Search

High sensitive cardiac troponin I (hs-cTnI) increases with inducible myocardial ischemia in patients with coronary artery disease (CAD). We aimed to assess if the change in hs-cTnI levels with exercise stress testing is associated with major adverse cardiac events (MACE). A cohort of 365 (age 62 ± 9 years, 77% men) patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging with treadmill testing. Plasma hs-cTnI level was measured at rest and at 45 min after stress. Multivariable Fine & Gray’s subdistribution hazards models were used to determine the association between the change in hs-cTnI and MACE, a composite end point of cardiovascular death, myocardial infarction, and unstable angina requiring revascularization. During a median follow-up of 3 years, 39 (11%) patients experienced MACE. After adjustment, for each two-fold increment in hs-cTnI with stress, there was a 2.2 (95% confidence interval 1.3–3.6)-fold increase in the hazard for MACE. Presence of both a high resting hs-cTnI level (>median) and ≥ 20% stress-induced hs-cTnI elevation was associated with the highest incidence of MACE (subdistribution hazards models 4.6, 95% confidence interval 1.6 to 13.0) compared with low levels of both. Risk discrimination statistics significantly improved after addition of resting and change in hs-cTnI levels to a model including traditional risk factors and inducible ischemia (0.67 to 0.71). Conversely, adding inducible ischemia by SPECT did not significantly improve the C-statistic from a model including traditional risk factors, baseline and change in hs-cTnI (0.70 to 0.71). In stable CAD patients, higher resting levels and elevation of hs-cTnI with exercise are predictors of adverse cardiovascular outcomes beyond traditional cardiovascular risk factors and presence of inducible ischemia.

Although cardiovascular disease (CVD) is a major health challenge in Malaysia, many Malaysians are unaware of their CVD risk. The measurement of biomarkers in the general population may help to identify at-risk individuals before the onset of symptomatic CVD. The aim of this community health screening project was to determine the distribution of high-sensitivity troponin I (hsTnI) and other biomarkers of CVD risk in the general population of Johor, Malaysia. A sampling of self-declared healthy volunteers was conducted during the 2016 Kembara Mahkota community event in Johor. Levels of hsTnI, B-type natriuretic peptide (BNP) and homocysteine (HCY) were analyzed using the ARCHITECT immunoassay and clinical chemistry platforms utilizing fresh venous blood samples. Based on previous data, biomarker levels indicative of high risk were >10 and >12 ng/mL for hsTnI in women and men, respectively, BNP >50 pg/mL in the overall population, and HCY >13.6 µmol/L in women and >16.2 µmol/L in men. A total of 2744 volunteers participated in biomarker testing. Biomarker measurements showed that up to 10% of participants had moderate or high CVD risk based on hsTnI, approximately 2% were above the BNP threshold and >50% of subjects were above the HCY threshold. General population biomarker testing shows distribution of biomarker levels that may be indicative of CVD risk or the presence of disease and suggests that biomarker-guided risk strategies should be more widely implemented to determine the impact they would have on early detection and prevention of disease.

BACKGROUND Early detection of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients remains a challenge, especially in China. We sought to create an online calculator of serum biomarkers to detect HCC among patients with chronic hepatitis B (CHB). METHODS Participants with HBV-HCC, CHB, HBV-related liver cirrhosis (HBV-LC), benign hepatic tumors, and healthy controls (HCs) were recruited at 11 Chinese hospitals. Potential serum HCC biomarkers, protein induced by vitamin K absence or antagonist-II (PIVKA-II), α-fetoprotein (AFP), lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and α-L-fucosidase (AFU) were evaluated in the pilot cohort. The calculator was built in the training cohort via logistic regression model and validated in the validation cohort. RESULTS In the pilot study, PIVKA-II and AFP showed better diagnostic sensitivity and specificity compared with AFP-L3 and AFU and were chosen for further study. A combination of PIVKA-II and AFP demonstrated better diagnostic accuracy in differentiating patients with HBV-HCC from patients with CHB or HBV-LC than AFP or PIVKA-II alone [area under the curve (AUC), 0.922 (95% CI, 0.908–0.935), sensitivity 88.3% and specificity 85.1% for the training cohort; 0.902 (95% CI, 0.875–0.929), 87.8%, and 81.0%, respectively, for the validation cohort]. The nomogram including AFP, PIVKA-II, age, and sex performed well in predicting HBV-HCC with good calibration and discrimination [AUC, 0.941 (95% CI, 0.929–0.952)] and was validated in the validation cohort [AUC, 0.931 (95% CI, 0.909–0.953)]. CONCLUSIONS Our results demonstrated that a web-based calculator including age, sex, AFP, and PIVKA-II accurately predicted the presence of HCC in patients with CHB. ClinicalTrials.gov Identifier NCT03047603

