Genetically proxied appendicular lean mass and stroke risk: A two-step mendelian randomization study.

BACKGROUND AND PURPOSE: Prior observational studies have suggested a strong correlation between sarcopenia and stroke, but the causal link between them remains uncertain. This study aims to investigate the associations between genetically predicted sarcopenia-related traits and stroke using a two-step Mendelian randomization (MR) approach. METHODS: Genome-wide association study (GWAS) summary data for sarcopenia-related traits were acquired from the UK Biobank. Genetic associations for ischemic stroke (IS) and its subtypes were selected from the MEGASTROKE consortium comprising European ancestry participants. GWAS summary data for cerebral hemorrhage were obtained from the FinnGen consortium, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). MR estimates were calculated using the inverse-variance weighted (IVW) method. The robustness of results was assessed for heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs). RESULTS: Higher appendicular lean mass (ALM) exhibited a potential causal association with a reduced incidence of large artery atherosclerosis (LAA) (odds ratio [OR] = 0.81, 95% confidence interval [CI]:0.71-0.93; P = 0.003) and small vessel disease (SVD) (OR = 0.83, 95% CI:0.74-0.94; P = 0.002). The associations of ALM with IS and ICH were compromised after adjusting for body fat and physical activity with multivariable MR. Two-step MR mediation analysis explored 33 candidate mediators, among which hypertension and SBP accounted for more than 10% of the mediation proportion in the relationship between ALM and stroke and its subtypes. CONCLUSION: Our research findings indicate that lower ALM is associated with a increased risk of stroke . It is necessary to explore the specific protective mechanisms of higher ALM for preventing stroke occurrence.

Impact of Soccer-Based Training Interventions on Anthropometric Measures Among Children and Adolescents With Overweight/Obesity: A Systematic Review, Meta-Analysis, and Assessment of Certainty of Evidence.

PURPOSE: This systematic review and meta-analysis aimed to systematically examine and summarize recent evidence on the effects of soccer-based training (SBT) on anthropometric measures in children and adolescents with overweight/obesity. METHODS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines, a thorough literature search across 7 electronic databases was conducted on October 11, 2023. The studies' methodological quality was evaluated using the QualSyst tool, followed by conducting a meta-analysis with a random-effects model, and the certainty of evidence was assessed. RESULTS: Six studies were included, with 4 studies of strong methodological quality and 2 studies of moderate methodological quality. The results of the meta-analysis revealed SBT decreases fat mass percentage (effect size [ES] = 0.47 [small]; P = .002), with no significant effect of SBT on body mass index (ES = 0.180 [small]; P = .275), body mass (ES = 0.183 [trivial]; P = .212), fat-free mass (ES = 0.074 [trivial]; P = .635), or waist circumference (ES = 0.358 [small]; P = .053). The certainty of evidence was moderate for all outcomes. CONCLUSIONS: SBT appears to decrease fat mass percentage, without affecting body mass, body mass index, fat-free mass, or waist circumference in obese/overweight children and adolescents. These findings require further investigation given the moderate certainty of evidence. REGISTRATION: The protocol of this review was registered in the Open Science Framework database (https://doi.org/10.17605/OSF.IO/8P4V2).

Associations between Essential Amino Acid Intake and Functional Health Outcomes in Older Adults: Analysis of the National Health and Nutrition Examination Survey, 2001-2018.

