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.

Key role of postchallenge hyperglycemia for the presence and extent of coronary atherosclerosis: an angiographic study.

BACKGROUND: The associations between impaired glucose tolerance (IGT) and postchallenge diabetes with the presence and extent of angiographically characterized coronary atherosclerosis are unclear. MATERIALS AND METHODS: We enrolled 1040 consecutive Caucasian patients undergoing coronary angiography for the evaluation of coronary artery disease (CAD). An oral 75-g glucose tolerance test was performed in patients without previously diagnosed diabetes. RESULTS: From our patients, 394 had normal glucose tolerance (NGT), 190 impaired glucose tolerance (IGT), 90 isolated postchallenge diabetes (postchallenge glucose >or=200 mg/dl), and 366 type 2 diabetes previously established or newly diagnosed on the basis of fasting glucose (conventional diabetes). Coronary atherosclerosis was more frequent in patients with IGT, isolated postchallenge diabetes, or conventional diabetes when compared to NGT subjects (87.9, 95.6, 89.1 versus 80.7%; p=0.030, 0.001, 0.043, respectively). The prevalence of significant coronary stenoses >or=50%, compared to NGT subjects (57.4%), was similar in IGT patients (59.5%; p=0.628), but significantly higher in patients with isolated postchallenge diabetes (77.8%; p=0.001) or conventional diabetes (68.0%; p=0.002). Also the number of significant stenoses compared to NGT subjects was similar in IGT patients, but significantly higher in those with isolated postchallenge or conventional diabetes. These results were confirmed after multivariate adjustment. CONCLUSIONS: Abnormal glucose tolerance is strongly and independently associated with angiographically characterized coronary atherosclerosis. In IGT, non-significant coronary atherosclerosis is more frequent than in NGT; the prevalence and number of significant stenoses increases when postchallenge diabetes evolves.

Relationship between the adipose-tissue hormone resistin and coronary artery disease.

BACKGROUND: Data on the cardiovascular risk associated with the adipose-tissue-related hormone resistin are scarce. METHODS: We measured serum resistin and established vascular risk factors in 547 consecutive patients (age 63+/-10 years) undergoing coronary angiography for the evaluation of stable coronary artery disease. Prospectively, we recorded major coronary events and cumulative vascular events over 4 years. RESULTS: 60% of our patients had significant coronary stenoses with a lumen narrowing > or =50%. Serum resistin was moderately but significantly correlated with age (r=0.139; p=0.001), high-sensitivity C-reactive protein (hsCRP; r=0.228; p<0.001) and decreasing renal function (r=0.240; p<0.001). However, there was no significant difference of serum resistin between patients with CAD and those in whom angiography did not show CAD (4.5 [3.1-5.8] vs. 4.3 [3.4-5.3] ng/ml; p=0.545) and between patients with > or =50% coronary narrowings and those without such lesions (4.5 [3.2-5.9] vs. 4.3 [3.1-5.5] ng/ml; p=0.265). Prospectively, Cox regression analyses neither indicated an association between serum resistin and major coronary events nor between serum resistin and cumulative vascular events. CONCLUSIONS: Among coronary patients serum resistin is significantly correlated with hsCRP, age and decreasing renal function but resistin is neither associated with the presence of significant coronary stenoses nor with the incidence of future vascular events.

Low serum adiponectin is independently associated with both the metabolic syndrome and angiographically determined coronary atherosclerosis.

