iconstar paper   HIV Articles  
Back grey arrow rt.gif
 
 
"Grip strength is a strong predictor of cardiovascular mortality and a moderately strong predictor of incident cardiovascular disease" new study finds
 
 
  Download the PDF here
 
Download the PDF here
 
"The association between grip strength and incident cardiovascular disease persisted after adjustment for confounding factors, thus prompting speculation as to whether loss of muscular strength might be part of the causal cascade leading to cardiovascular events. We were unable to discern the mechanism responsible for the inverse association between muscle strength and incident cardiovascular disease. Unmeasured factors, such as endothelial dysfunction and autonomic imbalance, both of which can be improved by exercise,23, 24, 25 as well as arterial stiffness, might mediate the association between muscle strength and cardiovascular events"
 
below is the Commentary "Grip strength and mortality: a biomarker of aging?" and the original research article "Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study"
 
Authors of original study (below) summarize: "In people of diverse economic and sociocultural backgrounds, grip strength is a strong predictor of cardiovascular mortality and a moderately strong predictor of incident cardiovascular disease. Grip strength is also predictive for non-cardiovascular mortality, but is not predictive of incident non-cardiovascular disease. Low grip strength is associated with higher case-fatality rates in people who develop cardiovascular or non-cardiovascular disease. These findings suggest that muscle strength is a risk factor for incident cardiovascular disease and can predict the risk of death in people who develop either cardiovascular or non-cardiovascular disease.......Importantly, grip strength has a stronger association with cardiovascular mortality than with incident cardiovascular disease, with an effect-size that was twice as large for cardiovascular death as for cardiovascular disease. This finding implies that the increased risk of incident cardiovascular disease associated with lower grip strength is insufficient to account for its more profound increased risk for cardiovascular death and suggests that low grip strength is associated with increased susceptibility to cardiovascular death in people who do develop cardiovascular disease. The high case-fatality rates in people who developed cardiovascular disease is consistent with this postulate.......The association between grip strength and incident cardiovascular disease persisted after adjustment for confounding factors, thus prompting speculation as to whether loss of muscular strength might be part of the causal cascade leading to cardiovascular events. We were unable to discern the mechanism responsible for the inverse association between muscle strength and incident cardiovascular disease. Unmeasured factors, such as endothelial dysfunction and autonomic imbalance, both of which can be improved by exercise,23, 24, 25 as well as arterial stiffness, might mediate the association between muscle strength and cardiovascular events.26 Further research is needed to understand whether improved muscle strength directly reduces the risk of incident cardiovascular disease.........Our findings with respect to cardiovascular disease and cardiovascular mortality are consistent with two studies from the Swedish military conscription register,2, 22 the results of which showed a 35% reduction in the risk of cardiovascular mortality in high grip-strength groups relative to the group with the lowest decile grip strength and a more modest (5%) reduction in the risk of cardiovascular disease per SD increase in grip strength. These Swedish studies were, however, limited to men, aged 16-19 years"
 
"Our study suggests that measurement of grip strength is a simple, inexpensive risk-stratifying method to assess risk of death, particularly in individuals who develop a major illness, and that muscle strength is a risk marker for incident cardiovascular disease in a number of countries and populations. Further research is needed to determine how people with low muscle strength might be helped to improve their outlook."
 
"The observational nature of this study does not allow us to make strong conclusions on the causal role of muscular strength in death or cardiovascular disease. Although we adjusted for many potential confounders, we cannot exclude the possibility that residual confounding underlies the associations between grip strength and these outcomes. To enhance follow-up, we only sampled households with residents who intended to remain at the same address for at least 4 years, but there is no reason to expect that this could have affected the validity of our results, although it might exclude people with no fixed address."
 
