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Results for “Protein risk score”

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PubMed2026

Machine Learning-Driven Prediction of Coronary Artery Disease Risk Based on UK Biobank Plasma Proteomics.

BACKGROUND: Coronary artery disease (CAD) is a leading global cause of mortality, yet the predictive accuracy of conventional risk models is limited. Here, we integrate conventional risk factors, polygenic risk scores, and large-scale proteomics to develop a unified model for enhanced CAD risk prediction. METHODS: Using data from UK Biobank, participants with plasma proteomics and genetic risk data were included after excluding prevalent CAD. Participants from England were split into training (n=32 330) and internal validation (n=13 857) sets, and Scotland/Wales participants formed an external validation set (n=5775). Incident CAD was ascertained from linked health records. A 202-protein proteomic risk score was derived by least absolute shrinkage and selection operator Cox regression, and CatBoost models were trained using conventional risk factors alone and with incremental addition of polygenic risk scores and protein proteomic risk scores; Shapley Additive Explanations-guided forward selection identified a compact protein panel. RESULTS: Across cohorts, the median age was 58 years and ∼45% were men. Protein proteomic risk score was dose-dependently associated with CAD risk. Compared with conventional risk factors alone, integrating polygenic risk scores and protein proteomic risk scores improved discrimination, with the area under the curve increasing from 0.750 (95% CI, 0.732-0.767) to 0.789 (95% CI, 0.772-0.805) in internal validation and from 0.717 (95% CI, 0.683-0.750) to 0.762 (95% CI, 0.732-0.791) in external validation. A 9-protein panel (GDF15 [growth differentiation factor 15], MMP12 [matrix metalloproteinase 12], NPPB [natriuretic peptide B], PGF [placental growth factor], REN [renin], ADGRG2 [adhesion G-protein coupled receptor], ACE2 [angiotensin-converting enzyme 2], CDCP1 [CUB domain-containing protein 1], CXCL17 [C-X-C motif chemokine ligand 17)]) captured most proteomic predictive information. CONCLUSIONS: Our findings demonstrate that integrating conventional risk factors, polygenic risk scores, and proteomic data improves CAD risk prediction. This study highlights the utility of proteomics in precision cardiovascular medicine and simplified risk stratification tools.

Humans↗

PubMed2026

Proteomic signatures for sudden cardiac death and related intermediate phenotypes.

BACKGROUND: Novel markers for sudden cardiac death (SCD) are needed. OBJECTIVE: This study aimed to explore whether a protein risk score derived from a large-scale proteomics dataset improves risk prediction of SCD in the general population. METHODS: A total of 52,705 individuals with 1459 unique plasma protein measurements were included from the UK Biobank Pharma Proteomics Project. A protein risk score was developed using lasso-penalized Cox regression on 40,722 participants enrolled at the English centers and validated on 11,983 participants enrolled at the remaining centers. RESULTS: The protein risk score formula developed from the derivation set comprised 64 unique plasma proteins including latent-transforming growth factor beta-binding protein 2, protein tyrosine phosphatase receptor sigma, and spondin-1. In the test set, a per standard deviation increase in protein risk score was associated with a hazard ratio of 2.60 (95% confidence interval [CI] 2.12-3.18) for SCD. Adding a protein risk score to SCD clinical risk factors resulted in a concordance index increase of 0.063 (95% CI 0.037-0.105) for SCD. For ventricular arrhythmia-mediated SCDs, an increase in concordance index when a protein risk score was added to SCD clinical risk factors was 0.070 (95% CI 0.010-0.188). A protein risk score added to SCD clinical risk factors resulted in a risk reclassification of 16.9% (95% CI 9.0-24.7) at a 10-year risk threshold of 5%. A protein risk score was significantly associated with intermediate phenotypes of SCD including corrected QT prolongation, an increase in left ventricular mean myocardial thickness, and a decrease in left ventricular global longitudinal strain. CONCLUSION: A protein risk score derived from a single plasma sample significantly improved risk prediction of SCD and related intermediate phenotypes.

