ABSTRACT
Purpose
This study examined the independent and combined associations of handgrip strength weakness and asymmetry with incident stroke risk among adults aged ≥ 50 years.
Method
Data were derived from the Survey of Health, Ageing and Retirement in Europe. Handgrip strength was objectively measured, while stroke was self‐reported as physician‐diagnosed. Asymmetry was defined using the ratio of left to right handgrip strength based on the “10% rule” and additionally assessed as the absolute difference between hands. Weakness was defined as < 16 kg for women and < 27 kg for men. Participants were further categorized into four groups according to weakness and asymmetry status. Cox proportional hazards models were applied to estimate associations.
Results
Among 24 923 participants followed for a mean of 9.6 years, 1839 incident strokes occurred. Handgrip weakness was associated with higher stroke incidence (17.52 vs. 7.29 per 1000 person‐years) and a 55% increased risk compared with no weakness. Handgrip asymmetry was linked to a higher incidence (8.15 vs. 7.17 per 1000 person‐years) and a 13% increased risk. Each 1‐SD increase in asymmetry corresponded to a 2% higher risk. The highest risk was observed in participants with both weakness and asymmetry (18.29 per 1000 person‐years; HR: 1.70; 95% CI: 1.35–2.14). Interaction analyses indicated that the joint effect did not exceed the sum or product of individual effects.
Conclusion
Handgrip weakness and asymmetry independently increased stroke risk, with the highest risk observed when both were present, yet their combined effect did not exceed what would be expected from each factor alone.
Keywords: aging, handgrip strength asymmetry, handgrip strength weakness, stroke
Handgrip weakness and asymmetry were independently associated with an increased risk of incident stroke, with the highest risk observed when both were present, yet their combined effect did not exceed what would be expected from each factor alone.
1. Introduction
A stroke, the most common form of cerebrovascular disease, can be broadly defined as an acute or chronic injury to the central nervous system caused by vascular pathology, often accompanied by a range of clinical manifestations [1]. Common symptoms include sudden limb weakness, facial drooping, paralysis, and slurred speech [2]. Stroke represents a major public health challenge in modern society, owing not only to its high mortality but also to the wide range of long‐term consequences it imposes [3]. It frequently leads to substantial physical, cognitive, and psychological impairments, significantly reducing patients' quality of life and generating a considerable burden on families, healthcare systems, and social care services. This burden is particularly pronounced in Europe, where stroke incidence and prevalence continue to rise, driven by population aging, demographic expansion, increasing prevalence of chronic diseases, and shifts in lifestyle‐related risk factors [4]. Given these challenges, there is a pressing need for simple, reliable, and cost‐effective tools to identify individuals at elevated risk of stroke, enabling earlier prevention and intervention.
Handgrip strength has emerged as a practical, inexpensive, and reliable measure that not only reflects muscular function but also serves as an indicator of overall health and functional status [5]. Low handgrip strength, often referred to as muscular weakness, has been consistently associated with increased risks of cardiovascular disease [6], cancer [7], and premature mortality [8, 9]. In addition to absolute strength, pronounced asymmetry between the two hands has recently attracted attention as a potential marker of early neurovascular and muscular impairments, as well as central motor system dysfunction that may go undetected through conventional strength assessments [10, 11, 12]. In this context, handgrip strength asymmetry may reveal subtle health risks that absolute strength alone cannot capture.
Importantly, assessing handgrip strength weakness and asymmetry in combination may offer a more comprehensive risk profile than evaluating either measure independently. Previous studies have shown that individuals presenting with both low handgrip strength and asymmetry face higher risks of disease accumulation [13], cognitive decline [14], and functional impairment [11, 15]. In the context of cardiovascular and cerebrovascular disease, evidence from a single study suggests that handgrip strength weakness may be associated with an increased risk of stroke [16], and further research is needed to confirm this finding. Moreover, the role of handgrip strength asymmetry, and particularly the combined impact with weakness on incident stroke risk remains largely unexplored. Theoretically, pronounced asymmetry may reflect impaired motor unit coordination, reduced force precision [10, 11], and hemispheric imbalances in neural activation [17, 18], which could parallel early cerebrovascular changes [19]. Despite this, population‐based evidence is lacking. Therefore, this study aims to investigate both the independent and joint associations of handgrip strength weakness and asymmetry with the risk of new‐onset stroke.
