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AIMS: We recently reported that genetic variability in the TKT gene encoding transketolase, a key enzyme in the pentose phosphate pathway, is associated with measures of diabetic sensorimotor polyneuropathy (DSPN) in recent-onset diabetes. Here, we aimed to substantiate these findings in a population-based KORA F4 study. MATERIALS AND METHODS: In this cross-sectional study, we assessed seven single nucleotide polymorphisms (SNPs) in the transketolase gene in 952 participants from the KORA F4 study with normal glucose tolerance (NGT; n = 394), prediabetes (n = 411), and type 2 diabetes (n = 147). DSPN was defined by the examination part of the Michigan Neuropathy Screening Instrument (MNSI) using the original MNSI > 2 cut-off and two alternative versions extended by touch/pressure perception (TPP) (MNSI > 3) and by TPP plus cold perception (MNSI > 4). RESULTS: After adjustment for sex, age, BMI, and HbA1c, in type 2 diabetes participants, four out of seven transketolase SNPs were associated with DSPN for all three MNSI versions (all p ≤ 0.004). The odds ratios of these associations increased with extending the MNSI score, for example, OR (95% CI) for SNP rs62255988 with MNSI > 2: 1.99 (1.16-3.41), MNSI > 3: 2.27 (1.26-4.09), and MNSI > 4: 4.78 (2.22-10.26); SNP rs9284890 with MNSI > 2: 2.43 (1.42-4.16), MNSI > 3: 3.46 (1.82-6.59), and MNSI > 4: 4.75 (2.15-10.51). In contrast, no associations were found between transketolase SNPs and the three MNSI versions in the NGT and prediabetes groups. CONCLUSIONS: The link of genetic variation in transketolase enzyme to diabetic polyneuropathy corroborated at the population level strengthens the concept suggesting an important role of pathways metabolising glycolytic intermediates in the evolution of diabetic polyneuropathy.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Polimorfismo de Nucleótido Simple , Transcetolasa , Humanos , Transcetolasa/genética , Femenino , Masculino , Neuropatías Diabéticas/genética , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/etiología , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Estudios Transversales , Anciano , Predisposición Genética a la Enfermedad , Estado Prediabético/genética , Estado Prediabético/complicaciones , Pronóstico , Adulto , Estudios de SeguimientoRESUMEN
AIMS: The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN). MATERIALS AND METHODS: Cross-sectional analyses were based on 1032 participants aged 61-82 years from the population-based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1-SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini-Hochberg procedure. RESULTS: Higher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), pB-H = 0.044) and PDGFRα (platelet-derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), pB-H = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM-B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all pB-H for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all pB-H>0.05). CONCLUSIONS: This study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination.
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Biomarcadores , Humanos , Biomarcadores/sangre , Masculino , Femenino , Anciano , Estudios Transversales , Persona de Mediana Edad , Estudios Prospectivos , Anciano de 80 o más Años , Polineuropatías/sangre , Polineuropatías/epidemiología , Polineuropatías/diagnóstico , Polineuropatías/etiología , Estudios de Seguimiento , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/etiología , Pronóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/sangre , PrevalenciaRESUMEN
BACKGROUND: Metformin and sodium-glucose-cotransporter-2 inhibitors (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes. However, their detailed impacts on metabolic processes, particularly within the citric acid (TCA) cycle and its anaplerotic pathways, remain unclear. This study investigates the tissue-specific metabolic effects of metformin, both as a monotherapy and in combination with SGLT2i, on the TCA cycle and associated anaplerotic reactions in both mice and humans. METHODS: Metformin-specific metabolic changes were initially identified by comparing metformin-treated diabetic mice (MET) with vehicle-treated db/db mice (VG). These findings were then assessed in two human cohorts (KORA and QBB) and a longitudinal KORA study of metformin-naïve patients with Type 2 Diabetes (T2D). We also compared MET with db/db mice on combination therapy (SGLT2i + MET). Metabolic profiling analyzed 716 metabolites from plasma, liver, and kidney tissues post-treatment, using linear regression and Bonferroni correction for statistical analysis, complemented by pathway analyses to explore the pathophysiological implications. RESULTS: Metformin monotherapy significantly upregulated TCA cycle intermediates such as malate, fumarate, and α-ketoglutarate (α-KG) in plasma, and anaplerotic substrates including hepatic glutamate and renal 2-hydroxyglutarate (2-HG) in diabetic mice. Downregulated hepatic taurine was also observed. The addition of SGLT2i, however, reversed these effects, such as downregulating circulating malate and α-KG, and hepatic glutamate and renal 2-HG, but upregulated hepatic taurine. In human T2D patients on metformin therapy, significant systemic alterations in metabolites were observed, including increased malate but decreased citrulline. The bidirectional modulation of TCA cycle intermediates in mice influenced key anaplerotic pathways linked to glutaminolysis, tumorigenesis, immune regulation, and antioxidative responses. CONCLUSION: This study elucidates the specific metabolic consequences of metformin and SGLT2i on the TCA cycle, reflecting potential impacts on the immune system. Metformin shows promise for its anti-inflammatory properties, while the addition of SGLT2i may provide liver protection in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). These observations underscore the importance of personalized treatment strategies.
