Christa Meisinger

Background: Prior studies found that glycolysis-related metabolic markers—particularly lactate and glucose—are associated with short-term mortality after myocardial infarction (MI). However, information on glycolysis-wide metabolite alterations and short-term post-MI mortality remains insufficient. Therefore, this study investigated the associations of glucose, lactate, pyruvate, and citrate with short-term mortality after ST-elevation myocardial infarction (STEMI). Methods: This study was based on data from 724 STEMI patients enrolled in the population-based Augsburg Myocardial Infarction Registry. Arterial EDTA blood samples were drawn at the start of the catheterization procedure and plasma concentrations of the metabolites were quantified using a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform developed by Nightingale Health (Finland). Multivariable logistic regression models were used to assess the associations between glycolysis-related metabolites and 28-day mortality. P values were adjusted for multiple testing using the false discovery rate (FDR) method. Results: Overall, 677 patients survived the first 28 days after hospitalization, whereas 47 died within this period. Elevated plasma levels of glucose, lactate, pyruvate, and citrate were each significantly associated with an increased risk of short-term mortality. In the multivariable logistic regression models, the strongest association was observed for glucose (OR 2.10, 95% CI 1.53–2.88, p _adj ≤ 0.001) and the weakest association for pyruvate (OR 1.60, 95% CI 1.22–2.10, p _adj = 0.001). Conclusions: These findings indicate that metabolic disturbances, reflected by glycolysis-related metabolites, are associated with short-term mortality in STEMI patients, suggesting their potential prognostic value.

Background: Obesity is associated with altered immune function and may therefore influence the response to influenza vaccination. So, the objective was to investigate whether body mass index (BMI) affected influenza-specific antibody titers and immune cell counts after vaccination. Methods: A subgroup of 25 participants from the MEGA cohort, a prospective observational study in Augsburg, Germany, aged 25–65 years, was analyzed, including 18 normal-weight individuals and 7 participants with obesity. Influenza antibody titers and immune cell phenotypes were assessed at four visits over nine months following vaccination. Differences between normal-weight and obese individuals were analyzed graphically using boxplots and tested using the Wilcoxon signed-rank test and the Mann-Whitney-U-test. Results: At baseline, no significant differences in antibody titers were observed between BMI groups. Following vaccination, antibody titers increased in both groups and remained above pre-vaccination levels throughout follow-up. In the normal-weight group, the titers for all four analyzed antibodies differed significantly at every visit compared to visit 1. This was not the case in the obese group, where only the titers for the antibodies B/Colorado/06/2017 and B/Phuket/3073/2013 differed at the different visits in comparison to visit 1. Furthermore, obese participants showed a non-significant downward trend in Treg cell proportions over time; total T-cell counts did not demonstrate clear group-specific differences. B-cell proportions showed no consistent time trend, but significant within-group differences were observed between visits 1 and 4 in the normal-weight group and visits 1 and 2 in the obese group, with significant differences between groups at visits 1 and 3. Conclusion: The findings suggest that BMI may influence cellular immune responses after influenza vaccination, whereas antibody responses appeared broadly similar among BMI groups. Given the limited sample size these observations should be interpreted as exploratory. Larger studies are needed to clarify this relationship and to inform the development of tailored vaccination strategies for obese individuals.

The platelet-to-white-cell ratio has recently gained attention as a potential prognostic indicator. This study investigated the association between platelet-to-white-cell ratio at admission and long-term mortality in acute myocardial infarction patients, in comparison to leukocyte and platelet counts alone. The study included 4,964 patients aged 25–84 years with incident acute myocardial infarction hospitalized between 2010 and 2017, as recorded in the population-based Augsburg Myocardial Infarction Register. Platelet-to-white-cell ratio was calculated from admission platelets divided by leukocyte counts. Cox proportional hazards regression models were used to assess the associations between quartiles of platelet-to-white-cell ratio, of leukocytes, and of platelets with long-term all-cause mortality. During a median follow-up time of 4.7 years, 1,224 patients died. Platelet count in the highest quartile was observed to be associated with increased mortality risk (HR 1.32 (1.06–1.63). Platelet-to-white-cell ratio values were also found to be associated with risk of mortality. Multivariable adjusted HRs for the second, third, and fourth quartiles of platelet-to-white-cell ratio (vs. lowest quartile) were 0.64 (95% CI: 0.52–0.80), 0.83 (0.67–1.03), and 0.78 (0.62–0.98), respectively. Platelet-to-white-cell ratio at admission was associated with long-term mortality in patients with acute myocardial infarction. As a simple, cost-effective biomarker, platelet-to-white-cell ratio may support individualized risk stratification and clinical decision-making in acute myocardial infarction care.

