Handgrip strength measurement protocols for all-cause and cause-specific mortality outcomes in more than 3 million participants: a systematic review and meta-regression analysis.

Meta-analyses Handgrip strength measurement protocols for all-cause and causespecific mortality outcomes in more than 3 million participants: A systematic review and meta-regression analysis Rodrigo Nú~ nez-Cort es a , b , Borja del Pozo Cruz c , Daniel Gallardo-G omez d , e , Joaquín Calatayud f , g , * , Carlos Cruz-Montecinos a , b , h , Jos e Francisco L opez-Gil i , Rub en L opez-Bueno f , g , j a Department of Physiotherapy, Physiotherapy in Motion Multispeciality Research, Group (PTinMOTION), University of Valencia, Valencia, Spain b Department of Physical Therapy, Faculty of Medicine, University of Chile, Santiago, Chile c Centre for Active and Healthy Ageing, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark d Faculty of Education, Department of Physical Education and Sports, University of Seville, Seville, Spain e Epidemiology of Physical Activity and Fitness Across the Lifespan (EPAFit) Research Group, University of Seville, Seville, Spain f National Research Centre for the Working Environment, Copenhagen, Denmark g Exercise Intervention for Health Research Group (EXINH-RG), Department of Physiotherapy, University of Valencia, Valencia, Spain h Section of Research, Innovation and Development in Kinesiology, Kinesiology Unit, San Jos e Hospital, Santiago, Chile i Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain j Department of Physical Medicine and Nursing, University of Zaragoza, Zaragoza, Spain article info Article history: Received 28 June 2022 Accepted 11 September 2022 Keywords: Muscle strength dynamometer Risk assessment Death Quality summary Background &aims: Handgrip strength is a strong predictor of the risk of mortality. The objective of this systematic review was to analyse handgrip strength measurement protocols used in all-cause and causespecific mortality studies. Method: A systematic search of PubMed/MEDLINE, Web of Science and Scopus was conducted from inception to February 2022. Prospective cohort studies with objective measures of handgrip strength were included. Studies had to report at least one all-cause, cancer, or cardiovascular mortality outcome. The quality of the included studies was assessed using the Newcastle Ottawa Scale. Meta-regression was used to quantify the bias associated with handgrip strength values in relation to the use of different measurement protocols. Results: Forty-eight studies with a total of 3,135,473 participants (49.6% women) were included. Half of the studies controlled body position, 39.6% arm position, 33.3% elbow position, 12.5% wrist position, 13% handgrip duration, 23% hand-adjustment to dynamometer and 12.5% verbal encouragement. The number of measurements, the laterality of the hand tested, and the estimation method of the handgrip strength value varied considerably between the study protocols. The spline regression model showed a non-linear inverse association between the values of handgrip strength and the number of protocol items controlled. Handgrip strength was higher when the number of measurements per hand or arm position was not controlled. Conversely, handgrip strength was lower when elbow position was not controlled or verbal encouragement were not provided. Conclusion: In general, the protocols used to assess handgrip strength in mortality studies are incomplete and highly heterogeneous. Handgrip strength values were higher when studies controlled fewer handgrip strength measurement protocol variables. There is a need to improve the controlling of handgrip strength measurement protocols and to standardise the method to enhance the accuracy of mortality risk estimates associated with handgrip strength. PROSPERO registration number: CRD42022334929. ©2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). *Corresponding author. Exercise Intervention for Health Research Group (EXINH-RG), Department of Physiotherapy, University of Valencia, Valencia, Spain. E-mail address: [email protected] (J. Calatayud). Contents lists available at ScienceDirect Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu https://doi.org/10.1016/j.clnu.2022.09.006 