Humans↗

PubMed2026

Large-Scale Plasma Proteomics Enhances Prediction of Liver-Related Events Among Individuals With Prediabetes and Type 2 Diabetes: A Prospective Cohort Study in the UK Biobank.

OBJECTIVE: To develop a protein risk score (ProRS) for predicting liver-related events (LREs) in patients with diabetes and compare its predictive performance with the Fibrosis-4 Index (FIB-4) and an established polygenic risk score. RESEARCH DESIGN AND METHODS: This prospective cohort study included 13 516 individuals with prediabetes and type 2 diabetes (T2D) from the UK Biobank. Cox proportional hazards models and LASSO regression were applied to identify proteins associated with incident LREs and construct the ProRS. Predictive performance was assessed using Harrell's C-index, time-dependent area under the receiver operating characteristic curve, net reclassification improvement and integrated discrimination improvement. RESULTS: Over a median follow-up of 13.5 years, 171 (1.3%) incident LREs occurred. We identified 877 proteins associated with LRE risk, primarily enriched in inflammatory signalling, extracellular matrix remodelling and complement/coagulation cascades. In the training set, we developed a 24-protein ProRS (C-index, 0.842; 95% CI 0.797-0.884) that stratified individuals into low-, medium- and high-risk groups, with 10-year cumulative incidences of LREs of 0.2%, 1.2% and 14.2%, respectively. Compared with the low-risk group, the hazard ratio for LREs was 57.1 (95% CI 31.9-102) in the high-risk group. In the internal validation set, the ProRS model (C-index, 0.876; 95% CI 0.827-0.920) accurately predicted both short- and long-term LREs and outperformed FIB-4 index (C-index, 0.733; 95% CI 0.657-0.807) and polygenic risk score (C-index, 0.636; 95% CI 0.564-0.706). CONCLUSIONS: The protein risk score demonstrated superior performance compared with the FIB-4 index and the polygenic risk score in predicting incident LREs among individuals with prediabetes and T2D. The score allows stratification of individuals according to liver-related risk, though external validation in multi-ethnic cohorts is warranted.

Humans↗

PubMed2026

Proteomic Profiling Captures Residual Cardiovascular Risk Beyond the PREVENT Model in Individuals With Cardiovascular-Kidney-Metabolic Syndrome Stages 2-3.

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome reflects complex pathobiological interactions among metabolic disorders, kidney injury, and cardiovascular disease (CVD). Stages 2 and 3 represent critical phases of disease progression characterised by high pathological heterogeneity. This study aimed to develop a CVD protein risk score (PRS) for this population and evaluate its incremental predictive value over the PREVENT model. METHODS: This study included 24 017 participants with CKM Stages 2-3 from the UK Biobank. Using 2923 plasma proteins measured via the Olink platform, a PRS was developed in a training set (n = 19 218) using the LASSO method. In the validation set (n = 4799), the incremental predictive performance of this score over the PREVENT model was assessed using Harrell's C-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: A risk score comprising 63 proteins was constructed, primarily reflecting inflammation, kidney injury and matrix remodelling. Key proteins included growth differentiation factor 15 (GDF15), hepatitis A virus cellular receptor 1 (HAVCR1), matrix metallopeptidase 12 (MMP12) and NT-proBNP. In the validation set, after adjusting for PREVENT risk factors, individuals in the high PRS group had a 2.56-fold higher risk of CVD compared to those in the low score group (HR: 2.56, 95% CI: 1.96-3.37). Integrating the score into the PREVENT model improved the C-statistic by 0.034 (0.672-0.706) and achieved a 10-year NRI of 15.8% (95% CI: 9.5%-20.9%) and an IDI of 2.2% (95% CI: 1.3%-3.3%). CONCLUSION: Combining the PREVENT model with the PRS developed in this study enhances the prediction of future CVD events in the CKM Stages 2-3 population. This approach facilitates the capture of residual risk and supports precision risk stratification and management for this high-risk group.

Humans↗

PubMed2026

Large-Scale Plasma Proteomics Identifies Early Molecular Deviations and Improves Risk Prediction for Heart Failure Among Individuals With Obesity.