Background: Amino acid metabolism plays a critical role in cardiovascular disease, yet its prognostic value in ST-elevation acute myocardial infarction (STEMI) remains underexplored. Therefore, we investigated whether specific plasma amino acid concentrations at admission for STEMI are associated with 28-day mortality. Methods: This analysis was based on data from 724 patients with STEMI aged 29 to 98 years who were admitted to the University Hospital Augsburg between May 2009 and July 2013. Immediately after admission arterial blood samples were taken from these patients and a panel of amino acids was measured by a high-throughput nuclear magnetic resonance spectroscopy platform (Nightingale Health, Finland). Multivariable logistic regression models were conducted to examine the associations between the amino acids phenylalanine, tyrosine, glycine, alanine, histidine, glutamine, as well as branched-chain amino acids (BCAAs; a group that includes valine, isoleucine, and leucine) and 28-day mortality. P values were False discovery rate (FDR) adjusted. Results: Altogether, 47 patients died within 28 days after admission. There were significant positive associations found between plasma levels of phenylalanine, glycine, tyrosine, valine, and alanine and 28-day mortality. Phenylalanine showed the highest effect estimate (OR: 1.84; 95% CI 1.34–2.53). No significant associations were observed for the remaining amino acids. Conclusions: The acute phase of STEMI is associated with changes in plasma amino acid levels that may reflect alterations in energy metabolism and metabolic stress. The associations between amino acid fluctuations and 28-day mortality highlight the potential of metabolomic profiling to refine early risk stratification.

Summary Using highly precise measurements, we found obstructive sleep apnea (OSA) was linked to poorer bone health at most sites. Higher oxygen saturation, rather than sleep efficiency, was beneficial. Total sleep duration was partially nonlinearly related to bone health. Patients with chronic sleep problems should be screened for low BMD. Aim Previous studies have shown associations between sleep characteristics and bone health, but findings are inconsistent. This study investigated the relationships between objectively measured sleep characteristics and bone mineral density (BMD) as well as bone mineral content (BMC) using dual-energy X-ray absorptiometry (DXA) measurements at various skeletal sites. Methods The analysis included data from 4690 participants aged 40–70 years in the Human Phenotype Project (HPP) cohort. Associations between total sleep time, mean oxygen saturation (%), sleep efficiency, and obstructive sleep apnea (OSA) indices—respiratory disturbance index (RDI), apnea-hypopnea index (AHI), and oxygen desaturation index (ODI)—measured by a sleep apnea monitoring device, and BMD/BMC assessed by DXA imaging of various skeletal components were examined using multivariable linear regression models. All associations were tested for interactions with age. Results OSA indices (AHI, ODI, RDI) showed linear or non-linear inverse associations with BMD or BMC at most bone sites. The negative associations of AHI and ODI with spine outcomes were non-linear, with stronger effects at higher index ranges. Total sleep time was inversely associated with BMC of the legs, femoral neck, and femoral shaft, with consistent estimates for BMD. U-shaped associations were observed between total sleep time and BMC of both arms and spine L2. Oxygen saturation was positively associated with BMD and BMC of the total body, arms, head, and spine. Sleep efficiency showed no association with any outcomes. Age-stratified analyses revealed stronger estimates in younger participants. Conclusions OSA appears to be associated with reduced BMD and BMC, even in individuals without other major health conditions. These findings highlight the need for increased clinical awareness, including BMD screening for OSA patients, and, on the other hand, the detection of sleep problems in patients with osteoporosis or reduced BMD and BMC.

Background: Ischaemic stroke etiology, as defined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, has been associated with differences in survival and functional outcomes when assessed using the modified Rankin Scale (mRS). This study investigated whether similar patterns are reflected in patient-reported physical functioning during the first year post-stroke. Methods: We analysed data from the Stroke Cohort Augsburg (SCHANA), a prospective study of adults with confirmed ischaemic stroke treated at a tertiary care hospital in Southern Germany between 2018 and 2022. Physical functioning was assessed at 3- and 12-month post-discharge by using the physical domain score of the Stroke Impact Scale (SIS). Associations with stroke etiology were examined using linear mixed-effects models to improve precision and account for variable follow-up availability. Results: The final analytic sample included 1,044 patients and was characterised by predominantly mild neurological impairment at admission (median NIHSS 2.0). In adjusted linear mixed-effects models, stroke etiology was not significantly associated with patient-reported physical functioning. No etiologic subgroup differed significantly from the cardioembolic reference group (all p > 0.05). Conclusions: Among patients with predominantly mild ischaemic stroke, patient-reported physical functioning varied little across TOAST-defined subtypes. This may reflect limited between-group variation in stroke severity at baseline and conceptual differences between patient-reported and clinician-assessed outcome measures such as the mRS.

Background: Previous investigations have shown that the absence of typical breast symptoms is associated with unfavorable outcomes after an acute myocardial infarction (AMI). Delayed diagnosis and therapy could not explain these results, so other causes seem to be involved. Therefore, in the present analysis the association between inflammatory plasma proteins and typical chest pain symptoms in hospitalized patients with acute ST-elevation myocardial infarction (STEMI) was investigated. Methods: Data from 395 STEMI patients registered by the population-based Myocardial Infarction Registry Augsburg between 2009 and 2013 were used for analysis. The OLINK inflammatory panel including a total of 92 cytokines was measured in arterial blood samples, which were obtained immediately after hospital admission within the scope of cardiac catheterization. The associations between the inflammation markers and typical chest pain were examined by multiple logistic regression analyses. Results: Altogether, 10.9% of the STEMI patients did not present with typical chest pain. The inflammatory markers IL8, IL6, FGF-21, CD40, CST5, ADA, OPG, PD-L1, TNFRSF9 and STAMBP were significantly inversely associated with typical chest pain after FDR-adjustment. The strongest associations were found for FGF-21, CST5 and CD40. Conclusions: These results suggest that a dysregulated inflammatory status is associated with a lack of typical chest pain in AMI patients. Beyond acute-phase inflammatory interleukins elevated within the early phase of an AMI, such as IL-6, hepatokines and transmembrane proteins seem to be associated with AMI symptoms. Further research into the causal mechanisms of these associations is necessary.

