Anti-SARS-CoV-2 Antibodies versus Vaccination Status in CAD Patients with COVID-19: A Prospective, Propensity Score-Matched Cohort Study.

OBJECTIVES: Despite the currently prevailing, milder Omicron variant, coronary artery disease (CAD) patients constitute a major risk group in COVID-19, exhibiting 2.6 times the mortality risk of non-CAD patients and representing over 22% of non-survivors. No data are currently available on the efficacy of antibody levels in CAD patients, nor on the relevance of vaccination status versus antibody levels for predicting severe courses and COVID-19 mortality. Nor are there definitive indicators to assess if individual CAD patients are sufficiently protected from adverse outcomes or to determine the necessity of booster vaccinations. METHODS: A prospective, propensity-score-matched, multicenter cohort study comprising 249 CAD patients and 903 controls was conducted. Anti-SARS-CoV-2-spike antibodies were measured on hospital admission. Prespecified endpoints were in-hospital mortality, intensive care, and oxygen administration. RESULTS: After adjustment for potential confounders, CAD patients exhibited 4.6 and 6.1-times higher mortality risks if antibody levels were <1200 BAU/mL and <182 BAU/mL, respectively, compared to CAD patients above these thresholds (aOR 4.598, 95%CI 2.426-8.714, p < 0.001; 6.147, 95%CI 2.529-14.941, p < 0.001). Risk of intensive care was 3.7 and 4.0 (p = 0.003; p < 0.001), and risk of oxygen administration 2.6 and 2.4 times higher below these thresholds (p = 0.004; p = 0.010). Vaccination status was a weaker predictor of all three outcomes than both antibody thresholds. CONCLUSION: Antibody levels are a stronger predictor of outcome in CAD patients with COVID-19 than vaccination status, with 1200 BAU/mL being the more conservative threshold. Measuring anti-SARS-CoV-2 antibodies in CAD patients may ensure enhanced protection by providing timely booster vaccinations and identifying high-risk CAD patients at hospital admission.

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.

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.

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.

Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies.

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.

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.

Prognostic value of anti-SARS-CoV-2 antibodies: a systematic review.

OBJECTIVES: Globally, over 772 million cases of COVID-19 have been reported. New variants of interest with corresponding spikes in case numbers continue to be identified. Vulnerable patients, including older adults or patients with severe comorbidities, continue to be at risk. A large body of evidence has been accumulated regarding anti-SARS-CoV-2-antibodies and COVID-19 but the usefulness of antibody measurements remains unclear. This systematic review aims to assess the prognostic value of anti-SARS-CoV-2-antibodies and their usefulness for guiding booster vaccinations. METHODS: Studies in English and published between January 2020 and October 2023 were included. Studies that relied on multiparameter-models or comprised fewer than 100 participants were excluded. PubMed and via the WHO COVID-19 research database, Embase and Medline databases were searched. Study selection and quality assessment was conducted independently by two researchers. RESULTS: After screening 1,160 studies, 33 studies comprising >30 million individuals were included. Anti-SARS-CoV-2-antibodies were strongly associated with reduced risk of SARS-CoV-2-infection and better outcomes, including mortality. Risk of infection and COVID-19 severity decreased with increasing antibody levels. CONCLUSIONS: Anti-SARS-CoV-2-antibodies are useful for early identification of high-risk patients and timely adjustment of therapy. Protective thresholds may be applied to advise booster vaccinations but verification in separate cohorts is required.

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.

Anti-SARS-CoV-2 Antibody Testing: Role and Indications.

Since the onset of the COVID-19 pandemic in March 2020, over 769 million confirmed COVID-19 cases, including close to 7 million COVID-19-related deaths, have been reported. Although mortality rates have dropped notably compared to the first months of the pandemic, spikes in reported cases and mortality rates continue to be registered. Both recent spikes in case numbers and the continued emergence of new variants suggest that vulnerable patient groups, including older adults, immunocompromised patients, and patients with severe comorbidities, are going to continue to be affected by COVID-19. In order to curb the pandemic, relieve the pressure on primary care facilities, and reduce mortality rates, global vaccination programs have been established by the WHO, with over 13.5 billion vaccine doses having been administered globally. In most immunocompetent individuals, vaccination against COVID-19 results in the production of anti-SARS-CoV-2 spike antibodies. However, certain patient subsets have inadequate or reduced immune responses, and immune responses are known to decrease with age. General recommendations on the timing of booster vaccinations may therefore be insufficient to protect vulnerable patients. This review aims to evaluate the clinical role of anti-SARS-CoV-2 antibodies, focusing on measurement indications, prognostic value, and potential as a correlate of protection to guide future booster vaccination strategies.

