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Experimental Gerontology Jun 2024Large scale population norms for peak oxygen uptake (VO) during cycle ergometry (CE) have been published for men and women across a wide range of ages. Although upper... (Review)
Review
BACKGROUND
Large scale population norms for peak oxygen uptake (VO) during cycle ergometry (CE) have been published for men and women across a wide range of ages. Although upper body functional capacity has an important role in activities of daily living far less is known regarding the effect of age and sex on upper body functional capacity (i.e. arm crank ergometry; ACE). The aim of this review was to determine the effect of age and sex on VO obtained during ACE and CE in the same participants.
METHOD
The review was pre-registered with PROSEPERO (Ref: CRD42022349566). A database search using Academic Search Complete including CINAHL complete, CINHAL Ultimate, Medline, PubMed, SPORTDiscus was undertaken.
RESULTS
The initial search yielded 460 articles which was reduced to 243 articles following removal of duplicates. Twenty-five articles were subsequently excluded based on title resulting in 218 articles considered for retrieval. Following review of the abstracts, 78 further articles were excluded leaving 140 to be assessed for eligibility. Eighty-five articles were subsequently excluded, resulting in 55 articles being included. The decrease in VO with age during CE was consistent with previous studies. Decreases in VO during ACE with age, although paralleling those of CE, appeared to be of greater functional importance. When changes in VO were considered below the age of 50 years little change was observed for absolute VO during ACE and CE. In contrast, relative VO demonstrated decreases in VO for both ACE and CE likely reflecting increases in body mass and body fat percentage with age. After 50 years of age absolute and relative VO demonstrated more similar and subtle responses. Heterogeneity across studies for both absolute and relative VO between ACE and CE was large. Although strict inclusion criteria were applied, the inter-individual variation in sample populations was likely the main source of heterogeneity. There was a considerable lack data sets available for ages above 40 years of age.
CONCLUSIONS
These responses suggest that upper body VO decreases in line with that of the lower body but, due to the lower peak values achieved during ACE, decreases in VO may have more profound functional impact compared to that for the lower body. Using absolute and relative measures of VO results in different age-related profiles when considered below 50 years of age. To further our understanding of whole body ageing more data is required for participants in mid and later life. The association between VO and underlying physiological factors with age needs to be studied further, particularly in conjunction with activities of daily living and independent living.
Topics: Humans; Oxygen Consumption; Age Factors; Exercise; Female; Male; Sex Factors; Aging; Exercise Test; Aged; Middle Aged; Adult
PubMed: 38604251
DOI: 10.1016/j.exger.2024.112427 -
Hypertension Research : Official... Jun 2024Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos....
Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos. They have been shown to be involved in maintaining homoeostasis as well as playing a role in the development of pathology including hypertension and cardiovascular disease. It is estimated that there is 10-10 circulating EVs/mL in the plasma of healthy individuals derived from various sources. While the effect of EVs on vascular haemodynamic parameters will be dependent on the details of the model studied, we systematically searched and summarized current literature to find patterns in how exogenously injected EVs affected vascular haemodynamics. Under homoeostatic conditions, evidence from wire and pressure myography data demonstrate that injecting isolated EVs derived from cell types found in blood and blood vessels resulted in the impairment of vasodilation in blood vessels ex vivo. Impaired vasodilation was also observed in rodents receiving intravenous injections of human plasma EVs from cardiovascular diseases including valvular heart disease, acute coronary syndrome, myocardial infarction and end stage renal disease. When EVs were derived from models of metabolic syndromes, such as diabetes, these EVs enhanced vasoconstriction responses in blood vessels ex vivo. There were fewer publications that assessed the effect of EVs in anaesthetised or conscious animals to confirm whether effects on the vasculature observed in ex vivo studies translated into alterations in vascular haemodynamics in vivo. In the available conscious animal studies, the in vivo data did not always align with the ex vivo data. This highlights the importance of in vivo work to determine the effects of EVs on the integrative vascular haemodynamics.