Background: The relationships between habitual essential amino acid (EAA) intake and body composition, muscle strength, and physical function in older US adults are not well defined. Objectives: This cross-sectional study evaluated associations between usual EAA intakes and body composition, muscle strength, and physical function in US adults ≥65 y. Methods: The Food and Nutrient Database for Dietary Studies (FNDDS) 2001-2018 was linked to the US Department of Agriculture Standard Reference database to access existing amino acid composition data for FNDDS ingredients. FNDDS ingredients without existing amino acid composition data were matched to similar ingredient codes with available data. Usual EAA, leucine, lysine, and sulfur-containing amino acid (SAA; methionine + cysteine) intakes (g/d) from National Health and Nutrition Examination Survey 2001-2018 were calculated for individuals ≥65 y (n = 10,843). Dependent variables included muscle strength measured by isometric grip test, body mass index (BMI), waist circumference, dual-energy X-ray absorptiometry-measured appendicular lean mass and whole-body fat mass, and self-reported physical function (that is, tasks of daily living). Regression analyses were used to determine covariate-adjusted relationships between EAA, leucine, lysine, and SAA intake and functional health outcomes. P < 0.0013 was considered significant. Results: EAA, leucine, lysine, and SAA intakes, covaried with physical activity level and usual protein intake, were not associated with muscle strength or self-reported physical function in males or females or with body composition in males. EAA intakes were positively associated with waist circumference in females (ß ± SEM, 2.1 ± 0.6 cm, P = 0.0007). Lysine intakes were positively associated with BMI (3.0 ± 0.7 kg/m2, P < 0.0001) and waist circumference (7.0 ± 1.7 cm, P = 0.0001) in females. Conclusions: Habitual EAA, leucine, lysine, and SAA intakes, covaried with physical activity level and usual protein intake, were not associated with lean mass, muscle strength, or physical function in adults ≥65 y. However, EAA intakes, particularly lysine, were positively associated with measures of adiposity in older females.This trial was registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/25V63) as osf.io/25v63).

Normative Values and Anthropometric Prediction Models for Lean Mass and Fat Mass in the Northeastern Thai Population.

Background: Data on reference values for lean mass (LM) and fat mass (FM) in the Southeast Asian populations are currently lacking. Therefore, we aimed to estimate the normative values and generate anthropometric prediction models for LM and FM in the Thai population. Methods: Consecutive community-dwelling individuals aged 20-90 years were recruited from Srinagarind Hospital, Khon Kaen, Thailand, between 2010 and 2015. LM and FM were measured using dual energy X-ray absorptiometry. Age and sex stratified percentile of LM and FM were presented. Anthropometric prediction models for LM and FM were developed by using linear regression to generate competing models. Results: A total of 832 individuals (334 males and 498 females) were included in the study. The mean ± SD age, LM, and FM were 50.0 ± 16.2 years, 38.9 ± 8.0 kg, and 15.5 ± 7.7 kg, respectively. LM decreased with age from 49.4 kg in 20-29 years group to 42.3 kg in ≥70 years group in male and 34.6 kg in 30-39 years group to 30.8 kg in ≥70 years group in females. FM has an inverse U-shaped association with age, which peaked at 11.9 kg in 60-69 years group in males and 20.7 kg in 50-59 years group in females. Among the various anthropometric models, the models incorporating age, sex, weight, and height were considered the best fit for predicting both LM and FM. Conclusion: In the Thai population, peak LM was reached during early adulthood and decline with age, whereas FM showed an inverse U-shaped association with age. The prediction models incorporating age, sex, weight, and height were proposed as practical tools for assessing LM and FM in clinical practice.

The association between non­high­density lipoprotein cholesterol to high­density lipoprotein cholesterol ratio (NHHR) and low muscle mass in adults aged 20-59: a population-based study in the United States.

BACKGROUND: The ratio between non-high-density lipoprotein cholesterol and high-density lipoprotein cholesterol (NHHR) is a reliable marker for assessing the risk linked to lipid metabolism disorders. Sarcopenia, characterized by age-related loss of muscle mass and strength/function, includes the assessment of muscle mass, muscle strength, and muscle-specific strength. However, research into NHHR's relationship with low muscle mass risk remains unexplored. METHODS: Our study utilized a cross-sectional approach, examining data derived from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Through multivariable linear and logistic regression, we investigated the relationships of the NHHR with muscle mass and low muscle mass. We visualized the results using smoothing curves and assessed threshold effects. We also performed various subgroup and sensitivity analyses. RESULTS: This research encompassed 9,012 participants and demonstrated significant nonlinear associations between NHHR and ALMBMI or low muscle mass risk in a generalized additive model (GAM), pinpointing critical NHHR values (3.328 and 3.367) where changes in NHHR significantly impacted ALMBMI and low muscle mass risk. CONCLUSIONS: The NHHR demonstrates a significant association with an increased risk of low muscle mass among middle-aged Americans. This ratio has potential as a predictive marker for low muscle mass. Further exploration of NHHR is expected to aid in advancing preventive and therapeutic measures for this condition.