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Ciclo del Ácido Cítrico , Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Riñón , Hígado , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Metformina/farmacología , Animales , Ciclo del Ácido Cítrico/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Humanos , Hipoglucemiantes/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangre , Masculino , Hígado/metabolismo , Hígado/efectos de los fármacos , Riñón/metabolismo , Riñón/efectos de los fármacos , Femenino , Quimioterapia Combinada , Ratones Endogámicos C57BL , Metabolómica , Biomarcadores/sangre , Persona de Mediana Edad , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Estudios Longitudinales , Ratones , Anciano , Resultado del TratamientoRESUMEN
PURPOSE: We aimed to examine the association between dietary patterns and type 2 diabetes mellitus (T2DM) while considering the potential effect modification by metabolic phenotypes (metabotypes). Additionally, we aimed to explore the association between dietary scores and prediabetes. METHODS: A total of 1460 participants (11.8% with T2DM) from the cross-sectional population-based KORA FF4 study were included. Participants, classified into three metabotype subgroups, had both their FSAm-NPS dietary index (underpinning the Nutri-Score) and ultra-processed foods (UPF) intake (using NOVA classification) calculated. Glucose tolerance status was assessed via oral glucose tolerance tests (OGTT) in non-diabetic participants and was classified according to the American Diabetes Association criteria. Logistic regression models were used for both the overall and metabotype-stratified analyses of dietary scores' association with T2DM, and multinomial probit models for their association with prediabetes. RESULTS: Participants who had a diet with a higher FSAm-NPS dietary index (i.e., a lower diet quality) or a greater percentage of UPF consumption showed a positive association with T2DM. Stratified analyses demonstrated a strengthened association between UPF consumption and T2DM specifically in the metabolically most unfavorable metabotype (Odds Ratio, OR 1.92; 95% Confidence Interval, CI 1.35, 2.73). A diet with a higher FSAm-NPS dietary index was also positively associated with prediabetes (OR 1.19; 95% CI 1.04, 1.35). CONCLUSION: Our study suggests different associations between poorer diet quality and T2DM across individuals exhibiting diverse metabotypes, pointing to the option for stratified dietary interventions in diabetes prevention.
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Accurate risk prediction for myocardial infarction (MI) is crucial for preventive strategies, given its significant impact on global mortality and morbidity. Here, we propose a novel deep-learning approach to enhance the prediction of incident MI cases by incorporating metabolomics alongside clinical risk factors. We utilized data from the KORA cohort, including the baseline S4 and follow-up F4 studies, consisting of 1454 participants without prior history of MI. The dataset comprised 19 clinical variables and 363 metabolites. Due to the imbalanced nature of the dataset (78 observed MI cases and 1376 non-MI individuals), we employed a generative adversarial network (GAN) model to generate new incident cases, augmenting the dataset and improving feature representation. To predict MI, we further utilized multi-layer perceptron (MLP) models in conjunction with the synthetic minority oversampling technique (SMOTE) and edited nearest neighbor (ENN) methods to address overfitting and underfitting issues, particularly when dealing with imbalanced datasets. To enhance prediction accuracy, we propose a novel GAN for feature-enhanced (GFE) loss function. The GFE loss function resulted in an approximate 2% improvement in prediction accuracy, yielding a final accuracy of 70%. Furthermore, we evaluated the contribution of each clinical variable and metabolite to the predictive model and identified the 10 most significant variables, including glucose tolerance, sex, and physical activity. This is the first study to construct a deep-learning approach for producing 7-year MI predictions using the newly proposed loss function. Our findings demonstrate the promising potential of our technique in identifying novel biomarkers for MI prediction.