2. Methods
2.1. Study Design and Participants
Data for this study was obtained from waves 1 to 8 of the Survey of Health, Ageing and Retirement in Europe (SHARE), a cross‐national panel study examining various aspects of life among individuals aged 50 years and older [20]. Wave 3 was excluded as it did not include relevant exposure or outcome data. To ensure an adequate follow‐up period, baseline was defined as the first wave in which a participant completed a handgrip strength assessment during wave 1 or 2. Participants were then followed from that point through waves 4 to 8, until they either reported the onset of stroke or were lost to follow‐up, whichever occurred first.
Of the initial 46 646 participants, 6924 individuals with a history of major cardiovascular or cerebrovascular conditions at baseline were excluded to reduce potential reverse causality. Additional exclusions were made for individuals lacking handgrip strength measurements, follow‐up data, those younger than 50 years, or those with missing covariate information (Figure 1). The final analytic sample comprised 24 923 participants drawn from the following countries: Austria, Germany, Sweden, the Netherlands, Spain, Italy, France, Denmark, Greece, Switzerland, Belgium, Israel, the Czech Republic, and Poland. The SHARE study received ethical approval from ethics committees in each participating country, and written informed consent was obtained from all participants.
FIGURE 1.
Flowchart of participant selection.
2.2. Handgrip Strength Measurement (Exposure)
Handgrip strength was measured on each hand using a handheld dynamometer (Smedley, S Dynamometer, TTM, Tokyo; maximum capacity 100 kg). Following standard SHARE procedures, participants were asked to bend their elbow at a 90° angle while either standing or seated, ensuring the wrist remained in a neutral position and the upper arm rested vertically alongside the torso. Trained interviewers provided standardized verbal instructions, encouraging participants to exert maximal force while gripping the device for a few seconds.
To assess handgrip strength asymmetry, the handgrip strength ratio was calculated as the ratio between handgrip strength measurements of the left and right hands. Based on the “10% rule” proposed by Armstrong and Oldham [21], which suggests that the dominant hand is typically around 10% stronger than the nondominant hand, a difference of up to 10% between hands is generally considered physiological. This 10% threshold has also been demonstrated in other studies as a pragmatic approximation for upper‐limb strength asymmetry [22]. Higher thresholds are likely to reflect more severe levels of asymmetry [23]. Therefore, handgrip strength asymmetry was primarily assessed using the ratio between handgrip strength measurements of the two hands. Participants with a handgrip strength ratio < 0.9 or > 1.1 were classified as having handgrip strength asymmetry. This ratio‐based measure is direction‐independent and does not depend on hand dominance or left/right labeling. In addition, asymmetry was also analyzed as a continuous variable using the handgrip strength difference (HGSD), defined as the absolute difference between left and right handgrip strength.
The maximum handgrip strength value was determined by selecting the stronger result between the two hands. Low handgrip strength was defined according to the most recent criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2), with cut‐off values derived from European population data: less than 16 kg for women and less than 27 kg for men [24]. Handgrip strength exceeding these thresholds was classified as normal. Furthermore, based on the presence or absence of weakness and asymmetry, participants were categorized into four groups: (1) normal strength and symmetry, (2) asymmetry only, (3) weakness only, and (4) both weakness and asymmetry.
2.3. Stroke (Outcome) and Potential Confounders
Stroke was the primary outcome, assessed as a binary variable based on self‐reported physician diagnosis. Given that the exact date of stroke onset was not available, we followed a commonly used approach by defining the timing of stroke onset as the midpoint between the last interview in which no stroke was reported and the first interview in which a stroke was reported [25]. Informed by prior research [26], we included potential confounders that may affect the association between handgrip strength and stroke risk. All potential confounders were measured at baseline, contemporaneously with the exposure assessment. These comprised demographic characteristics (age, sex, marital status, education level, wealth status, and country), lifestyle factors (body mass index [BMI], physical activity, smoking, and alcohol consumption), and chronic health conditions (hypertension, diabetes, lung disease, and cancer). Chronic conditions were identified based on self‐reported physician diagnoses or the use of relevant medications.
