Prospective association between handgrip strength and cardiac structure and function in UK adults
Prospective association between handgrip strength and cardiac structure and function in UK adults
Sebastian E. Beyer 0 1
Mihir M. Sanghvi 1
Nay Aung 1
Alice Hosking 1
Jackie A. Cooper 1
JoseÂ Miguel Paiva 1
Aaron M. Lee 1
Kenneth Fung 1
Elena Lukaschuk 1
Valentina Carapella 1
Murray A. Mittleman 0 1
Soren Brage 1 2
Stefan K. Piechnik 1
Stefan Neubauer 1
Steffen E. Petersen 1
0 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America, 2 William Harvey Research Institute, NIHR Biomedical Research Center at Barts, Queen Mary University of London , London , United Kingdom , 3 Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford , West Wing , John Radcliffe Hospital , Headington, Oxford , United Kingdom , 4 Cardiovascular Epidemiology Research Unit, Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts , United States of America
1 Editor: Pasquale Abete, Universita degli Studi di Napoli Federico II , ITALY
2 MRC Epidemiology Unit, University of Cambridge , Cambridge , United Kingdom
Data Availability Statement: The data in this study
are owned by a third party, the UK Biobank (www.
ukbiobank.ac.uk) and legal constraints do not
permit public sharing of the data. The UK Biobank,
however, is open to all bona fide researchers
anywhere in the world. Thus, the data used in this
communication can be easily and directly accessed
by applying through the UK Biobank Access
Management System (www.ukbiobank.ac.uk/
Handgrip strength, a measure of muscular fitness, is associated with cardiovascular (CV)
events and CV mortality but its association with cardiac structure and function is unknown.
The goal of this study was to determine if handgrip strength is associated with changes in
cardiac structure and function in UK adults.
Methods and results
Left ventricular (LV) ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume
(ESV), stroke volume (SV), mass (M), and mass-to-volume ratio (MVR) were measured in
a sample of 4,654 participants of the UK Biobank Study 6.3 ± 1 years after baseline using
cardiovascular magnetic resonance (CMR). Handgrip strength was measured at baseline
and at the imaging follow-up examination. We determined the association between
handgrip strength at baseline as well as its change over time and each of the cardiac
outcome parameters. After adjustment, higher level of handgrip strength at baseline was
associated with higher LVEDV (difference per SD increase in handgrip strength: 1.3ml,
95% CI 0.1±2.4; p = 0.034), higher LVSV (1.0ml, 0.3±1.8; p = 0.006), lower LVM (-1.0g,
-1.8 ±-0.3; p = 0.007), and lower LVMVR (-0.013g/ml, -0.018 ±-0.007; p<0.001). The
association between handgrip strength and LVEDV and LVSV was strongest among younger
individuals, while the association with LVM and LVMVR was strongest among older
Funding: This work was supported by the following
institutions: KF is supported by The Medical
College of Saint Bartholomew's Hospital Trust, an
independent registered charity that promotes and
advances medical and dental education and
research at Barts and The London School of
Medicine and Dentistry. AL and SEP acknowledge
support from the NIHR Cardiovascular Biomedical
Research Centre at Barts and from the
ªSmartHeartº EPSRC program grant (EP/P001009/
1). SN and SKP are supported by the Oxford NIHR
Biomedical Research Centre and the Oxford British
Heart Foundation Centre of Research Excellence.
This project was enabled through access to the
MRC eMedLab Medical Bioinformatics
infrastructure, supported by the Medical Research
Council (grant number MR/L016311/1). The work
of SB was funded by the Medical Research Council
(MC_UU_12015/3). NA is supported by a
Wellcome Trust Research Training Fellowship
(203553/Z/Z). The authors SEP, SN and SKP
acknowledge the British Heart Foundation (BHF)
for funding the manual analysis to create a
cardiovascular magnetic resonance imaging
reference standard for the UK Biobank imaging
resource in 5000 CMR scans (PG/14/89/31194).
Competing interests: Steffen Petersen provides
consultancy to Circle Cardiovascular Imaging Inc.,
Calgary, Canada. The other authors declare that
they have no competing interests. This does not
alter our adherence to PLOS ONE policies on
sharing data and materials.
Better handgrip strength was associated with cardiac structure and function in a pattern
indicative of less cardiac hypertrophy and remodeling. These characteristics are known to
be associated with a lower risk of cardiovascular events.