0261-5614/©2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Clinical Nutrition 41 (2022) 2473e2489 1. Introduction Handgrip strength is one of the most used proxies for assessing overall muscle strength. It is simple, inexpensive, and quick which makes it ideal to be applied in clinical and large-scale research settings [1e4]. Handgrip strength is considered an indicator of different health outcomes, such as disability [3,5], sarcopenia [4,6], morbidity [7e9], and mortality [10e15]. Handgrip strength has shown high levels of validity and reliability using different devices [16e19]. However, in research settings, the measurement protocol for characterising handgrip strength may vary considerably, making comparisons among studies difficult [20]. This may also result in different sizes of handgrip estimates. For example, the handgrip strength of the hand may vary according to different elbow positions [21,22]. As recommended elsewhere [20,23], critical methodological considerations when reporting handgrip strength in research studies include the position of the arm, wrist and lower extremity; the number of tests performed; the stimulus during the evaluation; and the score (relative or absolute) to be used as the outcome. However, studies often do not provide sufficient information on the protocol followed [20]. A recent scoping review focused on older adults concluded that the methodology used to measure handgrip strength varied considerably among the included studies, which could lead to different results [24]. Considering that all-cause and cause-specific mortality is a crucial public health outcome, heterogeneity of measurement may affect estimates in studies examining the associations between handgrip strength and mortality outcomes. Thus, it is necessary to analyse the available evidence to identify the heterogeneity in the protocols used in such studies. The objective of this systematic review was to analyse handgrip strength measurement protocols used in all-cause and causespecific mortality studies. We also aimed to estimate the bias associated with handgrip strength values in relation to the use of different measurement protocols. 2. Methods This systematic review was pre-registered in the PROSPERO International Prospective Register of Systematic Reviews (reference number CRD42022334929) and was conducted following the PRISMA 2020 guidelines [25]. 2.1. Search strategy A systematic search of PubMed/MEDLINE, Web of Science (WOS) and Scopus was conducted from inception to February 2022. The specific search strategies are shown in the Supplement (Table S1). Title/abstract and full-text screening were conducted independently by RLB and RNC, with disagreements resolved by adjudication by a third author (BdPC). The reference lists of eligible articles and topic-related reviews were also screened for additional studies. All records were analysed in Endnote X7 software (Clarivate Analytics, New York, USA). 2.2. Selection criteria We included (1) prospective cohort studies (2) with either a single or repetitive measures of handgrip strength that (3) were written in English, and (4) used any type of objectively measurement of handgrip strength. To be included, (5) studies had to report on at least one all-cause, cancer or cardiovascular mortality outcome; and (6) had to include participants aged 18 years or over. We excluded studies for which the effect of handgrip strength could not be isolated. We also excluded studies with either hospitalised or institutionalised participants, as well as studies focusing specifically on clinical populations or health conditions. All editorials, letters, reviews, in vivo and in vitro studies were excluded. 2.3. Data extraction Data from studies that met the inclusion criteria were independently retrieved by RLB and RNC and disagreements were resolved by consensus between all authors. From each included study, we extracted the number of participants, age, sex, follow-up time, type of dynamometer, protocol for handgrip strength, and main results of the study. Information on either handgrip dynamometer tool or measurement protocol could not be retrieved from the following published reports: Fujita et al. [13]; Kim et al. [26]; Laukkanen et al. [27]; McLean et al. [28]; Soares et al. [29]; Peterman-Rocha et al. [30]; Sasaki et al. [11]; Taniguchi et al. [31]. Thus, we contacted the corresponding authors from such publications by e-mail and invited them to provide additional data on the handgrip measurement protocol. Of such studies, only one author provided the requested information [29]. 