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BACKGROUND: The reduction of myocardial infarction (MI) and narrowing the gap between the populations with and without diabetes are important goals of diabetes care. We analyzed time trends for sex-specific incidence rates (IR) of first MI (both non-fatal MI and fatal MI) as well as separately for first non-fatal MI and fatal MI in the population with and without diabetes. METHODS: Using data from the KORA myocardial infarction registry (Augsburg, Germany), we estimated age-adjusted IR in people with and without diabetes, corresponding relative risks (RR), and time trends from 1985 to 2016 using Poisson regression. RESULTS: There were 19,683 people with first MI (34% fatal MI, 71% men, 30% with diabetes) between 1985 and 2016. In the entire study population, the IR of first MI decreased from 359 (95% CI: 345-374) to 236 (226-245) per 100,000 person years. In men with diabetes, IR decreased only in 2013-2016. This was due to first non-fatal MI, where IR in men with diabetes increased until 2009-2012, and slightly decreased in 2013-2016. Overall, fatal MI declined stronger than first non-fatal MI corresponding to IRs. The RR of first MI substantially increased among men from 1.40 (1.22-1.61) in 1985-1988 to 2.60 (2.26-2.99) in 1997-2000 and moderately decreased in 2013-2016: RR: 1.75 (1.47-2.09). Among women no consistent time trend for RR was observed. Time trends for RR were similar regarding first non-fatal MI and fatal MI. CONCLUSIONS: Over the study period, we found a decreased incidence of first MI and fatal MI in the entire study population. The initial increase of first non-fatal MI in men with diabetes needs further research. The gap between populations with and without diabetes remained.
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Diabetes Mellitus , Infarto del Miocardio , Masculino , Humanos , Femenino , Incidencia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Riesgo , Tiempo , Factores de RiesgoRESUMEN
Objective: To compare health service use (HSU) between migrants and non-migrants in Germany. Methods: Using data from the population-based German National Cohort (NAKO), we compared the HSU of general practitioners, medical specialists, and psychologists/psychiatrists between six migrant groups of different origins with the utilization of non-migrants. A latent profile analysis (LPA) with a subsequent multinomial regression analysis was conducted to characterize the HSU of different groups. Additionally, separate regression models were calculated. Both analyses aimed to estimate the direct effect of migration background on HSU. Results: In the LPA, the migrant groups showed no relevant differences compared to non-migrants regarding HSU. In separate analyses, general practitioners and medical specialists were used comparably to slightly more often by first-generation migrants from Eastern Europe, Turkey, and resettlers. In contrast, the use of psychologists/psychiatrists was substantially lower among those groups. Second-generation migrants and migrants from Western countries showed no differences in their HSU compared to non-migrants. Conclusion: We observed a low mental HSU among specific migrant groups in Germany. This indicates the existence of barriers among those groups that need to be addressed.
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Migrantes , Humanos , Alemania , Servicios de Salud , Aceptación de la Atención de Salud , LenguajeRESUMEN
Blood coagulation is a complex physiological process critical for maintaining hemostasis, and disruptions in this system can lead to various health complications. Since the effects of specific food groups on a series of circulating coagulation parameters in the population are not well established, this study examines such associations in the population-based KORA-Fit study. A total of 595 subjects (263 men and 332 women) born between 1945 and 1964 and living in the study region of Augsburg were included in the study. Habitual food intake was estimated based on a combination of repeated 24-h food lists (24HFLs) and a food frequency questionnaire (FFQ). Antithrombin III, D-dimers, factor VIII, fibrinogen, protein C, protein S, aPTT, Quick value and INR were measured in citrate plasma. Multivariable linear regression models were applied to investigate associations between the consumption of specific foods of plant or animal origin and hemostatic factors. We found that the consumption of plant-based food groups, including green leafy vegetables (rich in vitamin K1), were hardly associated with coagulation parameters. Surprisingly, a high consumption of dairy products and especially butter were associated with higher D-dimer concentrations. These findings need further evaluation in prospective studies.