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.

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.

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.

Circulating glypican-4 is a new predictor of all-cause mortality in patients with heart failure.

BACKGROUND: Heart failure confers a high burden of morbidity and mortality. However, risk prediction in heart failure patients still is limited. Blood-based biomarkers hold promise to improve clinical risk assessment. Recently we have identified circulating glypican-4 (GPC4) as a significant predictor of mortality in coronary angiography patients and patients with peripheral artery disease. The impact of serum GPC4 on mortality in patients with heart failure is unknown and is addressed in this prospective cohort study. METHODS: We prospectively recorded all-cause mortality in 288 patients with heart failure. GPC4 levels were measured using an enzyme-linked immunosorbent assay at baseline. RESULTS: During the 24-month follow-up period, 28.1% (n = 81) of the patients died. Serum GPC4 significantly predicted all-cause mortality (hazard ratio (HR) per doublingof GPC4 = 3.57 [2.31-5.53]; P < 0.001). Subgroup analysis showed that GPC4 was significantly associated with all-cause mortality in patients with reduced ejection fraction (HR per doubling = 3.25 [1.75-6.04]; P < 0.001) as well as in those with preserved ejection fraction (HR per doubling = 3.07 [1.22-7.70]; P = 0.017). The association between serum GPC4 and all-cause mortality remained significant in multivariable Cox regression analysis correcting for traditional risk factors (P = 0.035). Results from C-statistics indicated an additional prognostic value of GPC4 relative to NT-proBNP for the prediction of two-year all-cause mortality (P = 0.030). CONCLUSION: Circulating GPC4 independently predicts all-cause mortality in patients with heart failure.

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.

Triglycerides revisited: is hypertriglyceridaemia a necessary therapeutic target in cardiovascular disease?

Despite the atherosclerotic cardiovascular disease (ASCVD) risk reduction achieved by low-density lipoprotein cholesterol (LDL-C) lowering therapy, residual ASCVD risk still exists. Previous epidemiological studies have suggested high plasma triglyceride (TG) levels as a risk factor or risk marker for ASCVD independent of LDL-C levels. In this review, we highlighted the underlying pathophysiology of hypertriglyceridaemia, the mechanistic action of therapeutic agents, the interpretation of conflicting results on recent clinical trials, and the present options for primary and secondary prevention. The benefits of fibrates-induced reduction in TG and increase in high-density lipoprotein cholesterol might outweigh the disadvantages of increasing LDL-C levels in primary prevention. In secondary CVD prevention, using eicosapentaenoic acid without docosahexaenoic acid, in addition to statins, will be beneficial. This comprehensive review may prove useful for the development of novel approaches that target hypertriglyceridaemia in future.

Evaluation of SARS-CoV-2 antibody levels on hospital admission as a correlate of protection against mortality.

BACKGROUND: Millions of people have now been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is still unclear which antibody levels provide protection against mortality. It is further unknown whether measuring antibody concentrations on hospital admission allows for identifying patients with a high risk of mortality. OBJECTIVES: To evaluate whether anti-SARS-CoV2-spike antibodies on hospital admission predict in-hospital mortality in patients with coronavirus disease 2019. METHODS: We conducted a prospective, multicentre cohort study on 1152 hospitalized patients who tested positive for SARS-CoV-2 with a polymerase chain reaction-based assay. Patients were classified by vaccination status. Anti-SARS-CoV-2 spike antibodies were determined on hospital admission. The investigated end point was in-hospital mortality for any cause. RESULTS: Spike antibodies on hospital admission were significantly lower in non-survivors in both non-vaccinated (73 U/ml, 95%CI 0-164 vs. 175 U/ml, 95%CI 124-235, p = 0.002) and vaccinated patients (1056 U/ml, 95%CI 701-1411 vs. 1668 U/ml, 95%CI 1580-1757, p < 0.001). Further, spike antibodies were significantly lower in fully vaccinated and boostered patients who died compared to those who survived (mean 883 U/ml, 95%CI 406-1359 vs. 1292 U/ml, 95%CI 1152-1431, p = 0.017 and 1485 U/ml, 95%CI 836-2133 vs. 2050 U/ml, 95%CI 1952-2149, p = 0.036). Patients infected with the currently prevailing Omicron variant were three times more likely to die if spike antibodies were <1200 U/ml (OR 3.458, 95%CI 1.562-7.656, p = 0.001). After adjusting for potential confounders, this value increased to an aOR of 4.079 (95%CI 1.809-9.198, p < 0.001). CONCLUSION: Anti-SARS-CoV2 spike-antibody levels on hospital admission are inversely associated with in-hospital mortality. Hospitalized patients with lower antibody levels have a higher risk of mortality.

