Machine Learning Approach to Metabolomic Data Predicts Type 2 Diabetes Mellitus Incidence.

Metabolomics, with its wealth of data, offers a valuable avenue for enhancing predictions and decision-making in diabetes. This observational study aimed to leverage machine learning (ML) algorithms to predict the 4-year risk of developing type 2 diabetes mellitus (T2DM) using targeted quantitative metabolomics data. A cohort of 279 cardiovascular risk patients who underwent coronary angiography and who were initially free of T2DM according to American Diabetes Association (ADA) criteria was analyzed at baseline, including anthropometric data and targeted metabolomics, using liquid chromatography (LC)-mass spectroscopy (MS) and flow injection analysis (FIA)-MS, respectively. All patients were followed for four years. During this time, 11.5% of the patients developed T2DM. After data preprocessing, 362 variables were used for ML, employing the Caret package in R. The dataset was divided into training and test sets (75:25 ratio) and we used an oversampling approach to address the classifier imbalance of T2DM incidence. After an additional recursive feature elimination step, identifying a set of 77 variables that were the most valuable for model generation, a Support Vector Machine (SVM) model with a linear kernel demonstrated the most promising predictive capabilities, exhibiting an F1 score of 50%, a specificity of 93%, and balanced and unbalanced accuracies of 72% and 88%, respectively. The top-ranked features were bile acids, ceramides, amino acids, and hexoses, whereas anthropometric features such as age, sex, waist circumference, or body mass index had no contribution. In conclusion, ML analysis of metabolomics data is a promising tool for identifying individuals at risk of developing T2DM and opens avenues for personalized and early intervention strategies.

Plasma apolipoprotein M predicts overall survival in metastatic breast cancer patients.

PURPOSE: Apolipoprotein M (APOM) is a plasma apolipoprotein closely involved with lipid metabolism and inflammation. In vitro studies suggest that APOM may also have a tumor-suppressive role in breast cancer. In the present study, we aimed to evaluate the impact of plasma APOM levels on the prognosis of breast cancer patients. METHODS: We measured APOM levels using an enzyme-linked immunosorbent assay in 75 patients with ER-positive/HER2-negative metastatic breast cancer. The endpoint was overall survival (OS) at 24 months. RESULTS: During the 24-month follow-up period, 34.7% of the patients died. Baseline APOM levels were significantly reduced in patients who deceased during follow-up compared to survivors (42.7 ± 14.5 µg/mL versus 52.2 ± 13.8 µg/mL; P = 0.003). Cox regression analysis showed a hazard ratio of 0.30 [95% confidence interval 0.15-0.61]; P < 0.001 per doubling of APOM levels. Correction for age, C-reactive protein, menopausal state, histology of the primary tumor, metastatic site, number of metastases, endocrine resistance, scheduled therapy line, and kind of scheduled therapy indicated that circulating APOM predicted OS independently of these parameters (HRper doubling = 0.23 [0.09-0.56; P = 0.001). CONCLUSIONS: Our study suggests that circulating APOM is significantly linked with reduced mortality in metastatic breast cancer patients.

Myricetin attenuates hypoxia-induced inflammation in human adipocytes.

BACKGROUND: Adipose tissue hypoxia plays a crucial role in the development of chronic low-grade systemic inflammation which has been associated with the pathogenesis of obesity-related diseases. Myricetin is a natural compound present in numerous plant-based foods with presumed anti-inflammatory and beneficial health effects. The impact of this flavonoid on hypoxia-induced expression of inflammatory adipokines and hypoxia-regulated pathways is unknown so far and has been addressed in the present study. METHODS: Differentiated human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were cultured with or without myricetin under normoxic and hypoxic conditions for varying time periods. The effect of hypoxia and myricetin on the expression of the investigated adipokines was measured by real-time RT-PCR. Western blot analysis was used for the detection of transcription factors involved in hypoxia-regulated pathways. RESULTS: Myricetin interfered in the hypoxia-induced regulation of adipokines and the underlying pathways, which are involved in transmitting the inflammatory response. It strongly repressed hypoxia-induced expression of apelin, leptin, chemerin, asprosin, and DPP-4 and HIF-1α accumulation in the nucleus was diminished. Furthermore, the activation of the key regulators in the inflammatory response NF-κB, Akt, and CREB was suppressed by myricetin under hypoxic conditions. Myricetin also decreased hypoxia-induced accumulation of the pro-tumorigenic transcription factors Snail and Slug in the nucleus. CONCLUSION: Taken together, our results indicated that myricetin regulated hypoxia-induced expression of adipokines and hypoxia-regulated pathways in human adipocytes. Our study therefore provided evidence of the anti-inflammatory effects of myricetin in hypoxia-treated human adipocytes.

