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  • Counteracting microgravity: preserving cardiovascular health in low earth orbit | Military Medical Research

    Counteracting microgravity: preserving cardiovascular health in low earth orbit | Military Medical Research

    • Letter to the Editor
    • Open access
    • Published:

    Military Medical Research

    volume 12, Article number: 53 (2025)
    Cite this article

    As space exploration transitions from short orbital missions to extended stays on the International Space Station (ISS) and, ultimately, interplanetary travel, astronaut health has emerged as a critical focus. In particular, safeguarding cardiovascular function has become an operational imperative. Yet beyond safeguarding those in orbit, the physiological adaptations observed in microgravity offer a compelling lens through which to examine persistent challenges in terrestrial medicine, from orthostatic intolerance in the elderly to deconditioning in critical care survivors. By studying how the human cardiovascular system functions in the absence of gravity, we can gain valuable insights and strategies for managing circulatory and autonomic dysfunction here on Earth.

    On Earth, the cardiovascular system is constantly working against gravity to maintain blood flow to vital organs. When an individual moves from lying down to standing, approximately 500 ml of blood shifts to the lower extremities. This triggers the arterial baroreflex, a reflex arc that detects changes in blood pressure through baroreceptors in the carotid sinus and aortic arch. These receptors initiate a cascade via the autonomic nervous system to increase heart rate, vascular tone, and cardiac contractility, thus maintaining cerebral perfusion [1, 2]. This system is finely balanced and essential to daily function. In microgravity, however, this dynamic is fundamentally altered.

    Without gravitational pull, the body’s fluid distribution becomes uniform, causing a cephalad shift in blood volume and a reduction in plasma volume by 10–15% [3]. Central venous pressure falls, and the stimuli required to maintain baroreflex tone are diminished. Over time, this leads to deconditioning of the baroreflex itself. Astronauts returning from extended missions often experience symptoms such as dizziness, postural tachycardia, and even syncope, clinically related to postural orthostatic tachycardia syndrome or orthostatic hypotension [4]. The parallels to conditions affecting aging adults and patients recovering from prolonged immobilisation are striking.

    Compounding these regulatory changes is the issue of cardiac atrophy. Like skeletal muscle, cardiac tissue remodels in response to mechanical load. Terrestrially, physical activity and gravitational resistance maintain myocardial mass and strength. In space, the heart is effectively deconditioned. Long-duration studies, including those from skylab and the ISS, have shown that cardiac mass, stroke volume, and exercise tolerance decrease over time in microgravity [3, 5]. Although these changes are generally reversible post-mission, they pose significant risks for astronaut health and performance, especially during re-entry or extravehicular activity.

    Importantly, long-duration missions pose not only the challenge of altered gravity but also cumulative exposure to cosmic and electromagnetic radiation, which may, over time, compromise the functionality of organs and biological systems. These compounding stressors demand integrating approaches to both astronaut safety and terrestrial medicine.

    With the prospect of deep-space exploration, including missions to Mars that may last up to 3 years, the physiological burden becomes even more pressing. Not only is the duration longer, but astronauts will be unable to rely on rapid medical evacuation. Preliminary data suggest that cardiovascular adaptation may differ by sex, potentially influenced by hormonal regulation of vascular tone and autonomic function [5]. Female astronauts, for instance, may exhibit greater susceptibility to orthostatic symptoms. Although the evidence is still emerging, these findings underscore the need for personalised approaches to pre-flight screening, in-flight monitoring, and countermeasure design.

    The study of suborbital flight has produced new evidence that improves our knowledge about the effects of brief extreme gravitational changes on neuroendocrine and immunological homeostasis. Bosco et al. [6] found that short suborbital missions resulted in measurable decreases in plasma dopamine levels. These missions were also associated with increased cortisol and brain-derived neurotrophic factor levels, alongside systemic pro-oxidative and pro-inflammatory changes [6]. The research supports the conclusion that brief gravitational changes during minutes to hours create substantial stress for autonomic regulation and neurovascular integrity. The observed neurochemical changes may contribute to the acute fatigue symptoms, mood changes, and executive function deficits that astronauts experience after short flights. The study demonstrates that space mission planning and rehabilitation protocols need to consider both mechanical and cardiovascular stressors, neuroendocrine resilience, and oxidative balance. The research provides new opportunities to study autonomic dysfunction and stress hypersensitivity, and inflammation in Earth-based conditions.

    Exercise remains the cornerstone of cardiovascular protection in space. On the ISS, astronauts engage in a regimented program that includes 60 min of aerobic training and 40–60 min of resistance training daily [7, 8]. These routines mimic the physiological demands of terrestrial activity, helping to maintain cardiac output, vascular compliance, and skeletal muscle mass. The parallels to exercise recommendations for Earth-bound populations are clear. Guidelines for cardiovascular disease prevention advocate at least 150 min of moderate aerobic activity and 75 min of strength-based exercise per week, yet many adults fail to meet these targets [9]. In contrast, astronauts must meet them simply to maintain baseline function.

    Beyond exercise, technological innovations have begun to reshape in-flight countermeasures. One such development is the Gravity Loading Countermeasure Skinsuit (GLCS), which mimics the compressive and axial loading effects of gravity by applying tension from the shoulders to the feet. The GLCS has demonstrated potential in reducing spinal elongation, supporting posture, and preserving cardiovascular tone [10]. Importantly, it may also have applications for patients on Earth, particularly those suffering from orthostatic intolerance, chronic fatigue, or deconditioning from prolonged bed rest. Compression garments, resistance wearables, and simulated loading systems inspired by the GLCS are now being tested in rehabilitation and geriatric medicine.