Circulating inflammatory cytokines and sarcopenia-related traits: a mendelian randomization analysis.

Objective: To explore the causal relationships between 91 circulating inflammatory cytokines and sarcopenia-related traits (low hand grip strength, appendicular lean mass, and usual walking pace) by Mendelian randomized analysis. Methods: Independent genetic variations of inflammatory cytokines and sarcopenia-related traits were selected as instrumental variables from publicly available genome-wide association studies (GWAS). The MR analysis was primarily conducted using the inverse variance-weighted (IVW) method. Sensitivity analyses included Steiger filtering and MR PRESSO, with additional assessments for heterogeneity and pleiotropy. Results: The IVW method indicated a causal relationship between Vascular Endothelial Growth Factor A (VEGF-A) and low hand grip strength (OR = 1.05654, 95% CI: 1.02453 to 1.08956, P = 0.00046). Additionally, Tumor Necrosis Factor-beta (TNF-ß) was found to have a causal relationship with appendicular lean mass (ALM) (ß = 0.04255, 95% CI: 0.02838 to 0.05672, P = 3.96E-09). There was no evidence suggesting a significant causal relationship between inflammatory cytokines and usual walking pace. Conclusion: Our research substantiated the causal association between inflammatory cytokines, such as VEGF-A and TNF-ß, and sarcopenia. This finding may provide new avenues for future clinical treatments.

The relationship of body composition with bone mineral density and 10-year probability of hip fracture in postmenopausal women.

INTRODUCTION: Postmenopausal osteoporosis and fractures are widely prevalent. However, the relationship of body composition with bone health in this population remains unclear. The aim of this study was to investigate the association of body composition with bone mineral density (BMD) and 10-year probability of hip fracture in postmenopausal women. MATERIALS AND METHODS: This is a cross-sectional study. A total of 1285 subjects were included in our study. Body composition and BMD were assessed using dual-energy X-ray densitometry. The 10-year probability of hip fracture of participants was calculated. All participants were categorized into four groups: sarcopenic-obese (SO) group, sarcopenic-nonobese (S) group, nonsarcopenic-obese (O) group, or nonsarcopenic-nonobese control (C) group. Multivariate analyses and binary logistic regression were conducted to explore the relationship of body composition with BMD and 10-year probability of hip fracture. RESULTS: Participants in S group were 2.8, 4.7 and 4.8 times more likely to develop osteoporosis in the lumbar spine, the total hip and femoral neck sites, respectively. Lean mass was positively correlated with BMD, wherein lumbar spine BMD was significantly affected by appendicular lean mass, while total hip BMD and femoral neck BMD were mainly influenced by trunk lean mass. Total fat mass was positively associated with total hip and femoral neck BMD, but not with lumbar spine BMD. A significant correlation was observed between lean mass and 10-year probability of hip fracture. CONCLUSION: Changes in body composition in postmenopausal women could affect bone health. A decrease in regional lean mass may be associated with an increased risk of osteoporosis and fractures.

Body composition and body mass index are independently associated with widespread pain and experimental pain sensitivity in older adults: a pilot investigation.