Background: Obesity, particularly central adiposity, is a major risk factor for impaired glucose metabolism and type 2 diabetes. The biological mechanisms linking body fat distribution to glucose regulation remain incompletely understood. Therefore, we investigated the associations between body fat distribution and plasma markers of glucose metabolism in a population-based sample and examined the mediating role of hepatocyte growth factor (HGF) in this connection. Methods: The analysis was based on data from 238 participants of the MEGA study (German acronym for metabolic health study Augsburg) conducted between 2018 and 2021. Anthropometric measurements and a body composition analysis via bioelectrical impedance analysis (BIA) were conducted. HGF was measured from EDTA plasma based on the Proximity Extension Assay (Olink inflammation panel). Multivariable linear regression models were chosen to examine the associations between standardized anthropometric and BIA measurements and the outcome variables in non-diabetic individuals. Obesity measures included body mass index (BMI), waist circumference (WC), visceral adipose tissue (VAT), and waist-to-hip ratio (WHR), relative fat mass (RFMV), and absolute fat mass (AFMV). The outcome variables included fasting glucose, two-hour OGTT glucose, and HbA1c concentrations. Mediation effects of HGF between obesity measures and glucose parameters were assessed. Results: The observed positive associations between obesity measures and glucose metabolism were stronger for variables that are indicative of central obesity (WC, WHR, VAT), when compared to indices of general obesity (BMI, RFMV, AFMV). Fasting glucose showed the strongest positive association with WC (β = 5.10 mg/dL per one standard deviation increase; 95% CI 1.86–5.77). For two-hour plasma glucose, the strongest associations were observed with WHR (β = 21.00; 95% CI 14.57–27.44). HGF mediated between 7.0% and 9.1% of the total effects with two-hour glucose levels but not the associations with the other outcomes. No associations were found with HbA1c levels after accounting for multiple testing. Conclusions: These findings suggest HGF may contribute to the metabolic effects of different obesity measures on post-load glucose regulation, providing insights into obesity-related glucose dysregulation and potential targets for early intervention. However, the causal role of HGF remains unproven; further studies on the exact pathophysiological mechanisms are necessary.

Background: The prevalence of venous thromboembolism (VTE) and the impact of blood coagulation factors on the occurrence of VTE in the general population have been rarely studied. Methods: In the KORA-Fit (S4) study with n = 805 participants (53% females) with a mean age of 62.4 (SD 5.7) years, the prevalence of physician-diagnosed VTE was assessed during a face-to-face interview. Plasma concentrations of antithrombin, fibrinogen, factor VIII, d -dimer, protein C, and protein S activity were analyzed; additionally, aPTT and prothrombin time were assessed as screening tests. The associations between coagulation factors and VTE were analyzed using multivariable logistic regression models. Non-linear associations were explored using restricted cubic splines. Results: The self-reported prevalence of VTE was 3.2%. The blood coagulation factors examined did not differ between individuals with and without VTE, except for factor VIII. In multivariable analyses, protein C (adjusted p = 0.008), protein S (adjusted p = 0.008), and aPTT (adjusted p = 0.016) were non-linearly inversely associated with VTE. Conclusions: Our findings in a middle-aged and elderly population demonstrate significant associations between specific blood coagulation factors and the prevalence of VTE. However, these hypothesis-generating findings must be confirmed in prospective cohort studies. Also, research on the complex interactions between coagulation factors and patient-specific risk factors in the pathogenesis of VTE is warranted.

Background: This study investigated the association between depression and the incidence of gastro-oesophageal reflux disease (GERD) and examined whether the association interacts with age. The analysis was based on 457,958 participants aged 37–73 years from the UK-Biobank prospective cohort study. Methods: The baseline examination started 2006 and the participants were followed up until 2019–2023 (median follow-up time 13.52 years [interquartile range12.62–14.27]). Depression at baseline and incident GERD at follow-up were defined through sources of the British health system (ICD-codes) and self-report. Multivariable adjusted Cox regression models were used for analysis. Formal tests for interaction with sex and age were conducted. Results: Participants who developed GERD during follow-up were characterized by an unhealthier lifestyle and more comorbidities than individuals without GERD. In multivariable analysis, depression was associated with incident GERD (Hazard ratio 1.51 [1.46,1.55]; P < 0.001). The association decreased with increasing age. There was no interaction with sex. Conclusion: Depression and its psycho-physiological consequences may be associated with the development of GERD, in particular in middle-aged people. Consequently, increased attention of the treating physicians regarding an increased risk of GERD in depressed persons is important.