    The relevance of these countermeasures to terrestrial healthcare is growing. Many patients recovering from intensive care, cardiac surgery, or prolonged immobilisation experience the same core issues: reduced preload, impaired baroreflex sensitivity, and skeletal muscle wasting. The exercise regimens used in space have informed cardiac rehabilitation protocols on Earth, particularly for those with chronic heart failure or frailty syndromes. These overlaps suggest that space medicine can serve as a testbed for interventions that can be directly translated into clinical care.

    Looking ahead, the future of cardiovascular protection in space will likely centre around adaptability and personalisation. Research into artificial gravity, including short-radius centrifuges, is ongoing. These devices could provide intermittent gravitational loading during long-duration missions, better preserving cardiovascular and vestibular function. Simultaneously, the rise of wearable biosensors promises to revolutionise in-flight monitoring. Real-time tracking of electrocardiogram, blood pressure, hydration status, and heart rate variability can allow astronauts and patients alike to receive tailored interventions on the basis of dynamic physiological data [7].

    Further still, the integration of systems biology may usher in an era of precision countermeasures. Genomic and proteomic profiling could help identify astronauts at higher risk of cardiovascular deconditioning, informing bespoke exercise or pharmacological regimens. These same approaches are already gaining traction in cardiovascular care on Earth, from hypertension management to heart failure phenotyping. In this way, the convergence of aerospace medicine and precision health holds promise not only for space travellers but also for patients in hospitals, clinics, and homes around the world.

    In conclusion, the cardiovascular system’s adaptation to microgravity is more than an academic curiosity; it is a compelling example of how human physiology responds to extreme environmental conditions. Through rigorous observation and innovation, space agencies have developed countermeasures that preserve health in the most unnatural of settings. As we prepare for missions to the Moon, Mars, and beyond, the imperative to protect cardiovascular function will only intensify. Yet the greatest value of this research may be what it teaches us about healing on Earth. In a world facing rising chronic diseases, aging populations, and growing demands for rehabilitation, spaceflight offers a template for resilience and a vision of medicine without boundaries.

    Availability of data and materials

    Abbreviations

    GLCS:

    Gravity Loading Countermeasure Skinsuit

    ISS:

    International space station

    References

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    Authors and Affiliations

    1. University of Tasmania, Hobart, TAS, 7001, Australia

      Alan Silburn

    Contributions

    AS solely contributed to the conception, design, analysis, and drafting of the manuscript. The author read and approved the final manuscript.

    Corresponding author

    Correspondence to
    Alan Silburn.

    Ethics declarations

    Ethics approval and consent to participate

    This study did not require ethical approval as it involved a retrospective analysis of publicly available and anonymized information, with no direct involvement of human subjects.

    Consent for publication

    Not applicable.

    Competing interest

    The author declares that there are no competing interests.

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    Silburn, A. Counteracting microgravity: preserving cardiovascular health in low earth orbit.
    Military Med Res 12, 53 (2025). https://doi.org/10.1186/s40779-025-00642-y

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    Research Content and Methods

    Subjects and Groups

    A total of 87 older adults (aged ≥60 years) with T2DM, diagnosed at Huadong Hospital Affiliated with Fudan University between November 2021 and August 2024, were included in this study. This cohort comprised 50 patients with uncomplicated DM and 37 patients with diabetic kidney disease. Additionally, 20 age-matched individuals (aged ≥60 years) who visited the hospital for routine health check-ups during the same period were selected as healthy controls. These controls had no history of cardiac disease, as confirmed by medical history inquiry and echocardiography. The sample size for the control group was determined based on previous similar studies.

    All enrolled patients were between 60 and 80 years of age. The diagnoses of T2DM and diabetic kidney disease (DKD) were established by the hospital in accordance with the Chinese Guidelines for Clinical Diagnosis and Treatment of Diabetic Kidney Disease11 and the American Diabetes Association (ADA) 2021 Guidelines.12 The exclusion criteria were as follows: (1) end-stage renal disease requiring maintenance hemodialysis, peritoneal dialysis, or renal transplantation; (2) non-diabetic kidney diseases, including primary or secondary glomerular diseases, systemic diseases, hereditary kidney diseases, or normoalbuminuric DKD; (3) known cardiac diseases, such as heart failure, coronary artery disease, stable angina, prior myocardial infarction, history of percutaneous coronary intervention or coronary artery bypass grafting, atrial flutter or fibrillation, left or right bundle branch block, congenital heart disease, or the presence of an implanted pacemaker or implantable cardioverter-defibrillator; (4) left ventricular ejection fraction (LVEF) < 50%; (5) a history of or active malignant tumor.

    The study complied with the Declaration of Helsinki and was approved by the Ethics Review Committee of Huadong Hospital, affiliated with Fudan University (No. 2022K150). Written informed consent was obtained from all participants.

    Clinical Data Collection

    All participants underwent a comprehensive health assessment, including a physical examination and a structured interview. Basic demographic and anthropometric data, including age, sex, height, and weight, were collected. Body mass index (BMI) and body surface area (BSA) were subsequently calculated using standard formulae. Obesity was defined as a BMI of 24 kg/m² or greater.

    Following hospital admission, fasting blood samples were collected from all patients for a complete blood count, biochemical assays, routine urinalysis, glucose metabolism assessment, and other relevant indicators. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. A positive smoking history was defined as current or former smoking. Hypertension was diagnosed based on a systolic blood pressure ≥ 140 mmHg and/or a diastolic blood pressure ≥ 90 mmHg, measured on at least three separate occasions in a calm state and without the use of antihypertensive medication.

    Imaging Parameter Acquisition

    Data acquisition and analysis were performed using a GE Vivid E95 diagnostic ultrasound machine equipped with an M5S 2D probe (frequency range: 1–5 MHz). Synchronized limb lead electrocardiography and EchoPAC quantitative analysis software were also utilized.