Introduction: Chronic musculoskeletal (MSK) pain is prevalent in older adults and confers significant risk for loss of independence and low quality of life. While obesity is considered a risk factor for developing chronic MSK pain, both high and low body mass index (BMI) have been associated with greater pain reporting in older adults. Measures of body composition that distinguish between fat mass and lean mass may help to clarify the seemingly contradictory associations between BMI and MSK pain in this at-risk group. Methods: Twenty-four older adults (mean age: 78.08 ± 5.1 years) completed dual-energy x-ray absorptiometry (DEXA), and pain measures (Graded Chronic Pain Scale, number of anatomical pain sites, pressure pain threshold, mechanical temporal summation). Pearson correlations and multiple liner regression examined associations between body mass index (BMI), body composition indices, and pain. Results: Significant positive associations were found between number of pain sites and BMI (b = 0.37) and total fat mass (b = 0.42), accounting for age and sex. Total body lean mass was associated with pressure pain sensitivity (b = 0.65), suggesting greater lean mass is associated with less mechanical pain sensitivity. Discussion: The results from this exploratory pilot study indicate lean mass may provide additional resilience to maladaptive changes in pain processing in older adults, and highlights the importance of distinguishing body composition indices from overall body mass index to better understand the complex relationship between obesity and MSK pain in older adults.

Bone mineral density and body composition in Australians following plant-based diets vs. regular meat diets.

Background and aims: Bone mineral density (BMD) and body composition play an important role in maintaining metabolic health and physical functioning. Plant-based diets (PBDs) are known to be lower in protein and calcium, which can impact BMD and body composition. This study aimed to investigate the relationship between various PBDs compared to regular meat diet and whole-body BMD, body composition, and weight status. Methods: A cross-sectional study was conducted with adults (n = 240) aged 30-75 years, who habitually followed dietary patterns: vegan, lacto-vegetarian, pesco-vegetarian, semi-vegetarian, or regular meat eater (48 per group). Parameters were measured using dual-energy x-ray absorptiometry (DXA), and multivariable regression analyses were used to adjust for lifestyle confounders, socioeconomic factors, and BMI. Results: After adjustments, whole-body BMD and body composition were not significantly different between those following PBDs and regular meat diets, except for lacto-ovo vegetarians, who had significantly lower lean mass by -1.46 kg (CI: -2.78, -0.13). Moreover, lacto-ovo vegetarians had a significantly lower T-score by -0.41 SD (CI: -0.81, -0.01) compared to regular meat eaters. Waist circumference was significantly lower in individuals adhering to a PBD compared to a regular meat diet: vegans by -4.67 cm (CI: -8.10, -1.24), lacto-ovo vegetarians by -3.92 cm (CI: -6.60, -1.23), pesco-vegetarians by -3.24 cm (CI: -6.09, -0.39), and semi-vegetarians by -5.18 cm (CI: -7.79, -2.57). There were no significant differences in lean mass (%), fat mass (% and total), android/gynoid measures, body weight, or BMI across dietary patterns. All dietary patterns met the recommended dietary intake for calcium and protein, and 25-hydroxy-vitamin D status was comparable across groups. Conclusions: This cross-sectional study found that adhering to a PBD characterized by varying degrees of dairy and meat restriction is not associated with meaningful changes in BMD or body composition, provided that the dietary patterns are planned appropriately with adequate levels of calcium and protein.

Central Lean Mass Distribution and the Risks of All-Cause and Cause-Specific Mortality in 40,283 UK Biobank Participants.

INTRODUCTION: The purpose of this study was to investigate the association of central lean mass distribution with the risk of mortality. METHODS: This cohort study included 40,283 UK Biobank participants. Cox proportional hazards regression models were used to estimate the association of central lean mass distribution, i.e., trunk-to-leg lean mass ratio, assessed by dual-energy X-ray absorptiometry, with the risk of mortality. RESULTS: The median age of the participants was 65 years, and 52% were women. During a median follow-up of 4.18 years, 674 participants died, of whom 366 were due to cancer and 126 were due to cardiovascular causes. Compared with the lowest tertile of a trunk-to-leg lean mass ratio, the multivariable-adjusted (age, sex, ethnicity, lifestyle, comorbidities, body mass index, and appendicular muscle mass index) hazards ratios of the highest tertile of trunk-to-leg lean mass ratio were 1.55 (95% CI: 1.23-1.94), 1.69 (95% CI: 1.26-2.26), and 1.14 (95% CI: 0.72-1.80) for all-cause, cancer, and cardiovascular mortality, respectively. Neutrophil-to-lymphocyte ratio mediated 9.3% (95% CI: 3.3%-40.4%) of the association of trunk-to-leg lean mass ratio with all-cause mortality. There was evidence for additive interactions of trunk-to-leg lean mass ratio with older age and poor diet quality for all-cause mortality. CONCLUSION: Trunk-to-leg lean mass ratio, assessed by dual-energy X-ray absorptiometry, was positively associated with the risks of all-cause and cancer mortality, independent of general obesity and central obesity, in UK middle-aged and older adults. Central lean mass distribution may interact synergistically with aging and poor diet quality to further increase the risk of death.