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Ingestión de Alimentos , Hemostáticos , Masculino , Animales , Humanos , Femenino , Estudios Prospectivos , Verduras , Productos Lácteos , DietaRESUMEN
BACKGROUND: In this study, we investigated various acute myocardial infarction (AMI) symptoms and their associations with short-term (28 day) and long-term mortality. METHODS: The analysis was based on 5900 patients, aged 25 to 84 years, with first-time AMI recorded by the population-based Myocardial Infarction Registry Augsburg between 2010 and 2017. Median follow-up time was 3.8 years (interquartile range: 1.1-6.3). As part of a face-to-face interview, the presence (yes/no) of 11 most common AMI symptoms at the acute event was assessed. Using multivariable-adjusted logistic regression and Cox regression models, the association between various symptoms and all-cause mortality was investigated. P values of the regression models were false discovery rate adjusted. RESULTS: Pain in various body parts (chest pain, left and right shoulder/arm/hand, between shoulder blades), sweating, nausea/vomiting, dizziness and fear of death/feeling of annihilation were significantly associated with a decreased 28-day mortality after AMI. The pain symptoms and sweating were also significantly associated with a decreased long-term mortality. Shortness of breath was significantly associated with a higher long-term mortality. CONCLUSIONS: The absence of several symptoms, including typical chest discomfort (chest pain or retrosternal pressure/tightness), is associated with unfavourable outcomes after AMI. This finding has implications for patient management and public health measures designed to encourage appropriate and prompt medical consultation of patients with atypical AMI symptoms.
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Infarto del Miocardio , Sistema de Registros , Humanos , Masculino , Femenino , Infarto del Miocardio/mortalidad , Infarto del Miocardio/complicaciones , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Factores de Tiempo , Estudios de Seguimiento , Dolor en el Pecho/etiología , Dolor en el Pecho/diagnóstico , Alemania/epidemiología , Tasa de Supervivencia/tendencias , Causas de Muerte/tendenciasRESUMEN
Background: The objective of this study was to investigate the differences in presenting symptoms between patients with and without diabetes being diagnosed with an acute myocardial infarction (AMI). Methods: A total of 5,900 patients with a first-time AMI were included into the analysis. All patients aged between 25 and 84 years were recorded by the population-based Myocardial Infarction Registry in Augsburg, Germany, between 2010 and 2017. The presence (yes/no) of 12 AMI typical symptoms during the acute event was assessed within the scope of a face-to-face interview. Multivariable adjusted logistic regression models were calculated to analyze the associations between presenting symptoms and diabetes mellitus in AMI patients. Results: Patients with diabetes had significantly less frequent typical pain symptoms, including typical chest pain. Also, other symptoms like sweating, vomiting/nausea, dizziness/vertigo and fear of death/feeling of annihilation occurred significantly more likely in non-diabetic patients. The only exception was the symptom of shortness of breath, which was found significantly more often in patients with diabetes. In multivariable-adjusted regression models, however, the observed effects were attenuated. In patients younger than 55 years, the associations between diabetes and various symptoms were mainly missing. Conclusions: Type 2 diabetes mellitus is a risk factor not only for the development of AMI, but is also associated with an adverse outcome after AMI. Atypical clinical presentation additionally complicates the diagnostic process. It is therefore essential for physicians to be aware of the more often atypical symptoms that diabetic AMI patients report.