    Acquisition of Conventional Echocardiographic Parameters

    Prior to echocardiography, all patients underwent resting blood pressure measurement and electrocardiographic recording in the supine position. All participants were in normal sinus rhythm throughout the examination. Conventional echocardiography was initially performed to exclude any previously undetected structural heart disease. Standard measurements were obtained for the left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), left ventricular ejection fraction (LVEF), interventricular septal thickness (IVST), and left ventricular posterior wall thickness (LVPWT). Pulsed-wave Doppler echocardiography was used to measure the early (E) and late (A) diastolic filling velocities at the mitral valve orifice. Subsequently, from the apical four-chamber view, the early diastolic mitral annular velocities (e’) were measured at the septal and lateral walls of the mitral annulus. The E/A and E/e’ ratios were then calculated. Furthermore, the left ventricular mass index (LVMI) was calculated using a standardized formula.

    Acquisition of Two-Dimensional Speckle-Tracking Echocardiographic Parameters

    Images of three consecutive cardiac cycles were acquired from the apical two-chamber, three-chamber, and four-chamber views using the M5S 2D probe. For speckle tracking analysis, the region of interest was defined as the myocardium between the epicardial and endocardial borders, thereby encompassing the entire left ventricular myocardium. Subsequently, strain values were calculated for each of the three apical views. The GLS was then determined by averaging the peak systolic strain values from all 17 segments across the three standard views and was reported as an absolute value. In this study, left ventricular myocardial segmentation was performed using a 17-segment model. Specifically, the left ventricle was divided into three levels (basal, mid-cavity, and apical). The basal and mid-cavity levels were each subdivided into six equal segments (60° each) in the short-axis orientation, while the apical level was divided into four equal segments (90° each). The most distal portion of the apex, beyond the end of the ventricular cavity, was defined as the apical cap, completing the 17-segment model.

    The population flow chart in this study is shown in Figure 1.

    Figure 1 Flow chart of the population in this study.

    Abbreviations: T2DM, type 2 diabetes mellitus; DKD, Diabetic kidney disease.

    Diagnostic Criteria and Calculation Formulae

    Relevant Diagnostic Criteria

    The threshold for subclinical left ventricular systolic dysfunction in patients with DM and preserved LVEF was set at GLS < 18%.10 The threshold for left ventricular diastolic dysfunction was set at E/e’ > 14.13

    All patients with DM were divided into three groups based on the urine albumin/creatinine ratio (UACR):

    1. Normoalbuminuria group (UACR < 30 mg/g, n = 50).

    2. Microalbuminuria group (UACR = 30–300 mg/g, n = 25).

    3. Macroalbuminuria group (UACR ≥ 300 mg/g, n = 12).

    Calculation Formulae

    HOMA-IR = fasting blood glucose × fasting insulin/22.5; TYG = ln [fasting triglycerides (TG, mg/dl) × fasting blood glucose (FBG, mg/dl)]/2; NLR (neutrophil/lymphocyte ratio) = neutrophil count/lymphocyte count; SII (Systemic Immunoinflammatory Index) = platelet count × neutrophil count/lymphocyte count; SIRI (Systemic Inflammatory Response Index) = monocyte count × neutrophil count/lymphocyte count.

    Statistical Analysis

    All statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Normally distributed continuous variables are presented as mean ± standard deviation (SD). Comparisons between two groups were made using the independent samples t-test, while comparisons among multiple groups were conducted using one-way analysis of variance (ANOVA). Non-normally distributed continuous variables are expressed as median (interquartile range, IQR), and were analyzed using the Mann–Whitney U (M-W) test for two-group comparisons and the Kruskal–Wallis (K-W) test for multiple-group comparisons. Categorical data are reported as frequencies (percentages) and were compared using the chi-squared (χ²) test. Logistic regression analysis was employed to identify factors independently associated with subclinical left ventricular systolic and diastolic insufficiency, to calculate the odds ratios (ORs) and their 95% confidence intervals (CIs). A two-tailed P-value of less than 0.05 was considered statistically significant.

    Results

    Comparison of General Information and Echocardiographic Indicators of All Subjects

    Comparison of General Information

    The baseline characteristics of the study participants are presented in Table 1. The healthy control group (n=20) had a median age of 68.50 (66.00, 73.00) years and comprised 55% males, with 25% being former or current smokers. The mean body mass index (BMI) was 23.05 ± 2.14 kg/m², the mean systolic blood pressure (SBP) was 125.40 ± 9.48 mmHg, and the median diastolic blood pressure (DBP) was 78.00 (74.00, 83.75) mmHg.

    Table 1 Baseline Characteristics of All Subjects

    For the uncomplicated DM group (n=50), the median age was 69.00 (62.75, 73.00) years, with 48% males and 10% former or current smokers. The mean BMI was 23.81 ± 2.58 kg/m², the mean SBP was 131.20 ± 14.73 mmHg, and the median DBP was 76.00 (68.00, 82.50) mmHg.

    In the DKD group (n=37), the median age was 68.00 (64.00, 71.50) years, and 27% were male. The mean BMI was 24.01 ± 2.55 kg/m², mean SBP was 139.35 ± 16.32 mmHg, and median DBP was 80.00 (69.00, 84.50) mmHg.

    No statistically significant differences were observed among the three groups regarding age, BMI, smoking history, white blood cell count, platelet count, erythrocyte distribution width (RDW), or triglycerides.

    Uncomplicated DM Group Vs Control Group

    No statistically significant differences (P > 0.05) were observed among the three groups for age, BMI, systolic blood pressure, diastolic blood pressure, smoking history, white blood cell count, or platelet count. However, compared with the control group, the uncomplicated DM group exhibited statistically significant differences (P < 0.05) in several parameters. Specifically, levels of C-reactive protein (CRP), free triiodothyronine (T3), low-density lipoprotein (LDL), and cholesterol were significantly lower in the uncomplicated DM group, whereas glycated hemoglobin, fasting blood glucose, and the rate-pressure product (RPP) were significantly higher.

