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Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals.

ABSTRACT: To identify circulating proteins predictive of acute cardiovascular disease events in the general population, we performed a proteomic screen in plasma from asymptomatic individuals. A "Discovery cohort" of 25 individuals who subsequently incurred a cardiovascular event within 3 years (median age?=?70 years, 80% male) was matched to 25 controls remaining event-free for?>?5 years (median age?=?72 years, 80% male). Plasma proteins were assessed by data independent acquisition mass spectrometry (DIA-MS). Associations with cardiovascular events were tested using Cox regression, adjusted for the New Zealand Cardiovascular Risk Score. Concentrations of leading protein candidates were subsequently measured with ELISAs in a larger (n?=?151) independent subset. In the Discovery cohort, 76 plasma proteins were robustly quantified by DIA-MS, with 8 independently associated with cardiovascular events. These included (HR?=?hazard ratio [95% confidence interval] above vs below median): fibrinogen alpha chain (HR?=?1.84 [1.19-2.84]); alpha-2-HS-glycoprotein (also called fetuin A) (HR?=?1.86 [1.19-2.93]); clusterin isoform 2 (HR?=?1.59 [1.06-2.38]); fibrinogen beta chain (HR?=?1.55 [1.04-2.30]); hemoglobin subunit beta (HR?=?1.49 [1.04-2.15]); complement component C9 (HR?=?1.62 [1.01-2.59]), fibronectin isoform 3 (HR?=?0.60 [0.37-0.99]); and lipopolysaccharide-binding protein (HR?=?1.58 [1.00-2.49]). The proteins for which DIA-MS and ELISA data were correlated, fibrinogen and hemoglobin, were analyzed in an Extended cohort, with broader inclusion criteria and longer time to events, in which these two proteins were not associated with incident cardiovascular events. We have identified eight candidate proteins that may independently predict cardiovascular events occurring within three years in asymptomatic, low-to-moderate risk individuals, although these appear not to predict events beyond three years.

SUBMITTER: Lasse M

PROVIDER: S-EPMC7907085 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals.

Lassé Moritz M Pilbrow Anna P AP Kleffmann Torsten T Andersson Överström Elin E von Zychlinski Anne A Frampton Christopher M A CMA Poppe Katrina K KK Troughton Richard W RW Lewis Lynley K LK Prickett Timothy C R TCR Pemberton Christopher J CJ Richards Arthur M AM Cameron Vicky A VA

Scientific reports 20210225 1

To identify circulating proteins predictive of acute cardiovascular disease events in the general population, we performed a proteomic screen in plasma from asymptomatic individuals. A "Discovery cohort" of 25 individuals who subsequently incurred a cardiovascular event within 3 years (median age = 70 years, 80% male) was matched to 25 controls remaining event-free for > 5 years (median age = 72 years, 80% male). Plasma proteins were assessed by data independent acquisition mass spectrometry (DI ...[more]

PMID: 33633217

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Project description:BackgroundBody CT scans are frequently performed for a wide variety of clinical indications, but potentially valuable biometric information typically goes unused. We investigated the prognostic ability of automated CT-based body composition biomarkers derived from previously-developed deep-learning and feature-based algorithms for predicting major cardiovascular events and overall survival in an adult screening cohort, compared with clinical parameters.MethodsMature and fully-automated CT-based algorithms with pre-defined metrics for quantifying aortic calcification, muscle density, visceral/subcutaneous fat, liver fat, and bone mineral density (BMD) were applied to a generally-healthy asymptomatic outpatient cohort of 9223 adults (mean age, 57.1 years; 5152 women) undergoing abdominal CT for routine colorectal cancer screening. Longitudinal clinical follow-up (median, 8.8 years; IQR, 5.1-11.6 years) documented subsequent major cardiovascular events or death in 19.7% (n=1831). Predictive ability of CT-based biomarkers was compared against the Framingham Risk Score (FRS) and body mass index (BMI).FindingsSignificant differences were observed for all five automated CT-based body composition measures according to adverse events (p<0.001). Univariate 5-year AUROC (with 95% CI) for automated CT-based aortic calcification, muscle density, visceral/subcutaneous fat ratio, liver density, and vertebral density for predicting death were 0.743(0.705-0.780)/0.721(0.683-0.759)/0.661(0.625-0.697)/0.619 (0.582-0.656)/0.646(0.603-0.688), respectively, compared with 0.499(0.454-0.544) for BMI and 0.688(0.650-0.727) for FRS (p<0.05 for aortic calcification vs. FRS and BMI); all trends were similar for 2-year and 10-year ROC analyses. Univariate hazard ratios (with 95% CIs) for highest-risk quartile versus others for these same CT measures were 4.53(3.82-5.37) /3.58(3.02-4.23)/2.28(1.92-2.71)/1.82(1.52-2.17)/2.73(2.31-3.23), compared with 1.36(1.13-1.64) and 2.82(2.36-3.37) for BMI and FRS, respectively. Similar significant trends were observed for cardiovascular events. Multivariate combinations of CT biomarkers further improved prediction over clinical parameters (p<0.05 for AUROCs). For example, by combining aortic calcification, muscle density, and liver density, the 2-year AUROC for predicting overall survival was 0.811 (0.761-0.860).InterpretationFully-automated quantitative tissue biomarkers derived from CT scans can outperform established clinical parameters for pre-symptomatic risk stratification for future serious adverse events, and add opportunistic value to CT scans performed for other indications.

Project description:BACKGROUND:Current guidelines for assessing the risk of experiencing a hospitalized cardiovascular (CV) event discourage stress testing of asymptomatic individuals; however, these recommendations are based on evidence gathered primarily from those aged <?60 years, and do not address the possibility of unrecognized "silent myocardial ischemia" in middle aged and older adults. METHODS:We performed dobutamine cardiovascular magnetic resonance (CMR) stress testing in 327 consecutively recruited participants aged >?55 years without CV-related symptoms nor known coronary artery disease, but otherwise at increased risk for a future CV event due to pre-existing hypertension or diabetes mellitus for at least 5 years. After adjusting for the demographics and CV risk factors, log-rank test and Cox proportional hazards models determined the additional predictive value of the stress test results for forecasting hospitalized CV events/survival. Either stress-induced LV wall motion abnormalities or perfusion defects were used to indicate myocardial ischemia. RESULTS:Participants averaged 68?±?8 years in age; 39% men, 75% Caucasian. There were 38 hospitalized CV events or deaths which occurred during a mean follow-up of 58 months. Using Kaplan-Meier analyses, myocardial ischemia identified future CV events/survival (p?<? 0.001), but this finding was more evident in men (p?<? 0.001) versus women (p?=?0.27). The crude hazard ratio (HR) of myocardial ischemia for CV events/survival was 3.13 (95% CI: 1.64-5.93; p?<?0.001). After accounting for baseline demographics, CV risk factors, and left ventricular ejection fraction/mass, myocardial ischemia continued to be associated with CV events/survival [HR: 4.07 (95% CI: 1.95-8.73) p?<?0.001]. CONCLUSIONS:Among asymptomatic middle-aged individuals with risk factors for a sentinel CV event, the presence of myocardial ischemia during dobutamine CMR testing forecasted a future hospitalized CV event or death. Further studies are needed in middle aged and older individuals to more accurately characterize the prevalence, significance, and management of asymptomatic myocardial ischemia. TRIAL REGISTRATION:( ClinicalTrials.gov identifier): NCT00542503 and was retrospectively registered on October 11th, 2007.

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Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals.

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Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals.

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