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BACKGROUND: The risk of cardiovascular disease (CVD) mortality in individuals with an alerting reaction, assessed by hypertension in the first blood pressure (BP) reading but normal BP in further readings, remains unknown in the general population. METHODS AND RESULTS: In a sample of 11 146 adults (51.5% men and 48.5% women) with a mean age of 47.1âyears (SDâ±â12.3) from a German population-based cohort, we analyzed risk factors and CVD mortality risk associated with an alerting reaction. An alerting reaction was prevalent in 10.2% of the population and associated with sociodemographic, lifestyle, and somatic CVD risk factors. Within a mean follow-up period of 22.7âyears (SDâ±â7.05âyears; max: 32âyears; 253 201 person years), 1420 (12.7%) CVD mortality cases were observed. The CVD mortality rate associated with an alerting reaction was significantly higher than in normotension (64 vs. 32âcases/10 000 person-years), but lower than hypertension (118âcases/10 000 person-years). Correspondingly, the alerting reaction was associated with a 23% higher hazard ratio of CVD mortality than normal blood pressure [hazard ratio 1.23 (95% confidence interval 1.02-1.49), P â=â0.04]. However, adjustment for antihypertensive medication use attenuated this association [1.19 (0.99-1.44), P â=â0.06]. CONCLUSION: The results may warrant monitoring of an alerting reaction as a preventive measure of CVD mortality in untreated individuals with elevated first BP readings, as well as optimized treatment in treated individuals.
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Enfermedades Cardiovasculares , Hipertensión , Adulto , Masculino , Humanos , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/etiología , Presión Sanguínea/fisiología , Estudios Prospectivos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Determinación de la Presión Sanguínea , Factores de RiesgoRESUMEN
Objective: Measurements utilizing commercially available sets of reagents for determination of steroid hormone profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS) have become increasingly important for routine laboratories. However, method-specific publications of reference intervals obtained from sufficiently large studies are often missing. Methods: After validation of performance characteristics, a widely available kit for steroid analysis by LC-MS/MS was used to measure concentrations of 15 endogenous steroids (aldosterone, cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, estradiol, testosterone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, 11-deoxycorticosterone, progesterone) in more than 500 blood samples from a population-based study. While randomly selected from a larger cohort, the samples equally represented both sexes and covered a wide range of adult age groups. Age- and sex-specific reference intervals were calculated, and correlation with BMI was assessed. Results: Performance characteristics of the assay matched expectations for 9 of 15 steroids. For most of them, reference intervals obtained from our study population were comparable to those reported by others, with age and sex being the major determinants. A sex-specific correlation with BMI was found for seven steroids. We identified limitations regarding sensitivity of the method for quantification of progesterone in males and postmenopausal females. Concentrations of aldosterone, 21-deoxycortisol, estradiol, 11-deoxycorticosterone, and dihydrotestosterone could not be quantified in a large percentage of samples. Conclusions: The reference intervals for nine steroids will support meaningful interpretation for steroid profiles as measured by a widely used kit for LC-MS/MS-based quantification. Laboratories using such kits must be aware of potential limitations in sensitivity for some steroids included in the profile. Significance Statement: Quantification of steroid hormones is a cornerstone for diagnosis of several diseases. Commonly used immunoassays have limitations in specificity. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a promising alternative, particularly if methods are harmonized across laboratories. The use of kits from commercial suppliers might support this. Clinical interpretation of steroid concentrations requires availability of appropriate reference intervals (RIs), but studies on RIs reported in the literature differ in preanalytical and analytical procedures. Here, we provide RIs for steroids measured by a widely available kit under preanalytical conditions mirroring common clinical practice. Such RIs might facilitate interpretation for those using the same method and comparable conditions in clinical routine.
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Objective: The presence and intensity of symptoms vary in patients with unilateral vestibular hypofunction. We aimed to determine which saccadic and vestibulo-ocular reflex parameters best predict the presence of symptoms in unilateral vestibular hypofunction in order to better understand vestibular compensation and its implications for rehabilitation therapy. Methods: Video head impulse test data were analyzed from a subpopulation of 23 symptomatic and 10 currently symptom-free participants with unilateral vestibular hypofunction, embedded in the KORA (Cooperative Health Research in the Region of Augsburg) FF4 study, the second follow-up of the KORA S4 population-based health survey (2,279 participants). Results: A higher number of catch-up saccades, a higher percentage of covert saccades, and a larger retinal error at 200 ms after the onset of the head impulse were associated with relevant symptoms in participants with unilateral vestibular hypofunction (p = 0.028, p = 0.046, and p = 0.038, respectively). After stepwise selection, the number of catch-up saccades and retinal error at 200 ms remained in the final logistic regression model, which was significantly better than a null model (p = 0.014). Age, gender, saccade amplitude, saccade latency, and VOR gain were not predictive of the presence of symptoms. Conclusion: The accuracy of saccadic compensation seems to be crucial for the presence of symptoms in unilateral vestibular hypofunction, highlighting the role of specific gaze stabilization exercises in rehabilitation. Early saccades, mainly triggered by the vestibular system, do not seem to compensate accurately enough, resulting in a relevant retinal error and the need for more as well as more accurate catch-up saccades, probably triggered by the visual system.
