement in their quality of life and less public health costs. 42 A deeper study is still required to understand how some classes of medications affect the way of living in elderly people.

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Our study showed that the types of medications can actually impact the rate of falls in elderly people.
Certainly, a deeper analysis is required to understand the physiological mechanism behind this relation. Then clinicians would be able to guide those old people and their carriers to prevent falls, and thus causing less public spending on the public health care system. Consequently, a better quality of life in this population may be achieved.  Tables   Due to technical limitations, Tables 1 and 2  Figures Figure 1 The biplot shows the correlations among the metabolic syndrome (MetS) factors, the number of medications, and risk of falls (red arrows). The plot numbers represent individuals and the red arrows show tendency according to the variance components.