Low vs Middle vs High Income Countries [from Jules: it is noteworthy that grip strength is worse in lower income countries & best in high income countries suggesting aging concerns are greater in lower & middle vs high income countries]

HCV1.gif

Comment Grip strength and mortality: a biomarker of aging?........."Both muscular endurance and muscle strength are indicators of muscular fitness. Reduced muscle strength, as measured by grip strength, has been associated with an increased risk of mortality in many studies"
 
"Grip strength was inversely associated with all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, and stroke, and no significant association between grip strength and incident diabetes was found. After adjustment, we found no strong association between grip strength and the risk of hospital admission for pneumonia or COPD, injury from fall, or fracture. In high-income countries, the risk of cancer and grip strength were positively associated, but this association was not found in middle-income and low-income countries (table 2)."
 
"Grip strength is a simple but powerful predictor of future disability, morbidity, and mortality. The relation between grip strength and future mortality has been shown, not only in older people1 but also in middle-aged2 and young people.....Leong and colleagues now show6 that grip strength predicts not only all-cause mortality (hazard ratio for every 5 kg decrease in grip strength 1°16, 95% CI 1°13-1°20) but also cardiovascular mortality (1°17, 1°11-1°24), non-cardiovascular mortality (1°17, 1°12-1°21), and cardiovascular disease occurrence (myocardial infarction [1°07, 1°02-1°11], and stroke [1°09, 1°05-1°15]) across a range of country and income settings. These findings seem relatively specific because no association was found with incident diabetes, cancer, pneumonia, hospital admission for respiratory illness, injury from a fall, or fracture. Furthermore, case-fatality rates in incident cases of cardiovascular disease were higher in people with low grip strength......How should these findings be interpreted? First, the scale and scope of the study provide definitive replication: there can be no doubt that grip strength predicts future all-cause mortality across a range of populations. Second, that grip strength is related specifically to cardiovascular mortality and morbidity suggests a potential mechanistic explanation. Third, the finding that grip strength is a more powerful predictor of cardiovascular outcomes than systolic blood pressure raises important questions about risk prediction and why these cause-specific associations exist."
 
The findings from this study add to the growing evidence that skeletal muscle function is an important component of health, ageing, and disease. Poor muscle strength has been proposed to directly affect mortality through its association with increased disability. However, the findings from PURE suggest that associations with cardiovascular disease and its risk factors might be an additional pathway......An intriguing implication is that grip strength might act as a biomarker of ageing across the life course.9 This is not a new idea, but findings from PURE add support. Loss of grip strength is unlikely to lie on a single final common pathway for the adverse effects of ageing, but it might be a particularly good marker of underlying ageing processes, perhaps because of the rarity of muscle-specific diseases contributing to change in muscle function."
 
"In view of the significant association between grip strength and all-cause mortality, cardiovascular mortality, and incident cardiovascular disease in the PURE study population, we did a post-hoc comparison of the prognostic importance of grip strength with systolic blood pressure (a robust causal factor for death) and with physical activity levels (expressed as the natural logarithm of metabolic equivalent of task [MET]-min per week of activity). After adjustment, grip strength is a stronger predictor of death (HR per SD reduction in grip strength 1°37, 95% CI 1°28-1°47; p<0°0001) than is systolic blood pressure (1°15, 1°10-1°21; p<0°0001) and has similar predictive value for cardiovascular-related death (1°45, 1°30-1°63; p<0°0001), whereas systolic blood pressure exhibited a larger association with incident cardiovascular-related disease (HR 1°39, 95% CI 1°32-1°47; p<0°0001) than did grip strength (1°21, 1°13-1°29; p<0°0001) (table 3). Physical activity levels were worse predictors of death (1°07, 1°02-1°11; p=0°002), cardiovascular-related death (1°09, 1°02-1°16; p=0°01), and incident cardiovascular-related disease (1°04, 0°991-1°09; p=0°1) than either grip strength or systolic blood pressure."
 
[from Jules: grip strength is one of several components of frailty marker test]

HCV2.gif

The Lancet July 2015
 
Grip strength is a simple but powerful predictor of future disability, morbidity, and mortality. The relation between grip strength and future mortality has been shown, not only in older people1 but also in middle-aged2 and young people.3 The evidence has been summarised in systematic reviews4 and in a meta-analysis.5 However, important questions remain, such as whether the association between grip strength and future mortality is generalisable across countries of widely varying socioeconomic circumstances and, particularly, what might explain the associations. In The Lancet, Darryl Leong and colleagues6 address the first question comprehensively and provide clues as to how the second question might be further explored.
 