2.4. Data synthesis Following the indications of previous protocols such as the Southampton protocol [20], and the American Society of Hand Therapists (ASHT) protocol [32], we clustered studies in relation to different measuring protocol variables including type of handgrip dynamometer, laterality of the hand tested, body position, arm position, elbow position, wrist position, hand-adjustment to dynamometer, number of repetitions per arm, maximum handgrip strength estimation, handgrip strength test duration, recovery time, and any other additional measures that could characterised the protocol used. 2.5. Risk of bias and quality of evidence The risk of bias and quality of included studies was assessed individually by three reviewers (RLB, BdPC, and RNC) using the Newcastle Ottawa Scale [33]. Each included study was judged using a rating system in three domains of bias: selection (four points); comparability (two points); and exposure/outcome (three points). The sum of points indicates the methodological quality of each study. Thus, the score ranges from 0 to 9 points. 2.6. Statistical analyses We conducted all the analyses using R software (version 3.5.1) [34]. To assess the association between handgrip strength values and number of controlled variables concerning handgrip strength measurement protocols, a spline regression model allowing for heterogeneity among studies as well as accounting for cohort sizes was conducted. Either mean or median handgrip strength values were considered for each individual study in relation to the number of protocol measurement variables reported. We assessed the potential nonlinear association for all the protocol measurement variables using a restricted cubic spline model with three knots at the 10th, 50th and 90th percentile of pooled handgrip strength [35]. Departure from linearity was assessed using a Wald test. We also tested additional linear and quadratic regressions observing no better fitting of the model. A subgroup analysis was performed taking into account the following categories I) Sex (male or female); II) Population (mean (SD) age 65 years or <65 years); III) Race (Asian, Caucasian or Hispanic/Latino); IV) Reported handgrip strength value (maximum value or mean value). Studies that did not detail this information were not considered for subgroup R. Nú~ nez-Cort es, B.P. Cruz, D. Gallardo-G omez et al. Clinical Nutrition 41 (2022) 2473e2489 2474 analysis. In a secondary analysis, for the individual protocol measurement variables, a Bayesian multilevel regression was used, where all individual variables were entered into the model. Conditional effects were the handgrip strength values according to the subgroup within a variable (i.e., 0 or 1, variable not reported or reported respectively) [36]. Estimations are reported with 95% confidence intervals. 3. Results 3.1. Study selection A total of 2735 potential eligible studies were identified through initial electronic searches and removal of duplicates. After screening publications by title and abstract we obtained 55 potentially eligible studies for inclusion and retrieved full-text articles. Finally, full-text articles were retrieved and, after applying the inclusion criteria, 48 studies remained in the final selection for the systematic review [11,13e15,26e31,37e74]. The flowchart of the study selection process is shown in Fig. 1. 3.2. Study characteristics The characteristics of included studies are displayed in Table 1. Studies were conducted in the United Kingdom (10 studies), the United States (7), multi-country (7), Japan (5), South Korea (4), the Netherlands (2), Norway (2), Finland (2), Germany (1), Singapore (1), Taiwan (1), China (1), Brazil (1), France (1), Israel (1), Russia (1), Italy (1). The year of publication ranged from 1995 [13,27] and 2022 [52,60]. A total of 3,135,473 participants (49.6% female) were enrolled in the included studies, and the age of participants ranged from 35 [11]to85 years [46]. The sample size ranged from 436 [71] to 502,293 participants [41]. The duration of follow-up ranged from 2.3 [42] to 44 years [64]. 