2.4. Statistical Analysis
Continuous and categorical variables were compared using Student's t‐test and chi‐square test, respectively. Descriptive results are reported as mean (standard deviation [SD]) for continuous variables and frequency (percentage) for categorical variables. Incidence rates were reported using person‐years to provide a clearer picture of event occurrence. To examine the association between handgrip strength status and incident stroke, we conducted four sets of analyses. First, participants were classified into two groups, those with handgrip strength weakness and those without, with the non‐weak group serving as the reference. Second, we categorized participants by handgrip strength symmetry (symmetric vs. asymmetric), using the symmetric group as the reference. Third, we assessed the association between HGSD, treated as a continuous variable, and the risk of stroke. Finally, we examined the joint effect of handgrip strength weakness and asymmetry by dividing participants into four mutually exclusive groups: symmetric and not weak, weak only, asymmetric only, and both asymmetric and weak. In this analysis, the group with symmetric grip and no weakness served as the reference. Each analytical set used Cox proportional hazards regression analyses with stepwise adjustment: Model I was adjusted for demographic factors; Model II additionally for lifestyle factors; and Model III further for chronic conditions.
To further evaluate whether the combined effect of handgrip weakness and asymmetry exceeds what would be expected from each factor individually (i.e., to assess potential synergistic effects), we assessed both multiplicative and additive interactions. Multiplicative interaction was tested by including an interaction term (weakness × asymmetry) in the Cox regression model. Additive interaction, which can reflect whether the absolute risk increase from the joint exposure exceeds the sum of the individual risk increases, was quantified using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI).
The primary analysis was based on complete case data. Several sensitivity analyses were performed to assess the robustness of our findings: (1) multiple imputation for missing data (N = 616); (2) exclusion of participants with less than 12 months of follow‐up (N = 165); (3) exclusion of participants with extreme values of HGSD, defined as HGSD below the 1st percentile or above the 99th percentile (N = 233); (4) redefinition of handgrip strength asymmetry as a handgrip strength ratio < 0.8 or > 1.2; (5) redefinition of handgrip strength asymmetry as a handgrip strength ratio < 0.7 or > 1.3; and (6) redefinition of handgrip strength asymmetry using a dominance‐based approach by calculating the ratio of dominant handgrip strength to nondominant handgrip strength (N = 28 observations deleted due to missing hand dominance information), with asymmetry defined as a ratio < 1.0 or > 1.1. These alternative definitions were applied to examine whether different operationalizations of asymmetry would materially affect the observed associations. Additionally, subgroup analyses were conducted stratified by age, sex, marital status, and education level.
3. Result
Over a mean follow‐up period of 9.60 (SD: 4.48) years, a total of 24 923 participants were included in the final analysis, among whom 1839 (7.38%) experienced new‐onset stroke (Table 1). The overall incidence rate of stroke was 7.68 per 1000 person‐years during follow‐up. Participants who developed stroke were more likely to be older, male, living alone, have lower educational attainment and lower wealth status, engage less frequently in moderate‐to‐vigorous physical activity (MVPA), have higher BMI, report chronic conditions, and exhibit both handgrip strength asymmetry and weakness. Furthermore, compared to those with symmetric handgrip strength and no weakness, participants with both handgrip strength asymmetry and weakness had a higher proportion of older adults, females, individuals living alone, those with lower education and wealth levels, lower MVPA participation, underweight status, and a higher prevalence of chronic diseases (Table S1).
TABLE 1.
Participant characteristics by stroke status.