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Background: The aim of this study was to investigate the association between inflammatory plasma protein concentrations and long-term mortality in patients with ST-elevation myocardial infarction (STEMI). Methods: For 343 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 inflammatory plasma proteins were measured at the index event using the OLINK inflammation panel. In multivariable-adjusted Cox regression models, the association between each plasma protein and all-cause long-term mortality was investigated. Median follow-up time was 7.6 (IQR: 2.4) years. For plasma protein that showed a strong association with long-term mortality, a 5-year survival ROC analysis was performed. Results: One plasma protein, namely Fibroblast Growth Factor 23 (FGF-23), was particularly well associated with long-term mortality in the multivariable-adjusted Cox model with an FDR-adjusted p-value of <0.001 and a Hazard Ratio (HR) of 1.57 [95% CI: 1.29-1.91]. In the 5-years ROC analysis, an AUC of 0.6903 [95% CI: 0.594-0.781] was estimated for FGF-23. All other plasma protein didnt show strong associations, each marker with FDR-adjusted p-values >0.05 in the multivariable-adjusted Cox models. Conclusions: FGF-23 is independently associated with long-term mortality after STEMI and might play an important role in the response to myocardial injury. The results suggest FGF-23 to be a useful marker in the long-term treatment of STEMI patients and a potential target for drug development.
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BACKGROUND: Population-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population. METHODS: After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54-74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status. RESULTS: In the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients. CONCLUSION: In this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.
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Factor VIII , Hemostáticos , Masculino , Humanos , Femenino , Antitrombina III , Proteína S , Proteína C , Coagulación Sanguínea , Anticoagulantes , FibrinógenoRESUMEN
The coexistence of several chronic diseases is very common in older adults, making it crucial to understand multimorbidity (MM) patterns and associated mortality. We aimed to determine the prevalence of MM and common chronic disease combinations, as well as their impact on mortality in men and women aged 65 years and older using the population-based KORA-Age study, based in South of Germany. The chronic disease status of the participants was determined in 2008/9, and mortality status was followed up until 2016. MM was defined as having at least two chronic diseases. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and the 95% confidence intervals (CIs) for associations between MM and all-cause mortality. During the study period 495 men (24.6%) and 368 women (17.4%) died. Although the MM prevalence was almost the same in men (57.7%) and women (60.0%), the overall effect of MM on mortality was higher in men (HR: 1.81, 95% CI: 1.47-2.24) than in women (HR: 1.28, 95% CI: 1.01-1.64; p-value for interaction <0.001). The type of disease included in the MM patterns had a significant impact on mortality risk. For example, when both heart disease and diabetes were included in the combinations of two and three diseases, the mortality risk was highest. The risk of premature death does not only depend on the number of diseases but also on the specific disease combinations. In this study, life expectancy depended strongly on a few diseases, such as diabetes, hypertension, and heart disease.
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Background: In contrast to studies in patients, an association between obesity and blood coagulation factors has not been established in the population. If confirmed it could become a target for primary prevention. Objective: To investigate the relationship between Body Mass Index (BMI) and waist circumference (WC) with plasma concentrations of antithrombin III, D-dimers, fibrinogen D, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value, and international normalized ratio (INR) in the general population. Materials and Methods: Participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study who took part in the KORA Fit follow-up (2018-2019, aged 54-74 years) examination were eligible. Citrate plasma samples were collected in fasted participants. After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men) with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the association between BMI or WC with hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the prevalence of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol, and serum triglycerides. Results: In the multivariable models (with or without health conditions), significant positive associations with BMI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein S, and quick value, while INR and antithrombin III were inversely associated. Similar to BMI, WC was significantly associated with all hemostatic factors, except for aPTT. Conclusion: In this population-based study, both increasing BMI and WC affect the blood coagulation system. Thus, modification of a prothrombotic coagulation profile emerged as a potential target for primary prevention in obese subjects.
