1. Introduction

Handgrip strength (HGS) is a relevant indicator of patients’ nutritional status. Numerous clinical and epidemiological studies have demonstrated the predictive value of HGS for short- and long-term mortality and morbidity, as well as for disease severity and outcome ^[1]. HGS has also been related to length of hospitalization and re-hospitalization rates. A study of 120 elderly patients (≥75 years old) suggested that HGS was inversely proportional to duration of hospital stay ^[2]. Furthermore, a 1-kg increase in HGS was associated with a 3% increase in likelihood of discharge to one’s normal residence. Conversely, lower HGS at hospital admission was associated with a longer hospital stay and decreased probability of surviving to discharge ^[3].

In addition to gender, age, and nutrition, HGS was found to be closely related to inflammatory activity in inpatients ^[4]. Inflammation has been suggested to affect skeletal muscle metabolism and reduce HGS ^{[5, 6, 7]}. In this study, we investigated whether levels of the inflammatory marker C reactive protein (CRP) ^[8], as determined by a high-sensitivity C reactive protein (hs-CRP) test, are associated with HGS among inpatients.

2. Materials and Methods

A total of 530 inpatients (299 males and 231 females) that were treated at the medical wards in Beijing Friendship Hospital from June 1^st to December 31^st, 2012 were enrolled consecutively. Patient ages ranged from 18 years to 87 years; the mean age was 56.4 ± 15.2 years. Patients were recruited from the following departments: respiratory medicine (19.6%, n = 104), cardiology (14.5%, n = 77), neurology (15.7%, n = 83), hematology (4.5%, n = 24), nephrology (4.9%, n = 26), gastroenterology (5.1%, n = 27), hepatic medicine (19.6%, n = 104), endocrinology (4.7%, n = 25), other departments (11.3%, n = 60). The experimental protocol was established in accordance with the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Beijing Friendship Hospital. Written informed consent was obtained from each participant.

Patients were required to meet the following inclusion criteria: 1) 18–90 years of age, 2) able to stand and perform vertical HGS measurements independently, 3) presented with a non-critical illness (critical illnesses require immediate or intensive treatments). Patients were excluded from the study if they were pregnant, had hemiplegia, neuromuscular diseases, coma, osteoarthropathy, moderate-to-severe neurological cognitive impairment or retinal detachment.

HGS was measured by a mechanical handgrip dynamometer (Xiangshan dynamometer EH101, Zhongshan, Guangdong, China) within 24 hours after admission. After explaining the procedure to each patient, HGS measurements were performed and recorded. Patients were standing upright. They held the dynamometer with their palms inward and the dynamometer display outward. The dynamometer did not touch patients’ trunk or clothing during measurements. Patients were encouraged to perform a maximal isometric contraction. The maximum HGS value with the dominant hand was recorded ^[9].

Age, body mass index (BMI), nutrition intake, amount of recent weight loss, changes in diet, and diagnosis were determined within 24 hours after admission by patient surveys. BMI was calculated from height and weight data obtained from anthropometric measurements. Nutrition risk was scored according to the Nutritional Risk Screening 2002 guidelines (NRS 2002). Patients with final scores ≥3 were considered to be at nutritional risk ^[10].

Patients were weighed to the nearest 0.1 kg using an electronic scale (Suhong RGZ-120, Jiangsu, China) while wearing light clothing. Height was measured with a stadiometer (Suhong RGZ-120, Jiangsu, China) to the nearest 0.1 cm. BMI was expressed as the ratio of weight (in kg) over the square of height (in m). A BMI < 18.5 kg/m² was considered to be underweight ^[11].

Concentrations of hs-CRP were determined within 24 hours after admission by an automated biochemical analyzer (Hitachi 7600, Japan). The normal range for hs-CRP results was considered to be 0–3 mg/L.

The study was designed and conducted by doctors and dietitians at the Beijing Friendship Hospital to ensure that the investigation was feasible and results would be valid. Training and pilot experiments were performed prior to data acquisition.

Linear regression was used to assess the relationships between variables. T-tests, Mann-Whitney U tests, and Kruskal-Wallis H tests were used to test for significant differences. All statistical analyses were performed with the Statistical Package for Social Sciences for Windows (SPSS, version 16.0; SPSS, Inc., an IBM Company, Chicago, IL). Results were considered significant when p values were <0.05.

3. Results

The baseline characteristics of the study are summarized in Table 1. The total number of patients was 530 (299 men, 56.4%; 231 women, 43.6%). The mean hs-CRP level was 6.8 ± 18.2mg/L, and hs-CRP levels ranged from 0 to 160 mg/L. Most patients (358; 67.5%) had normal hs-CRP values (0–3 mg/L), which represents normal amounts of inflammation. A total of 172 patients (32.5%) had values above 3 mg/L that indicated high levels of inflammation.