Cardiovascular disease (CVD) accounts for 17.3 million deaths per year worldwide and is
expected to account for 23.6 million by 2030 [
]. It is, therefore, important to identify
predictors of CVD incidence to be able to initiate evidence-based primary prevention among
individuals at elevated risk. Handgrip strength is an inexpensive, reproducible and easy to
implement measure of muscular fitness that has been repeatedly shown to be associated with
CVD incidence [2±7], independent of measures of body composition such as muscle area and
The association between handgrip strength and CVD has been demonstrated in various
settings. Sasaki et al [
] showed that the strength of the association between handgrip strength
and cardiovascular mortality is similar among men and women and Ortega et al [
] showed an
association between handgrip strength and premature cardiovascular death among
adolescents. More recently, the Prospective Urban Rural Epidemiology (PURE) study demonstrated
that the relationship between grip strength and CVD is consistent across a wide range of
country-specific incomes [
]. Further study is needed to investigate potential underlying
pathophysiologic mechanisms linking handgrip strength to CVD incidence.
Recently, several pathways have been proposed through which sarcopenia, a cause of low
handgrip strength, could contribute to heart failure with preserved ejection fraction [
Among those are activation of systemic inflammation [
] and insulin resistance [
changes seen in patients with heart failure with preserved ejection fraction include concentric
left ventricular remodeling and concentric hypertrophy [
]. Thus, the observed association
between handgrip strength and CVD incidence may be due to less cardiac remodeling and
hypertrophy among individuals with better handgrip strength. The use of cardiac magnetic
resonance (CMR) imaging is the reference standard to accurately determine cardiac structure
and function [
]. However, no studies exist that have described the relationship with
The goal of this study is to investigate the association between muscular fitness as repeatedly
assessed by handgrip strength and cardiac structure and function as measured by CMR in a
large sample of UK adults.
The UK Biobank (http://www.ukbiobank.ac.uk) is a prospective cohort study of more than
500,000 men and women aged 40±69 at the time of recruitment between 2006 and 2010 in 22
centers across the UK. The baseline assessment of study participants included an extensive
questionnaire, a physical assessment including height, weight, body fat, blood pressure, pulse
rate, and handgrip strength, and collection of biological samples. Follow-up of participants
was conducted via linkage to health record systems and re-contact with the participants. The
study complies with the Declaration of Helsinki. All participants provided written consent and
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UK Biobank's scientific protocol and operational procedures were reviewed and approved by
the North West Research Ethics Committee in the UK.
We excluded participants with any history of cardiovascular conditions Details are available in
the supporting information (S1 Methods).
Cardiovascular magnetic resonance imaging
The UK Biobank invited participants back for a comprehensive imaging visit [
including a 20-minute CMR examination at 1.5 Tesla with a goal to perform 100,000 CMR scans.
The current study represents an interim data release with 5,065 participants.
The CMR protocol and image analysis have been previously described [
]. In brief, CMR
imaging is being performed in Cheadle, United Kingdom, on a clinical wide bore 1.5 Tesla
scanner (MAGNETOM Aera, Syngo Platform VD13A, Siemens Healthcare, Erlangen,
Germany). 18 channels anterior body surface coil was used in combination with a 12 elements of
an integrated 32 element spine coil and electrocardiogram (ECG) gating for cardiac
synchronization. Acquisitions include piloting and sagittal, transverse and coronal partial coverage of
the chest and abdomen. For cardiac function, three long axis cines (horizontal long axisÐ
HLA, vertical long axisÐVLA, and left ventricular outflow tractÐLVOT cines both sagittal
and coronal) and a complete short axis (SA) stack of balanced steady state free precession
(bSSFP) cines, covering the left ventricle (LV) and right ventricle (RV) are acquired [
all measured cardiac parameters, a CMR reference standard has been created for the UK
Biobank using 5,065 CMR scans as previously described [
]. The manual analysis of CMR scans
was performed across two core laboratories based in London and Oxford using cvi42
post-processing software (Version 5.1.1, Circle Cardiovascular Imaging Inc., Calgary, Canada).
Handgrip strength measurement
Handgrip strength was measured at baseline and at the imaging visit using a Jamar J00105
hydraulic hand dynamometer. The participant was asked to squeeze the handle of the
dynamometer as strongly as possible for three seconds. At both visits, one measurement was
obtained from each hand.