Background: Serological tests for anti-SARS-CoV-2 antibodies can provide valuable information in epidemiologic and public health research. However, the data is limited on serological response post COVID-19 infection. Objective: To investigate the use of ARCHITECT SARS CoV-2 IgG II Quantitative assay to quantify the IgG antibodies in recovered COVID-19 infections. Methods: Abbott SARS-CoV-2 IgG assays were performed using the ARCHITECT Quantitative chemiluminescent microparticle immunoassay to detect IgG against SARS-CoV-2 S1 receptor binding domain (RBD) in serum and plasma. Patients having IgG concentrations above ≥50 AU/mL were defined as positive. We analyzed 333 COVID-19 patients who were tested negative by RT-PCR not more than three months after testing positive. Results: The mean age of the population was 34.3 years and 95% were male. About 93% of the patients had mild disease and rest had moderate disease. The mean IgG levels in the entire cohort was 1860.27 AU/mL, the lowest and highest value detected by ARCHITECT SARS CoV-2 IgG II Quantitative Assay (Abbott Laboratories, USA) were 39.8 AU/mL and 43657.4 AU/mL, respectively. While patients with moderate COVID-19 disease had numerically higher IgG levels than patients with mild disease, the difference was not statistically significant (1787.7 AU/mL vs. 2865.39 AU/mL, p=0.21). In 97% of the patients, IgG antibodies could be detected up to 95 days after testing negative on RT-PCR. Conclusion: Patients with moderate COVID-19 disease may develop higher IgG antibodies than in patients with mild disease. Antibodies can be detected in majority of recovered individuals for more than 90 days which may be valuable in developing future vaccination strategy.

Purpose The purpose of this study was to examine the association of circulating concentrations of high-sensitivity cardiac troponin I (hs-cTn) in the various trimesters of pregnancy in patients with and without hypertension. Methods This was a prospective cross-sectional study of pregnant and postnatal women aged between 18-35 years with no coexisting diseases. Serum samples were analysed for hs-TnI. Results A total of 880 women (mean age = 29.1 years [standard deviation = 5.1 years]) were recruited with 129 (14%), 207 (24%), and 416 (47%) patients in the first, second, and third trimesters, respectively. Ninety (10%) participants were recruited in the postnatal period. During pregnancy 28 (3%) patients were classified as having pregnancy-induced hypertension and 10 (1%) as preeclampsia. High-sensitivity cardiac troponin I was measurable in 546 (62%) participants with a median of 1 ng/L (range 0 to 783 ng/L). Troponin concentrations were above the 99th percentile in 19 (2%) individuals. Patients with pregnancy-induced hypertension and preeclampsia had higher concentrations of hs-TnI (median 11 ng/L [interquartile range (IQR) 6 to 22 ng/L] vs 12ng/L [IQR 3 to 98 ng/L] vs 1 ng/L [IQR 0 to 1 ng/L]). In logistic regression modeling hs-cTnI concentration remained an independent predictor of pregnancy-induced hypertension or preeclampsia in both unadjusted and adjusted models (odds ratio 9.3 [95% confidence interval 5.8 to 16.3] and 11.5 [95% confidence interval 6.3 to 24.1], respectively, per doubling of hs-TnI concentrations). Conclusions Cardiac troponin measured using a high-sensitivity assay is quantifiable in the majority of young pregnant women with 2% of individuals having concentration above the 99th percentile sex-specific threshold. Patients with pregnancy-induced hypertension or preeclampsia had higher cardiac troponin concentrations. Cardiac troponin was a strong independent predictor of pregnancy-induced hypertension or preeclampsia in pregnant and postnatal women.