    DKD Group Vs Control Group

    Compared with the control group, the DKD group exhibited significantly higher levels of systolic blood pressure, percentage of neutrophils, glycated hemoglobin, fasting blood glucose, urea nitrogen, serum creatinine, NLR, SIRI, and RPP (all P < 0.05). Conversely, the DKD group had significantly lower levels of lymphocyte percentage, hemoglobin, high-density lipoprotein (HDL), LDL, cholesterol, and eGFR (all P < 0.05).

    DKD Group Vs Uncomplicated DM Group

    Compared with the uncomplicated DM group, the DKD group demonstrated significantly higher levels of systolic blood pressure, CRP, neutrophil percentage, urea nitrogen, serum creatinine, uric acid, and NLR (all P < 0.05). Conversely, the DKD group had significantly lower levels of lymphocyte percentage, hemoglobin, eGFR, and HDL (all P < 0.05). There were no statistically significant differences between the two groups regarding white blood cell count, platelet count, monocyte percentage, RDW, glycated hemoglobin, fasting blood glucose, triglycerides, or cholesterol (all P > 0.05).

    Comparison of Ultrasound Indicators

    Conventional Echocardiographic Indicators

    No significant differences were observed in conventional echocardiographic indicators—including LAD, LVEDd, LVESd, IVST, LVPWT, LVEF, SV, LVEDV, HR, E, A, E/A, and E/e’—between the uncomplicated DM group and the control group, or between the DKD group and the uncomplicated DM group (Table 2). However, when comparing the DKD group with the control group, the A-value was significantly higher in the DKD group (P < 0.05). All other conventional echocardiographic indicators showed no statistically significant differences between these two groups.

    Table 2 Comparison of Echocardiographic Indicators in All Subjects

    Comparison of Two-Dimensional Speckle-Tracking Echocardiographic Indicators

    Two-dimensional speckle-tracking echocardiography revealed that the global longitudinal strain (GLS) was significantly lower in the DKD group (mean = 15.86 ± 2.12%) compared to both the uncomplicated DM group and the control group (P < 0.05) (Table 2). Furthermore, subclinical left ventricular systolic insufficiency, defined as GLS < 18%, was identified in 56 of the 107 study participants. Notably, this condition was present in 30 patients (81.08%) in the DKD group, a proportion significantly higher than that observed in the uncomplicated DM group and the control group (P < 0.05).

    In the comparison between the uncomplicated DM group and the control group, no statistically significant differences were observed (P > 0.05). However, the mean GLS (%) in the DM group was slightly lower than that in the control group (18.18 ± 2.29 vs 19.21 ± 1.83). Within the uncomplicated DM group, 21 individuals exhibited subclinical left ventricular systolic insufficiency (GLS < 18%), accounting for 42.00% of the group, which was higher than the 25.00% observed in the control group (5 individuals). Nevertheless, these differences between the groups did not reach statistical significance (P > 0.05).

    Comparison of Baseline Characteristics and Ultrasound Indicators of Patients with DM at Different Albuminuria Levels

    A total of 87 patients from the uncomplicated DM and DKD groups were stratified into three subgroups based on their Urinary Albumin-to-Creatinine Ratio (UACR). Statistically significant differences across these subgroups were observed for gender and the percentage of smokers (Supplementary Table 1). In contrast, no significant differences were found in age, BMI, the prevalence of hypertension, or the duration of DM.

    Comparisons of baseline characteristics among the three groups revealed the following. Relative to the control group, the microalbuminuria group exhibited significantly higher levels of blood urea nitrogen, serum creatinine, and a higher percentage of subjects with significantly impaired renal function (eGFR < 60 mL/min/1.73 m²). Conversely, this group had significantly lower levels of 25-(OH)D, serum albumin, and eGFR.

    Similarly, the macroalbuminuria group demonstrated significantly higher values than the control group for the percentage of smokers, percentage of neutrophils, blood urea nitrogen, serum creatinine, percentage of significantly impaired renal function (eGFR < 60 mL/min/1.73 m²), blood uric acid, fasting C-peptide, and NLR. In contrast, the macroalbuminuria group had significantly lower percentages of lymphocytes, and lower levels of 25-(OH)D, serum albumin, and eGFR.

    In the direct comparison between the macroalbuminuria and microalbuminuria groups, glycated hemoglobin was the only parameter that was significantly lower in the macroalbuminuria group. No other significant differences were observed in the remaining baseline characteristics or laboratory indices.

    The comparison of conventional echocardiographic indicators among the three groups revealed that SV (stroke volume, mL) and LVEDV (left ventricular end-diastolic volume, mL) in the macroalbuminuria group were significantly higher than those in both the microalbuminuria and normoalbuminuria groups (Supplementary Table 2). Although the means of SV and LVEDV in the microalbuminuria group were slightly elevated compared to the normoalbuminuria group, these differences did not reach statistical significance. No statistically significant differences were observed among the three groups in terms of LAD, LVEDd, LVESd, IVST, LVPWT, LVEF, LVMI, HR, E, E/A, IVRT, and E/e’. Furthermore, the prevalence of left ventricular diastolic insufficiency, defined as E/A < 0.8 or E/e’ > 14, did not differ significantly among the groups (P > 0.05).

    Two-dimensional speckle-tracking echocardiography revealed that the left ventricular global longitudinal strain (GLS) was significantly worse (ie, higher values) in both the microalbuminuria and macroalbuminuria groups compared to the normoalbuminuria group (P < 0.001; Supplementary Table 3). Among all 87 patients with diabetes mellitus (DM), subclinical left ventricular systolic dysfunction, defined as GLS < 18%, was identified in 51 cases (58.62%). When stratified by group, the proportion of patients with subclinical dysfunction was significantly higher in the macroalbuminuria group (91.70%) than in the normoalbuminuria group (42.00%, P < 0.05). Similarly, the microalbuminuria group also exhibited a higher proportion (76.00%) compared to the normoalbuminuria group (P < 0.05). Although the prevalence of subclinical dysfunction was greater in the macroalbuminuria group than in the microalbuminuria group (91.70% vs 76.00%), this difference did not reach statistical significance (P > 0.05).