Associations of long-term exposure to air pollution and noise with body composition in children and adults: Results from the LEAD general population study.

BACKGROUND: While long-term air pollution and noise exposure has been linked to increasing cardiometabolic disease risk, potential effects on body composition remains unclear. This study aimed to investigate the associations of long-term air pollution, noise and body composition. METHODS: We used repeated data from the LEAD (Lung, hEart, sociAl, boDy) study conducted in Vienna, Austria. Body mass index (BMI; kg/m2), fat mass index (FMI; z-score), and lean mass index (LMI; z-score) were measured using dual-energy x-ray absorptiometry at the first (t0; 2011-ongoing) and second (t1; 2017-ongoing) examinations. Annual particulate matter (PM10) and nitrogen dioxide (NO2) concentrations were estimated with the GRAMM/GRAL model (2015-2021). Day-evening-night (Lden) and night-time (Lnight) noise levels from transportation were modeled for 2017 following the European Union Directive 2002/49/EC. Exposures were assigned to residential addresses. We performed analyses separately in children/adolescents and adults, using linear mixed-effects models with random participant intercepts and linear regression models for cross-sectional and longitudinal associations, respectively. Models were adjusted for co-exposure, lifestyle and sociodemographics. RESULTS: A total of 19,202 observations (nt0 = 12,717, nt1 = 6,485) from participants aged 6-86 years (mean age at t0 = 41.0 years; 52.9 % female; mean PM10 = 21 µg/m3; mean follow-up time = 4.1 years) were analyzed. Among children and adolescents (age ≤ 18 years at first visit), higher PM10exposure was cross-sectionally associated with higher FMI z-scores (0.09 [95 % Confidence Interval (CI): 0.03, 0.16]) and lower LMI z-scores (-0.05 [95 % CI: -0.10, -0.002]) per 1.8 µg/m3. Adults showed similar trends in cross-sectional associations as children, though not reaching statistical significance. We observed no associations for noise exposures. Longitudinal analyses on body composition changes over time yielded positive associations for PM10, but not for other exposures. CONCLUSION: Air pollution exposure, mainly PM10, was cross-sectionally and longitudinally associated with body composition in children/adolescents and adults. Railway/road-traffic noise exposures showed no associations in both cross-sectional and longitudinal analyses.

Reproducibility of Air Displacement Plethysmography in Term and Preterm Infants-A Study to Enhance Body Composition Analysis in Clinical Routine.

The quality-initiative analysis of weekly duplicate PEAPOD® body composition measurements was conducted from clinical practice (January to September 2021) on preterm and term infants without respiratory support. Statistical analysis, including regression analysis, Bland-Altman plots and cv-root-mean-square tests, was performed. A total of 188 duplicate (376 individual) measurements were collected from 119 infants (88 preterm, 31 term). The median absolute difference between duplicates was 31.5 g for fat-free mass (FFM). Linear correlation analysis showed R2 = 0.97 for FFM. The absolute differences in FFM and fat mass did not significantly correlate with increasing age. The %FFM differed (p = 0.02) across body weight groups of 1 kg < BW ≤ 2 kg (1.8%; IQR: 0.8, 3.6) and BW > 3 kg (0.9%; IQR: 0.3, 2.1). The median absolute differences were 1 g (IQR: 0.4, 3.1) for body weight and 5.6 mL (IQR: 2.1, 11.8) for body volume. Body volume estimation is charged with a constant absolute error, which is the main factor for differences between repeated body composition assessments. This error becomes more prominent in infants with lower body weights. Nevertheless, reproducibility of weekly PEAPOD testing is sufficient to monitor body compartment changes, offering a foundation for nutritional decisions in both preterm and term infants.