Serum glypican-4 is associated with the 10-year clinical outcome of patients with peripheral artery disease.

BACKGROUND: Patients with peripheral artery disease (PAD) are at increased risk of cardiovascular events and mortality compared with non-PAD populations. Blood based biomarkers may improve clinical risk assessment. Recently, we found significant associations of serum glypican-4 (GPC4) with cardiovascular events and mortality in coronary angiography patients. The impact of serum GPC4 on the clinical outcome in PAD patients is unknown and has been addressed in a prospective cohort study. METHODS: We measured GPC4 levels using an enzyme-linked immunosorbent assay in 295 PAD patients. The primary endpoint was major adverse cardiovascular events (MACE); we further investigated vascular mortality and all-cause mortality over 10 years of follow-up. RESULTS: Serum GPC4 levels were positively linked with age, low kidney function, C-reactive protein (CRP), and the use of cardiovascular medications. During the 10-year follow-up period, MACE, vascular mortality, and all-cause mortality occurred in 43.1%, 33.4%, and 45.4%, respectively, of the patients. High serum GPC4 was significantly associated with all three endpoints (each log-rank P-value <0.001). In Cox regression analysis serum GPC4 significantly predicted MACE, vascular mortality, and all-cause mortality independently from traditional risk factors including age, sex, T2DM, hypertension, low kidney function, severity of PAD, smoking, and CRP, with adjusted hazard ratios [95% confidence interval] for one standard deviation change of serum GPC4 of 1.38 [1.06-1.80], 1.84 [1.28-2.64], and 1.94 [1.51-2.51], respectively. CONCLUSION: We conclude that serum GPC4 is a predictor of the 10-year clinical outcome in patients with PAD.

Evaluation of the association of serum glypican-4 with prevalent and future kidney function.

Serum glypican-4 (GPC4) has been identified as an insulin-sensitizing adipokine serving as a marker for body mass index and insulin resistance in humans. The association of circulating GPC4 with kidney function is to date largely unexplored. Therefore, we aimed to evaluate the association between serum GPC4 and prevalent as well future kidney function in a prospective cohort study. The study included 456 Caucasian coronary angiography patients. After a median follow up period of 3.4 years, data on kidney function was reassessed in all patients. Chronic kidney disease (CKD) was defined by decreased estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or albuminuria. At baseline, serum GPC4 was significantly associated with decreased eGFR (adjusted odds ratio (OR) per standard deviation = 4.75 [2.66-8.48]; P < 0.001), albuminuria (OR = 1.49 [1.15-1.92]; P = 0.002), and, accordingly, with CKD (OR = 1.75 [1.35-2.26]; P < 0.001). GPC4 levels also significantly and independently predicted the incidence of newly diagnosed decreased eGFR (OR = 2.74 [1.82-4.14]; P < 0.001, albuminuria (OR = 1.58 [1.01-2.46]; P = 0.043, and CKD (OR = 2.16 [1.45-3.23]; P < 0.001). ROC analysis indicated an additional predictive value of GPC4 to a basic prediction model for newly diagnosed CKD and eGFR < 60 mL/min/1.73 m2. Our study, therefore, indicates that high serum GPC4 is associated with decreased prevalent and future kidney function.

Data on the association of serum glypican-4 with future major adverse cardiovascular events and mortality in patients undergoing coronary angiography.

This data article is associated to the research article titled 'Serum glypican-4 is a marker of future vascular risk and mortality in coronary angiography patients' (Muendlein et al., 2022). The present article provides additional prospective data on the association of serum glypican-4 (GPC4) with the incidence of future major adverse cardiovascular events (MACE), vascular mortality, and overall mortality in a cohort of 760 coronary angiography patients. Serum GPC4 levels significantly differed between patients with or without an event during follow up. The results were confirmed in subgroup analyses with respect to age, sex, type 2 diabetes mellitus, obesity, the presence of significant coronary stenoses, and renal function, as well as medical treatment. That said, an interaction term between GPC4 and impaired renal function and between GPC4 and the use of beta blockers on the incidence of future fatal events reached statistical significance. In addition, C-statistics were performed showing an additional predictive value of categorized GPC4 to a basic risk model including traditional risk factors for overall mortality.