BACKGROUND: We aimed at investigating serum adiponectin in patients with the metabolic syndrome (MetS), in patients with angiographically diagnosed coronary artery disease (CAD), and in patients who had both, the MetS and CAD. METHODS: We enrolled 687 consecutive patients undergoing coronary angiography for the evaluation of CAD. RESULTS: From our patients, 178 had neither the MetS (Adult Treatment Panel III definition) nor significant CAD (MetS-/CAD-), 91 had the MetS, but not significant CAD (MetS+/CAD-), 251 did not have the MetS but had significant CAD (MetS-/CAD+), and 167 had both, the MetS and significant CAD (MetS+/CAD+). Serum adiponectin was highest (12.1+/-8.3 microg/ml) in MetS-/CAD- subjects. It was significantly lower in MetS+/CAD- (9.5+/-7.3 microg/ml; p=0.001) and in MetS-/CAD+ patients (9.2+/-5.3 microg/ml; p<0.001) and lowest in MetS+/CAD+ patients (6.7+/-3.8 microg/ml) in whom it was significantly lower than in MetS-/CAD-, MetS+/CAD-, and MetS-/CAD+ patients (p<0.001 for all comparisons). In analysis of covariance the MetS and significant CAD proved associated with serum adiponectin in a mutually independent manner. CONCLUSIONS: Low serum adiponectin is independently associated with both the MetS and coronary atherosclerosis.

The -11377 C>G promoter variant of the adiponectin gene, prevalence of coronary atherosclerosis, and incidence of vascular events in men.

No prospective data demonstrating an association between the -11377 C > G adiponectin gene promoter variant and cardiovascular risk are available. We therefore prospectively evaluated the cardiovascular risk associated with adiponectin gene single nucleotide polymorphisms (SNPs) including SNP -11377 in a consecutive series of men undergoing coronary angiography. We recorded vascular events over four years in 402 men undergoing coronary angiography for the evaluation of coronary artery disease. No significant associations of SNPs +276 G > T and +45 T > G with serum adiponectin, with significant coronary stenoses >50%, or with vascular events were observed. However, for SNP -11377 C > G, serum adiponectin levels significantly decreased (p(trend) = 0.003), and the prevalence of significant coronary stenoses significantly increased from the CC over the GC to the GG genotype (p(trend) = 0.004). Prospectively, the risk of vascular events significantly increased from the CC over the CG to the GG genotype of this SNP (adjusted hazard ratios 1.555 [0.957 - 2.525] and 2.309 [1.067 - 4.998], respectively; p(trend) = 0.014). The -11377 C > G adiponectin gene promoter variant is i) associated with decreased serum adiponectin levels, ii) correlated with the presence of coronary atherosclerosis and iii) significantly predictive of vascular events among men undergoing coronary angiography.

Relationship between glomerular filtration rate and the adipokines adiponectin, resistin and leptin in coronary patients with predominantly normal or mildly impaired renal function.

BACKGROUND: Due to their molecular weight, it is possible that the adipokines adiponectin, resistin and leptin accumulate when glomerular filtration rate (GFR) is decreased. In reduced renal clearance, altered serum concentrations of these proteins might affect cardiovascular risk. The objective of the study was to investigate the relationship between adipokine concentrations and GFR. METHODS: The association between GFR, as determined by the abbreviated MDRD equation, and the concentrations of the adipokines adiponectin, resistin and leptin was assessed in a cohort of coronary patients (n=538; 363 male, 165 female). After calculation of correlations between GFR and adipokine concentrations, the association was further assessed by analysis of covariance following adjustment for age, gender, BMI, presence of type 2 diabetes, presence of hypertension, history of smoking as well as for serum lipid concentrations. RESULTS: Mean GFR in our study population was 68.74+/-15.27 ml/min/1.73 m(2). 74.3% of the patients had a GFR >60 ml/min/1.73 m(2), 24% of the patients had a GFR between 30 and 60 ml/min/1.73 m(2), and 1.7% of the patients had a GFR <30 ml/min/1.73 m(2). There were significant inverse correlations between adiponectin (r=-0.372; p<0.001), resistin (r=-0.227; p<0.001) and leptin (r=-0.151; p=0.009) concentrations and GFR. After multivariate adjustment, the associations remained significant for adiponectin and resistin. Subgroup analysis in patients with GFR >60 ml/min/1.73 m(2) showed a significant correlation between GFR and adiponectin as well as leptin concentrations. However, after adjustment, these associations no longer were significant. CONCLUSIONS: There is an independent association between GFR and the serum concentrations of adiponectin and resistin. However, this association is not present at GFR >60 ml/min/1.73 m(2). This finding suggests that adipokine concentrations in mildly impaired and normal renal function are influenced by factors other than GFR.