Causal association of sarcopenia with hepatocellular carcinoma risk in European population: a Mendelian randomization study.

Background: The causal association of sarcopenia with the incidence risk of hepatocellular carcinoma (HCC) in the European population, and the potential mediating role of C-reactive protein (CRP), remains unclear. This study employed a bidirectional two-sample, two-step Mendelian randomization (MR) analysis to investigate the causality and identify the mediator. Methods: Summary statistics for HCC, CRP, and sarcopenia-related traits, including appendicular lean mass (ALM), hand grip strength (HGS), and walking pace (WP), were acquired from publicly available databases. We conducted bidirectional MR and Steiger tests of directionality to check the presence of reverse causality. Additionally, a two-step MR analysis was used to assess the mediating effect of CRP in the causality between sarcopenia and HCC. Tests for heterogeneity and horizontal pleiotropy were performed. Results: As ALM increases, the risk of HCC occurrence decreases [odds ratio (OR), 95% confidence interval (CI): 0.703, 0.524-0.943; P = 0.019]. And, genetically predicted low-HGS (OR, 95%CI: 2.287, 1.013-5.164; P = 0.047) was associated with an increased incidence risk of HCC, with no reverse causality. However, we found no evidence supporting a causality between WP and HCC. CRP was identified as the mediator of the causal effect of ALM and low-HGS on HCC, with corresponding mediating effects of 9.1% and 7.4%. Conclusions: This MR study effectively demonstrates that lower ALM and low-HGS are linked to an elevated risk of HCC within the European population, and the causality was not bidirectional. Furthermore, CRP serves as a mediator in the associations. These findings may help mitigate HCC risk among individuals with sarcopenia.

Appendicular lean mass index and motor function in ambulatory patients with Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Appendicular lean mass index (ALMI) has been linked to motor function in patients with Duchenne muscular dystrophy (DMD). However, quantification of the relationship between ALMI and disease-specific clinical outcome assessment trajectories is needed. The purpose of this study was to determine associations between dual-energy x-ray absorptiometry (DXA) derived estimates of ALMI and motor function in ambulatory patients with DMD. METHODS: A retrospective analysis of longitudinal clinical visit data from 137 glucocorticoid-treated patients with DMD collected via structured motor assessment protocol evaluated associations between ALMI and motor function indexed by the North Star Ambulatory Assessment (NSAA) and 10 Meter Walk/run Test (10MWT). Body composition was assessed using DXA. ALMI was calculated by dividing arm and leg lean mass by height in m2; fat mass index (FMI) was calculated by dividing whole body fat mass by height in m2. Linear mixed-effects models were used to estimate associations between ALMI and motor function, controlling for age and FMI. RESULTS: The full prediction model (age, age,2 ALMI, and FMI) explained 57% of the variance in NSAA scores and 63% of the variance in 10MWT speed. A 1 kg/m2 higher ALMI value predicted a 5.4-point higher NSAA score (p < .001) and 0.45 m/s faster 10MWT speed (p < .001). A 1 kg/m2 higher FMI value predicted a 1.5-point lower NSAA score (p < .001) and 0.14 meters/second slower 10MWT speed (p < .001). DISCUSSION: DXA-derived estimates of ALMI and FMI are associated with motor function in DMD and may explain variation in DMD disease progression.

DXA-based appendicular composition measures in healthy aging Caucasian Greek women: a cross-sectional study.