Leong and colleagues6 investigated the relation between grip strength, cause-specific mortality, and incident disease in 139 691 participants aged 35-70 years from three high-income, ten middle-income, and four low-income countries during a median follow-up period of 4 years. This work forms part of the Prospective Urban Rural Epidemiology (PURE) Study, designed to investigate societal effects on chronic non-communicable diseases in 17 countries. The international breadth and methodological rigour of the undertaking has already led to a series of high-impact articles, one of which described cardiovascular risk and events.7 Leong and colleagues now show6 that grip strength predicts not only all-cause mortality (hazard ratio for every 5 kg decrease in grip strength 1°16, 95% CI 1°13-1°20) but also cardiovascular mortality (1°17, 1°11-1°24), non-cardiovascular mortality (1°17, 1°12-1°21), and cardiovascular disease occurrence (myocardial infarction [1°07, 1°02-1°11], and stroke [1°09, 1°05-1°15]) across a range of country and income settings. These findings seem relatively specific because no association was found with incident diabetes, cancer, pneumonia, hospital admission for respiratory illness, injury from a fall, or fracture. Furthermore, case-fatality rates in incident cases of cardiovascular disease were higher in people with low grip strength. How should these findings be interpreted? First, the scale and scope of the study provide definitive replication: there can be no doubt that grip strength predicts future all-cause mortality across a range of populations. Second, that grip strength is related specifically to cardiovascular mortality and morbidity suggests a potential mechanistic explanation. Third, the finding that grip strength is a more powerful predictor of cardiovascular outcomes than systolic blood pressure raises important questions about risk prediction and why these cause-specific associations exist.
 
The work has some limitations. Leong and colleagues6 highlight the limitations of observational epidemiology to address causal pathways. In terms of specificity of the findings, issues of ascertainment bias might be relevant; identification of mortality might be less problematic than determination of incident disease. With respect to the morbidity data, cases of cardiovascular disease can be more straightforward to identify than falls and related injuries, perhaps explaining the absence of an association between grip strength with the latter outcome. The investigators noted an unexpected association between low muscle strength and low risk of cancer in high-income countries, but not in low-income countries. This association warrants further investigation, although in the context of multiple analyses and absence of consistency with a previous study,8 the association might have arisen by chance. The ability to explore mechanisms underlying the associations with cardiovascular disease was limited because, understandably, the breadth of the data collection in PURE came at the expense of depth. Future rounds of data collection will have the potential to address these mechanisms. The investigators did consider the possibility of reverse causation, but the associations between grip strength and mortality were robust to exclusion of participants who died within 6 months of grip-strength measurement, and exclusion of participants with pre-existing cardiovascular disease or cancer.
 
The findings from this study add to the growing evidence that skeletal muscle function is an important component of health, ageing, and disease. Poor muscle strength has been proposed to directly affect mortality through its association with increased disability. However, the findings from PURE suggest that associations with cardiovascular disease and its risk factors might be an additional pathway. Of course, this association does not explain why grip strength should be related to cardiovascular disease, and Leong and colleagues6proffer only the non-specific, though plausible, suggestion that low grip strength represents poor health. This explanation is not entirely consistent with the findings of other studies3 that show long-term associations between grip strength in young people and subsequent mortality.
 
An intriguing implication is that grip strength might act as a biomarker of ageing across the life course.9 This is not a new idea, but findings from PURE add support. Loss of grip strength is unlikely to lie on a single final common pathway for the adverse effects of ageing, but it might be a particularly good marker of underlying ageing processes, perhaps because of the rarity of muscle-specific diseases contributing to change in muscle function. Interestingly, similar age-related changes have been reported in other species, such as Caenorhabditis elegans.10, 11 Life-course normative data12 have been described in a UK setting, and birth and ageing cohort studies, particularly those with long-term longitudinal data,13 provide ideal opportunities to explore this hypothesis. Furthermore, linkage of epidemiological findings to new approaches in muscle biology could yield informative insights into the nature of human ageing.