Prevalence of decreased glomerular filtration rate in patients seeking non-nephrological medical care--an evaluation using IDMS-traceable creatinine based MDRD as well as Mayo Clinic quadratic equation estimates.

BACKGROUND: Data on the prevalence of decreased glomerular filtration rate in Europe are limited. Most of the available studies did not employ laboratory methods providing creatinine concentrations traceable to the reference method, i.e. isotope dilution mass spectrometry (IDMS). METHODS: We therefore conducted a cross-sectional study in the principality of Liechtenstein consecutively enrolling adult patients seeking non-nephrological medical care from whom serum samples were referred for renal function assessment. All measurements were done in one central laboratory. The estimated glomerular filtration rate (eGFR) was calculated based on the determination of IDMS-traceable creatinine by a kinetic Jaffe method (Roche Diagnostics, Switzerland) by means of the MDRD and Mayo Clinic quadratic equations. We further estimated the incidence of end stage renal disease during the next 5 years. RESULTS: For 43% (n=9378) of the entire population>or=25 years renal function assessment was available. An eGFR indicating chronic kidney disease (CKD) stages 3-5 was found in 4.93% when using the MDRD equation and in 3.98 % when using the Mayo Clinic quadratic equation. The two equations had a very good agreement in classifying patients to have an eGFR consistent with CKD stages 3-5 (Cohen's kappa 0.887). Further calculations suggested that among patients aged 80 or younger, annually 42 per 100,000 are going to develop an eGFR<15 ml/min/1.73 m2 over the next 5 years. CONCLUSIONS: 4-5% of patients seeking non-nephrological medical advice have an eGFR consistent with CKD stages 3-5, and a considerable number of subjects is expected to develop end stage renal disease over a 5 year period. In order to obtain comparable kidney function estimates among different institutions it is not only important to use standardized methods to measure creatinine but rather to employ standardized methods to calculate a GFR estimate.

Evaluation of two fully automated novel enzyme-linked immunosorbent assays for the determination of human adiponectin in serum.

BACKGROUND: In contrast to RIA, recently available ELISAs provide the potential for fully automated analysis of adiponectin. To date, studies reporting on the diagnostic characteristics of ELISAs and investigating on the relationship between ELISA- and RIA-based methods are rare. METHODS: Thus, we established and evaluated a fully automated platform (BEP 2000; Dade-Behring, Switzerland) for determination of adiponectin levels in serum by two different ELISA methods (competitive human adiponectin ELISA; high sensitivity human adiponectin sandwich ELISA; both Biovendor, Czech Republic). Further, as a reference method, we also employed a human adiponectin RIA (Linco Research, USA). Samples from 150 patients routinely presenting to our cardiology unit were tested. RESULTS: ELISA measurements could be accomplished in less than 3 h, measurement of RIA had a duration of 24 h. The ELISAs were evaluated for precision, analytical sensitivity and specificity, linearity on dilution and spiking recovery. In the investigated patients, type 2 diabetes, higher age and male gender were significantly associated with lower serum adiponectin concentrations. Correlations between the ELISA methods and the RIA were strong (competitive ELISA, r=0.82; sandwich ELISA, r=0.92; both p<0.001). However, Deming regression and Bland-Altman analysis indicated lack of agreement of the 3 methods preventing direct comparison of results. The equations of the regression lines are: Competitive ELISA=1.48 x RIA-0.88; High sensitivity sandwich ELISA=0.77 x RIA+1.01. CONCLUSIONS: Fully automated measurement of adiponectin by ELISA is feasible and substantially more rapid than RIA. The investigated ELISA test systems seem to exhibit analytical characteristics allowing for clinical application. In addition, there is a strong correlation between the ELISA methods and RIA. These findings might promote a more widespread use of adiponectin measurements in clinical research.