| No stroke | Stroke | p | |
|---|---|---|---|
| Total, N (%) | 23 084 (100) | 1839 (100) | |
| Follow‐up years, mean (SD) | 9.88 (4.41) | 6.18 (3.92) | < 0.001 |
| Age (years), mean (SD) | 62.15 (9.00) | 66.69 (9.07) | < 0.001 |
| Age (years), N (%) | < 0.001 | ||
| < 65 | 14 832 (64.25) | 761 (41.38) | |
| ≥ 65 | 8252 (41.38) | 1078 (58.62) | |
| Gender, N (%) | < 0.001 | ||
| Female | 12 920 (55.97) | 904 (49.16) | |
| Male | 10 164 (44.03) | 935 (50.84) | |
| Marital status | < 0.001 | ||
| Accompanied | 17 454 (75.61) | 1294 (70.36) | |
| Living alone | 5630 (24.39) | 545 (29.64) | |
| Education | < 0.001 | ||
| Primary school and below | 10 699 (46.35) | 987 (53.67) | |
| Secondary school | 7604 (32.94) | 530 (28.82) | |
| College and above | 4781 (20.71) | 322 (17.51) | |
| Wealth | < 0.001 | ||
| Q1 | 5652 (24.48) | 563 (30.61) | |
| Q2 | 5714 (24.75) | 507 (27.57) | |
| Q3 | 5837 (25.29) | 401 (21.81) | |
| Q4 | 5881 (25.48) | 368 (20.01) | |
| Smoking status | 0.90 | ||
| Never | 12 208 (52.89) | 983 (53.45) | |
| Former | 6183 (26.78) | 486 (26.43) | |
| Current | 4693 (20.33) | 370 (20.12) | |
| Drinking | 0.08 | ||
| Yes | 11 702 (50.69) | 893 (48.56) | |
| No | 11 382 (49.31) | 946 (51.44) | |
| MVPA frequency | < 0.001 | ||
| Rare | 1452 (6.29) | 189 (10.28) | |
| Less than once per week | 901 (3.90) | 91 (4.95) | |
| Once per week | 2532 (10.97) | 215 (11.69) | |
| Twice or more per week | 18 199 (78.84) | 1344 (73.08) | |
| BMI (kg/m2), mean (SD) | 26.44 (4.21) | 26.99 (4.29) | < 0.001 |
| BMI (kg/m2), N (%) | < 0.001 | ||
| < 18.5 | 203 (0.88) | 17 (0.92) | |
| 18.5–24.9 | 8951 (38.78) | 608 (33.06) | |
| 25–29.9 | 9913 (42.94) | 829 (45.08) | |
| ≥ 30 | 4017 (17.40) | 385 (20.94) | |
| Hypertension | < 0.001 | ||
| Yes | 7476 (32.39) | 830 (45.13) | |
| No | 15 608 (67.61) | 1009 (54.87) | |
| Diabetes | < 0.001 | ||
| Yes | 1945 (8.43) | 295 (16.04) | |
| No | 21 139 (91.57) | 1544 (83.96) | |
| Lung | < 0.001 | ||
| Yes | 979 (4.24) | 116 (6.31) | |
| No | 22 105 (95.76) | 1723 (93.69) | |
| Cancer | 0.03 | ||
| Yes | 989 (4.28) | 99 (5.38) | |
| No | 22 095 (95.72) | 1740 (94.62) | |
| Handgrip strength weakness and asymmetry | < 0.001 | ||
| Normal strength and symmetry | 10 509 (45.53) | 757 (41.16) | |
| Weakness only | 405 (1.75) | 59 (3.21) | |
| Asymmetry only | 11 535 (49.97) | 922 (50.14) | |
| Both weakness and asymmetry | 635 (2.75) | 101 (5.49) |
Abbreviations: BMI, body mass index; HGSD, handgrip strength difference; MVPA, moderate‐to‐vigorous physical activity; SD, standard deviation.
During follow‐up, the incidence rate of stroke was 7.29 per 1000 person‐years among participants without handgrip weakness and 17.52 per 1000 person‐years among those with weakness. After adjustment for all covariates, handgrip weakness was associated with a 55% higher risk of stroke compared with no weakness (hazard ratio [HR]: 1.55; 95% confidence interval [CI]: 1.29–1.86). Handgrip asymmetry was also associated with a slightly increased risk of stroke (HR: 1.13; 95% CI: 1.02–1.24), with an incidence rate of 8.15 versus 7.17 per 1000 person‐years in symmetric individuals. When HGSD was analyzed as a continuous variable, each 1‐SD increase in HGSD was associated with a 2% higher risk of stroke (HR: 1.02; 95% CI: 1.01–1.03, Table 2).
TABLE 2.