Volatilomic Signatures of AGS and SNU-1 Gastric Cancer Cell Lines.

In vitro studies can help reveal the biochemical pathways underlying the origin of volatile indicators of numerous diseases. The key objective of this study is to identify the potential biomarkers of gastric cancer. For this purpose, the volatilomic signatures of two human gastric cancer cell lines, AGS (human gastric adenocarcinoma) and SNU-1 (human gastric carcinoma), and one normal gastric mucosa cell line (GES-1) were investigated. More specifically, gas chromatography mass spectrometry has been applied to pinpoint changes in cell metabolism triggered by cancer. In total, ten volatiles were found to be metabolized, and thirty-five were produced by cells under study. The volatiles consumed were mainly six aldehydes and two heterocyclics, whereas the volatiles released embraced twelve ketones, eight alcohols, six hydrocarbons, three esters, three ethers, and three aromatic compounds. The SNU-1 cell line was found to have significantly altered metabolism in comparison to normal GES-1 cells. This was manifested by the decreased production of alcohols and ketones and the upregulated emission of esters. The AGS cells exhibited the increased production of methyl ketones containing an odd number of carbons, namely 2-tridecanone, 2-pentadecanone, and 2-heptadecanone. This study provides evidence that the cancer state modifies the volatilome of human cells.

Lipid profiles of patients with manifest coronary versus peripheral atherosclerosis - Is there a difference?

AIM: Peripheral arterial disease (PAD) and coronary artery disease (CAD) are both caused by atherosclerosis. Serum lipids and lipoproteins are predictive of the development of atherosclerosis but it is not clear if they differ in the two manifestations, PAD and CAD. We tested whether a more detailed characterization of the lipid and lipoprotein patterns of PAD and CAD allows a clear differentiation between the two atherosclerotic phenotypes. METHODS: A cohort of 274 statin-naïve patients with either newly diagnosed imaging proven PAD (n = 89) or stable CAD (n = 185) was characterized using nuclear magnetic resonance- and liquid chromatography-tandem mass spectrometry-based advanced lipid and lipoprotein analysis. An independent cohort of 1239 patients with PAD and CAD was used for validation. RESULTS: We found a significant difference in markers of inflammation as well as ceramide and phosphatidylcholine levels between patients with PAD and CAD. In contrast, basic lipid markers including total cholesterol, LDL cholesterol, HDL cholesterol, lipoprotein(a) or detailed lipoprotein profiles did not differ significantly between patients with PAD and CAD. Applying ratios and scores derived from ceramides and phosphatidylcholines further improved the discrimination between PAD and CAD. These significant differences were independent of body composition, from the status of smoking or type 2 diabetes mellitus, and also from apolipoprotein C-III and other inflammatory parameters which were different between CAD and PAD. CONCLUSION: The present study clearly suggests that PAD and CAD differ in terms of their ceramide- and phosphatidylcholine-based lipid patterns but not in lipoprotein characteristics.

Evaluation of the associations between circulating microRNAs and kidney function in coronary angiography patients.

Circulating microRNAs (miRNAs) have been linked to chronic kidney disease. Little is known about the association between circulating miRNAs and kidney function in patients at high cardiovascular risk. We therefore investigated the association between a panel of candidate miRNAs and kidney function, based on estimated glomerular filtration rate (eGFR), in two independent cohorts of patients undergoing coronary angiography. The present study totally included 438 patients undergoing coronary angiography, who were divided into a discovery cohort (n = 120) and a validation cohort (n = 318). A candidate miRNA panel comprising 50 renal miRNAs was selected from the literature, and expression levels of circulating miRNAs were determined by real-time PCR. Out of the initially tested candidate miRNAs, 38 miRNAs were sufficiently detectable in plasma. Their association with kidney function was evaluated in the discovery cohort. Associations of seven of these miRNAs with eGFR were significant after multiple testing correction via false discovery rate estimation. To verify obtained results, miRNAs with significant false discovery rates were further analyzed in the validation cohort. miR-106b-5p, miR-16-5p, miR-19b-3p, miR-20a-5p, miR-25-3p, and miR-451a proved to be significantly associated with eGFR also in the validation cohort (all P < 0.001). Association between the identified renal miRNAs and kidney function was confirmed by analysis of covariance adjusting for age, sex, type 2 diabetes, hypertension, and albumin-to-creatinine ratio. In conclusion, our study showed that miR-16-5p, miR-19b-3p, miR-20a-5p, miR-25-3p, miR-106b-5p, and miR-451a are significantly linked to kidney function in patients undergoing coronary angiography.