Background Multiple biomarkers have been independently and additively associated with major adverse cardiovascular events in patients with coronary artery disease. We investigated the prognostic value of suPAR (soluble urokinase‐type plasminogen activator receptor) and hsTnI (high‐sensitivity troponin I) levels in symptomatic patients with no obstructive coronary artery disease. We hypothesized that high levels of these biomarkers will be associated with the risk of future adverse outcomes. Methods and Results Plasma levels of suPAR and hsTnI were measured in 556 symptomatic patients with no obstructive coronary artery disease. A biomarker risk score was calculated by counting the number of biomarkers above the median in this cohort (suPAR>2523 pg/mL and hsTnI>2.7 pg/mL). Survival analyses were performed with models adjusted for traditional risk factors. All‐cause death and major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, and heart failure) served as clinical outcomes over a median follow‐up of 6.2 years. Mean age was 57±10 years, 49% of the cohort patients were female, and 68% had a positive stress test. High suPAR and hsTnI levels were independent predictors of all‐cause death (hazard ratio=3.2 [95% CI, 1.8–5.7] and 1.3 [95% CI, 1.0–1.7], respectively; both P P Conclusions Among symptomatic patients with no obstructive coronary artery disease, higher levels of suPAR and hsTnI were independently and additively associated with an increased risk of adverse events. Whether modification of these biomarkers will improve risk in these patients needs further investigation.

This study aimed to build a valid diagnostic nomogram for assessing the cancer risk of the pulmonary lesions identified by chest CT.A total of 691 patients with pulmonary lesions were recruited from three centers in China. The cut-off value for each tumor marker was confirmed by minimum P value method with 1000 bootstrap replications. The nomogram was based on the predictive factors identified by univariate and multivariate analysis. The predictive performance of the nomogram was measured by concordance index and calibrated with 1000 bootstrap samples to decrease the overfit bias. We also evaluated the net benefit of the nomogram via decision curve analysis. Finally, the nomogram was validated externally using a separate cohort of 305 patients enrolled from two additional institutions.The cut-off for CEA, SCC, CYFRA21-1, pro-GRP, and HE4 was 4.8 ng/mL, 1.66 ng/mL, 1.83 ng/mL, 56.55 pg/mL, and 63.24Lpmol/L, respectively. Multivariate logistic regression model (LRM) identified tumor size, CEA, SCC, CYFRA21-1, pro-GRP, and HE4 as independent risk factors for lung cancer. The nomogram based on LRM coefficients showed concordance index of 0.901 (95% CI: 0.842-0.960; P 0.001) for lung cancer in the training set and 0.713 (95% CI: 0.599-0.827; P 0.001) in the validation set. Decision curve analysis reported a net benefit of 87.6% at 80% threshold probability superior to the baseline model.Our diagnostic nomogram provides a useful tool for assessing the cancer risk of pulmonary lesions identified in CT screening test.

Supplemental Digital Content is available in the text., Background: Variations in cardiac troponin concentrations by age, sex, and time between samples in patients with suspected myocardial infarction are not currently accounted for in diagnostic approaches. We aimed to combine these variables through machine learning to improve the assessment of risk for individual patients. Methods: A machine learning algorithm (myocardial-ischemic-injury-index [MI3]) incorporating age, sex, and paired high-sensitivity cardiac troponin I concentrations, was trained on 3013 patients and tested on 7998 patients with suspected myocardial infarction. MI3 uses gradient boosting to compute a value (0–100) reflecting an individual’s likelihood of a diagnosis of type 1 myocardial infarction and estimates the sensitivity, negative predictive value, specificity and positive predictive value for that individual. Assessment was by calibration and area under the receiver operating characteristic curve. Secondary analysis evaluated example MI3 thresholds from the training set that identified patients as low risk (99% sensitivity) and high risk (75% positive predictive value), and performance at these thresholds was compared in the test set to the 99th percentile and European Society of Cardiology rule-out pathways. Results: Myocardial infarction occurred in 404 (13.4%) patients in the training set and 849 (10.6%) patients in the test set. MI3 was well calibrated with a very high area under the receiver operating characteristic curve of 0.963 [0.956–0.971] in the test set and similar performance in early and late presenters. Example MI3 thresholds identifying low- and high-risk patients in the training set were 1.6 and 49.7, respectively. In the test set, MI3 values were