3.3. Characteristics of the protocols Eighty-five percent of the included studies controlled the type of dynamometer used. Twenty-eight studies measured handgrip strength in both hands (58%),12 in the dominant hand (25%), one in the nondominant hand (2%), and seven did not control which hand Fig. 1. Study selection process. R. Nú~ nez-Cort es, B.P. Cruz, D. Gallardo-G omez et al. Clinical Nutrition 41 (2022) 2473e2489 2475 Table 1 Description of included articles. Study, year Country Participants (N) Age (years) Covariates Follow-up duration Handheld dynamometer Protocol Main results NewcastleeOttawa Scale Arvandi, 2016 Germany 1066 Mean (SD) 76 (11) Women: 536 BMI: Yes Physical activity: Yes Chronic condition: Yes 3.0 years. Jamar. Dominant hand. Three trials. Maximum value. Sex-specific tertiles. ±1 kg. Grip strength is inversely associated with mortality risk in older adults. 8/9 Andrasfay, 2020 Taiwan 887 Mean (SD) 70.1 (8.7) Women:430 BMI: No Physical activity: No Chronic condition: No 4.0 years. North Coast. Both hands. Three trials. Maximum value. ±1 kg. Conditional on the baseline measurement, a one standard deviation (SD) decline in grip strength is associated with a 61% increased risk of mortality. 6/9 Bae, 2019 South Korea 9393 Mean (SD) 61 (10.7) Women:5235 BMI: Yes Physical activity: Yes Chronic condition: Yes 8.0 years. Tanita, 6103. Sit or stand-up. Arms one side of the trunk. Elbows 90  degrees. 5s. Average maximum value of both hands. Sex specific quartiles. ±1 kg. Robust independent relationships between weaker handgrip strength and higher allcause mortality 9/9 Cai, 2021 Multi-country 13,231 65 and over Women:7073 BMI: Yes Physical activity: Yes Chronic condition: Yes 4.0 years. Smedley. Stand or sit. Upper arms tight against the trunk. Elbows 90  degrees. 5 s squeezing. ±1 kg. Inverse linear association of handgrip with all-cause mortality. 6/9 Celis-Morales, 2018 UK 502,293 Mean (SD) 56.5 (8.1) Women: 260,063 BMI: Yes Physical activity: Yes Chronic condition: Yes 7.1 years. Jamar, J00105. Single 3-s maximal grip effort. Both arms. Seated upright. Elbow flexed at 90  . Forearm facing forward and resting on an armrest. Mean maximum strength of both hands. ±1kg Lower grip strength was associated with higher cardiovascular, cancer and all-cause mortality risk. 9/9 Chua, 2020 Singapur 13,789 Mean (SD) 74 (6.0) Women: 8133 BMI: Yes Physical activity: No Chronic condition: Yes 2.3 years. Takei, TKK5401 Grip D. Upright. Arms let down naturally. ±0.1 kg (accuracy) Two trials for each hand. Highest value obtained from each hand. Mean of both hands. Handgrip strength was inversely associated with risk of mortality in a dose-dependent manner. 7/9 Eekhoff, 2019 Netherlands 1505 Mean (SD) 76.0 (6.6) Women: 778 BMI: Yes Physical activity: No Chronic condition: Yes 15.4 years. Takei, TKK 5001. Average grip strength of maximum handgrip of both hands. ±1 kg. Hand-size adjusted. Handgrip strength predicted all-cause mortality. 8/9 Farmer, 2019 UK 452,931 Mean (SD) 55.9 (8.9) Women: 247,183 BMI: Yes 6.1 years. Jamar. Low handgrip strength was associated with 8/9 R. Nú~ nez-Cort es, B.P. Cruz, D. Gallardo-G omez et al. Clinical Nutrition 41 (2022) 2473e2489 2476 Physical activity: Yes Chronic condition: Yes Maximum handgrip strength of the dominant hand. increased risk of allcause mortality but not cardiovascular mortality. Fujita, 1995 Japan 6259 Mean (SD) Men 53.6 (9.0) Women 54.5 (8.5) Women: 3142 BMI: No Physical activity: No Chronic condition: No 6.1 years. Unknown. Average of right and left hands. 1kg Risk of death due to allcauses observed for men with lower handgrip values, but not in women. 6/9 Gao, 2021 China 3686 65 and over Women: 1809 BMI: Yes Physical activity: No Chronic condition: Yes 7.0 years. Yuejian, TM WL- 1000. Standing position. Elbows at right angles. Two measures in each hand. Average of four measurements. The decline of handgrip significantly increased all-cause mortality. 8/9 Granic, 2017 UK 845 85 and over Women:374 BMI: Yes Physical activity: Yes Chronic condition: Yes 9.6 years. Takei, A5401. Two measurements for each hand. Mean of the four measurements. Sex-specific quartiles. Higher baseline grip strength and 5-year increase in GS were protective of mortality. 