AIMS: Heart failure (HF) is a major global public health challenge, with obesity being one of its key risk factors. Although several HF risk prediction models have been developed in the general population, few are specifically tailored to individuals with obesity. This underscores the urgent need for precise biomarkers to improve individual risk stratification and enable personalized prevention strategies. We aimed to develop and validate a plasma proteomics-based protein risk score (PRS) to predict incident HF among individuals with obesity. MATERIALS AND METHODS: We analysed 9831 participants with obesity (BMI ≥ 30 kg/m2) from the UK Biobank with baseline measurements of 2911 circulating proteins and up to 16 years of follow-up. Multivariable Cox regression identified proteins associated with incident HF after comprehensive covariate adjustment. A PRS was constructed using LASSO regression and evaluated in a held-out test set. Protein trajectories before HF onset were reconstructed using LOESS modelling. To enhance clinical feasibility, a minimal protein panel was identified using LightGBM with forward feature selection. RESULTS: A total of 727 participants developed HF during follow-up. Multivariable cox analyses identified 578 proteins significantly associated with HF. LASSO regression further selected 81 proteins to build the PRS, which showed a strong association with HF risk in both training (HR 3.57; 95% CI 3.19-4.00) and test cohorts (HR 2.45; 95% CI 2.20-2.74). Adding the PRS improved prediction beyond age and sex (ΔC = 0.091) and beyond the Pooled Cohort Equations to Prevent Heart Failure (PCP-HF) model (ΔC = 0.052), with consistent gains in NRI and IDI. Proteomic deviations were detectable up to 16 years before diagnosis. A four-protein panel (GDF15, NT-proBNP, TNFRSF10B, CTHRC1) achieved robust discrimination (AUC 0.789), outperforming NT-proBNP alone (AUC 0.695) and complementing the PCP-HF model (combined AUC 0.803). DISCUSSION: Large-scale plasma proteomics substantially improves HF risk prediction in individuals with obesity and reveals long-standing molecular alterations preceding clinical onset. A simplified four-protein panel maintains robust predictive accuracy and provides a practical approach for the early detection and targeted prevention of obesity-related HF.

Humans↗

PubMed2003

Plasma concentration of C-reactive protein and the calculated Framingham Coronary Heart Disease Risk Score.

BACKGROUND: Although C-reactive protein (CRP) predicts vascular risk, few data are available evaluating the relation between CRP and the Framingham Coronary Heart Disease Risk Score (FCRS). METHODS AND RESULTS: CRP levels were compared with calculated 10-year FCRS in a cross-sectional survey of 1666 individuals free of cardiovascular disease. Among men and women not using hormone replacement therapy (HRT), CRP levels were significantly related to 10-year Framingham Coronary Heart Disease Risk categories [total cholesterol (TC) score for men and women: r=0.29 and r=0.22, respectively; LDL cholesterol score for men and women: r=0.29 and r=0.22, respectively, all probability values <0.01]. However, CRP levels correlated minimally with individual components of the FCRS, which included age (r(men)=0.17, r(women)=-0.003), TC (r(men)=-0.02, r(women)=-0.006), HDL-C (r(men)=0.13), LDL-C (r(men)=-0.0002, r(women)=0.012), blood pressure (rmen=0.18, r(women)=0.22), diabetes (r(men)=0.10, r(women)=0.07), and smoking (r(men)=0.16, r(women)=0.14) status. For women taking HRT, no significant relation was observed between CRP and the FCRS, although the power to detect effects in this subgroup is limited. CONCLUSIONS: Our data demonstrate that CRP levels significantly correlate with calculated 10-year Framingham Coronary Heart Disease Risk in men and women not taking HRT but correlate minimally with most individual components of the FCRS. These data provide additional support for continued evaluation of CRP as a potential adjunct in the global prediction of cardiovascular risk.

Age Distribution↗

PubMed2004

Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores.