Statistical analysis and model development
The primary exposures of interest in our models were (i) Handgrip strength at baseline and
(ii) change in handgrip strength between baseline and the imaging visit. Even though handgrip
strength was measured in both hands, we limited the analysis to the highest measurement at
each visit because of very high correlations between handgrip strength measurements.
The outcomes of interest were derived from the manually verified CMR results [
included: (i) left ventricular ejection fraction (LVEF), (ii) left ventricular end-diastolic volume
(LVEDV), (iii) left ventricular end-systolic volume (LVESV), (iv) left ventricular stroke
volume (LVSV), (v) left ventricular mass (LVM), and (vi) left ventricular mass to volume ratio
(LVMVR), a CMR measure of cardiac adaptation previously described [
In all statistical models, we adjusted for: (i) baseline demographics, (ii) cardiac risk factors,
(iii) drivers of muscle mass, and (iv) physical activity level, measured in metabolic equivalent
of task (MET) minutes [
], mean centered as detailed in Table 1 (full details are available in
the supporting information [S1 Methods and S1 Table]). All potential confounders were
selected a priori.
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We used separate multivariable linear regression models to investigate the relationship
between baseline handgrip strength and change in handgrip strength and each of the cardiac
outcome parameters and expressed the results per standard deviation (SD) increase in
handgrip strength / change in handgrip strength (mean centered). To evaluate whether the observed
associations differed by age, sex and physical activity level (MET minutes), we included
product terms between handgrip strength and each of these potential modifiers.
Although missingness was generally low, we used multiple imputation by chained equations
(MICE) to generate 10 complete datasets  (full details are available in the supporting
information [S1 Methods]). In brief, we used predictive mean matching with three nearest
neighbors for continuous variables, logistic regression for binary variables, and multinomial logistic
regression for categorical variables. Rubin's rule [
] was used to pool estimates and standard
errors of the beta coefficients as well as predictions [
]. Chi-square values of likelihood
ratio test were pooled as recommended by Meng and Rubin [
]. Figures shown are for a
single imputed data set in order to be able to use Stata's commands `adjustrcspline', `margins',
and `marginsplot'. Confidence intervals pooled across all ten imputation sets were less than 1%
wider than those presented in the figures.
We conducted the following sensitivity analyses: (i) an analysis with the
restricted-cubicspline-transformed exposures, investigating the relationship between handgrip strength and
the cardiac outcome parameters We used restricted cubic spline transformations with five
knots and knot locations as recommended by Harrell [
] if a non-linear relationship was
observed between handgrip strength or change in handgrip strength and any outcome
conditional on the covariates. Non-linearity was defined as a p-value of <0.05 of a likelihood-ratio
(LR) test comparing the model with the transformed predictor to the model including only the
linear term; (ii) an analysis excluding hypertension, systolic blood pressure, diastolic blood
pressure, and diabetes mellitus given the possibility that these might be important mediators
of the association between handgrip strength on the cardiac outcomes rather than confounders
]; and (iii) an analysis of participants with complete data. We used Stata v.14.1
(StataCorp, College Station, Texas, USA) for all statistical analyses.
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By April 2017, cardiac parameters had been measured in 5,065 individuals. Of those, the left
ventricular function was analyzed in 4,874 participants. After exclusion of 220 individuals with
prior cardiovascular disorders, 4,654 individuals (46.5% male, mean 55.8 years of age) were
included in our study (Fig 1). Mean baseline handgrip strength was 34.9 kg. Individuals with
higher levels of handgrip strength were younger, taller, heavier, and had a higher household
income. However, other demographic characteristics were similar among handgrip strength
Fig 1. Study population.
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strata (Table 1). The amount of missing data ranged from 0% to 9.6% (duration of moderate
physical activity / week).
Association of baseline handgrip strength with cardiac structure and
Table 2 shows the associations between baseline handgrip strength and cardiac outcome
parameters after adjustment for all covariates. Higher baseline handgrip strength was
significantly associated with higher LVEDV (difference per SD increase in handgrip strength 1.3ml,
95% CI 0.1±2.4; p = 0.036) and LVSV (1.0ml, 0.3±1.7; p = 0.007). There was a significant
negative association with LVM (-1.0g, -1.8 ±-0.3; p = 0.007) and LVMVR (-0.012g/ml,
-0.18 ±-0.007; p<0.001). No clear association was found between handgrip strength and LVEF
There was evidence that the association between baseline handgrip strength and LVEDV,
LVSV, LVM, and LVMVR varied by age, but not between men and women or across levels of
physical activity. The association with LVEDV and LVSV was strongest among younger
individuals, while the association with LVM and LVMVR was strongest among older individuals.