Table 1. Characteristics of the study sample

Download as

PowerPoint Slide

Larger image(png format)

• Tables index

Veiw figure

View current table in a new window

View next table

The mean HGS was 29.2 ± 10.1 kgF and ranged from 6.5 kgF to 60.4 kgF. Values of HGS, hs-CRP, and nutrition risk score were significantly different between male and female patients (p < 0.05). Female patients had lower HGS, lower nutrition risk screening scores, and higher hs-CRP values than male patients (Table 1). Values of HGS values differed relative to age strata (18–45, 45–60, 60+) in both male (χ²=45.258, p < 0.001) and female (χ²=22.339, p < 0.001) patients. Both male and female patients in the 45–60-year-old age band showed the highest HGS, while those in the ≥60-year-old age band had the lowest HGS (Table 2).

Table 2. HGS of study sample according to sex and age strata

Download as

PowerPoint Slide

Larger image(png format)

• Tables index

Veiw figure

View current table in a new window

View previous table

View next table

The HGS of patients with no or mild inflammation (hs-CRP 0–3 mg/L) differed significantly from the HGS of patients with clinically concerning inflammation (hs-CRP > 3 mg/L) (31.9 ± 0.5 vs. 23.4 ± 0.8 kgF, U = 14610, W = 29488, p < 0.001). HGS was inversely related to inflammation levels. Bivariate correlational analysis showed a strong association between hs-CRP level and HGS (r = -0.552, p < 0.001). Furthermore, linear regression analysis also revealed a significant linear relationship between hs-CRP level and HGS (β-coefficient = -0.2, p < 0.001). As shown in Table 3, we observed an independent inverse association between hs-CRP level and HGS (p < 0.05). The following variables also emerged as risk factors or potential confounders: age, sex, and nutrition risk screening score (p < 0.05).

Table 3. Analysis of factors influencing HGS

Download as

PowerPoint Slide

Larger image(png format)

• Tables index

Veiw figure

View current table in a new window

View previous table

4. Discussion

The linear regression results presented here show significant impacts of age, sex, nutritional status, and inflammation on HGS, consistent with previous studies ^{[12, 13, 14, 15, 16]}. Several studies have shown that people experience a gradual loss of muscle mass and strength after the age of 40 at a rate of 1.5–3.5% per year ^[9]. Undernourished patients (identified by NRS-2002) also had lower than typical HGS ^[14]. Results from animal experiments have suggested that inflammation induces muscle weakness ^{[15, 16]}.

There are two possible clinical mechanisms responsible for the association between inflammation and HGS. First, inflammation increases production of cytokines, such as CRP, interleukin-6,and tumor necrosis factor-α, which can lower HGS by reducing muscle protein synthesis, increasing skeletal muscle breakdown, altering the resting membrane potential of skeletal muscle, and decreasing contractility ^{[15, 16]}. Second, inflammation and diseases may affect appetite, which can reduce the intake of protein and affect the conversion of ATP to creatine phosphate, thereby reducing the available energy supply (see Figure 1). Results from other studies ^{[17, 18]} have also suggested that malnutrition was prevalent among inpatients. In addition to disease, over- or undernutrition can also cause inflammation. Moreover, HGS, which reflects nutritional status, has been found to correlate with length of hospital stay, mortality and re-hospitalization rates, and outcomes ^[1]. Hence, making reasonable nutritional support a clinical priority may help reduce inflammatory activity and, ultimately, affect muscle metabolism, enhance muscle strength, and improve quality of life of patients, especially those who are at nutritional risk.

Download as

• PPT
  PowerPoint Slide
• PNG
  Larger image(png format)

Veiw figureFigures index

•  NEW
  View larger figure in new window

Figure 1. Hypothesis of the pathogenesis of impaired muscle function during inflammation

The association between inflammation and muscle strength has been well-studied in patients with critical illnesses for whom inflammation decreases muscle strength. However, this relationship in the non-critically ill has not been thoroughly investigated. This study showed a significant association between HGS and hs-CRP test results in patients with non-critical illnesses after excluding the effects of confounders (i.e. age, sex, BMI, and nutrition risk screening scores).

We did not analyze the quantitative impact of each hs-CRP level (0–3 mg/L and > 3 mg/L) on HGS. Also, several factors that may affect HGS were not addressed in this study, such as fat-free mass, manual labor intensity, and disease. In the future, more detailed studies should be conducted to examine the relationship between inflammation and HGS.

In conclusion, we observed a significant association between inflammation and HGS in hospitalized patients with non-critical illnesses. Relieving inflammation may help to improve HGS and recovery of HGS may lead to improved outcomes with respect to relieving inflammation, shorter hospital stays, decreased re-hospitalization rates, and decreased mortality rates ^{[1, 2, 3]}. In future studies, we will investigate in depth whether and how nutrition support can improve patients’ nutritional status and relieve inflammation and the association of such support with HGS and disease recovery.

Acknowledgment

This research was not the subject of a specific grant from any funding agency in the public, commercial, or non-profit sectors.

Conflicts of Interest

The authors have no financial conflicts of interest.