    Comparison of Baseline Characteristics and Echocardiographic Indicators of Patients with DM Grouped According to GLS < 18%

    The 87 subjects were stratified into two groups based on the presence of subclinical left ventricular systolic dysfunction, defined as GLS < 18%: the GLS < 18% group (n = 51) and the GLS ≥ 18% group (n = 36).

    As presented in Table 3, patients in the GLS < 18% group exhibited significantly higher levels of UACR, proteinuria prevalence, leukocyte count, neutrophil percentage, blood urea nitrogen, prevalence of eGFR < 60 (mL/min/1.73 m²), serum creatinine, uric acid, fasting insulin, fasting C-peptide, triglycerides, HOMA-IR, triglyceride-glucose index (TyG), NLR, SIRI, and RPP compared to the GLS ≥ 18% group (P < 0.05). Conversely, the same group had significantly lower levels of lymphocyte percentage, eGFR, and HDL (P < 0.05).

    Table 3 Baseline Characteristics of Patients with T2DM Grouped According to GLS < 18%

    No statistically significant differences were observed between the two groups regarding age, BMI, systolic and diastolic blood pressure, hypertension prevalence, smoking history, DM duration, glycated hemoglobin, or fasting blood glucose (P > 0.05).

    E and E/A values in the group with GLS < 18% were significantly lower, and the percentage of E/A <0.8 was significantly higher than that in the group with GLS ≥ 18%, suggesting that subjects who developed subclinical left ventricular systolic insufficiency might have concomitant left ventricular diastolic dysfunction (Table 4).

    Table 4 Characteristics of Cardiac Ultrasound Indicators in Patients with T2DM Grouped According to GLS < 18%

    Analysis of Risk Factors for Subclinical Left Ventricular Systolic Insufficiency in Patients with DM

    All 87 older adults with DM were included, and GLS < 18% was set as the dependent variable (Table 5). A univariate logistic regression analysis was performed on clinical data that were statistically different from those analyzed above or considered traditional risk factors for cardiovascular disease (CVD). Variables included general information (age, gender, BMI, DM duration, and smoking history), UACR, blood indicators related to renal function (eGFR, blood urea nitrogen, serum creatinine, and blood uric acid), serum albumin and lipid indicators (triglycerides, cholesterol, HDL, and LDL), glucose metabolism indicators (fasting blood glucose, fasting insulin, fasting C-peptide, glycated hemoglobin, and HOMA-IR) and inflammation-related serological indicators (white blood cell count, percentage of neutrophils, SIRI, SII, etc).

    Table 5 Univariate Logistic Regression Analysis for the Development of Subclinical Left Ventricular Systolic Insufficiency in Patients with T2DM

    Statistically significant indicators in the univariate analysis, including gender, proteinuria, white blood cell count, percentage of neutrophils, blood urea nitrogen, eGFR, serum creatinine, uric acid, HDL, fasting C-peptide, HOMA, fasting blood glucose, triglycerides (combined as Tyg), and RPP, traditional risk factors for CVD, including age, obesity, and hypertension, DM duration, and smoking history, as well as the development of subclinical left ventricular systolic insufficiency (GLS < 18%) were included as dependent variables to perform a multivariate logistic stepwise regression analysis among the 87 DM patients and the 37 DKD patients respectively, with the results shown below (Table 5, Figure 2):

    Figure 2 vForest plot.Multivariate Logistic Regression Analysis of the Development of Subclinical Left Ventricular Systolic Insufficiency in Patients with T2DM.

    Abbreviations: OR, odds ratio; CI, confidence interval; GLS, global longitudinal strain.eGFR, Estimated glomerular filtration rate.

    The multivariate logistic regression analysis showed that proteinuria, eGFR, triglycerides, and HOMA were significant risk factors for subclinical left ventricular systolic insufficiency in older adults with T2DM. In regression model 1, as the eGFR decreased, the risk of developing subclinical left ventricular systolic insufficiency in the subjects gradually increased. eGFR was an independent risk factor for GLS < 18% (OR = 0.974, 95% CI = 0.949–1.000, P < 0.05). Triglycerides were also a risk factor for the development of subclinical left ventricular systolic insufficiency, and with the elevation of triglycerides, the risk was progressively higher (OR = 3.069, 95% CI = 1.002–9.395, P < 0.05). The HOMA-IR was calculated to quantify insulin resistance.14 With the increase in insulin resistance, the probability of subclinical left ventricular systolic insufficiency in older adults with T2DM progressively increased (OR = 1.249, 95% CI = 1.027–1.521, P < 0.05). In model 1, the risk of subclinical left ventricular systolic function in the DKD group with positive proteinuria was 4.063 times that in the uncomplicated DM group with negative proteinuria (P < 0.05). However, unfortunately, after including only patients in the DKD group, none of the above risk factors remained statistically significant in model 2 (Supplementary Table 4).

    Discussion

    This study aims to explore the risk factors associated with impaired left ventricular longitudinal myocardial systolic function in asymptomatic older adults with T2DM and preserved LVEF. Our data analysis identified proteinuria, insulin resistance, reduced eGFR, and hypertriglyceridemia as independent risk factors for early subclinical left ventricular systolic dysfunction in asymptomatic older adults with T2DM and preserved LVEF.