Topics: Animals; Humans; Cardiovascular Diseases; Extracellular Vesicles; Hemodynamics
PubMed: 38600279
DOI: 10.1038/s41440-024-01659-x -
British Journal of Sports Medicine May 2024To examine and summarise evidence from meta-analyses of cohort studies that evaluated the predictive associations between baseline cardiorespiratory fitness (CRF) and... (Meta-Analysis)
Meta-Analysis
Cardiorespiratory fitness is a strong and consistent predictor of morbidity and mortality among adults: an overview of meta-analyses representing over 20.9 million observations from 199 unique cohort studies.
OBJECTIVE
To examine and summarise evidence from meta-analyses of cohort studies that evaluated the predictive associations between baseline cardiorespiratory fitness (CRF) and health outcomes among adults.
DESIGN
Overview of systematic reviews.
DATA SOURCE
Five bibliographic databases were searched from January 2002 to March 2024.
RESULTS
From the 9062 papers identified, we included 26 systematic reviews. We found eight meta-analyses that described five unique mortality outcomes among general populations. CRF had the largest risk reduction for all-cause mortality when comparing high versus low CRF (HR=0.47; 95% CI 0.39 to 0.56). A dose-response relationship for every 1-metabolic equivalent of task (MET) higher level of CRF was associated with a 11%-17% reduction in all-cause mortality (HR=0.89; 95% CI 0.86 to 0.92, and HR=0.83; 95% CI 0.78 to 0.88). For incident outcomes, nine meta-analyses described 12 unique outcomes. CRF was associated with the largest risk reduction in incident heart failure when comparing high versus low CRF (HR=0.31; 95% CI 0.19 to 0.49). A dose-response relationship for every 1-MET higher level of CRF was associated with a 18% reduction in heart failure (HR=0.82; 95% CI 0.79 to 0.84). Among those living with chronic conditions, nine meta-analyses described four unique outcomes in nine patient groups. CRF was associated with the largest risk reduction for cardiovascular mortality among those living with cardiovascular disease when comparing high versus low CRF (HR=0.27; 95% CI 0.16 to 0.48). The certainty of the evidence across all studies ranged from very low-to-moderate according to Grading of Recommendations, Assessment, Development and Evaluations.
CONCLUSION
We found consistent evidence that high CRF is strongly associated with lower risk for a variety of mortality and incident chronic conditions in general and clinical populations.
Topics: Humans; Cardiorespiratory Fitness; Cardiovascular Diseases; Adult; Heart Failure; Mortality; Meta-Analysis as Topic
PubMed: 38599681
DOI: 10.1136/bjsports-2023-107849 -
Clinical Therapeutics May 2024L-carnitine supplementation has been recommended to improve cardiometabolic health markers in diabetic patients. Our purpose was to assess the dose-dependent effects of... (Meta-Analysis)
Meta-Analysis Review
The Effects of L-Carnitine Supplementation on Weight Loss, Glycemic Control, and Cardiovascular Risk Factors in Patients With Type 2 Diabetes: A Systematic Review and Dose-response Meta-Analysis of Randomized Controlled Trials.
PURPOSE
L-carnitine supplementation has been recommended to improve cardiometabolic health markers in diabetic patients. Our purpose was to assess the dose-dependent effects of l-carnitine supplementation on cardiometabolic risk factors in patients with type 2 diabetes.
METHODS
PubMed/Medline, Scopus, and Web of Science were searched until May 2022 for randomized controlled trials that examined the impact of l-carnitine supplementation on cardiometabolic risk factors in adults with type 2 diabetes. The mean difference (MD) and its 95% confidence interval (CI) were estimated utilizing a random-effects model. Nonlinear dose-response associations were modeled with restricted cubic splines. The certainty of evidence was rated using the GRADE approach.