Independent and combined associations of handgrip strength weakness and asymmetry with incident stroke.
| Incidence rates (per 1000 person‐years) | Model I | Model II | Model III | |
|---|---|---|---|---|
| Weakness | ||||
| No | 7.29 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Yes | 17.52 | 1.69 (1.42–2.02) | 1.59 (1.33–1.91) | 1.55 (1.29–1.86) |
| Asymmetry | ||||
| No | 7.17 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Yes | 8.15 | 1.16 (1.05–1.28) | 1.14 (1.03–1.26) | 1.13 (1.02–1.24) |
| HGSD | ||||
| Continuous | — | 1.02 (1.01–1.03) | 1.02 (1.01–1.03) | 1.02 (1.01–1.03) |
| Combined effect of weakness and asymmetry | ||||
| Normal strength and symmetry | 6.87 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Weakness only | 16.34 | 1.70 (1.28–2.25) | 1.62 (1.22–2.15) | 1.56 (1.19–2.13) |
| Asymmetry only | 7.68 | 1.15 (1.04–1.28) | 1.14 (1.02–1.26) | 1.13 (1.01–1.25) |
| Both weakness and asymmetry | 18.29 | 1.93 (1.54–2.41) | 1.78 (1.41–2.24) | 1.70 (1.35–2.14) |
Note: Model I was adjusted for demographic factors (age, sex, marital status, education, wealth, and country); Model II additionally adjusted for lifestyle factors (BMI, physical activity, smoking, and alcohol consumption); and Model III further adjusted for chronic conditions (hypertension, diabetes, lung disease, and cancer).
Abbreviation: HGSD, handgrip strength difference.
In the joint analysis of handgrip weakness and asymmetry, participants with normal strength and symmetry had an incidence rate of 6.87 per 1000 person‐years and served as the reference group. Compared with them, those with only weakness had an incidence rate of 16.34 per 1000 person‐years and were associated with a 56% increase in hazard of stroke (HR: 1.56; 95% CI: 1.19–2.13). The group with only asymmetry had a slightly higher incidence rate (7.68 per 1000 person‐years) and was related to a 13% higher risk of stroke (HR: 1.13; 95% CI: 1.01–1.25). Participants with both weakness and asymmetry were associated with a 70% greater hazard of stroke (HR: 1.70; 95% CI: 1.35–2.14) and had an incidence rate of 18.29 per 1000 person‐years.
All six sensitivity analyses yielded results consistent with the primary analysis (Tables S2–S7). Specifically, the associations of handgrip strength weakness, asymmetry, and their combination with incident stroke remained statistically significant and directionally stable across all alternative model specifications. These findings were robust to multiple imputation for missing data, exclusion of participants with follow‐up less than 12 months, exclusion of extreme HGSD values (1st and 99th percentiles), and three alternative definitions of handgrip strength asymmetry. Subgroup analyses stratified by age, sex, marital status, and education level similarly demonstrated consistent associations (Figures S1–S4).
As shown in Table 3, multiplicative interaction was not significant, with a HR of 1.00 (95% CI: 0.71–1.41), indicating that the joint relative risk did not differ from the product of the individual effects. Additive interaction showed an SI of 1.08 (95% CI: 0.22–1.94), suggesting a slight positive interaction in relative terms. However, the RERI was 0.05 (95% CI: −0.48 to 0.59) and the AP due to interaction was 0.03 (95% CI: −0.28 to 0.34). Both of these measures were very small and not statistically significant, indicating that the absolute risk increase due to the joint effect was minimal. Overall, these findings suggest that handgrip weakness and asymmetry independently increase stroke risk, with little evidence of meaningful synergistic interaction.
TABLE 3.
Multiplicative and additive interaction of handgrip weakness and asymmetry on incident stroke.
| Interaction type | Measures | Result (estimate, 95% CI) |
|---|---|---|
| Multiplicative interaction | Weakness × asymmetry | 1.00 (0.71–1.41) |
| Additive interaction | RERI | 0.05 (−0.48 to 0.59) |
| AP | 0.03 (−0.28 to 0.34) | |
| SI | 1.08 (0.22 to 1.94) |
Abbreviations: AP, attributable proportion due to interaction; RERI, relative excess risk due to interaction; SI, synergy index.