Real-time PCR based detection of the lactase non-persistence associated genetic variant LCT-13910C>T directly from whole blood.

Primary hypolactasia is the main cause of lactose intolerance in adults. It is strongly associated with the single genetic variant LCT-13910C>T, located upstream of the lactase encoding gene. Consequently, analysis of LCT-13910C>T has been recommended as a direct genetic test for the trait. The aim of our study was to develop a TaqMan probe based real-time PCR protocol for the detection of the LCT-13910C>T variant directly from whole blood, circumventing DNA isolation. The LCT-13910C>T variant was determined using the DirectBlood Genotyping PCR Kit (myPOLS Biotec, Konstanz, Germany) together with an in-house TaqMan primer-probe assay. Validity and specificity of the assay was evaluated using EDTA anti-coagulated whole blood samples and corresponding DNA samples. Results from real-time PCR were compared with results obtained by Sanger sequencing from 105 blinded whole blood samples. Validity and specificity of the assay using whole blood were comparable to those using purified genomic DNA as substrate in PCR. Genetic analysis of blood samples were in complete agreement with results obtained by Sanger sequencing. In conclusion, we present a reliable real-time PCR protocol for the detection of the LCT-13910C>T variant directly from whole blood further facilitating diagnosis of primary hypolactasia in symptomatic patients.

A prospective, multicenter pilot study to investigate the feasibility and safety of a 1-year controlled exercise training after adjuvant chemotherapy in colorectal cancer patients.

INTRODUCTION: Despite advances in adjuvant chemotherapy, 20-30% of patients in stages II-III colorectal cancer will eventually relapse. Observational studies showed a reduction in relapse rate, colon cancer-specific mortality, and overall mortality by physical activity. Results from prospective randomized interventional studies to confirm these observational data are lacking. The aims of this prospective single-arm multicenter pilot study are to evaluate feasibility and safety of exercise training after adjuvant chemotherapy in colorectal cancer patients. PATIENTS AND METHODS: The training was performed three times per week for 1 year and was increased gradually in three phases until reaching 18 metabolic equivalent task hours per week. RESULTS: Overall, 30 patients were included. The planned training intensity could be achieved in all three phases. Patients experienced a performance increase of median 35.5 watt, a weight-loss of a median of 3.0 kg, and a reduction in body fat content of median 1.0% during this exercise training. The analysis showed early study termination due to non-compliance in 10/30 patients (33.3%), disease progression in 4 patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20 patients showed a non-significant reduction in insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin levels, and a non-significant increase in C-peptide levels. CONCLUSION: Exercise training is feasible in patients with colorectal cancer after completion of adjuvant chemotherapy. The main problem encountered during the study was compliance. To improve compliance of exercise training, several measures were adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.

Occurrence of the JAK2 V617F mutation in patients with peripheral arterial disease.

The acquired JAK2 V617F mutation is common in patients with myeloproliferative neoplasms. We previously showed that JAK2 V617F is also found in coronary patients, most of them affected by coronary atherosclerosis. Peripheral arterial disease (PAD) is another important manifestation of atherosclerosis. However, prevalence of the JAK2 V617F mutation and its effect on clinical or hematologic characteristics is unknown in PAD patients. In the present study we determined the prevalence of JAK2 V617F in a cohort of 287 patients with sonographically proven PAD and compared mutation frequency with mutational status of 997 healthy people from the KORA F4 study. JAK2 V617F screening and quantification of allele burden in both cohorts was performed with same allele-specific quantitative real-time PCR method. From a total of 287 PAD patients, 9 individuals were tested positive for the JAK2 V617F mutation. One patient showed elevated hemoglobin values, indicating polycythemia vera. Observed JAK2 V617F frequency (3.1%) in PAD patients showed a 5-fold, highly significant increase compared with healthy people (P < 0.001). Furthermore, occurrence of the mutation in PAD patients was significantly decreased in patients using aspirin (P = 0.003). We conclude that the prevalence of JAK2 V617F mutation is significantly increased in PAD patients compared to the general population. Future studies are warranted to confirm our observations and to define the underlying mechanisms behind our findings.