As the global population of older persons increases, age-related medical conditions will have a greater impact on public health. DXA-derived bone and soft tissue metrics are associated with adverse clinical events in aging persons. This study aims to investigate the regional body composition of the appendices by whole-body DXA scans, and the age-related relationships between measures of bone and soft tissue in healthy Caucasian females of a Greek origin residing in the Mediterranean area. Body composition of the legs and the arms was analyzed, and lean mass (LM) and fat mass (FM) metrics were calculated in 330 women aged 20-85 years, using DXA. Peak bone mineral density (BMD) of the legs and arms was achieved between ages 20-30 and 41-50 years, respectively. The overall BMD reduction with age was for the legs 43% and the arms 32.2% (p < 0.001). Peak %LM of the legs and the arms was achieved between ages 20-30. The overall reduction of %LM with age was for the legs 22.5% (p < 0.001) and arms 6.6% (p < 0.05). Peak %FM of the legs and arms was attained between ages 31-40 and 61-70, respectively. The overall %FM reduction with age was for the legs and arms 7.5% and 1.9% (p > 0.05). In appendicular sites, Greek women reach peak values of bone mass in the legs first, in early adulthood. Bone loss predominates in the legs as women age. Also, with advancing age Greek women show preferential significant decreases of %LM and %FM in the legs as opposed to the arms. Although variation in appendicular bone and soft tissue metrics is present, the implications of variable biological crosstalks among the tissue components as women age may ultimately lay the foundation for future clinical trials aimed at healthy aging.

Causal associations between sarcopenia-related traits and intervertebral disc degeneration: a two-sample mendelian randomization analysis.

BACKGROUND: Sarcopenia (SP) and intervertebral disc degeneration (IVDD) have a higher incidence in the elderly population. Previous studies have indicated a potential association between SP and IVDD. The objective of this study is to elucidate the potential causal relationship between sarcopenia-related traits and IVDD through Two-sample Mendelian randomization (MR) analysis. METHODS: We utilized a genome-wide association study conducted on the European population to collect aggregated data on sarcopenia and IVDD. Inverse variance weighting was primarily employed, supplemented by MR Egger, weighted median, simple model, and weighted model methods. Additionally, sensitivity analysis was performed to assess the robustness of the findings. RESULTS: Appendicular lean mass is positively associated with "Other intervertebral disc disorders" (OIDD) and "Prolapsed or slipped disc" (POSD) (OIDD: p = 0.002, OR = 1.120; POSD: p < 0.001, OR = 1.003), while grip strength (GS) is positively associated with POSD (left: p = 0.004, OR = 1.008; right: p < 0.001, OR = 1.010). It is worth mentioning that walking pace has significant causal relationship with "Low back pain" (LBP), "Lower back pain or/and sciatica" (LBPOAS), "Sciatica with lumbago" (SWL) and OIDD (LBP: p < 0.001, OR = 0.204; LBPOAS: p < 0.001, OR = 0.278; SWL: p = 0.003, OR = 0.249; OIDD: p < 0.001, OR = 0.256). CONCLUSION: The present study revealed the causal relationship between SP-related traits and IVDD and recommended to prevent and treat sarcopenia as a means of preventing IVDD in clinic practice.

The causal relationship between sarcopenia-related traits and ischemic stroke: Insights from univariable and multivariable Mendelian randomization analyses.

AIMS: The causal relationship between sarcopenia-related traits and ischemic stroke (IS) remains poorly understood. This study aimed to explore the causal impact of sarcopenia-related traits on IS and to identify key mediators of this association. METHODS: We conducted univariable, multivariable two-sample, and two-step Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. This included data for appendicular lean mass (ALM), hand grip strength (HGS), and usual walking pace (UWP) from the UK Biobank, and IS data from the MEGASTROKE consortium. Additionally, 21 candidate mediators were analyzed based on their respective GWAS data sets. RESULTS: Each 1-SD increase in genetically proxied ALM was associated with a 7.5% reduction in the risk of IS (95% CI: 0.879-0.974), and this correlation remained after controlling for levels of physical activity and adiposity-related indices. Two-step MR identified that six mediators partially mediated the protective effect of higher ALM on IS, with the most significant being coronary heart disease (CHD, mediating proportion: 39.94%), followed by systolic blood pressure (36.51%), hypertension (23.87%), diastolic blood pressure (15.39%), type-2 diabetes mellitus (T2DM, 12.71%), and low-density lipoprotein cholesterol (7.97%). CONCLUSION: Our study revealed a causal protective effect of higher ALM on IS, independent of physical activity and adiposity-related indices. Moreover, we found that higher ALM could reduce susceptibility to IS partially by lowering the risk of vascular risk factors, including CHD, hypertension, T2DM, and hyperlipidemia. In brief, we elucidated another modifiable factor for IS and implied that maintaining sufficient muscle mass may reduce the risk of such disease.