FINDINGS
Twenty-one randomized trials with 2041 patients with type 2 diabetes were included. We found that every 1 g/d supplementation with l-carnitine significantly reduced body mass index (MD: -0.37 kg/m, 95% CI: -0.59, -0.15; I =93%, n=13, GRADE=low), HbA (MD: -0.16%, 95% CI: -0.32, -0.01; I = 94%, n = 18, GRADE = moderate), and low-density lipoprotein cholesterol (MD: -0.11 mmol/L, 95% CI: -0.16, -0.05; I = 91%, n = 11, GRADE = high). There were also reductions in serum triglycerides (MD: 0.07 mmol/L), total cholesterol (MD: -0.13 mmol/L), and fasting plasma glucose (MD: -0.17 mmol/L). A U-shaped effect was demonstrated for body mass index, with the largest reduction at 2 g/d. A linear reduction was seen for serum triglycerides, total cholesterol, and fasting plasma glucose up to l-carnitine supplementation of 4 g/d.
IMPLICATIONS
L-carnitine supplementation resulted in a small reduction in serum lipids and plasma glucose in patients with type 2 diabetes. However, due to high statistical heterogeneity, the results should be interpreted very cautiously.
Topics: Carnitine; Diabetes Mellitus, Type 2; Humans; Randomized Controlled Trials as Topic; Dietary Supplements; Glycemic Control; Blood Glucose; Weight Loss; Dose-Response Relationship, Drug; Cardiovascular Diseases; Heart Disease Risk Factors; Glycated Hemoglobin
PubMed: 38594107
DOI: 10.1016/j.clinthera.2024.03.002 -
BMC Cardiovascular Disorders Apr 2024The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency.
METHODS
PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023.
RESULTS
Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals.
CONCLUSIONS
The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Genetic Predisposition to Disease; Cholesterol, LDL; Dyslipidemias; ATP Binding Cassette Transporter, Subfamily G, Member 2; Neoplasm Proteins
PubMed: 38589776
DOI: 10.1186/s12872-024-03821-2 -
Communications Medicine Apr 2024Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized...
BACKGROUND
Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies.
METHODS
We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment.
RESULTS
Here we show that 152 studies that met extraction criteria most commonly characterized heterogeneity before diagnosis (91/152). Autoantibody type/target was most frequently examined, followed by autoantibody number. Recurring themes included correlations of autoantibody number, type, and titers with progression, differing phenotypes based on order of autoantibody seroconversion, and interactions with age and genetics. Only 44% specifically described autoantibody assay standardization program participation.
CONCLUSIONS
Current evidence most strongly supports the application of autoantibody features to more precisely define T1D before diagnosis. Our findings support continued use of pre-clinical staging paradigms based on autoantibody number and suggest that additional autoantibody features, particularly in relation to age and genetic risk, could offer more precise stratification. To improve reproducibility and applicability of autoantibody-based precision medicine in T1D, we propose a methods checklist for islet autoantibody-based manuscripts which includes use of precision medicine MeSH terms and participation in autoantibody standardization workshops.
PubMed: 38582818
DOI: 10.1038/s43856-024-00478-y -
Clinical Breast Cancer Jul 2024Poly-ADP ribose polymerase inhibitor (PARPi) is approved for HER2-negative advanced breast cancer with BRCA1/2 mutation. In recent years, many studies have explored the... (Meta-Analysis)
Meta-Analysis
Poly-ADP ribose polymerase inhibitor (PARPi) is approved for HER2-negative advanced breast cancer with BRCA1/2 mutation. In recent years, many studies have explored the application of PARPi in neoadjuvant therapy, but failed to reach a unified conclusion. PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase, and key oncological meetings for trials were searched for studies reporting neoadjuvant regimens with PARPi in HER2-negative breast cancer. Pathological complete response (pCR), residual cancer burden (RCB), breast-conservation surgery rate (BCSR), clinical response, and adverse events were extracted and pooled in a meta-analysis using the Mantel Haenszel random/fixed effects model. Subgroup analyses of pCR were conducted according to BRCA1/2 status, and hormone receptor (HR) status. Five studies (N = 1223) were included, the addition of PARPi to neoadjuvant regimens significantly increased pCR rates (HR 1.45, 95%CI 1.09-1.92, P = .01, I = 86%). In subgroup analysis, the addition of PARPi increased the pCR rate both in HR-positive (n = 383) and HR-negative (n = 431) subgroups, which showed a dominant effect of PARPi regardless of HR status (HR 2.07, 95%CI 1.33-3.23, P = .001, I = 0%; HR 1.85, 95%CI 1.39-2.26, P < .0001, I = 0%, respectively). However, when we performed a subgroup analysis based on the status of BRCA1/2, no further benefit for PARPi was found. Adverse reactions were generally tolerable. Other outcome indexes, including RCB, clinical response, BCSR, and PARPi did not show a clinical benefit. Regardless of BRCA1/2 status, PARPi in neoadjuvant therapy, can improve the pCR rate of HER2-negative breast cancer, especially in HR-positive patients. Thus, we should have performed larger randomized trials and provided a stronger evidence-based basis.