    Proteinuria is recognized as a marker of microvascular dysfunction. The Urinary Albumin-to-Creatinine Ratio (UACR), a robust indicator for screening proteinuria, is now incorporated into numerous clinical guidelines. Its primary role is to identify patients with type 2 diabetes mellitus (T2DM) who have persistent microalbuminuria, thereby guiding the initiation of intensive prophylactic therapy with cardioprotective medications.15. According to our results, the proteinuria is a risk factor for subclinical left ventricular systolic insufficiency in older adults with T2DM in both univariate and multivariate logistic regression models, which is in line with the conclusions made by Peter P6 and Yasuhide5 et al, suggesting that albuminuria could be used as a biomarker to screen DM patients for increased cardiovascular risk. An earlier study at our hospital showed that, in older adults with DKD, patients with macroalbuminuria had a significantly higher risk of developing subclinical left ventricular systolic insufficiency than those with microalbuminuria. However, this difference was not statistically significant in this study, although the subjects showed a gradual decrease in GLS and a gradual increase in the percentage of GLS < 18% as the albuminuria became more severe, which may be related to the small sample size of the macroalbuminuria group.

    Elevated glucose or altered insulin sensitivity has been found to affect cardiac function by altering the cardiac extracellular matrix (ECM).16,17 It has been suggested that both fasting glucose, which reflects instantaneous glucose levels, and glycosylated hemoglobin, which reflects long-term glycemic control, can be used as markers to screen DM patients who are at an increased risk of CVD.18 However, in many studies, controlling glycosylated hemoglobin or fasting blood glucose alone cannot alleviate the burden of left ventricular dysfunction in mouse models or prevent cardiovascular complications in diabetic patients.19–21 Our results correspond to it. Another researcher suggests reversing the adverse effects of acute hyperglycemia on left ventricular systolic myocardial mechanics by increasing blood glucose variability.22,23 In the field of prevention and management of DCM in older adults, effective glycemic management remains to be further investigated and guided. Insulin resistance might be an important trigger for systolic dysfunction in T2DM patients.24 Among the subjects included in this study, we quantified insulin resistance by HOMA-IR and Tyg.25 These indicators were significantly different between the two groups, demonstrated to be risk factors for GLS < 18% in the univariate or multivariate logistic regression analysis, once again proving the promoting effect of insulin resistance on the onset of DCM.

    Studies that examined endocardial myocardial biopsy samples have shown significant interstitial fibrosis with infiltration of inflammatory leukocytes in patients with HFpEF.26 Inflammatory indicators such as white blood cell count, NLR, as well as SII and SIRI, reflect systemic inflammation and immune balance in the body. High SIRI is an independent risk factor for DKD, while elevated SII is associated with an increased risk of kidney disease progression in biopsy-confirmed DKD cases.27 In this experiment, we found that the white blood cell count, NLR, and SIRI in the group with GLS < 18% were significantly higher than those in the group with GLS ≥ 18%, validating the role of inflammation in mediating the pathogenesis of DCM in the older population. Biomarkers reflecting inflammation, as cost-effective and readily available indicators of inflammation, may be applied to the early screening of subclinical left ventricular systolic dysfunction in older T2DM patients.

    Hypertriglyceridemia is implicated in myocardial steatosis, leading to subclinical left ventricular systolic and diastolic dysfunction.28,29 In the geriatric DM cohort of this study, high triglycerides, as a risk factor for GLS < 18%, remained statistically significant in the multivariate logistic regression analysis, which was consistent with previous findings.5 Triglyceride overload in the myocardium of patients with DM is reversible30 and can be intervened therapeutically by caloric restriction (CR). A more scientific and detailed incorporation of lifestyle intervention therapies, including diet and exercise, into the health management of patients with DM at high risk of cardiovascular events may help reduce the risk of CVD in older adults with T2DM.31

    In this study, eGFR was also found to be an independent risk factor for the development of subclinical left ventricular systolic insufficiency in older adults with T2DM, which was consistent with previous findings.32 But this result was not statistically significant in the model that included only DKD patients likely due to the limited number of macroalbuminuria samples.

    Many studies considered left ventricular diastolic dysfunction to be the earliest dysfunction in the course of DCM.33 However, with the increasing use of 2D and 3D STE parameters in clinical and research settings, new cardiac ultrasound indicators, represented by GLS, have shown tremendous value in the screening of subclinical myocardial dysfunction. Recent research has included GLS in its analyses, demonstrating that systolic dysfunction, instead of diastolic dysfunction, is the first manifestation of DCM.7,24 Among the subjects included in this study, when e/e’ was considered as a criterion, we found that in different levels of proteinuria grouping, the proportion of patients with subclinical left ventricular systolic dysfunction was much higher than that of patients with diastolic dysfunction, suggesting that, at least in the older population we studied, significant diastolic dysfunction might not be developed in early DM, with subclinical systolic dysfunction being the predominant issue. Meanwhile, in the group with GLS < 18%, the proportion of patients with E/E’ > 14 was more limited, suggesting that subclinical systolic insufficiency preceded or coexisted with diastolic insufficiency in a significant proportion of DM patients. The application of abnormal systolic strain as a marker to evaluate myocardial function and screen older adults with T2DM with high cardiovascular risks may yield more sensitive results.