7/9 Ho, 2019 UK 356,721 Mean (SD) 55.7 (8.1) Women: 194,540 BMI: Yes Physical activity: No Chronic condition: No 5.0 years. Jamar, J00105. Single 3-s maximal grip effort. Both arms. Seated upright. Elbow flexed at 90  . Forearm facing forward and resting on an armrest. Mean maximum strength of both hands. ±1kg Higher grip strength was associated with lower risk of all-cause mortality. These associations did not meaningfully differ when grip-strength was expressed in absolute or relative terms. 8/9 Karlsen, 2017 Norway 2529 Mean (SD) 72.6 (4.8) Women: 2529 2529 BMI: Yes Physical activity: Yes Chronic condition: Yes 15.6 years. Martin Vigorimeter. Seated. Hand-adjusted. 3 attempts and 1 min rest between them. Mean of the 2 highest tests. Handgrip strength is associated with allcause mortality in elderly women but not with cancer and cardiovascular mortality. 8/9 Kim, 2017 UK 403,199 Range 40e69 Women: 220,193 BMI: Yes Physical activity: No Chronic condition: Yes 7.0 years. Jamar, J00105. Once each hand. Participants choose grip position. Hand-adjustable. Seated. 90  angle of their elbow. Squeezing for 3 s. Lower grip is a predictor of higher allcause mortality in men and women, as well as a predictor of higher cardiovascular disease in men but not in women. 9/9 Kim, 2018 UK 70,913 (Individuals with cancer, heart attack or stroke were removed) Mean (SD) 57.2 (8.2) Women: 37,655 BMI: Yes Physical activity: No Chronic condition: Yes 5.7 years. Jamar, J00105. Calibrated each day. Once each hand. Participants choose grip position. Hand-adjustable. Seated. 90  angle of their elbow. Squeezing for 3 s. Improving both CRF and muscle strength, as opposed to either of the two alone, may be the most effective behavioral strategy to reduce all-cause and cardiovascular mortality risk. 9/9 Kim, 2019 South Korea 5859 Mean (SD) 63.2 (8.8) Women: 3191 BMI: Yes Physical activity: Yes Chronic condition: Yes 7.9 years. Tanita, 6103. Seated. Elbow flexed at 90  . Neutral forearm and wrist. These results demonstrate that lower handgrip strength is an independent predictor 8/9 (continued on next page) R. Nú~ nez-Cort es, B.P. Cruz, D. Gallardo-G omez et al. Clinical Nutrition 41 (2022) 2473e2489 2477 Table 1 (continued) Study, year Country Participants (N) Age (years) Covariates Follow-up duration Handheld dynamometer Protocol Main results NewcastleeOttawa Scale Two trials for each hand. Average of four measures. Accuracy 0.125 kg of all-cause and cardiovascular mortality. Kim, 2020 South Korea 2927 67 and over Women: 1530 BMI: Yes Physical activity: No Chronic condition: No 10.0 years. Unknown. Twice for each hand. Maximum value among the 4 tests. These findings suggest that handgrip strength has a significant impact on elderly mortality and does so in a negatively gradient manner. 6/9 Kim, 2022 South Korea 9229 Mean (SD) 60.7 (0.1) Women: 5098 BMI: Yes Physical activity: Yes Chronic condition: Yes 9.4 years. Tanita, 6103. Standing posture. Twice for each hand. Elbow at their side and flexed at right angle. Neutral wrist position. Average of both hands' maximum strength. Relative handgrip strength calculated. Handgrip strength is strongly associated with an increased risk mortality. 9/9 Kishimoto, 2014 Japan 2527 40 and over Women: 1463 BMI: Yes Physical activity: Yes Chronic condition: Yes 19.0 years. Smedley. Two trials for each hand. Maximum value of the four. The width of the handle was adjusted such that the second phalanx was against the inner stirrup. Higher levels of handgrip strength were significantly associated with decreased risks of all-cause and cardiovascular death but not cancer death. 8/9 Laukkanen, 1995 Finland 463 Range 75e84 Women: Unknown BMI: No Physical activity: No Chronic condition: Yes 4.0e4.8 years. Unknown. Dominant hand. Handgrip strength divided by BMI. Lower handgrip strength significantly associates with allcause mortality. 4/9 Laukkanen, 2020 Finland 861 Mean (SD) 69.0 (3.0) Women: 454 BMI: Yes Physical activity: Yes Chronic condition: Yes 12.6e18.4 years. Martin-Balloon- Vigorimeter. Upright position. Arms parallel to the body. Two measures of the dominant hand. Average of the two measures. Values of handgrip strength divided by weight. Relative handgrip strength is inversely associated with allcause and cardiovascular mortality events. 