4. Discussion
In this large prospective cohort of European adults aged over 50 years, we observed that both handgrip strength weakness and asymmetry were independently associated with an increased risk of incident stroke. Moreover, our results indicated that greater degrees of handgrip strength asymmetry were associated with progressively higher stroke risk. More importantly, participants who exhibited both weakness and asymmetry had the highest stroke risk compared with those who maintained normal, symmetric handgrip strength. These findings highlight that reduced muscular strength and imbalanced force between hands may each represent important markers of underlying health deterioration, and that individuals with coexisting weakness and asymmetry may constitute a particularly vulnerable subgroup for future cerebrovascular events. Fortunately, their combined effect does not appear to exacerbate risk beyond what would be expected from each factor independently.
The incidence rate of stroke in our cohort is comparable to that reported in previous epidemiological studies [27], supporting the representativeness of the study population. Importantly, our findings are consistent with accumulating evidence that reduced muscular strength is associated with an increased risk of incident stroke. For instance, a population‐based longitudinal cohort study in Swedish men reported that, compared with those in the highest tertile of muscle strength, individuals in the lowest tertile had a 39% higher risk of stroke over a 5–42‐year follow‐up period (HR: 1.39; 95% CI: 1.27–1.53) [28]. Similarly, a study conducted in European, American, and Chinese populations found that participants in the lowest quartile of dominant handgrip strength, absolute handgrip strength, and relative handgrip strength had a 21%–42% higher risk of new‐onset stroke than those in the highest quartile [29]. In addition, another study with subtype‐specific analyses reported that lower handgrip strength was associated with a higher risk of both ischemic and hemorrhagic stroke [30].
Evidence on handgrip strength asymmetry and stroke risk remains limited. To our knowledge, only one study in middle‐aged and older Chinese adults has examined this association, reporting that handgrip strength asymmetry alone was not independently associated with new‐onset stroke [26]. This finding differs from ours, as we observed that handgrip strength asymmetry alone was independently associated with new‐onset stroke and that a greater HGSD was significantly associated with a higher risk of new‐onset stroke. These discrepancies may be partly explained by the shorter follow‐up duration in that study (4 vs. 9.6 years in ours) and differences in study populations (Chinese adults aged ≥ 45 years vs. European adults aged ≥ 50 years). When assessing the combined effect of handgrip strength asymmetry and weakness, however, their results were similar to ours: compared with individuals without either impairment, the presence of both asymmetry and weakness was associated with an approximately 80% higher risk of stroke [26].
Handgrip strength weakness may reflect a state of systemic vulnerability associated with increased stroke risk. Low grip strength has been linked to vascular aging and subclinical atherosclerosis, including endothelial dysfunction and arterial stiffness, which may impair cerebral perfusion and increase susceptibility to ischemic events [31]. It is also a recognized marker of sarcopenia and frailty, conditions characterized by chronic low‐grade inflammation, insulin resistance, and reduced physiological reserve [32, 33], all of which contribute to cardiovascular and cerebrovascular risk. In addition, handgrip strength may reflect central nervous system integrity. Emerging neuroimaging evidence suggests that lower grip strength is associated with reduced brain volume and poorer white matter integrity [34], which in turn have been linked to cerebrovascular pathology and increased risk of stroke [35]. Finally, low grip strength is closely associated with unhealthy lifestyle habits, such as physical inactivity, which are established risk factors for stroke [36]. Collectively, these pathways support handgrip weakness as an integrative marker of vascular, metabolic, muscular, and neural health, explaining its association with incident stroke.
The mechanisms linking handgrip strength asymmetry to new‐onset stroke remain incompletely understood. One plausible explanation is that handgrip strength asymmetry reflects early subclinical cerebrovascular and central motor system dysfunction. Early cerebral small vessel disease and white matter changes may develop in a gradual and spatially heterogeneous manner across brain regions, contributing to differential involvement of corticospinal pathways and regional cerebral perfusion between hemispheres [37, 38]. Given the contralateral organization of motor control, such asymmetric neurovascular involvement may manifest as inter‐limb differences in grip strength before overt neurological symptoms occur and may be particularly relevant to early manifestations of chronic ischemic cerebrovascular disease [39, 40]. However, these mechanisms remain hypothetical and speculative and cannot be verified in the present study due to the absence of neuroimaging data and therefore require confirmation in future studies.
