Abstract

BackgroundBiomarkers may help clinicians predict cardiovascular risk. We aimed to determine if the addition of endocrine, metabolic, and obesity-associated biomarkers to conventional risk factors improves the prediction of cardiovascular and all-cause mortality.Methodology/Principal FindingsIn a population-based cohort study (the Study of Health in Pomerania) of 3,967 subjects (age 20–80 years) free of cardiovascular disease with a median follow-up of 10.0 years (38,638 person-years), we assessed the predictive value of conventional cardiovascular risk factors and the biomarkers thyrotropin; testosterone (in men only); insulin-like growth factor-1 (IGF-1); hemoglobin A1c (HbA1c); creatinine; high-sensitive C-reactive protein (hsCRP); fibrinogen; urinary albumin-to-creatinine ratio; and waist-to-height ratio (WHtR) on cardiovascular and all-cause death.During follow-up, we observed 339 all-cause including 103 cardiovascular deaths. In Cox regression models with conventional risk factors, the following biomarkers were retained as significant predictors of cardiovascular death after backward elimination: HbA1c, IGF-1, and hsCRP. IGF-1 and hsCRP were retained as significant predictors of all-cause death.For cardiovascular death, adding these biomarkers to the conventional risk factors changed the C-statistic from 0.898 to 0.910 (p = 0.02). The net reclassification improvement was 10.6%. For all-cause death, the C-statistic changed from 0.849 to 0.853 (P = 0.09).Conclusions/SignificanceHbA1c, IGF-1, and hsCRP predict cardiovascular death independently of conventional cardiovascular risk factors. These easily assessed endocrine and metabolic biomarkers might improve the ability to predict cardiovascular death.

Highlights

  • Scoring systems based on classic risk factors, including sex, age, hypertension, dyslipidemia, and smoking, predict the future risk of cardiovascular events or death [1,2,3,4,5]; these risk factors explain only part of cardiovascular risk.attempts have been made to improve the prediction of cardiovascular risk by adding multiple novel biomarkers to the classic risk factors

  • The reclassification for cardiovascular death was 10.61% (95%-CI 20.28–24.86) as shown in table 8. In this population-based cohort study, we analyzed whether combining endocrine and metabolic parameters with a marker of abdominal obesity improved the prediction of cardiovascular death with conventional risk factors

  • We identified a set of additional biomarkers, including low insulin-like growth factor-1 (IGF-1), hemoglobin A1c (HbA1c), and high-sensitive C-reactive protein (hsCRP) that caused a moderate but significant improvement in the prediction of cardiovascular deaths and correctly reclassified 11% of the population at risk

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Summary

Introduction

Attempts have been made to improve the prediction of cardiovascular risk by adding multiple novel biomarkers to the classic risk factors. These biomarkers have included markers of inflammation, kidney function, cardiac damage, endothelial function, metabolism, and oxidative stress, among others [6,7,8,9,10,11]. These novel markers’ abilities to improve prediction were mostly disappointing. We aimed to determine if the addition of endocrine, metabolic, and obesity-associated biomarkers to conventional risk factors improves the prediction of cardiovascular and allcause mortality

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