Evaluation of the prevalence and prospective clinical impact of the JAK2 V617F mutation in coronary patients.

The JAK2 V617F mutation is not only found in the majority of patients with myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), but also has been reported in individuals without overt MPN. A close relation of the JAK2 V617F mutation to atherothrombotic events has been described, at least in patients with MPN. The prevalence of the JAK2 V617F mutation and its clinical impact in coronary patients is unknown. To address this issue, DNA samples from 1,589 subjects undergoing coronary angiography with up to 11 years of follow up were genotyped using allele-specific real-time PCR assays. Prevalence of the JAK2 V617F mutation was 1.32% (n = 21) in coronary patients. Two JAK2 V617F positive patients showed baseline platelet counts indicative for ET and a third patient developed ET during follow up, finally resulting in a percentage of 0.188% of ET cases. This corresponds to an up to fivefold accumulation of ET cases in coronary patients compared with the general population. Our study showed no impact of the JAK2 V617F mutation on future atherothrombotic events or overall survival (HR = 1.04 [0.33-3.27]; P = 0.949 and HR = 0.35 [0.05-2.46]; P = 0.288, respectively). Therefore, our data suggest that JAK2 V617F positive coronary patients are not at increased risk for future atherothrombotic complications. Routine mutation screening in coronary patients is, therefore, not warranted. However, number of ET cases appears to be accumulated in coronary patients. For this reason, we recommend JAK2 V617F testing only in coronary patients showing abnormal blood cell counts for further clarification.

Ceramides improve cardiovascular risk prediction beyond low-density lipoprotein cholesterol.

Aims: Low-density lipoprotein cholesterol (LDL-C) is the best documented cardiovascular risk predictor and at the same time serves as a target for lipid-lowering therapy. However, the power of LDL-C to predict risk is biased by advanced age, comorbidities, and medical treatment, all known to impact cholesterol levels. Consequently, such biased patient cohorts often feature a U-shaped or inverse association between LDL-C and cardiovascular or overall mortality. It is not clear whether these constraints for risk prediction may likewise apply to other lipid risk markers in particular to ceramides and phosphatidylcholines. Methods and results: In this observational cohort study, we recorded cardiovascular mortality in 1195 patients over a period of up to 16 years, comprising a total of 12 262 patient-years. The median age of patients at baseline was 67 years. All participants were either consecutively referred to elective coronary angiography or diagnosed with peripheral artery disease, indicating a high cardiovascular risk. At baseline, 51% of the patients were under statin therapy. We found a U-shaped association between LDL-C and cardiovascular mortality with a trough level of around 150 mg/dL of LDL-C. Cox regression analyses revealed that LDL-C and other cholesterol species failed to predict cardiovascular risk. In contrast, no U-shaped but linear association was found for ceramide- and phosphatidylcholine-containing markers and these markers were able to significantly predict the cardiovascular risk even after multivariate adjustment. Conclusion: We thus suggest that ceramides- and phosphatidylcholine-based predictors rather than LDL-C may be used for a more accurate cardiovascular risk prediction in high-risk patients.

Interplay of inflammatory markers and anti-SARS-CoV-2 antibodies in COVID-19 mortality: A prospective cohort study.