BACKGROUND: High-sensitivity C-reactive protein (hsCRP) is a strong independent risk factor for cardiovascular events, and levels of hsCRP of <1, 1 to <3, and > or =3 mg/L have been suggested to define low-, moderate-, and high-risk groups. However, the positive predictive value of very low (<0.5 mg/L) and very high levels of hsCRP (>10.0 mg/L) is uncertain. METHODS AND RESULTS: Baseline levels of hsCRP were evaluated among 27 939 apparently healthy women who were followed up for myocardial infarction, stroke, coronary revascularization, or cardiovascular death. Crude and Framingham Risk Score (FRS)-adjusted relative risks (RRs) of incident cardiovascular events were calculated across a full range of hsCRP levels. Cardiovascular risks increased linearly from the very lowest (referent) to the very highest levels of hsCRP. Crude RRs for those with baseline hsCRP levels of <0.5, 0.5 to <1.0, 1.0 to <2.0, 2.0 to <3.0, 3.0 to <4.0, 4.0 to <5.0, 5.0 to <10.0, 10.0 to <20.0, and > or =20.0 mg/L were 1.0, 2.2, 2.5, 3.1, 3.7, 4.2, 4.9, 6.3, and 7.6, respectively (P for trend <0.001). After adjustment for FRS, these risks were 1.0, 1.6, 1.6, 1.7, 1.9, 2.2, 2.3, 2.8, and 3.1 (P for trend <0.001). All risk estimates remained significant in analyses stratified by FRS and after control for diabetes. Of the total cohort, 15.1% had hsCRP <0.50 mg/L, and 5.4% had hsCRP >10.0 mg/L. CONCLUSIONS: Both very low (<0.5 mg/L) and very high (>10 mg/L) levels of hsCRP provide important prognostic information on cardiovascular risk. hsCRP is clinically useful for risk prediction across a full range of values and across a full range of FRS.

C-Reactive Protein↗

PubMed2026

Plasma proteomics and coronary artery calcium score: synergistic, concordant and contrasting predictions of cardiovascular outcomes in The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Coronary artery calcium (CAC) scores inform subclinical atherosclerotic cardiovascular disease (ASCVD) burden, helping guide preventative treatments. However, prediction of cardiovascular (CV) events by CAC is largely limited to ASCVD outcomes. This study investigated whether a previously validated proteomic test for predicting a broad composite of four-year CV events could enhance the prognostic utility of CAC. METHODS: We used a 27-protein CV risk score (Prot-CVR), derived from ~5,000 SomaScan™ Assay plasma protein measurements, to predict four-year risk of a composite CV and mortality outcome (myocardial infarction, stroke/TIA, heart failure hospitalization, death) in 2,122 participants with ≥1 CV risk factors from the Multi-Ethnic Study of Atherosclerosis (MESA) observational cohort at exam 5 and compared predictions to CAC Agatston scores. Discriminatory performance was assessed using C-Index and 4-year area under the curve (AUC). Cox Proportional Hazard (CoxPH) ratios were calculated for the composite outcome, ASCVD outcome (myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death), and individual events. Changes in Prot-CVR and CAC scores from baseline to MESA exam 5 (+10-years) in CV event versus event-free participants were assessed using 2-tailed paired t-tests. CoxPH regression models of CV event status distributed by Prot-CVR, CAC, and relevant co-variates were evaluated for performance relative to individual models. RESULTS: Individual Prot-CVR and CAC models predicting the composite outcome had comparable 4-year AUCs, but Prot-CVR had a higher C-index (0.68 (0.65-0.70) versus 0.63 (0.60-0.65), p=0.001) and greater hazard ratios for the composite outcome (p<0.001), death (p<0.001), and heart failure (p=0.015). A combined CoxPH model of Prot-CVR + CAC + Age had a higher 4-year AUC (0.72, p<0.05) and C-Index (0.71, p<0.05) than Prot-CVR or CAC alone. Both Prot-CVR and CAC scores detected an increase in risk prior to an approaching CV event in ~10-year sensitivity-to-change analysis. For 49.6% of MESA population with CAC=0 at baseline, Prot-CVR was greater in composite event versus event free participants at 4 years (0.23 versus 0.15, p=0.006) and full follow-up (0.18 versus 0.13, p<0.001). CONCLUSION: Protein testing complements CAC for CV risk assessment although the improvement is modest. Prot-CVR may resolve which patients with CAC=0 are at heightened CV risk.