Objectives Alpha-fetoprotein (AFP) has been widely used in clinical practice for decades. However, large-scale survey of serum reference interval for ARCHITECT AFP is still absent in Chinese population. This study aimed to measure serum AFP levels in healthy Chinese Han subjects, which is a sub-analysis of an ongoing prospective, cross-sectional, multi-center study ( ClinicalTrials.gov Identifier: NCT03047603 ). Methods This analysis included a total of 530 participants (41.43 ± 12.14 years of age on average, 48.49% males), enrolled from 5 regional centers. Serum AFP level was measured by ARCHITECT immunoassay. Statistical analysis was performed using SAS 9.4 and R software. Results AFP distribution did not show significant correlation with age or sex. The overall median and interquartile range of AFP was 2.87 (2.09, 3.83) ng/mL. AFP level did not show a trend of increasing with age. The new reference interval was 2.0–7.07 ng/mL (LOQ– 97.5th percentiles). Conclusions The reference interval for ARCHITECT AFP is updated with the data of adequate number of healthy Han adults. This new reference interval is more practical and applicable in Chinese adults.

ImportanceThe third Universal Definition of Myocardial Infarction aimed to standardize the approach to the diagnosis and management of myocardial infarction. High-sensitivity cardiac troponin testing was recommended, as these assays have improved precision at low concentrations, but concerns over specificity may have limited implementation.ObjectiveTo determine the global adoption of high-sensitivity cardiac troponin assays and key recommendations from the Universal Definition.Design, Setting and ParticipantsGlobal survey of 1,902 medical centers across 23 countries evenly distributed across all five continents. Included respondents were involved in the diagnosis and management of patients with suspected acute coronary syndrome at their institutions.Main Outcomes and MeasuresStructured questionnaire detailing the primary biomarker used for myocardial infarction, diagnostic thresholds and critical elements of clinical pathways for comparison to the third Universal Definition recommendations.ResultsCardiac troponin was the primary diagnostic biomarker for myocardial infarction at 96% of all sites surveyed. Only 41% of centers had adopted high-sensitivity cardiac troponin assays, with wide variation from 7% in North America to 60% in Europe. Sites using high-sensitivity assays more frequently employed serial sampling pathways (91% vs. 78%) and the 99th percentile diagnostic threshold (74% vs. 66%) when compared to sites using the previous generation of troponin assays. Furthermore, sites using high-sensitivity assays more often used earlier serial sampling (≤3 hours) and accelerated diagnostic pathways. However, fewer than 1 in 5 sites using high-sensitivity assays had adopted sex-specific thresholds (18%).Conclusions and RelevanceProgress has been made in adopting the recommendations of the Universal Definition of Myocardial Infarction, particularly in the use of the 99th percentile diagnostic threshold and serial sampling. However, high-sensitivity assays are used in a minority of sites and sex-specific thresholds in even fewer. These findings highlight regions where additional efforts are required to improve the risk stratification and diagnosis of patients with myocardial infarction.

Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been widely used as a biomarker for liver cancer diagnosis in Japan for decades. However, the reference intervals for serum ARCHITECT PIVKA-II have not been established in the Chinese population. Thus, this study aimed to measure serum PIVKA-II levels in healthy Chinese subjects.This is a sub-analysis from the prospective, cross-sectional and multicenter study (ClinicalTrials.gov Identifier: NCT03047603). A total of 892 healthy participants (777 Han and 115 Uygur) with complete health checkup results were recruited from 7 regional centers in China. Serum PIVKA-II level was measured by ARCHITECT immunoassay. All 95% reference ranges were estimated by nonparametric method.The distribution of PIVKA-II values showed significant difference with ethnicity and sex, but not age. The 95% reference range of PIVKA-II was 13.62-40.38 mAU/ml in Han Chinese subjects and 15.16-53.74 mAU/ml in Uygur subjects. PIVKA-II level was significantly higher in males than in females (P 0.001). The 95% reference range of PIVKA-II was 15.39-42.01 mAU/ml in Han males while 11.96-39.13 mAU/ml in Han females.The reference interval of serum PIVKA-II on the Architect platform was established in healthy Chinese adults. This will be valuable for future clinical and laboratory studies performed using the Architect analyzer. Different ethnic backgrounds and analytical methods underline the need for redefining the reference interval of analytes such as PIVKA-II, in central laboratories in different countries.