HCV3.gif

----------------------------
 
Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study
 
The Lancet 2015 July
 
Summary
 
Background

 
Reduced muscular strength, as measured by grip strength, has been associated with an increased risk of all-cause and cardiovascular mortality. Grip strength is appealing as a simple, quick, and inexpensive means of stratifying an individual's risk of cardiovascular death. However, the prognostic value of grip strength with respect to the number and range of populations and confounders is unknown. The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries.
 
Methods
 
The Prospective Urban-Rural Epidemiology (PURE) study is a large, longitudinal population study done in 17 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years and if household members intended to stay at that address for another 4 years. Participants were assessed for grip strength, measured using a Jamar dynamometer. During a median follow-up of 4°0 years (IQR 2°9-5°1), we assessed all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, stroke, diabetes, cancer, pneumonia, hospital admission for pneumonia or chronic obstructive pulmonary disease (COPD), hospital admission for any respiratory disease (including COPD, asthma, tuberculosis, and pneumonia), injury due to fall, and fracture. Study outcomes were adjudicated using source documents by a local investigator, and a subset were adjudicated centrally.
 
Findings
 
Between January, 2003, and December, 2009, a total of 142 861 participants were enrolled in the PURE study, of whom 139 691 with known vital status were included in the analysis. During a median follow-up of 4°0 years (IQR 2°9-5°1), 3379 (2%) of 139 691 participants died. After adjustment, the association between grip strength and each outcome, with the exceptions of cancer and hospital admission due to respiratory illness, was similar across country-income strata. Grip strength was inversely associated with all-cause mortality (hazard ratio per 5 kg reduction in grip strength 1°16, 95% CI 1°13-1°20; p<0°0001), cardiovascular mortality (1°17, 1°11-1°24; p<0°0001), non-cardiovascular mortality (1°17, 1°12-1°21; p<0°0001), myocardial infarction (1°07, 1°02-1°11; p=0°002), and stroke (1°09, 1°05-1°15; p<0°0001). Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure. We found no significant association between grip strength and incident diabetes, risk of hospital admission for pneumonia or COPD, injury from fall, or fracture. In high-income countries, the risk of cancer and grip strength were positively associated (0°916, 0°880-0°953; p<0°0001), but this association was not found in middle-income and low-income countries.
 
Interpretation
 
This study suggests that measurement of grip strength is a simple, inexpensive risk-stratifying method for all-cause death, cardiovascular death, and cardiovascular disease. Further research is needed to identify determinants of muscular strength and to test whether improvement in strength reduces mortality and cardiovascular disease.
 
introduction
 
Physical fitness is an important predictor of mortality and morbidity.1, 2 Physical fitness consists of cardiorespiratory fitness and muscular fitness. Both muscular endurance and muscle strength are indicators of muscular fitness. Reduced muscle strength, as measured by grip strength, has been associated with an increased risk of mortality in many studies.2, 3, 4, 5, 6, 7, 8, 9, 10, 11 However, the mechanism by which low muscle strength might predispose to death is uncertain. Grip strength measurement is appealing as a quick and inexpensive way to stratify an individual's risk of death. However, the information on the prognostic value of grip strength is largely derived from high-income countries, and data from low-income or middle-income countries are rare. The prognostic value of grip strength in these settings is uncertain but would be useful as an inexpensive and simple test.
 
The Prospective Urban-Rural Epidemiology (PURE) study is a prospective cohort study of more than 154 000 community-based individuals from 17 high-income, middle-income, and low-income countries. The aim of the PURE study was to examine the association between societal factors, risk factors, and chronic non-communicable diseases across various sociocultural and economic environments.
 