Journal Article↗

PubMed2005

Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of Women's Health Across the Nation (SWAN).

BACKGROUND: We evaluated ethnic differences in the 10-year risk of myocardial infarction or coronary death derived from Framingham risk equation and in a composite measure of emerging cardiovascular disease risk factors in women and whether statistical adjustments for educational attainment, geographic location, and lifestyle attenuated the magnitude of the ethnic differences in risk. METHODS: Two thousand eight hundred thirty-four premenopausal women free of stroke, heart disease, or diabetes and aged of 42 to 52 years (1400 whites, 729 African American, 226 Hispanic, 231 Chinese, and 248 Japanese) had measurements of blood pressure, lipids and lipoproteins, waist circumference, glucose, insulin, lipoprotein(a), fibrinogen, factor VII, plasminogen activator inhibitor, tissue-type plasminogen activator antigen, and high-sensitivity C-reactive protein. Framingham risk score and number of risk factors in the top quartile of the distribution of risk factors not included in the Framingham score (called composite burden) were calculated. RESULTS: The unadjusted mean values for the two summary scores were higher among African Americans and Hispanics than other groups. Statistical adjustments for education and geographical site accounted for a majority of the ethnic differences, with an additional small effect of lifestyle for the composite burden score. Largest ethnic differences were apparent for waist circumference, lipoprotein(a), high-sensitivity C-reactive protein, and untreated blood pressure. CONCLUSIONS: A substantial part of the risk associated with ethnicity can be attributed to socioeconomic status and geographical location. As the ethnic composition of the United States population becomes more diverse, it is important to appreciate the cardiovascular disease risk factor burden present in some minority groups.

Adult↗

PubMed2002

Procalcitonin, C-reactive protein and APACHE II score for risk evaluation in patients with severe pneumonia.

OBJECTIVE: Procalcitonin (PCT) is a peptide that is found elevated in patients with sepsis and severe infections. In healthy persons PCT serum levels are below 0.1 ng/mL. The aim of this study was to investigate the value of serum PCT determination for risk evaluation in patients with pneumonia. METHODS: We focused on the correlation of PCT with the clinical status of the patient and prognosis of the disease. In a prospective study, in a nonsurgical intensive care unit the following parameters were assessed regularly in 93 patients with documented pneumonia: C-reactive protein (CRP), white blood cell count (WBC), body temperature, PCT and Acute Physiology and Chronic Health Evaluation (APACHE) II score. RESULTS: At the onset of infection 50% of the patients had elevated PCT levels above 2 ng/mL. The model of multivariate analysis of all tested parameters on days 0-5 stratified for clinical outcome (change in clinical classification or death) showed local significance for APACHE II score only. None of the other parameters in this model serves as an isolated indicator for change of clinical status or death. An intra-individual change of body temperature or CRP was never significantly associated with a change in the clinical status of the patient. CONCLUSION: Change in PCT on admission and at the end of the observation period significantly indicated a clinical change.

APACHE↗

PubMed2006

Does high-sensitivity C-reactive protein add prognostic value to the TIMI-Risk Score in individuals with non-ST elevation acute coronary syndromes?