Frailty in Midlife as a Predictor of Changes in Body Composition from Midlife into Old Age: A Longitudinal Birth Cohort Study.

INTRODUCTION: Few studies have investigated the association between frailty and subsequent body composition. METHODS: We performed separate linear mixed model analyses to study the associations between changes in the participant frailty status assessed by a frailty index (FI) and subsequent body mass index (BMI), lean mass index (LMI), fat mass index (FMI), and FMI to LMI ratio values assessed on three occasions over 17 years. The analyses were carried out among 996 participants spanning from age 57 to 84 years. RESULTS: With advancing age, LMI and BMI decreased, whereas FMI and FMI to LMI ratio increased. Participants with "stable frailty," followed by those with "increasing frailty" experienced faster decreases in LMI and faster increases in FMI and FMI to LMI ratio values from midlife into old age relative to those in the group "stable not frail." Contrastingly, those in the highest third of absolute annual increase in FMI and FMI to LMI ratio became more frail faster from midlife into old age relative to those in the lowest third. CONCLUSIONS: We found evidence of an adverse health outcome of frailty where lean indices declined faster and fat indices and fat-to-lean ratios increased faster from midlife into old age. The changes resembled those that occurred with aging, but at a faster pace. The relationship between body composition and frailty is likely bidirectional, where high or increasing levels of fat are associated with the risk of becoming more frail earlier, but where a longer duration of frailty may increase the risk of faster age-related changes to body composition.

Appendicular lean mass and the risk of stroke and Alzheimer's disease: a mendelian randomization study.

BACKGROUND: Appendicular lean mass (ALM) is a good predictive biomarker for sarcopenia. And previous studies have reported the association between ALM and stroke or Alzheimer's disease (AD), however, the causal relationship is still unclear, The purpose of this study was to evaluate whether genetically predicted ALM is causally associated with the risk of stroke and AD by performing Mendelian randomization (MR) analyses. METHODS: A two-sample MR study was designed. Genetic variants associated with the ALM were obtained from a large genome-wide association study (GWAS) and utilized as instrumental variables (IVs). Summary-level data for stroke and AD were generated from the corresponding GWASs. We used random-effect inverse-variance weighted (IVW) as the main method for estimating causal effects, complemented by several sensitivity analyses, including the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Multivariable analysis was further conducted to adjust for confounding factors, including body mass index (BMI), type 2 diabetes mellitus (T2DM), low density lipoprotein-C (LDL-C), and atrial fibrillation (AF). RESULTS: The present MR study indicated significant inverse associations of genetically predicted ALM with any ischemic stroke ([AIS], odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89-0.97; P = 0.002) and AD (OR, 090; 95% CI 0.85-0.96; P = 0.001). Regarding the subtypes of AIS, genetically predicted ALM was related to the risk of large artery stroke ([LAS], OR, 0.86; 95% CI 0.77-0.95; P = 0.005) and small vessel stroke ([SVS], OR, 0.80; 95% CI 0.73-0.89; P < 0.001). Regarding multivariable MR analysis, ALM retained the stable effect on AIS when adjusting for BMI, LDL-C, and AF, while a suggestive association was observed after adjusting for T2DM. And the estimated effect of ALM on LAS was significant after adjustment for BMI and AF, while a suggestive association was found after adjusting for T2DM and LDL-C. Besides, the estimated effects of ALM were still significant on SVS and AD after adjustment for BMI, T2DM, LDL-C, and AF. CONCLUSIONS: The two-sample MR analysis indicated that genetically predicted ALM was negatively related to AIS and AD. And the subgroup analysis of AIS revealed a negative causal effect of genetically predicted ALM on LAS or SVS. Future studies are required to further investigate the underlying mechanisms.