OBJECTIVES: Despite high global vaccination coverage, it remains unclear how vaccination and anti-SARS-CoV-2 antibodies affect immune responses and inflammation levels in patients with COVID-19. It is further unclear whether the inflammatory response differs depending on antibody levels and whether the combination of antibody and inflammation levels in COVID-19 patients affects mortality rates. METHODS: We conducted a prospective multicenter cohort study that included 1031 hospitalized COVID-19 patients from five hospitals. Anti-SARS-CoV-2-spike antibodies, interleukin-6 (IL6), and CRP were measured on hospital admission. The prespecified endpoint was all-cause in-hospital mortality. RESULTS: We observed significantly lower levels of CRP (P<0.001) and IL6 (P<0.001) in patients with antibody levels above 1200 BAU/ml. After adjusting for potential confounders, patients with high levels of inflammatory markers (CRP>6 mg/dl or IL6>100 pg/ml) combined with low levels of anti-SARS-CoV-2-spike antibodies (<1200 BAU/ml) were approximately 8 times more likely to die than patients with low inflammatory responses and high antibody levels (CRP: aHR 7.973, 95% CI 2.744-23.169, P<0.001; IL6: aHR 8.973, 95% CI 3.549-22.688, P<0.001). CONCLUSION: Hospitalized COVID-19 patients presenting with high inflammatory markers and low antibody levels exhibited the highest mortality risks. Higher antibody levels are associated with lower levels of inflammation in hospitalized COVID-19 patients.

The value of earlier-in-life systolic and diastolic blood pressure for cardiovascular risk prediction.

Blood pressure (BP) varies over a lifetime. This cardiovascular observation study (OS) compared the predictive value of earlier- and later-in-life blood pressure (BP) in 1,497 cardiovascular disease patients utilizing readings taken during a health survey (HS) and 15 years later from the same subjects at the baseline of this OS. Prediction of the cardiovascular risk during the OS follow-up (21 years) was significantly more effective if the earlier BP readings at HS were used instead of recent OS readings (NRI = 0.30, p < 0.001). For HS readings, each 10 mm Hg increase of systolic and diastolic BP was associated with a 17% and 20% higher risk, respectively. At OS, systolic BP lost significance and diastolic BP reversed its association. Noteworthy, different BP categorizations (European vs. US guidelines) yielded similar results. This study highlights the poor predictive power of BP readings in elderly cardiovascular disease patients but emphasizes the significant prognostic value of earlier-in-life BP.

Current Practices of Medication Plans in Austrian Patients Undergoing Coronary Angiography: An In-Depth Analysis.

A complete medication plan (MPlan) increases medication safety and adherence and is crucial in care transitions. Countries that implemented a standardized MPlan reported benefits on patients' understanding and handling of their medication. Austria lacks such a standardization, with no available data on the issue. Objective: This study aimed to investigate the current state of all medication documentations (MDocs) at hospital admission in a population at high risk for polypharmacy in Austria. Methods: We enrolled 512 consecutive patients undergoing elective coronary angiography. Their MDocs and medications were recorded at admission. MDocs were categorized, whereby a MPlan was defined as a tabular list including medication name, dose, route, frequency and patient name. Results: Out of 485 patients, 55.1% had an MDoc (median number of drugs: 6, range 2-17), of whom 24.7% had unstructured documentation, 18.0% physicians' letters and 54.3% MPlans. Polypharmacy patients did not have a MDoc in 31.3%. Crucial information as the patients's name or the originator of the MDoc was missing in 31.1% and 20.4%, respectively. Patients with MDoc provided more comprehensive medication information (p = 0.019), although over-the-counter-medication was missing in 94.5% of MDocs. A discrepancy between the MPlan and current medication at admission existed in 64.4%. In total, only 10.7% of our patient cohort presented an MPlan that was in accordance with their current medication. Conclusion: The situation in Austria is far from a standardized MPlan generated in daily routine. Numerous MPlans do not represent the current medication and could pose a potential risk for the effectiveness and safety of pharmacotherapy.

25 years of lipid-lowering therapy: secular trends in therapy of coronary patients.