BACKGROUND: C-reactive protein (CRP) measured at hospital arrival of patients with non-ST elevation acute coronary syndromes (ACS) may add prognostic information to the TIMI-Risk Score. METHODS: Eighty-six consecutive patients admitted with unstable angina or non-ST-elevation acute myocardial infarction and symptoms onset within the prior 48 h were included. Recurrent cardiovascular events during hospitalization were defined as non-fatal myocardial infarction or death. Serum CRP was measured immediately at hospital arrival and its prognostic value in relation to in-hospital cardiovascular events was tested by the area under the ROC curve and adjusted for TIMI risk predictors by logistic regression analysis. In addition, a CRP modified TIMI-Risk score was created by adding 2 points if CRP greater than the cut-off proposed by the ROC curve analysis. The accuracy of this new score was compared with the usual TIMI-Risk Score. RESULTS: A significant predictive value of CRP in relation to in-hospital cardiovascular events was indicated by an area under the ROC curve of 0.80 (95% CI=0.66 to 0.93, p=0.009). C-reactive protein cut-off point of best prognostic performance was 7.2 mg/l. In the multivariate analysis, increased CRP (>7.2 mg/l) remained a significant predictor of events after adjustment for TIMI risk predictors (OR=14; 95% CI=1.6-121; p=0.018). The area under the ROC curve for the TIMI-Risk Score was 0.87 (95% CI=0.76-0.99, p=0.001). The addition of CRP to the TIMI-Risk Score improved its prognostic value (area under the ROC curve=0.93; 95% CI=0.87-0.99, p<0.001). The additional value of the new score is demonstrated by a higher specificity (86% vs. 63%, p<0.001) and positive predictive value (39% vs. 19%) in relation to the TIMI-Risk Score. CONCLUSIONS: CRP measured at admission of patients with non-ST-elevation acute coronary syndromes adds prognostic information to the TIMI-Risk Score. Additionally, the incorporation of this variable into the TIMI-Risk Score calculation is an effective manner to utilize CRP for risk stratification.

Aged↗

PubMed2004

C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany.

BACKGROUND: The Framingham Coronary Heart Disease (CHD) prediction score is recommended for global risk assessment in subjects prone to CHD. Recently, C-reactive protein (CRP) has emerged as an independent predictor of CHD. We sought to assess the potential of CRP measurements to enhance risk prediction based on the Framingham Risk Score (FRS) in a large cohort of middle-aged men from the general population. METHODS AND RESULTS: We measured CRP and traditional cardiovascular risk factors at baseline in 3435 white men of German nationality, 45 to 74 years of age. All men were drawn from 3 random samples of the general population in the Augsburg area located in Southern Germany in 1984 to 1985, 1989 to 1990, and 1994 to 1995 (response rate, 80%), and the FRS was calculated in all of them. Outcome was defined as nonfatal and fatal coronary events, including sudden cardiac death. During an average follow-up of 6.6 years, a total of 191 coronary events occurred. Cox regression showed a significant contribution of CRP to coronary event risk prediction independent of the FRS (P=0.0002). In stratified analysis for 5 categories of FRS, CRP significantly added prognostic information to the FRS in subjects in 2 intermediate risk categories (P=0.03 and P=0.02). CONCLUSIONS: Our results suggest that CRP enhances global coronary risk as assessed by the FRS, especially in intermediate risk groups. This might have implications for future risk assessment.

Adult↗

PubMed2006

C-reactive protein predicts carotid atherosclerosis progression in mild to moderate risk and middle-aged patients.

PURPOSE: The Framingham risk score is a popular tool for estimating cardiovascular risk, but there is debate about the value of C-reactive protein. This study investigated the utility of C-reactive protein to predict the progression of atherosclerosis in relation to the Framingham risk score and age. METHODS: This observational study enrolled 164 outpatients (mean age: 61 yr; range: 40 - 75 yr) receiving treatment for classical cardiovascular risk factors. They underwent serial ultrasonographic evaluation of their carotid arteries for 36 +/- 10 months. A carotid intima-media thickness > or = 1.1 mm was defined as plaque, and the number of plaques and plaque score (sum of all plaque thicknesses) were determined. Serum C-reactive protein concentrations and classical risk factors, including body mass index, were measured. RESULTS: C-reactive protein was related to annual changes in the number of plaques and the plaque score (r=0.26 and 0.28; P<0.01 and P<0.001, respectively), as well as the 10-year risk of cardiovascular disease estimated from the Framingham risk score (r=0.335, P<0.001). C-reactive protein was correlated with the annual changes of plaque number and plaque score (beta=0.21 and 0.23; P<0.05 and P<0.01) after adjusting for 10-year cardiovascular and other risk factors, especially in 64 patients comprising the 8-13% 10-year risk group (beta=0.33 for plaque score, P<0.05). CRP also showed a relationship with the progression of carotid atherosclerosis in 71 patients aged < or = 61 yr (beta=0.33 for plaque score, P<0.01). CONCLUSIONS: C-reactive protein can predict the progression of early carotid atherosclerosis in patients with mild to moderate cardiovascular risk and/or middle-aged patients.