Among 40 year olds, higher levels of handgrip strength at baseline were associated with higher
LVEDV (2.9ml, 1.1±4.8; p = 0.002) and LVSV (1.8ml, 0.7±3.0; p = 0.002). These associations
decreased with age. There was no clear association between baseline handgrip strength and
LVM or LVMVR among 40 year olds. However, these associations increased with age. Among
69 year olds, higher levels of handgrip strength at baseline were associated with lower LVM
(-2.8g, -3.9 ±-1.7; p<0.001) and LVMVR (-0.018g/ml, -0.026 ±-0.011; p<0.001) (Figs 2 and 3).
Association of change in handgrip strength with cardiac structure and
No association was found between change in handgrip strength and any of the CMR-based
measures of cardiac structure and function after adjustment for the covariates, nor was there
evidence that results varied by age, sex or physical activity (data not shown).
Numbers are difference (95% CI).
All estimates are adjusted for age, sex, ethnicity, time between baseline and imaging, height, weight, percent body fat,
waist circumference, hip circumference, Townsend score, household income, educational attainment, hypertension,
systolic blood pressure, diastolic blood pressure, diabetes mellitus, dyslipidemia, family history for cardiovascular
disease, smoking, alcohol consumption, cancer, and physical activity level.
SD, standard deviation; LVEF, left ventricular ejection fraction; LVEDV, left ventricular end-diastolic volume;
LVESV, left ventricular end-systolic volume; LVSV, left ventricular stroke volume; LVM, left ventricular mass;
LVMVR, left ventricular mass to volume ratio.
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Fig 2. Association between baseline handgrip strength and cardiac structure and function by age, adjusted for all covariates. The figure shows the
association between baseline handgrip strength and the cardiac outcome parameters by age after adjustment for all covariates. Intervals of baseline handgrip
strength were chosen to closely represent one standard deviation with a mean at approximately 35 kg. Error bars represent 95% CI. Baseline handgrip
strength has a stronger association with LVEDV and LVSV among younger individuals and a stronger association with LVM and LVMVR among older
individuals. HGS, handgrip strength; LVEF, left ventricular ejection fraction; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular
endsystolic volume; LVSV, left ventricular stroke volume; LVM, left ventricular mass; LVMVR, left ventricular mass to volume ratio.
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Fig 3. Association between baseline handgrip strength and the difference in cardiac structure and function by age, adjusted for all covariates. The figure shows
the difference in each cardiac outcome parameter per one standard deviation increase in baseline handgrip strength by age after adjustment for all covariates. Error
bars represent 95% CI. Baseline handgrip strength has a stronger association with LVEDV and LVSV among younger individuals and a stronger association with LVM
and LVMVR among older individuals. LVEF, left ventricular ejection fraction; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic
volume; LVSV, left ventricular stroke volume; LVM, left ventricular mass; LVMVR, left ventricular mass to volume ratio.
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There was no consistent evidence that the observed associations between handgrip strength
and the CMR-based measures of cardiac structure and function were non-linear (S1 Fig).
Neither the results from analyses that did not adjust for hypertension, systolic blood pressure,
diastolic blood pressure and diabetes, nor the results from analyses of participants with complete
data were materially different from the primary analyses.
The association between handgrip strength, a measure of muscular fitness, and measures of
cardiac structure and function was not previously known. This is the first study to show that
higher levels of handgrip strength are associated with higher LVEDV and LVSV, and lower
LVM and LVMVR. The association with LVEDV and LVSV decreased with age while the
association with LVM and LVMVR increased with age. These findings advance our understanding
of the pathophysiologic processes that may mediate the association between handgrip strength
and cardiovascular incidence and mortality.
Two large Swedish studies [
] showed lower cardiovascular disease incidence and
mortality among male adolescents with higher levels of handgrip strength. The PURE study 
recently demonstrated a similar association across people of a wide age range and diverse
economic and sociocultural backgrounds. Those studies did not, however, investigate possible
mechanisms responsible for the observed associations.