References

[1]	Norman, K.-Stobaus, N.-Gonzalez, M.C.-Schulzke, J.D.-Pirlich, M.: Hand grip strength: outcome predictor and marker of nutritional status. Clinical nutrition (Edinburgh, Scotland), 30, 2011, pp. 135-142.
	In article
[2]	Kerr, A.-Syddall, H.E.-Cooper, C.-Turner, G.F.-Briggs, R.S.-Sayer, A.A.: Does admission grip strength predict length of stay in hospitalised older patients? Age and ageing, 35, 2006, pp. 82-84.
	In article		View Article  PubMed
[3]	Mendes, J.-Azevedo, A.-Amaral, T.F.: Handgrip strength at admission and time to discharge in medical and surgical inpatients. JPEN Journal of parenteral and enteral nutrition, 38, 2014, pp. 481-488.
	In article		View Article  PubMed
[4]	Norman, K.-Stobaus, N.-Kulka, K.-Schulzke, J.: Effect of inflammation on handgrip strength in the non-critically ill is independent from age, gender and body composition. European journal of clinical nutrition, 68, 2014, pp. 155-158.
	In article		View Article  PubMed
[5]	Reid, W.D.-Rurak, J.-Harris, R.L.: Skeletal muscle response to inflammation--lessons for chronic obstructive pulmonary disease. Critical care medicine, 37, 2009, pp. S372-383.
	In article		View Article  PubMed
[6]	Wagenmakers, A.J.: Muscle function in critically ill patients. Clinical nutrition (Edinburgh, Scotland), 20, 2001, pp. 451-454.
	In article
[7]	Frost, R.A.-Lang, C.H.: mTor signaling in skeletal muscle during sepsis and inflammation: where does it all go wrong? Physiology (Bethesda, Md), 26, 2011, pp. 83-96.
	In article		View Article  PubMed
[8]	Doumatey, A.P.-Zhou, J.-Adeyemo, A.-Rotimi, C.: High sensitivity C-reactive protein (Hs-CRP) remains highly stable in long-term archived human serum. Clinical biochemistry, 47, 2014, pp. 315-318.
	In article		View Article  PubMed
[9]	Abizanda, P.-Navarro, J.L.-Garcia-Tomas, M.I.-Lopez-Jimenez, E.-Martinez-Sanchez, E.-Paterna, G.: Validity and usefulness of hand-held dynamometry for measuring muscle strength in community-dwelling older persons. Archives of gerontology and geriatrics, 54, 2012, pp. 21-27.
	In article		View Article  PubMed
[10]	Kondrup, J.-Rasmussen, H.H.-Hamberg, O.-Stanga, Z.: Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clinical nutrition (Edinburgh, Scotland), 22, 2003, pp. 321-336.
	In article
[11]	Disease prevention and control department moh, p.r. china: Chinese adult overweight and obesity prevention and control guidelines. Peking: People's Medical Publishing House, 2006.
	In article
[12]	Silva, C.-Amaral, T.F.-Silva, D.-Oliveira, B.M.-Guerra, A.: Handgrip strength and nutrition status in hospitalized pediatric patients. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 29, 2014, pp. 380-385.
	In article
[13]	Edington, J.-Barnes, R.-Bryan, F.-Dupree, E.-Frost, G.-Hickson, M.-Lancaster, J.-Mongia, S.-Smith ,J.-Torrance, A.-West, R.-Pang, F.-Coles, S.J.: A prospective randomised controlled trial of nutritional supplementation in malnourished elderly in the community: clinical and health economic outcomes. Clinical nutrition (Edinburgh, Scotland), 23, 2004, pp. 195-204.
	In article
[14]	Matos, L.C.-Tavares, M.M.-Amaral, T.F.: Handgrip strength as a hospital admission nutritional risk screening method. European journal of clinical nutrition, 61, 2007, pp. 1128-1135.
	In article		View Article  PubMed
[15]	Hamer, M.-Molloy, G.J.: Association of C-reactive protein and muscle strength in the English Longitudinal Study of Ageing. Age (Dordrecht, Netherlands), 31, 2009, pp. 171-177.
	In article		View Article  PubMed
[16]	Bicer, S.-Reiser, P.J.-Ching, S.-Quan, N.: Induction of muscle weakness by local inflammation: an experimental animal model. Inflammation research : official journal of the European Histamine Research Society [et al], 58, 2009, pp. 175-183.
	In article
[17]	Soeters, P.B.-Reijven, P.L.-van, Bokhorst.-de van der Schueren, M.A.-Schols, J.M.-Halfens, R.J.-Meijers, J.M.-van Gemert, W.G.: A rational approach to nutritional assessment. Clinical nutrition (Edinburgh, Scotland), 27, 2008, pp. 706-716.
	In article
[18]	Aniwidyaningsih, W.-Varraso, R.-Cano, N.-Pison, C.: Impact of nutritional status on body functioning in chronic obstructive pulmonary disease and how to intervene. Current opinion in clinical nutrition and metabolic care, 11, 2008, pp. 435-442.
	In article		View Article  PubMed