Methods
 
Study Design and participants

 
The design of the PURE study has been described previously.12 In brief, we selected countries to achieve substantial socioeconomic heterogeneity. For reasons of feasibility, we did not undertake proportionate sampling of all countries worldwide, or of regions within countries. At the start of the study, we classified selected countries according to the World Bank scheme as high-income (Canada, Sweden, and United Arab Emirates), upper middle-income (Argentina, Brazil, Chile, Malaysia, Poland, South Africa, and Turkey), lower middle-income (China, Colombia, and Iran), and low-income (Bangladesh, India, Pakistan, and Zimbabwe). To achieve country-income strata with similar numbers of participants, we grouped participants from high-income and upper middle-income countries together as participants of high-income countries.
 
Within participating communities, our goal was to enrol an unbiased sample of households. Households were eligible if at least one member was aged 35-70 years and if household members intended to stay at that address for another 4 years. Of the 142 861 participants who were enrolled in the PURE study, the 139 691 participants with known vital status were included in the present analysis. Results of previous analyses12, 13 have shown that the population included can be used to make comparisons across countries because the risk factor levels and mortality rates were similar to those seen in independent studies including the same countries. The PURE study was approved by the relevant research ethics committees in the participating countries. All participants provided written informed consent.
 
Procedures
 
For baseline characteristics, trained study personnel gave a standardised questionnaire to at least one household member aged 35-70 years. These questions elicited self-reported demographics, cardiovascular risk factors, comorbid disorders, education levels, employment status, physical activity levels, tobacco and alcohol use, and dietary patterns. Study personnel also measured participant anthropometrics and blood pressure. Physical activity level was assessed with the International Physical Activity Questionnaire (IPAQ)14 and was classified as low, moderate, or high (appendix). We assessed nutrient intake with food frequency questionnaires that were individualised and validated15, 16, 17 for the countries participating in the PURE study. On the basis of responses to the food frequency questionnaire, we estimated daily calorie intake and the proportion of calorie intake from protein. We calculated body-mass index (BMI; kg/m2) from weight and height.
 
Grip strength was measured by study personnel at the baseline visit with a Jamar dynamometer, according to a standardised protocol. For the first study participants, three measurements were made from the participant's non-dominant hand. During the course of the study, the protocol was amended so that three measurements were made from both hands of each participant. We used only the maximum values obtained from each hand.18 Where values were missing for one hand but were present for the other (38 974 missing dominant hand values and 929 missing non-dominant hand values), we estimated grip strength values for the missing hand using the coefficient and constant from the linear regression of non-dominant and dominant hand-grip strength. We calculated overall grip strength from the mean of the maximum values of non-dominant and dominant hand grip strength.
 
Information about participant vital status was obtained in person or by telephone calls at annual intervals.
 
Outcomes
 
We assessed time to all-cause mortality, cardiovascular mortality (defined as death due to myocardial infarction, stroke, heart failure, other cardiovascular cause, or sudden unexpected death), non-cardiovascular mortality, myocardial infarction, stroke, incident diabetes, pneumonia, hospital admission for pneumonia or COPD, hospital admission for any respiratory disease (including COPD, asthma, tuberculosis, or pneumonia), injury due to a fall, or fracture. We sought supporting documents for all outcomes. A local investigator, trained to apply standardised event-verification criteria, verified outcomes using the supporting documents. In a random subset of cases, a central adjudication committee assessed and confirmed or refuted outcomes using pre-specified definitions and criteria. If a participant was no longer living at their original address, their vital status was ascertained from other household members, when possible. If a participant had died and the cause of death was unknown, cause of death was determined by verbal autopsy.19 The verbal autopsy is a series of standardised questions given to household members about symptoms and events surrounding a death. This method has been previously validated against administrative registry data.19
 
Statistical analysis
 
We calculated hazard ratios (HR) of time to all-cause mortality with Cox proportional hazards models. To account for the clustered nature of the data, we used shared frailty models. The clustering variable was the community to which each individual belonged. The proportional hazards assumption was checked by visual inspection of log-log plots. For all other outcomes, we adopted a competing risks framework, in which death occurring in the absence of the outcome of interest was treated as a competing risk because the death precluded the occurrence of the event of interest. We present the results as cumulative incidence curves and we did the modelling with the approach of Fine and Gray,20 with effect-sizes presented as subdistribution HRs.
 