Topics: Female; Humans; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Neoadjuvant Therapy; Poly(ADP-ribose) Polymerase Inhibitors; Receptor, ErbB-2; Treatment Outcome
PubMed: 38580572
DOI: 10.1016/j.clbc.2024.02.020 -
Systematic Reviews Apr 2024Breast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of... (Meta-Analysis)
Meta-Analysis
Exploring the effectiveness of molecular subtypes, biomarkers, and genetic variations as first-line treatment predictors in Asian breast cancer patients: a systematic review and meta-analysis.
BACKGROUND
Breast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of molecular subtypes, biomarkers, and genetic variations has not been deeply explored in the Asian population. This study evaluated the effect of molecular subtype classification and the presence or absence of biomarkers and genetic variations on pathological complete response (pCR) after neoadjuvant treatment in Asian breast cancer patients.
METHODS
A systematic search was conducted in MEDLINE (PubMed), Science Direct, Scopus, and Cochrane Library databases. Studies were selected if they included Asian breast cancer patients treated with neoadjuvant chemotherapy and contained data for qualitative or quantitative analyses. The quality of the included studies was assessed using the Newcastle Ottawa Scale. Following the random effects model, pooled odds ratios or hazard ratios with 95% confidence intervals for pCR were analysed using Review Manager Software. Heterogeneity between studies was assessed using Cochran's Q-test and I test statistics.
RESULTS
In total, 19,708 Asian breast cancer patients were pooled from 101 studies. In the neoadjuvant setting, taxane-anthracycline (TA) chemotherapy showed better pCR outcomes in triple-negative breast cancer (TNBC) (p<0.0001) and human epidermal growth factor receptor 2 enriched (HER2E) (p<0.0001) than luminal breast cancer patients. Similarly, taxane-platinum (TP) chemotherapy also showed better pCR outcomes in TNBC (p<0.0001) and HER2E (p<0.0001). Oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, HER2-positive and high Ki-67 were significantly associated with better pCR outcomes when treated with either TA or TP. Asian breast cancer patients harbouring wildtype PIK3CA were significantly associated with better pCR outcomes when treated with TA in the neoadjuvant setting (p=0.001).
CONCLUSIONS
In the neoadjuvant setting, molecular subtypes (HER2E and TNBC), biomarkers (ER, PR, HER2, HR, Ki-67, nm23-H1, CK5/6, and Tau), and gene (PIK3CA) are associated with increased pCR rates in Asian breast cancer patients. Hence, they could be further explored for their possible role in first-line treatment response, which can be utilised to treat breast cancer more efficiently in the Asian population. However, it needs to be further validated with additional powered studies.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021246295.
Topics: Female; Humans; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Class I Phosphatidylinositol 3-Kinases; Genetic Variation; Ki-67 Antigen; Receptor, ErbB-2; Receptors, Estrogen; Taxoids; Triple Negative Breast Neoplasms
PubMed: 38576013
DOI: 10.1186/s13643-024-02520-5 -
Frontiers in Nutrition 2024Conjugated linoleic acid (CLA) is a geometrical isomer of linoleic acid, which has anti-inflammatory, anti-diabetic, anti-cancer, and anti-obesity properties. However,...