BACKGROUND AND AIM: Guidelines on dyslipidemia and lipid-lowering therapy (LLT) over the years recommend lower low-density lipoprotein cholesterol (LDL-C) goals by more intense therapy. Nevertheless, LDL­C has increased in the general population. Real-world trends of LLT medication as well as of LDL­C levels in cardiovascular high-risk patients are unclear. METHODS: From 2158 patients who were referred for elective coronary angiography, lipid medication was analyzed at admission in three cardiovascular observational studies (OS) over the last 25 years: OS1: 1999-2000, OS2: 2005-2008 and OS3: 2022-2023. The three studies were performed at the same cardiology unit of a tertiary care hospital in Austria. RESULTS: The proportion of patients without LLT significantly decreased from OS1 through OS2 to OS3 (49.4%, 45.6%, and 18.5%, respectively, ptrend < 0.001). Moreover, the percentage of patients under high-intensity statin treatment significantly increased from 0% to 5.1%, and 56.5% (ptrend < 0.001). Significantly more patients became treated by more than one compound (OS1: 1.8%, OS2: 1.6%, OS3: 31.2%; ptrend < 0.001). In the latest OS3, a trend to fixed-dose combination of statins with ezetimibe was observed. Mean LDL­C levels decreased from 129 mg/dL over 127 mg/dL to 83 mg/dL, respectively (ptrend < 0.001). Of the patients on high-intensity therapy 34% met the recent ESC/EAS goals (LDL-C < 55 mg/dL), but only 3% on non-intense therapy. CONCLUSION: We conclude that during the observational period of a quarter of a century, treatment intensity increased and LDL­C levels improved considerably. Guidelines apparently matter in this high-risk population and are considered by primary care physicians.

Circulating Glypican-4 Is a Predictor of 24-Month Overall Survival in Metastatic Breast Cancer.

INTRODUCTION: Endocrine treatment combined with CDK4/6 inhibitors is the preferred treatment strategy in patients presenting with ER-positive/HER2-negative breast cancer, but the clinical course remains highly variable among individual patients. There is an unmet need for prognostic or predictive biomarkers in this important group of patients. Recently, we have identified circulating glypican-4 (GPC4) as a new biomarker of inferior outcomes in patients with metastatic colorectal cancer. The impact of plasma GPC4 levels on the survival of breast cancer patients is unknown and has been addressed in the present study. METHODS: Our study included 47 patients with ER-positive/HER2-negative metastatic breast cancer prior to treatment with CDK4/6 inhibitors combined with endocrine therapy. The endpoint was overall survival (OS) at 24 months. GPC4 levels were measured in plasma using an enzyme-linked immunosorbent assay. RESULTS: Increased circulating GPC4 levels were significantly linked to advanced age, postmenopausal state, visceral metastases, and invasive lobular carcinoma. During the 2-year observational follow-up period, 25.5% of patients died. The area under the receiver operating characteristic curve (ROC-AUC) analysis revealed an AUC of 0.713 [0.555-0.871]; p = 0.029 for OS; and an optimal cutoff value of GPC4 for predicting OS of 4.77 ng/mL. No patient showing GPC4 values below this cutoff died during the observational period. Cox regression analysis showed a hazard ratio of 2.14 [95% confidence interval: 1.24-3.67]; p = 0.006 for one standard deviation change of plasma GPC4. CONCLUSIONS: Our study suggests circulating GPC4 as a significant predictor of poor survival in metastatic breast cancer patients.

Anti-SARS-CoV-2 antibody levels predict outcome in COVID-19 patients with type 2 diabetes: a prospective cohort study.

Patients with type 2 diabetes (T2D) constitute one of the most vulnerable subgroups in COVID-19. Despite high vaccination rates, a correlate of protection to advise vaccination strategies for novel SARS-CoV-2 variants of concern and lower mortality in this high-risk group is still missing. It is further unclear what antibody levels provide protection and whether pre-existing organ damage affects this threshold. To address these gaps, we conducted a prospective multicenter cohort study on 1152 patients with COVID-19 from five hospitals. Patients were classified by diabetes and vaccination status. Anti-SARS-CoV-2-spike-antibodies, creatinine and NTproBNP were measured on hospital admission. Pre-specified endpoints were all-cause in-hospital-mortality, ICU admission, endotracheal intubation, and oxygen administration. Propensity score matching was applied to increase comparability. We observed significantly lower anti-SARS-CoV-2-spike-antibodies in diabetic non-survivors compared to survivors (mean, 95% CI 351BAU/ml, 106-595 vs. 1123, 968-1279, p < 0.001). Mortality risk increased two-fold with each standard deviation-decrease of antibody levels (aHR 1.988, 95% CI 1.229-3.215, p = 0.005). T2D patients requiring oxygen administration, endotracheal intubation and ICU admission had significantly lower antibody levels than those who did not (p < 0.001, p = 0.046, p = 0.011). While T2D patients had significantly worse outcomes than non-diabetic patients, the differences were less pronounced compared to propensity-score-matched non-diabetic patients. Anti-SARS-CoV-2 spike antibodies on hospital admission are inversely associated with oxygen administration, endotracheal intubation, intensive care and in-hospital mortality in diabetic COVID-19 patients. Pre-existing comorbidities may have a greater impact on outcome than diabetes status alone.