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Antitrombina III , Hemostáticos , Masculino , Humanos , Femenino , Índice de Masa Corporal , Factores de Riesgo , Antitrombina III/análisis , Factor VIII , Circunferencia de la Cintura , Obesidad , Fibrinógeno/análisisRESUMEN
INTRODUCTION: Aldosterone excess is linked to cardiovascular events and mortality as well as to low-grade inflammation in the context of metabolic diseases. Whether mildly elevated aldosterone levels in the general population promote cardiovascular risk is still under debate. We analyzed the association of plasma aldosterone concentrations with incident cardiovascular events, cardiovascular and all-cause mortality as well as with biomarkers of subclinical inflammation in the population-based KORA F4 study. METHODS: Plasma aldosterone concentrations were measured with an in-house immunoflurometric assay. The analyses included 2935 participants (n=1076 for selected biomarkers of subclinical inflammation) with a median follow-up of 8.7 (8.2; 9.1) years. The associations were estimated using Cox proportional hazard and linear regression models adjusted for renin, sex, age, body mass index, arterial hypertension, diabetes, estimated glomerular filtration rate, low- and high-density lipoprotein cholesterol, physical activity, smoking, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, diuretics and calcium channel blockers. RESULTS: Aldosterone was significantly associated with all-cause mortality (hazard ratio per standard deviation increase: 1.20; 95% confidence interval 1.04-1.37), but not with cardiovascular mortality, incident cardiovascular events, or with biomarkers of subclinical inflammation. CONCLUSIONS: Aldosterone was associated with all-cause mortality in the population-based KORA F4 study, but the previously described associations of excess aldosterone with cardiovascular complications and biomarkers of subclinical inflammation could not be shown.
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Aldosterona , Hipertensión , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina , Sistema Renina-Angiotensina , Inflamación , BiomarcadoresRESUMEN
BACKGROUND: Hypertension represents one of the major risk factors for cardiovascular morbidity and mortality globally. Early detection and treatment of this condition is vital to prevent complications. However, hypertension often goes undetected, and even if detected, not every patient receives adequate treatment. Identifying simple and effective interventions is therefore crucial to fight this problem and allow more patients to receive the treatment they need. Therefore, we aim at investigating the impact of a population-based blood pressure (BP) screening and the subsequent "low-threshold" information treatment on long-term cardiovascular disease (CVD) morbidity and mortality. METHODS AND FINDINGS: We examined the impact of a BP screening embedded in a population-based cohort study in Germany and subsequent personalized "light touch" information treatment, including a hypertension diagnosis and a recommendation to seek medical attention. We pooled four waves of the KORA study, carried out between 1984 and 1996 (N = 14,592). Using a sharp multivariate regression discontinuity (RD) design, we estimated the impact of the information treatment on CVD mortality and morbidity over 16.9 years. Additionally, we investigated potential intermediate outcomes, such as hypertension awareness, BP, and behavior after 7 years. No evidence of effect of BP screening was observed on CVD mortality (hazard ratio (HR) = 1.172 [95% confidence interval (CI): 0.725, 1.896]) or on any (fatal or nonfatal) long-term CVD event (HR = 1.022 [0.636, 1.641]) for individuals just above (versus below) the threshold for hypertension. Stratification for previous self-reported diagnosis of hypertension at baseline did not reveal any differential effect. The intermediate outcomes, including awareness of hypertension, were also unaffected by the information treatment. However, these results should be interpreted with caution since the analysis might not be sufficiently powered to detect a potential intervention effect. CONCLUSIONS: The study does not provide evidence of an effect of the assessed BP screening and subsequent information treatment on BP, health behavior, or long-term CVD mortality and morbidity. Future studies should consider larger datasets to detect possible effects and a shorter follow-up for the intermediate outcomes (i.e., BP and behavior) to detect short-, medium-, and long-term effects of the intervention along the causal pathway.