The effect of conjugated linoleic acid supplementation in comparison with omega-6 and omega-9 on lipid profile: a graded, dose-response systematic review and meta-analysis of randomized controlled trials.
Conjugated linoleic acid (CLA) is a geometrical isomer of linoleic acid, which has anti-inflammatory, anti-diabetic, anti-cancer, and anti-obesity properties. However, the studies reported inconstant results about the CLA-related effects on lipid profiles. As a result, meta-analysis and systematic review were performed to survey the CLA supplementation-related effect on lipid profile including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG). To identify the relevant research, a systematic comprehensive search was initiated on the medical databases such as Scopus and PubMed/Medline until December 2022. The overall effect size was estimated by weighted mean difference (WMD) and 95% confidence interval (CI) in a random effect meta-analysis. In the final quantitative analysis, the meta-analysis considered 35 randomized controlled trials (RCTs) with 1,476 participants (707 controls and 769 cases). The pooled results demonstrated that CLA supplementation, compared with olive oil, significantly increased serum TG levels (WMD: 0.05 mmol/L; 95% CI: 0.01 to 0.1; = 0.04; I = 0.0%, = 0.91). With regard to TC level, CLA supplementation compared with placebo significantly reduced TC concentrations (WMD: -0.08 mmol/L; 95% CI: -0.14 to -0.02; < 0.001; I = 82.4%). Moreover, the non-linear dose-response analysis indicated a decreasing trend of TC serum level from the 15th week of CLA supplementation compared with olive oil (P = 0.01). The present meta-analysis and systematic review of 35 RCTs showed that the CLA intervention was able to raise the level of TG in comparison to olive oil; however, it can decrease TC level compared with placebo and olive oil.
PubMed: 38567248
DOI: 10.3389/fnut.2024.1336889 -
BMC Sports Science, Medicine &... Mar 2024Heart disease is one of the leading causes of death in Canada. Many heart disease patients are referred for cardiac rehabilitation, a multidisciplinary outpatient...
BACKGROUND
Heart disease is one of the leading causes of death in Canada. Many heart disease patients are referred for cardiac rehabilitation, a multidisciplinary outpatient program often consisting of exercise training. Cardiac rehabilitation has been proven to be a successful secondary preventative measure in reducing mortality and improving overall health in heart disease patients, and its completion is important for both sexes as there is growing evidence that women benefit as much as men, if not more, with regard to mortality. It is important to note that previous studies have shown that healthy men and women respond differently to aerobic and resistance training, possibly due to hormones, body composition, autonomic and/or cardiovascular differences. However, evaluating sex differences in the efficacy of standard cardiac rehabilitation programs has not yet been fully explored with many studies investigating clinical or anthropometric data but not physiological outcomes. This systematic review aimed to investigate physiological differences in male and female heart disease patients after cardiac rehabilitation. The inclusion criteria were purposefully broad to encompass many cardiac rehabilitation scenarios, many cardiac disease states, and various program lengths and intensities with the intention of highlighting strengths and weaknesses of the current body of literature.
METHODS
To conduct a synthesis without meta-analysis, a search strategy was generated to examine the relationships between heart disease patients, a supervised exercise program, physiological outcomes, and sex differences. The review was registered (Prospero: CRD42021251614) and the following databases were searched from inception to 19 December 2023: APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), Embase (Ovid), Emcare Nursing (Ovid), Medline All (Ovid; includes PubMed non-Medline), and Web of Science Core Collection. Eighty-eight studies pertaining to fitness, metabolism, body composition, respiratory function, cardiac function and C-reactive protein underwent data extraction.
RESULTS AND CONCLUSIONS
Importantly, this review suggests that men and women respond similarly to a wide-range of cardiac rehabilitation programs in most physiological variables. However, many studies discussing maximal oxygen consumption, functional capacity, six-minute walk distances, and grip strength suggest that men benefit more. Further research is required to address certain limitations, such as appropriate statistical methods and type/intensity of exercise interventions.
PubMed: 38549168
DOI: 10.1186/s13102-024-00867-9