It is unknown whether the association of high-sensitivity troponin I (hs-TnI) with adverse cardiovascular outcomes varies by the presence of chronic kidney disease (CKD). We examined the association of hs-TnI with adverse cardiovascular outcomes in those with and without CKD in 4,107 (mean age, 64 years; 63% men; 20% black) patients from the Emory Cardiovascular Biobank who underwent coronary angiography. CKD (n = 1,073) was defined as estimated glomerular filtration rate 30 mg/g at baseline. Cox regression was used to compute hazard ratios (HR) for the association between hs-TnI levels (per doubling of hs-TnI: log2[hs-TnI] + 1) and death, cardiovascular death, and major adverse cardiac events (MACE), separately. Hs-TnI was a stronger predictor of death (CKD: HR 1.23, 95% confidence interval [CI] 1.15 to 1.31; no CKD: HR 1.11, 95% CI 1.05 to 1.17, p-interaction = 0.023), cardiovascular death (CKD: HR 1.24, 95% CI 1.14 to 1.34; no CKD: HR 1.15, 95% CI 1.07 to 1.22, p-interaction = 0.12), and MACE (CKD: HR 1.18, 95% CI 1.11 to 1.25; no CKD: HR 1.11, 95% CI 1.06 to 1.16, p-interaction = 0.095) in CKD compared with non-CKD. The association between hs-TnI and death in patients with CKD was stronger for patients without obstructive coronary artery disease (no obstructive coronary artery disease: HR 1.60, 95% CI 1.27 to 2.01; obstructive coronary artery disease: HR 1.19, 95% CI 1.11 to 1.27, p-interaction = 0.041). In conclusion, hs-TnI is a stronger predictor of adverse cardiovascular events in patients who have CKD than those without, even in the absence of obstructive coronary artery disease. Hs-TnI may identify CKD patients who are high risk for adverse cardiovascular outcomes in whom aggressive risk factor modification strategies are warranted.

Background— Recent data suggest that circulating biomarkers may predict outcome in patients undergoing transcatheter aortic valve replacement (TAVR). We examined the association between inflammatory, myocardial, and renal biomarkers and their role in ventricular recovery and outcome after TAVR. Methods and Results— A total of 112 subjects undergoing TAVR were included in the prospective registry. Plasma levels of B-type natriuretic peptide, hs-TnI (high-sensitivity troponin I), CRP (C-reactive protein), GDF-15 (growth differentiation factor 15), GAL-3 (galectin-3), and Cys-C (cystatin-C) were assessed before TAVR and in 100 sex-matched healthy controls. Among echocardiographic parameters, we measured global longitudinal strain, indexed left ventricular mass, and indexed left atrial volume. The TAVR group included 59% male, with an average age of 84 years, and 1-year mortality of 18%. Among biomarkers, we found GDF-15 and CRP to be strongly associated with all-cause mortality ( P P P =0.01). Among survivors, functional recovery in global longitudinal strain (>15% improvement) and indexed left ventricular mass (>20% decrease) at 1 year occurred in 48% and 22%, respectively. On multivariate logistic regression, lower baseline GDF-15 was associated with improved global longitudinal strain at 1 year (hazard ratio=0.29; P P =0.03). Conclusions— Elevated GDF-15 correlates with lack of reverse remodeling and increased mortality after TAVR and improves risk prediction of mortality when added to the Society of Thoracic Surgeons score.

High levels of high sensitivity troponin I (hs-cTnI) are associated with higher risk of inducible myocardial ischemia (ISC) and adverse outcomes in patients with stable coronary artery disease (CAD). ISC is also associated with worse prognosis. We examined whether hs-cTnI levels and ISC are additive

WOS: 000404447400031, PubMed ID: 28663316, …, ThermoFisher; Research Council of Lithuania [MIP-049/2015]; Crossref Funder Registry, This study was funded by ThermoFisher. A. Mebazaa and J. Motiejunaite would like to acknowledge the support of the Research Council of Lithuania, grant number MIP-049/2015. Funding information for this article has been deposited with the Crossref Funder Registry.

High-sensitivity Troponin-I (hs-TnI) as a marker of myocardial injury is predictive of adverse outcomes in patients with coronary artery disease (CAD). Whether the relationship between hs-TnI and outcomes is dependent on underlying CAD severity is unknown. 2826 patients without AMI (mean age 62, 64