Adult↗

PubMed2005

Early prognostic usefulness of C-reactive protein added to the Thrombolysis In Myocardial Infarction risk score in acute coronary syndromes.

The aim of the present study was to evaluate whether an elevated plasma C-reactive protein (CRP) level provides any additional prognostic information to the validated Thrombolysis In Myocardial Infarction (TIMI) risk score in patients with acute coronary syndromes. For this purpose, 1,846 consecutive patients with either acute ST-segment elevation myocardial infarction (STEMI; 861 patients) or non-ST-segment elevation acute coronary syndrome (NSTEACS; 985 patients) were included. The incidence of 30-day death and 14-day composite of death, myocardial infarction (or repeat myocardial infarction) and recurrent ischemia was the prespecified primary end point in the STEMI and NSTEACS cohorts, respectively. The incidence of the primary end point was 9.8% and 23.6% in the STEMI and NSTEACS cohorts, respectively. A significantly increased risk of the primary end point was present with an increase in the STEMI and NSTEACS TIMI risk score (p(trend) < 0.001 for the 2 groups). A plasma CRP value of > or = 5 and > or = 3 mg/L (defined by receiver-operating characteristic analysis) was associated with a significantly increased risk of the primary end point in the STEMI and NSTEACS cohorts, respectively (p < 0.001 for the 2 cohorts), and it was true throughout the subgroups of STEMI and NSTEACS TIMI risk scores. In conclusion, an elevated plasma CRP level appears to be a marker that adds prognostic information to the validated STEMI and NSTEACS TIMI risk score. The plasma CRP and TIMI risk score may be used together for enhanced risk stratification in the setting of acute coronary syndromes.

Aged↗

PubMed2006

Implications of C-reactive protein or coronary artery calcium score as an adjunct to global risk assessment for primary prevention of CHD.

BACKGROUND: C-reactive protein (CRP) or coronary artery calcium (CAC) score have been suggested to identify a higher risk subset of intermediate-risk individuals, who potentially could be considered for more aggressive therapy. In the Multi-Ethnic Study of Atherosclerosis (MESA), we estimated the proportion of intermediate-risk participants whose risk status might change based on additional testing using CRP and/or CAC score. METHODS: Framingham 10-year CHD risk scores (FRS) were calculated and cross tabulations were used to determine the percent of individuals at intermediate-risk by FRS with a CRP >3mg/L and/or CAC score >100 AU. Similar analyses were performed using the gender-specific 75th percentile for CRP and CAC. RESULTS: Of the 30% of participants (N=1450) classified as intermediate-risk by FRS, 30% had a CRP >3mg/L and 33% had a CAC score >100 AU. Among intermediate-risk women, 49% had a CRP >3mg/L compared to 27% of intermediate-risk men (p<0.0001) while the same percent of intermediate-risk women and men (33%) had a CAC score >100 AU. Eleven percent or less of men or women had both a high CRP and CAC score whether conventional or gender-specific cut points were used. When the percent of intermediate-risk individuals with an elevated CRP and/or CAC score in MESA were applied to NHANES III data, over a million intermediate-risk individuals would move to high risk status if CRP or CAC screening directed treatment strategies were uniformly adopted in the U.S. CONCLUSION: There were differences in the number of intermediate-risk individuals reclassified as high risk depending on the screening test used, the cut points selected, and the demographics of the individuals being screened. These data highlight current limitations of broadly using risk markers such as CRP and CAC score in an intermediate-risk population.

Aged↗

PubMed1997

Quantitative measurement of autoantibodies to recombinant mitochondrial antigens in patients with primary biliary cirrhosis: relationship of levels of autoantibodies to disease progression.