Moreover, our findings suggest that handgrip weakness and asymmetry may represent two independent factors associated with stroke risk. Although individuals with both impairments exhibited the highest risk, their joint presence did not demonstrate evidence of a synergistic effect beyond their independent contributions. However, the observed association between handgrip strength asymmetry and stroke should be interpreted cautiously. Although the longitudinal association reached statistical significance in our study, the hazard ratios were relatively modest regardless of whether asymmetry was assessed using the ratio or absolute difference method. From a clinical perspective, this finding suggests that asymmetry by itself may not be sufficiently robust to support its use as a standalone screening tool in clinical practice. Nevertheless, because handgrip assessment is simple, inexpensive, and non‐invasive, evaluating both weakness and asymmetry alongside conventional cardiovascular risk factors may still help improve the identification of individuals at elevated risk who could benefit from further evaluation and preventive strategies. In addition, the absence of a significant interaction indicates that the coexistence of weakness and asymmetry does not necessarily imply the need for different clinical management compared with either factor alone. Accordingly, these indicators may be considered individually within routine risk assessment, while their combined assessment may provide additional value for risk stratification.
This study has several strengths. First, it draws on a large, nationally representative European cohort from 14 countries, with a long follow‐up period (mean 9.6 years), enabling robust assessment of the longitudinal association between handgrip strength measures and incident stroke. Second, the analyses accounted for a broad range of demographic, lifestyle, and clinical covariates, reducing the potential for confounding. Third, standardized protocols for handgrip strength measurement enhanced the reliability of exposure assessment, and the findings were consistent across six sensitivity analyses, supporting the robustness of the results.
Several limitations should also be noted. First, despite adjustment for multiple covariates, residual confounding cannot be fully excluded. In addition to factors such as dietary habits, inflammatory biomarkers, or genetic predisposition, other potential confounders may include acute or chronic disorders of the hand, wrist, or upper extremities; occupational exposures requiring preferential use of one hand; sports or recreational activities with unilateral demands, such as tennis; previous injuries or surgeries; and subclinical neurological conditions affecting one side. Second, handgrip strength was assessed only at baseline, preventing evaluation of changes in muscle strength or asymmetry over time, which may influence stroke risk. Third, the study population comprised European adults aged ≥ 50 years, which may limit generalizability to younger populations or other ethnic and cultural groups. Fourth, despite excluding participants with self‐reported major cardiovascular or cerebrovascular disease at baseline, undiagnosed conditions (including silent or subclinical brain infarctions) cannot be excluded and may have influenced baseline handgrip strength or asymmetry, potentially introducing reverse causation. Therefore, our findings should be interpreted as associative rather than causal. Fifth, stroke outcomes were ascertained based on self‐reported physician diagnosis, which may introduce misclassification. Although previous validation studies have shown good agreement between self‐reported stroke in SHARE and national registry data [41], the lack of objective neurological examinations and neuroimaging data remains a limitation. In addition, stroke onset time was estimated using the midpoint between assessment waves, which may introduce imprecision in event timing. These limitations may lead to non‐differential misclassification, potentially attenuating the observed associations. Finally, we only analyzed overall stroke because the SHARE database did not provide information on stroke subtypes or etiological mechanisms. Thus, we could not explore whether the associations of handgrip strength weakness and asymmetry differed across stroke subtypes.
5. Conclusion
In summary, our study demonstrates that both handgrip weakness and asymmetry were independently associated with higher stroke risk in older European adults, with greater asymmetry identifying those at progressively higher risk. The coexistence of weakness and asymmetry marked a particularly vulnerable subgroup, with no evidence that their combined effect exceeded what would be expected from their independent effects. These findings support the use of simple handgrip measurements to identify high‐risk individuals and highlight the importance of assessing both factors in clinical evaluation. Future research should explore the underlying mechanisms and evaluate whether interventions targeting muscle strength and asymmetry can effectively reduce stroke incidence.