8/9 Leong, 2015 Multi-country 139,691 Median (IQR) 50 (42e58) Women: 81,039 BMI: Yes Physical activity: Yes Chronic condition: Yes 4.0 years. Jamar. Three measures from the non-dominant hand, and three measures from each hand later. Mean of the maximum value of each hand. Measurement of grip strength is a simple, inexpensive riskpredictor for all-cause and cardiovascular death but not cancer death. 8/9 R. Nú~ nez-Cort es, B.P. Cruz, D. Gallardo-G omez et al. Clinical Nutrition 41 (2022) 2473e2489 2478 Ling, 2010 Netherlands 555 85 and over Women: 361 BMI: Yes Physical activity: No Chronic condition: Yes 9.5 years. Jamar. Upright position. Measurement arm parallel to the body. Width adjustment. Three measures. Highest recorded measure. Handgrip strength is a predictor of all-cause mortality in the oldest old population. 8/9 L opez-Bueno A, 2022 Multi-country 121,383 Mean (SD) 63.9 (10.2) Women: 66,576 BMI: Yes Physical activity: No Chronic condition: No 7.4 years. Smedley, S Dynamometer, TTM. Each hand measured twice. Elbow in a 90  angle flexion. Standing or sitting. Neutral wrist position. Upper arm set in a vertical position against the trunk. Maximum value of either hand. Sex-specific tertiles. Up to a threshold of 42 kg in men and 25 kg in women, increases in handgrip strength reduce the risk of allcause mortality. Whereas no consistent associations were observed for cancer mortality. 8/9 L opez-Bueno B, 2022 Multi-country 121,116 Mean (SD) 63.7 (10.0) Women: 66,576 BMI: Yes Physical activity: Yes Chronic condition: Yes 3.6 years. Smedley, S Dynamometer, TTM. Each hand measured twice. Elbow in a 90  angle flexion. Standing or sitting. Neutral wrist position. Upper arm set in a vertical position against the trunk. Maximum value of either hand. Higher handgrip strength reduces the risk of cardiovascular and all-cause mortality. Mc Grath, 2020 USA 19,729 50 and over Women: Unknown BMI: Yes Physical activity: No Chronic condition: Yes 12.0 years. Smedley. Fit to respondent's hand. Arm at their side at a 90  Angle. Two measures in each hand. Attempts alternating hands. Exceptions for the protocol. A causal association between weakness and mortality may exist. 8/9 Mc Lean, 2014 Multi-country 6280 68.5 and over Women: 1869 BMI: Yes Physical activity: No Chronic condition: No 10.0 years. Jamar. Unknown. The significant association of lower handgrip strength and all-cause mortality was observed in all the subgroups except from relative to BMI handgrip strength in women. 5/9 Minneci, 2015 Italy 561 Mean (SD) 72.9 (0.3) Women: 323 BMI: Yes Physical activity: No Chronic condition: Yes 7.0 years. Jamar. Dominant hand. Best of three measures. One measure per minute. Handgrip strength did not predict all-cause mortality. 7/9 Newman, 2006 USA 2292 70 and over Women: 1168 BMI: Yes 4.9 years. Jamar. Assessed in each hand. Participants with hand Grip strength reduction increases the risk of allcause mortality. 8/9 (continued on next page) R. Nú~ nez-Cort es, B.P. Cruz, D. Gallardo-G omez et al. Clinical Nutrition 41 (2022) 2473e2489 2479 Table 1 (continued) Study, year Country Participants (N) Age (years) Covariates Follow-up duration Handheld dynamometer Protocol Main results NewcastleeOttawa Scale Physical activity: Yes Chronic condition: Yes pain or recent surgery excluded. Nofuji, 2016 Japan 1085 Range 65e89 Women: 625 BMI: Yes Physical activity: Yes Chronic condition: Yes 10.3 years. Smedley. Dominant hand. Higher value from two trials. Sex-specific cut-off points. Weak grip strength predicted all-cause and cardiovascular mortality (T1). 7/9 Oksuzyan, 2017 Multi-country 15,130 Range 55e89 Women: 7942 BMI: Yes Physical activity: No Chronic condition: Yes 6.2e7.5 years. Smedley. Upper arm held against the trunk. Elbow in a 90  degree flexion. Three trials for each hand. Exclusion of those with fewer than three attempts or a difference of more than 20 kgs between attempts. Handgrip strength is a powerful predictor of all-cause mortality across countries. 8/9 Park, 2022 UK 324,486 Range 40e69 Women: 177,130 BMI: Yes Physical activity: Yes Chronic condition: Yes 4.0 years. Jamar, J00105. One measurement per hand. Average of the two measures. The study supports the causal effects of poor handgrip strength on the risks of all-cause, cancer and cardiovascular mortality. 