Lower handgrip strength among younger individuals was associated with a pattern
resembling concentric remodeling, a process characterized by a lower LVEDV, no difference in
LVM, and higher LVMVR [
]. Among older individuals, lower handgrip strength was
associated with a pattern resembling concentric hypertrophy, a process characterized by higher
LVM, no difference in LVEDV, and higher LVMVR [
]. It is not surprising that we did not
see an association between handgrip strength and LVEF, since such changes are only expected
to occur in LV decompensation. LV hypertrophy and concentric remodeling have been
associated with a marked increase in adverse CVD events in the general population [
] as well as
outcome events in patients with heart failure [
], which could link handgrip strength to CVD
Our results were not materially altered in models that did not adjust for other cardiac risk
factors such as hypertension and diabetes mellitus suggesting that these risk factors do not
strongly mediate the association between muscular fitness as assessed by handgrip strength
and the CMR-based measures of structure and function. This is in line with the PURE study
] that showed that the association between handgrip strength and cardiovascular disease
incidence and mortality persisted after adjustment for these risk factors.
The absence of an association between change in handgrip strength and any cardiac
outcome parameter was unexpected. However, several features of the study design preclude a
strong interpretation of those results: CMR was performed only once at the end of the study,
but not at baseline. The associations found for baseline handgrip strength therefore likely
represent the relationship between handgrip strength and the CMR-based measures over a time
period that far exceeds the study period.
Our study has several notable strengths including a large population-based study sample;
standardized data collection protocols as part of the UK Biobank prospective cohort study;
CMR-based measures of cardiac structure and function measured with a consistent research
protocol; and robust results across a wide range of sensitivity analyses.
Like all observational studies, our study also had some limitations. Even though we adjusted
for many potential confounders, residual confounding cannot be excluded. Furthermore,
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CMR was performed only once at the end of the study and therefore reverse causation cannot
be excluded. However, it seems unlikely given the consistency of the results with previous
studies investigating clinical outcomes. Finally, as a population based study the UK Biobank
was planned without administration of contrast agents and therefore gadolinium / relaxometry
imaging was not available.
In conclusion, better handgrip strength was associated with the CMR-based measures of
cardiac structure and function that are indicative of less cardiac hypertrophy and remodeling.
Those characteristics are known to be negatively associated with CVD incidence. Handgrip
grip strength might, thus, allow early identification of individuals at risk for development of
CVD. Focused surveillance and intervention may improve outcomes, but further research is
necessary to assess whether fitness training can reduce cardiac remodeling and prevent
S1 Table. Participant characteristics according to baseline handgrip strength.
S1 Fig. Association between transformed baseline handgrip strength and cardiac structure
This research has been conducted using the UK Biobank Resource under Application 2964.
The authors wish to thank all UK Biobank participants and staff.
Conceptualization: Sebastian E. Beyer, Alice Hosking, Murray A. Mittleman, Steffen E.
Data curation: JoseÂ Miguel Paiva, Aaron M. Lee, Kenneth Fung, Stefan K. Piechnik, Stefan
Neubauer, Steffen E. Petersen.
Formal analysis: Sebastian E. Beyer, Mihir M. Sanghvi, Jackie A. Cooper, Elena Lukaschuk,
Murray A. Mittleman, Steffen E. Petersen.
Funding acquisition: Steffen E. Petersen.
Investigation: Sebastian E. Beyer, Nay Aung, Murray A. Mittleman.
Methodology: Mihir M. Sanghvi, Jackie A. Cooper, JoseÂ Miguel Paiva, Aaron M. Lee,
Valentina Carapella, Murray A. Mittleman, Soren Brage, Steffen E. Petersen.
Project administration: Steffen E. Petersen.
Resources: Nay Aung, Aaron M. Lee.
Software: Aaron M. Lee.
Supervision: Mihir M. Sanghvi, Steffen E. Petersen.
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Writing ± original draft: Sebastian E. Beyer, Mihir M. Sanghvi, Nay Aung, Murray A.
Mittleman, Steffen E. Petersen.
Writing ± review & editing: Alice Hosking, Jackie A. Cooper, JoseÂ Miguel Paiva, Aaron M.
Lee, Kenneth Fung, Elena Lukaschuk, Valentina Carapella, Soren Brage, Stefan K. Piechnik,
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