Author Contributions
Y.L. and P.L. were responsible for conceptualization, methodology, and investigation. Y.L. conducted formal analysis and visualization. Both Y.L. and P.L. contributed to resources, software, and validation. Both authors drafted the original manuscript and contributed to writing – review and editing. All authors have read and approved the final manuscript.
Funding
The authors have nothing to report.
Ethics Statement
Ethical approval was obtained from local research ethics committees. These surveys were conducted in accordance with the ethical standards set forth in the 1964 Declaration of Helsinki and its subsequent amendments.
Consent
Written informed consent was provided by all participants.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Table S1: Participant characteristics by combined handgrip strength weakness and asymmetry status.
Table S2: Sensitivity analysis after Multiple Imputation (N = 616 imputed participants): associations of handgrip strength weakness and asymmetry with incident stroke.
Table S3: Sensitivity analysis after excluding participants with < 12 months of follow‐up (N = 165 observations deleted): associations of handgrip strength weakness and asymmetry with incident stroke.
Table S4: Sensitivity analysis after excluding participants in the extreme 1% of handgrip strength difference (N = 233 observations deleted): associations of handgrip strength weakness and asymmetry with incident stroke.
Table S5: Sensitivity analysis using a 20% handgrip strength asymmetry threshold: associations of handgrip strength weakness and asymmetry with incident stroke.
Table S6: Sensitivity analysis using a 30% handgrip strength asymmetry threshold: associations of handgrip strength weakness and asymmetry with incident stroke.
Table S7: Sensitivity analysis using a dominance‐based definition of handgrip strength asymmetry (N = 28 observations deleted due to missing hand dominance information): associations of handgrip strength weakness and asymmetry with incident stroke.
Figure S1: Subgroup analyses of the association between handgrip strength weakness and new‐onset stroke stratified by age, sex, marital status, and education level.
Figure S2: Subgroup analyses of the association between handgrip strength asymmetry and new‐onset stroke stratified by age, sex, marital status, and education level.
Figure S3: Subgroup analyses of the association between handgrip strength difference and new‐onset stroke stratified by age, sex, marital status, and education level.
Figure S4: Subgroup analyses of the association between the combined effect of handgrip strength weakness and asymmetry and new‐onset stroke, stratified by age, sex, marital status, and education level.
Data Availability Statement
The data that support the finding is available from Gateway to Global Aging Data (https://g2aging.org/) [42].
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1: Participant characteristics by combined handgrip strength weakness and asymmetry status.
Table S2: Sensitivity analysis after Multiple Imputation (N = 616 imputed participants): associations of handgrip strength weakness and asymmetry with incident stroke.
Table S3: Sensitivity analysis after excluding participants with < 12 months of follow‐up (N = 165 observations deleted): associations of handgrip strength weakness and asymmetry with incident stroke.
Table S4: Sensitivity analysis after excluding participants in the extreme 1% of handgrip strength difference (N = 233 observations deleted): associations of handgrip strength weakness and asymmetry with incident stroke.
Table S5: Sensitivity analysis using a 20% handgrip strength asymmetry threshold: associations of handgrip strength weakness and asymmetry with incident stroke.
Table S6: Sensitivity analysis using a 30% handgrip strength asymmetry threshold: associations of handgrip strength weakness and asymmetry with incident stroke.
Table S7: Sensitivity analysis using a dominance‐based definition of handgrip strength asymmetry (N = 28 observations deleted due to missing hand dominance information): associations of handgrip strength weakness and asymmetry with incident stroke.
Figure S1: Subgroup analyses of the association between handgrip strength weakness and new‐onset stroke stratified by age, sex, marital status, and education level.
Figure S2: Subgroup analyses of the association between handgrip strength asymmetry and new‐onset stroke stratified by age, sex, marital status, and education level.
Figure S3: Subgroup analyses of the association between handgrip strength difference and new‐onset stroke stratified by age, sex, marital status, and education level.
Figure S4: Subgroup analyses of the association between the combined effect of handgrip strength weakness and asymmetry and new‐onset stroke, stratified by age, sex, marital status, and education level.
Data Availability Statement
The data that support the finding is available from Gateway to Global Aging Data (https://g2aging.org/) [42].