    This study focuses on subclinical cardiac dysfunction in older adults (≥60 years old) with type 2 diabetes mellitus (T2DM), a population distinguished by unique pathophysiological characteristics and clinical management challenges. The aging process contributes to the development of cardiovascular complications in these patients through mechanisms such as impaired mitochondrial function in cardiomyocytes. Concurrently, aging introduces confounding factors, including limited physical activity, that can mask the early symptoms of myocardial dysfunction. The cardiac reserve function of older adults is limited, meaning that once they enter the stage of overt heart failure, the prognosis is extremely poor. According to data from the World Health Organization, the global population aged ≥60 years is projected to increase from 12% in 2015 to 22% by 2050. In China, for instance, the prevalence of diabetes among individuals aged 60 and older is 20.2%, approximately twice that of the general adult population. These trends underscore the critical need for a paradigm shift in prevention and control strategies, moving from a “symptom-driven” to a “subclinical damage-driven” approach. Such a shift is essential not only for improving individual patient outcomes but also for mitigating the overall cardiovascular disease burden in an aging society. The pathogenesis of diabetic cardiomyopathy (DCM) is recognized as multifactorial. Consequently, identifying risk factors linking diabetic kidney disease (DKD) to cardiovascular disease (CVD) represents a crucial first step toward developing targeted prevention and treatment. This study, therefore, aimed to analyze the risk factors for subclinical left ventricular systolic insufficiency in older patients with type 2 diabetes mellitus (T2DM). We employed global longitudinal strain (GLS) in lieu of left ventricular ejection fraction (LVEF) to assess ventricular function, seeking to detect subtle, early impairments in systolic function that are not discernible through conventional echocardiography. The study is technically innovative and fills a research gap in an older subgroup. Based on these results, we suggest that the risk factors identified in this experiment—high triglycerides, low eGFR, and insulin resistance—be considered as modifiable factors, providing a critical window of opportunity for early intervention to prevent cardiac function decline in older adults with type 2 diabetes. Besides, we recommend that GLS assessments be incorporated into routine screening protocols for older adults with T2DM who present with these risk factors, even in the absence of heart failure symptoms or a reduction in LVEF. This approach could facilitate the early detection of incipient DCM, enabling earlier clinical intervention and thereby improving patient outcomes and quality of life. However, this study has certain limitations. It is a single-center, cross-sectional study with a relatively small sample size. Moreover, some variables in the logistic regression analysis had wide confidence intervals, indicating a degree of statistical uncertainty. As an exploratory investigation, our findings are preliminary and should be interpreted with caution. Future multicenter studies with larger cohorts and longitudinal designs are warranted to validate and extend our findings. A notable limitation of this study is that coronary artery disease (CAD) was excluded based on medical history, electrocardiogram, and echocardiogram alone. As coronary angiography—the gold standard for CAD diagnosis—was not routinely performed, the possibility of asymptomatic CAD cannot be entirely ruled out. Furthermore, the selection of confounders for our logistic regression and sequential models was based on prior literature. This underscores the necessity for more comprehensive analyses, incorporating a broader range of potential variables, in future research.

    In conclusion, this study demonstrates that proteinuria, reduced eGFR, hypertriglyceridemia, and insulin resistance are independent risk factors for early subclinical left ventricular systolic insufficiency in asymptomatic older patients with type 2 diabetes mellitus (T2DM) and preserved left ventricular ejection fraction (LVEF). Our findings suggest that routine GLS assessment should be considered for patients in this demographic who present with these risk factors, even before the onset of heart failure symptoms or a measurable decline in LVEF.

    Data Sharing Statement

    The datasets used and/or analyzed during the current study are available from the corresponding author (Xiaoli Zhang, [email protected]) on reasonable request.

    Ethics Approval and Consent to Participate

    The study complies with the Declaration of Helsinki and was approved by the Ethics Review Committee of Huadong Hospital, affiliated with Fudan University (No. 2022K150). All participants have signed a written informed consent form.

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Funding

    This study was supported by the National Natural Science Foundation of China (Grant No. 82270714).

    Disclosure

    The authors declare that they have no competing interests in this work.

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    24. Minciună I-A, Orășan OH, Minciună I, et al. Assessment of subclinical diabetic cardiomyopathy by speckle-tracking imaging. Eur J Clin Invest. 2021;51(4):e13475. doi:10.1111/eci.13475

    25. Minh HV, Tien HA, Sinh CT, et al. Assessment of preferred methods to measure insulin resistance in asian patients with hypertension. J Clin Hypertens Greenwich Conn. 2021;23(3):529–537. doi:10.1111/jch.14155

    26. Westermann D, Lindner D, Kasner M, et al. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail. 2011;4(1):44–52. doi:10.1161/CIRCHEARTFAILURE.109.931451

    27. Liu W, Zheng S, Du X. Association of systemic immune-inflammation index and systemic inflammation response index with diabetic kidney disease in patients with type 2 diabetes mellitus. Diabetes, Metab Syndr Obes Targets Ther. 2024;17:517–531. doi:10.2147/DMSO.S447026

    28. Korosoglou G, Humpert PM, Ahrens J, et al. Left ventricular diastolic function in type 2 diabetes mellitus is associated with myocardial triglyceride content but not with impaired myocardial perfusion reserve. J Magn Reson Imaging JMRI. 2012;35(4):804–811. doi:10.1002/jmri.22879

    29. Rijzewijk LJ, van der Meer RW, Smit JWA, et al. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol. 2008;52(22):1793–1799. doi:10.1016/j.jacc.2008.07.062

    30. Hammer S, Snel M, Lamb HJ, et al. Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function. J Am Coll Cardiol. 2008;52(12):1006–1012. doi:10.1016/j.jacc.2008.04.068

    31. Senesi P, Ferrulli A, Luzi L, Terruzzi I. Diabetes mellitus and cardiovascular diseases: nutraceutical interventions related to caloric restriction. Int J Mol Sci. 2021;22(15):7772. doi:10.3390/ijms22157772

    32. Murtaza G, Virk HUH, Khalid M, et al. Diabetic cardiomyopathy – a comprehensive updated review, Prog. Cardiovasc Dis. 2019;62(4):315–326. doi:10.1016/j.pcad.2019.03.003

    33. Brooks BA, Franjic B, Ban CR, et al. Diastolic dysfunction and abnormalities of the microcirculation in type 2 diabetes. Diabetes Obes Metab. 2008;10:739–746. doi:10.1111/j.1463-1326.2007.00803.x

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  • The Cyberpunk 2077 team is seeking “brave netrunners” for something on 4th September, but won’t say what it is

    The Cyberpunk 2077 team is seeking “brave netrunners” for something on 4th September, but won’t say what it is

    The Cyberpunk 2077 team is teasing something for this Thursday, 4th September.