Adult Treatment Panel III 2001 but not International Diabetes Federation 2005 criteria of the metabolic syndrome predict clinical cardiovascular events in subjects who underwent coronary angiography.

OBJECTIVE: The International Diabetes Federation (IDF) has recently established a worldwide consensus definition of the metabolic syndrome. No prospective data are available on the cardiovascular risk associated with this new metabolic syndrome definition. RESEARCH DESIGN AND METHODS: In a prospective study of 750 coronary patients, we recorded vascular events over 4 years. RESULTS: From our patients, 37.3% (n = 280) had the metabolic syndrome according to the Adult Treatment Panel III (ATPIII) definition and 45.5% (n = 341) according to the IDF definition. The metabolic syndrome as defined by the ATPIII criteria significantly predicted vascular events (adjusted hazard ratio 1.745 [95% CI 1.255-2.427]; P = 0.001), but the metabolic syndrome as defined by IDF criteria did not (1.189 [0.859-1.646]; P = 0.297). Accordingly, event-free survival was significantly lower among patients who fulfilled the ATPIII but not the IDF criteria than among those who met the IDF but not the ATPIII criteria (P = 0.012). The metabolic syndrome as defined by ATPIII criteria remained significantly predictive of vascular events after adjustment for type 2 diabetes but not after additional adjustment for the metabolic syndrome components high triglycerides and low HDL cholesterol. These lipid traits in turn proved significantly predictive of vascular events even after adjustment for the metabolic syndrome. CONCLUSIONS: The ATPIII definition of the metabolic syndrome confers a significantly higher risk of vascular events than the IDF definition. However, among angiographied coronary patients, even the ATPIII definition of the metabolic syndrome does not provide prognostic information beyond its dyslipidemic features.

The metabolic syndrome, insulin resistance, and cardiovascular risk in diabetic and nondiabetic patients.

CONTEXT: The contribution of insulin resistance per se to the vascular risk conferred by the metabolic syndrome (MetS) is not known; conversely, it is uncertain whether insulin resistance confers vascular risk beyond the entity of the MetS. OBJECTIVE: The objective of this study was to investigate the impact of the MetS (Adult Treatment Panel III criteria) and insulin resistance (as estimated by the homeostasis model assessment index) on the incidence of vascular events. DESIGN AND PATIENTS: This was a prospective cohort study enrolling 750 consecutive patients undergoing coronary angiography for the evaluation of coronary artery disease. SETTING: The study was performed at a tertiary care clinical research center. MAIN OUTCOME MEASURE: The main outcome measure was the incidence of vascular events over 2.3 yr. RESULTS: Both the MetS and insulin resistance predicted vascular events after controlling for non-MetS risk factors [hazard ratio (HR), 2.74 (95% confidence interval, 1.71-4.39; P < 0.001) and 1.51 (1.24-1.84; P < 0.001), respectively]. After additional adjustment for insulin resistance, the MetS remained significantly predictive of vascular events [HR, 2.69 (1.57-4.64); P < 0.001], and conversely, insulin resistance remained significantly predictive of vascular events despite adjustment for the MetS [standardized HR, 1.41 (1.14-1.75); P = 0.002]. Additional adjustment for the presence of type 2 diabetes revealed that both the MetS [adjusted HR, 2.57 (1.47-4.51); P = 0.001] and homeostasis model assessment of insulin resistance [standardized adjusted HR, 1.37 (1.09-1.73); P = 0.007] significantly predicted vascular events independent from diabetes status. CONCLUSIONS: Both the MetS and insulin resistance are strong and mutually independent predictors of vascular risk among angiographed coronary patients.