We examined the clinical usefulness of measurements of antimitochondrial autoantibodies (AMA) in predicting disease progression in patients with primary biliary cirrhosis (PBC). We determined the relationships between AMA levels measured by indirect immunofluorescence (IF) and those measured by quantitative enzyme immunoassays (EIAs) using recombinant 2-oxo-acid dehydrogenase complex (2-OADC) proteins and the Mayo Risk Score, an established indicator of disease progression in primary biliary cirrhosis (PBC). Results of tests for AMA by either method correlated weakly (r = .24 to .30) with disease progression as indicated by Mayo Risk Scores. The levels of AMA to 2-OADC proteins varied by more than 200-fold between patients but remained relatively constant over time in individual patients. Despite being positively correlated with Mayo Risk Score results, the levels of AMA to 2-OADC proteins were not useful for predicting disease progression in individual patients with PBC. In addition, we found no significant differences in the levels of autoantibodies to 2-OADC proteins among patients with different histological stages of disease. Our results show that measurements of AMA by IF or by quantitative EIA methods with recombinant 2-OADC proteins are not useful parameters for predicting disease progression in patients with PBC.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed2005

Obesity-related correlation between C-reactive protein and the calculated 10-y Framingham Coronary Heart Disease Risk Score.

OBJECTIVE: To clarify the role of body mass index (BMI, kg/m(2)) adjustment in predictive models for cardiovascular events that add high-sensitivity C-reactive protein (hs-CRP) to the 10-y Framingham Coronary Heart Disease Risk Score (FCRS). DESIGN: A cross-sectional study in a group of apparently healthy individuals. SUBJECTS: In all, 1512 apparently healthy individuals (955 men and 557 women) at a respective age of 49.7+/-10.6 and 50.6+/-9.6 y. RESULTS: The Pearson correlation between hs-CRP and the calculated 10-y FCRS was lower when adjusted for BMI. This reduction was especially noted in women where it dropped from 0.247 to 0.09. The dominant role of hs-CRP concentrations was also noted in a linear regression model, again, especially noted in women (drop of the standardized coefficient from 0.517 for BMI to 0.08 for the FCRS). CONCLUSIONS: The correlation between hs-CRP and the 10-y FCRS is partly related to the presence of obesity. We raise the possibility that the addition of BMI to the predictive model of FCRS might attenuate the cost-effectiveness of CRP measurements for this specific risk assessment.

Biomarkers↗

PubMed2026

Multi-trait polygenic scores for COPD and COPD exacerbations implicate druggable proteins.

BACKGROUNDWe constructed multi-trait polygenic risk scores (PRSs) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validated their performance in diverse cohorts, and identified PRS-related proteins for potential therapeutic targeting.METHODSPRSmix+, a multi-trait PRS framework, is used to train a composite PRS (PRSmulti) in COPDGene non-Hispanic White participants (n = 6,647). Associations of PRSmulti with COPD status (GOLD 2-4 vs. GOLD 0 or ICD) and exacerbation frequency were tested in COPDGene African American (n = 2,466), ECLIPSE (n = 1,858), Mass General Brigham Biobank (n = 15,152), and All of Us (n = 118,566). Protein prediction models were applied to GWAS summary statistics from traits contributing to PRSmulti and were validated with proteomic data in COPDGene (n = 5,173) and UK Biobank (n = 5,012).RESULTSPRSmix+ selected 7 traits for PRSmulti. In multivariable models, PRSmulti was associated with COPD status (meta-analysis random effects [RE] OR 1.58 [95% CI: 1.28-1.94]) and exacerbation frequency (meta-analysis RE β 0.21 [95% CI: 0.11-0.31]), with higher effect sizes observed in smoking-enriched cohorts. PRSmulti outperformed traditional single-trait PRS in all tested cohorts. Using protein prediction models, we identified 73 proteins associated with the PRSs that were also validated with measured protein levels in COPDGene and UK Biobank. Of these proteins, 25 were linked to approved or investigational drugs. Notable targets include RAGE/sRAGE, IL1RL1, and SCARF2, all implicated in COPD pathogenesis and exacerbations.CONCLUSIONSMulti-trait PRS improves prediction of COPD and exacerbation risk. Integration with proteomic data identifies druggable protein targets, offering a promising avenue for precision medicine in COPD management.TRIAL REGISTRATIONCOPDGene: ClinicalTrials.gov NCT00608764; ECLIPSE: ClinicalTrials.gov NCT00292552.

Humans↗