To determine whether associations between grip strength and outcomes were uniform across countries of different income, we first modelled grip strength (divided by tertile) as part of an interaction term with country income (stratified as high income, middle income, or low income). If this interaction was significant (at α=0°05), there might be heterogeneity of the association between grip strength and outcome across country-income strata. For all exposures, effect estimates are presented per 5 kg reduction in grip strength.
 
We made adjustment for the following potential confounders of the association between grip strength and outcomes: age; sex; education level; employment status; physical activity level; tobacco and alcohol use; daily dietary energy intake; proportion of calorie intake from protein; self-reported hypertension, diabetes, heart failure, coronary artery disease, COPD, prior stroke, or cancer; BMI; and waist-to-hip ratio. We did the following five sensitivity analyses: an analysis, from which participants dying within 6 months of enrolment were excluded to reduce the influence of reverse causation, whereby individuals with advanced disease have reduced grip strength as a consequence of the disease and are also more likely to die from the disease; an analysis restricted to grip strength in the dominant hand; an analysis restricted to grip strength in the non-dominant hand; an analysis restricted to maximum grip strength values from either hand, in keeping with published recommendations;21 and an analysis excluding participants with cardiovascular disease or cancer at baseline. To examine the prognostic importance of grip strength in participants with incident disease, we calculated the case-fatality rates stratified by grip-strength tertile in participants with incident myocardial infarction, stroke, cancer, pneumonia, hospital admission for pneumonia or COPD, injury from a fall, or fracture. We used STATA 13.1 software for the analyses.
 
Role of the funding source
 
The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
 
Results
 
Participant characteristics were stratified by sex and grip-strength tertile (table 1). Baseline grip strength and vital status were recorded for 139 691 participants. Increased grip strength was associated with young age, male sex, high level of education, employment, high level of physical activity, high dietary calorie intake, of which a high proportion came from protein, and with increasing height, weight, and upper arm circumference. Previous use of alcohol or tobacco was associated with an increase in grip strength. Age and height-adjusted grip strength between countries (figure 1) and ethnic origin (figure 2) was heterogeneous. For men, grip strength values adjusted for age and height were 30°2 kg (SD 8°20) in low-income countries, 37°3 kg (8°19) in middle-income countries, and 38°1 kg (8°98) in high-income countries. For women, grip strength values adjusted for age and height were 24°3 kg (8°67) in low-income countries, 27°9 kg (8°07) in middle-income countries, and 26°6 kg (8°19) in high-income countries (figure 1). Low grip strength was associated with the presence of the following baseline comorbid disorders: hypertension, coronary artery disease, heart failure, stroke, or COPD. No clear association was noted between a previous diagnosis of cancer and grip strength.
 
During a median follow-up of 4°0 years (2°9-5°1), 3379 (2°4%) of 139 691 participants died. The cause was known for 2677 (79%) of 3379 deaths, whereas the cause of death was ascribed by verbal autopsy in 702 (21%) cases. Table 2 shows the number of deaths from cardiovascular and non-cardiovascular comorbidity and the number of cases of myocardial infarctions, strokes, diabetes, incident cancers, injuries related to a fall, hospital admissions for COPD or pneumonia, and hospital admission for any respiratory illness, as well as the associations between grip strength and these outcomes. After adjustment, the association between grip strength and each outcome, with the exceptions of cancer and hospital admission due to respiratory illness, was similar across country-income strata. Grip strength was inversely associated with all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, and stroke, and no significant association between grip strength and incident diabetes was found. After adjustment, we found no strong association between grip strength and the risk of hospital admission for pneumonia or COPD, injury from fall, or fracture. In high-income countries, the risk of cancer and grip strength were positively associated, but this association was not found in middle-income and low-income countries (table 2).
 
The sensitivity analyses yielded similar findings to the principal analysis (appendix). In all sensitivity analyses, the inverse association between grip strength and incident diabetes was significant, although the effect-size remained similar. Additionally, the grip-strength and country-income interaction terms were significant for hospital admission related to respiratory illness, and in some of the sensitivity analyses, grip strength and country income were significantly associated with cancer. The patterns of effect sizes, both overall and stratified by country income, were similar in the sensitivity analyses to the main analysis.
 