6/9 Peterman-Rocha, 2020 UK 469,830 Range 37e73 Women: 215,655 BMI: Yes Physical activity: Yes Chronic condition: Yes 6.9 years. Unknown. Unknown. Low handgrip strength is associated with higher all-cause, cardiovascular, and respiratory disease. 8/9 Peterson, 2020 USA 3050 65 and over Women: 1759 BMI: Yes Physical activity: No Chronic condition: Yes 16.0 years. Jamar, 5030J1. Hand adjusted. Preliminar trial. Standing position when no limitations. Two attempts. Relative to BMI. Longitudinal declines in strength are significantly associated with all-cause mortality. 9/9 Prasitsiriphon, 2018 Multi-country 11,037 50 and over Women: 1759 BMI: Yes Physical activity: No Chronic condition: Yes 3.0 years. Smedley. Standing or sitting. Elbow flexed at 90  . Neutral wrist position. 5 s maintenance. Maximum force of both hands. Sex-specific. Grip strength is a significant indicator of all-cause and cardiovascular mortality. 7/9 Rantanen, 2000 USA 6040 Range 45e68 Women: 0 BMI: Yes Physical activity: No Chronic condition: No 30.0 years. Smedley. Handle adjustment up to the second phalanx was against the inner stirrup. Three trials for each hand. Mid-life grip strength predicts long-term allcause mortality. 7/9 R. Nú~ nez-Cort es, B.P. Cruz, D. Gallardo-G omez et al. Clinical Nutrition 41 (2022) 2473e2489 2480 Best result was selected. Rantanen, 2012 USA 2239 Range 56e68 Women: 0 BMI: Yes Physical activity: Yes Chronic condition: Yes 44.0 years. Smedley. Sitting. Arm extended on a table. If necessary, the tester held the dynamometer. Handle adjustment up to the second phalanx was against the inner stirrup. Three trials for each hand. Best result selected. High midlife grip strength may increase the probability of extreme longevity. 8/9 Rolland, 2006 France 7250 Mean (SD) 80.5 (3.8) Women: 7250 BMI: Yes Physical activity: Yes Chronic condition: Yes 3.8 years. Martin Vigorimeter. Hand-adjusted. Upright. Arm vertical and dynamometer close to the body. Newton/m 2 . Maximum of three attempts. Handgrip strength significantly predicted all-cause mortality. 7/9 Sasaki, 2007 Japan 4912 Range 35e74 Women: 3217 BMI: Yes Physical activity: No Chronic condition: Yes 27.0 years. Unknown. Measured two times each hand. Standing position. Thigh level handheld. Calibrated devices. Selection of maximum measurement. Grip strength is an accurate and consistent predictor of all causes of mortality in middleaged and elderly persons. 9/9 Smith, 2019 UK 5240 Mean (SD) 65.9 (9.4) Women: 2818 BMI: Yes Physical activity: No Chronic condition: No 9.7 years. Smedley. Dominant hand. Average of three measurements. Right angle to their body when holding the device. Sex-specific tertiles No association between handgrip strength and mortality when controlled for inflammatory markers. 8/9 Snih, 2002 USA 2488 65 and over Women: 1433 BMI: Yes Physical activity: No Chronic condition: Yes 5.0 years. Jamar, 5030J1. Hand adjustment. Dominant hand. Two attempts. Higher measurement selected. Handgrip strength was highly predictive of allcause mortality. 7/9 Soares, 2019 Brazil 900 65 and over Women: 618 BMI: Yes Physical activity: No Chronic condition: Yes 8.4 years. Unknown. Dominant hand. Three attempts. Median cutoff points (weak: 34 kg men,  20.6 kg women). Lower handgrip strength was associated with higher all-cause mortality risk. 7/9 Stessman, 2017 Israel 2241 70 and over Women: 1090 BMI: Yes Physical activity: Yes Chronic condition: Yes 25.0 years. Takei. Three measurements from the strongest hand. Arm flexed at 90  the elbow while sitting. Highest measurement was used. A low handgrip strength was associated with significantly higher all-cause mortality. 8/9 (continued on next page) R. Nú~ nez-Cort es, B.P. Cruz, D. Gallardo-G omez et al. Clinical Nutrition 41 (2022) 2473e2489 2481 [21] Ng GYF, Fan ACC. Does elbow position affect strength and reproducibility of power grip measurements? Physiotherapy 2001;87:68e72. https://doi.org/ 10.1016/s0031-9406(05)60443-9. [22] Liao W-C, Wang C-H, Yu S-Y, Chen L-Y, Wang C-Y. Grip strength measurement in older adults in Taiwan: a comparison of three testing positions. Australas J Ageing 2014;33:278e82. 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