Association between Lipid Levels, Anti-SARS-CoV-2 Spike Antibodies and COVID-19 Mortality: A Prospective Cohort Study.

BACKGROUND: Recent studies suggest that both lipid levels and anti-severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) antibody levels are associated with outcome in coronavirus disease 2019 (COVID-19). While both parameters have separately been implicated in the neutralization and clearance of pathogens during severe infections, it is currently unclear whether the interplay of these parameters affects outcome in COVID-19. We therefore aimed to determine whether there was a relationship between lipoproteins, anti-SARS-CoV-2 antibodies, and COVID-19 mortality. METHODS: In this prospective, multicenter cohort study, we recruited 1152 hospitalized patients with COVID-19 from five hospitals. Total cholesterol (TC), LDL-C, HDL-C, triglycerides, and anti-SARS-CoV-2 spike antibodies were measured on hospital admission. The investigated endpoint was in-hospital mortality. RESULTS: LDL-C, HDL-C, and TC were significantly lower in non-survivors than in survivors (mg/dL, 95%CI; 56.1, 50.4-61.8 vs. 72.6, 70.2-75.0, p < 0.001; 34.2, 31.7-36.8 vs. 38.1, 37.2-39.1, p = 0.025; 139.3, 130.9-147.7 vs. 157.4, 54.1-160.6, p = 0.002). Mortality risk increased progressively with lower levels of LDL-C, HDL-C, and TC (aOR 1.73, 1.30-2.31, p < 0.001; 1.44, 1.10-1.88, p = 0.008; 1.49, 1.14-1.94, p < 0.001). Mortality rates varied between 2.1% for high levels of both LDL-C and anti-SARS-CoV-2 antibodies and 16.3% for low levels of LDL-C and anti-SARS-CoV-2 antibodies (aOR 9.14, 95%CI 3.17-26.34, p < 0.001). Accordingly, for total cholesterol and anti-SARS-CoV-2 antibodies, mortality rates varied between 2.1% and 15.0% (aOR 8.01, 95%CI 2.77-23.18, p < 0.001). CONCLUSION: The combination of serum lipid levels and anti-SARS-CoV-2 antibodies is strongly associated with in-hospital mortality of patients with COVID-19. Patients with low levels of LDL-C and total cholesterol combined with low levels of anti-SARS-CoV-2 antibodies exhibited the highest mortality rates.

Coronary Event Risk Test (CERT) as a Risk Predictor for the 10-Year Clinical Outcome of Patients with Peripheral Artery Disease.

(1) Background: Ceramides are a new kind of lipid biomarker and have already been demonstrated to be valuable risk predictors in coronary patients. Patients with peripheral artery disease (PAD) are a population with a worse prognosis and higher mortality risk compared to coronary artery disease (CAD) patients. However, the value of ceramides for risk prediction in PAD patients is still vague, as addressed in the present study. (2)Methods: This observational study included 379 PAD patients. The primary endpoint was all-cause mortality at 10 years of follow-up. A set of ceramides was measured by LC-MS/MS and combined according to the Coronary Event Risk Test (CERT) score, which categorizes patients into one of four risk groups (low risk, moderate risk, high risk, very high risk). (3) Results: Kaplan-Meier survival curves revealed that the overall survival of patients decreased with the increasing risk predicted by the four CERT categories, advancing from low risk to very high risk. Cox regression analysis demonstrated that each one-category increase resulted in a 35% rise in overall mortality risk (HR = 1.35 [1.16-1.58]). Multivariable adjustment, including, among others, age, LDL-cholesterol, type 2 diabetes, and statin treatment before the baseline, did not abrogate this significant association (HR = 1.22 [1.04-1.43]). Moreover, we found that the beneficial effect of statin treatment is significantly stronger in patients with a higher risk, according to CERT. (4) Conclusions: We conclude that the ceramide-based risk score CERT is a strong predictor of the 10-year mortality risk in patients with PAD.