In view of the significant association between grip strength and all-cause mortality, cardiovascular mortality, and incident cardiovascular disease in the PURE study population, we did a post-hoc comparison of the prognostic importance of grip strength with systolic blood pressure (a robust causal factor for death) and with physical activity levels (expressed as the natural logarithm of metabolic equivalent of task [MET]-min per week of activity). After adjustment, grip strength is a stronger predictor of death (HR per SD reduction in grip strength 1°37, 95% CI 1°28-1°47; p<0°0001) than is systolic blood pressure (1°15, 1°10-1°21; p<0°0001) and has similar predictive value for cardiovascular-related death (1°45, 1°30-1°63; p<0°0001), whereas systolic blood pressure exhibited a larger association with incident cardiovascular-related disease (HR 1°39, 95% CI 1°32-1°47; p<0°0001) than did grip strength (1°21, 1°13-1°29; p<0°0001) (table 3). Physical activity levels were worse predictors of death (1°07, 1°02-1°11; p=0°002), cardiovascular-related death (1°09, 1°02-1°16; p=0°01), and incident cardiovascular-related disease (1°04, 0°991-1°09; p=0°1) than either grip strength or systolic blood pressure. The inverse association between grip strength and death was consistent between the sexes (interaction p=1°0) and across age by tertile (interaction p=0°1). The inverse association between grip strength and cardiovascular-related death was also consistent between the sexes (interaction p=0°9) and across age (interaction p=0°4).
 
High grip strength was associated with low case-fatality rate in individuals with incident myocardial infarction, stroke, cancer, pneumonia, hospital admission for pneumonia or COPD, injury from a fall, or fracture (figure 3).
 
Discussion
 
In people of diverse economic and sociocultural backgrounds, grip strength is a strong predictor of cardiovascular mortality and a moderately strong predictor of incident cardiovascular disease. Grip strength is also predictive for non-cardiovascular mortality, but is not predictive of incident non-cardiovascular disease. Low grip strength is associated with higher case-fatality rates in people who develop cardiovascular or non-cardiovascular disease. These findings suggest that muscle strength is a risk factor for incident cardiovascular disease and can predict the risk of death in people who develop either cardiovascular or non-cardiovascular disease.
 
Importantly, grip strength has a stronger association with cardiovascular mortality than with incident cardiovascular disease, with an effect-size that was twice as large for cardiovascular death as for cardiovascular disease. This finding implies that the increased risk of incident cardiovascular disease associated with lower grip strength is insufficient to account for its more profound increased risk for cardiovascular death and suggests that low grip strength is associated with increased susceptibility to cardiovascular death in people who do develop cardiovascular disease. The high case-fatality rates in people who developed cardiovascular disease is consistent with this postulate. Our findings with respect to cardiovascular disease and cardiovascular mortality are consistent with two studies from the Swedish military conscription register,2, 22 the results of which showed a 35% reduction in the risk of cardiovascular mortality in high grip-strength groups relative to the group with the lowest decile grip strength and a more modest (5%) reduction in the risk of cardiovascular disease per SD increase in grip strength. These Swedish studies were, however, limited to men, aged 16-19 years, and only a few confounding factors were assessed. The results of our study show that these findings are generalisable for people of both sexes, of a wide age range and living in countries of all income strata.
 
The association between grip strength and incident cardiovascular disease persisted after adjustment for confounding factors, thus prompting speculation as to whether loss of muscular strength might be part of the causal cascade leading to cardiovascular events. We were unable to discern the mechanism responsible for the inverse association between muscle strength and incident cardiovascular disease. Unmeasured factors, such as endothelial dysfunction and autonomic imbalance, both of which can be improved by exercise,23, 24, 25 as well as arterial stiffness, might mediate the association between muscle strength and cardiovascular events.26 Further research is needed to understand whether improved muscle strength directly reduces the risk of incident cardiovascular disease.
 