    A rather mysterious post has popped up on social media from President Rosalind Myers (that is to say, Cyberpunk 2077’s president of the New United States of America and former CEO of Militech).

    “Our great nation is once again facing a mounting cybersecurity threat – from those who hide in the shadows, too cowardly to publicly proclaim their beliefs, who are viciously determined to tear down our flag and the values it upholds,” the post begins. “I will not accept this, and I know you won’t either.”

    The Cyberpunk 2077 directive then asks netrunners brave enough (so, you and me) to “join our efforts” to overcome “this grave threat”.

    The message from the president closes with the call to “take our recruitment test” and “prove yourself” by serving the NUSA. It doesn’t actually have a link or anything to take you to a recruitment test, though, but given it is all predated as a note from 4th September, I am going to say this will change on Thursday. I wonder if the threat is Team Cherry… (I jest of course).

    Some in the comments have suggested a new game plus mode could be on its way, while others are hoping for more content for Cyberpunk 2077’s Phantom Liberty DLC. What do you hope the Cyberpunk 2077 team is teasing?

    Image credit: CDPR

    This is a news-in-brief story. This is part of our vision to bring you all the big news as part of a daily live report.

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  • everything is eclipsed by the cakes in this sanitised Netflix adaptation

    everything is eclipsed by the cakes in this sanitised Netflix adaptation

    In his essay Decline of the English Murder, the writer George Orwell evokes the pleasure to be had in reading about killing. After a good meal (including pudding), you are in the mood to read: “the sofa cushions are soft underneath you, the fire is well alight, the air is warm.” And what is it, in “these blissful circumstances”, that you want to read about? “Naturally,” says Orwell, “a murder”.

    Substitute Orwell’s fires for contemporary radiators, and he might be describing the millions of readers in our own moment who have turned contentedly to stories of killing in the Thursday Murder Club books by Richard Osman. Comprising 2020’s title novel and three follow-ups (a fourth, The Impossible Fortune, is due in late September), these murder mysteries set in an idyllic retirement village in Kent have proved phenomenally successful.

    Why have so many people, including some not previously invested in crime fiction, been drawn to these novels? It is not as if the series has been scrubbed free of potentially off-putting material. The Thursday Murder Club itself, for example, features not only two new killings for the quartet of older investigators to unravel, but memories of brutal gangland executions and a tragic suicide.

    Such content, however, rarely ruffles The Thursday Murder Club’s smooth storytelling. The relaxed narrative voice, replicating Osman’s register as a genial quiz show host on TV, makes difficult things manageable. So, too, do the novel’s copious references to cakes: whenever a murder threatens to become too much, there is always a lemon drizzle or Viennese whirl to soothe.

    Now The Thursday Murder Club has been adapted for the screen, enjoying a short cinema release before its streaming on Netflix. This adaptation has Hollywood heft behind it: produced by Amblin Entertainment (Steven Spielberg’s company), directed by Chris Columbus (veteran of Home Alone, Mrs Doubtfire and two instalments of the Harry Potter franchise), and with music by Thomas Newman (whose other composing credits include the Bond films Skyfall and Spectre).

    If anything, Osman’s already sugared original has been further sweetened in its transit to the screen. The novel’s gangland subplot, for example, is shaved down to a few hints; and a doomed love affair that in the book precipitates suicide has been erased entirely. While some condensing is inevitable in transposing a 400-page novel to a two-hour film, the excisions made by Columbus and the co-screenwriters Katy Brand and Suzanne Heathcote are in the interests not only of economy, but of sanitisation for still further mass-market appeal.

    One of the delights offered by Osman’s original is its knowing references to other crime fiction. In a suggestive scene, the investigators talk about their own favourites in the genre. Patricia Highsmith says one; Ian Rankin says another; Mark Billingham says a third. Here they evoke kinds of crime fiction entirely distinct from the novel in which they are situated as characters.

    Columbus’s film doesn’t carry across such mischievous allusiveness. Given its medium, however, it can enlist visual pleasures unachievable by the print-bound Osman.

    In the 1980s, film theorist Tom Gunning coined the term “cinema of attractions”. This he offered as a way of characterising films that suspend or downplay the storytelling itself and seek instead to engage audiences by other means, such as spectacle that is unusual, beautiful or amusing.

    Gunning had especially in mind work produced in cinema’s inaugural decade from 1895 onwards, when a film’s running time was limited, allowing no scope for narrative development. But his idea is fruitful in thinking about filmmaking of later periods, too. If it offers us a framework for considering the Marvel Cinematic Universe – all those standalone CGI effects like the look of the villain Thanos or the rendering of otherworldly environments – it is also apt in reviewing the new Thursday Murder Club.

    The film engages in some narrative business, of course, offering a set of murders for investigation and solution. Who killed two of the figures behind upsetting plans to bulldoze the retirement village in favour of an event centre? Whose body is the unexpected extra one found in a tomb in the graveyard adjoining the complex?

    Arguably, however, the storytelling here is relatively uninvolving and peripheral to the film’s chief effects. Many viewers are likely to be absorbed instead by the abundant display of British and Irish acting royalty: in particular, Helen Mirren as resourceful former secret agent Elizabeth (“I have a wide portfolio of skills”), Pierce Brosnan as retired union leader Ron who is itching for new campaigns, and Ben Kingsley as suave former psychologist Ibrahim.

    The cakes are the real scene stealers in the film.
    Giles Keyte/Netflix

    And then, as in Osman’s novel, there are the cakes.

    Reviewing recipe books, the writer Angela Carter referred to the “awesome voluptuousness” taken on by food whenever it is photographed in that genre. Carter’s description fits perfectly the cakes we see in Columbus’s film. Indeed, the Victoria sponge and the coffee and walnut cake made by the fourth investigator Joyce (Celia Imrie) have a prodigious depth, a lavish creaminess, that threaten to act even these British stars off the screen.

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