That grip strength is strongly inversely associated with the risk of non-cardiovascular mortality, but not with incident non-cardiovascular diseases, is novel. Furthermore, case-fatality rates from non-cardiovascular diseases were high in individuals with low grip strength. These results suggest that low muscle strength might not play a major causal part in the occurrence of cancer, falls, fractures, or the need for hospital admission for respiratory illnesses, but that, as with incident cardiovascular disease, low muscle strength predisposes to a fatal outcome if these non-cardiovascular diseases develop. The absence of a strong association between grip strength and the risk of injury from a fall was unexpected. A systematic review27 of resistance training suggested that muscle strengthening alone might not improve balance. Thus, the mechanisms underlying falls are complex and probably involve sensorineural factors. This complexity might explain, in part, the absence of a strong association between grip strength and injury from a fall. Furthermore, evidence suggests that upper limb strength might not be a suitable surrogate for lower limb strength,28 which could be a more relevant marker of risk of falls.
 
We found no strong association between grip strength and incident diabetes. There is a paucity of previous evidence to establish an association between muscle strength and the risk of diabetes. Associations between reduced muscle strength and insulin resistance have been identified in adults at risk of diabetes29 and in adolescents.30 However, to our knowledge, we are the first to examine the association between muscle strength and the incidence of clinical diabetes. The inverse association before adjustment, which was not recorded after adjustment, suggests that confounders might account for previous suggestions of an association between muscle strength and diabetes. Our analysis revealed an unexpected association between grip strength and the risk of cancer. Low muscle strength was associated with a low cancer risk in high-income countries. This finding requires confirmation in further research and examination of different cancer subtypes.
 
The strength of our study is that it was done in a large cohort of participants from various countries, ethnic origins, and socioeconomic backgrounds and who were sampled in a representative manner. This permits our findings to be widely generalisable. Our study also incorporated a wide range of outcomes, many of which had never been assessed with muscle strength as an exposure, and accounted for a large number of potential covariates. The associations between grip strength and outcomes remained after excluding participants who died within 6 months of grip-strength measurement or participants with pre-existing cardiovascular disease or cancer, which partly allays concerns over reverse causation.
 
Panel
 
Research in context
 
Systematic review

 
We searched PubMed for relevant research published between Jan 1, 2005, and Jan 1, 2015, using the term "muscle strength" AND "mortality" OR "prognosis" OR "cardiovascular" OR "stroke" OR "cancer" OR "injury" OR "fall" OR "pneumonia" OR "chronic obstructive pulmonary disease". We screened papers by title and abstract to identify full-text reports that were relevant to the study aims. We also screened citation lists from these full-text reports to identify other relevant research. We considered papers if they contained an evaluation of the relation between muscle strength and at least one of the outcomes of interest. The papers cited in this report were selected to be representative of the existing evidence base, are not an exhaustive list of relevant research.
 
Interpretation
 
Existing evidence on the prognostic value of muscle-strength measurement was limited to high-income countries and focused on all-cause and cause-specific mortality. The results of our study show that there is heterogeneity in muscle strength in people living in different countries and country-income settings; not only is there a significant inverse association between muscle strength and the risk of mortality, but also the risk of incident cardiovascular disease; and low muscle strength is a biomarker of susceptibility in individuals with incident disease, and might identify a high-risk group in people who develop either cardiovascular or non-cardiovascular disease.
 
The observational nature of this study does not allow us to make strong conclusions on the causal role of muscular strength in death or cardiovascular disease. Although we adjusted for many potential confounders, we cannot exclude the possibility that residual confounding underlies the associations between grip strength and these outcomes. To enhance follow-up, we only sampled households with residents who intended to remain at the same address for at least 4 years, but there is no reason to expect that this could have affected the validity of our results, although it might exclude people with no fixed address.
 
Our study suggests that measurement of grip strength is a simple, inexpensive risk-stratifying method to assess risk of death, particularly in individuals who develop a major illness, and that muscle strength is a risk marker for incident cardiovascular disease in a number of countries and populations. Further research is needed to determine how people with low muscle strength might be helped to improve their outlook.

 
 
 
 
  iconpaperstack View Older Articles   Back to Top   www.natap.org