Multi-modality biomarkers in the early prediction of ischaemic heart disease in middle-aged men during a 21-year follow-up

BMC Cardiovasc Disord. 2021 Feb 2;21(1):65. doi: 10.1186/s12872-021-01886-x.


Background: Ischaemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. Biomarkers are useful prognostic predictors of IHD, but their long-term predictive value in a general population has not been adequately studied.

Purpose: To investigate the early predictive value of multi-modality biomarkers in addition to clinical risk factors in incident IHD in a random male general population sample followed from 50 to 71 years of age.

Method: "The Study of Men Born in 1943" is a longitudinal cohort study during follow-up. All the men underwent a baseline examination in 1993, where a panel of biomarkers were analysed and incident IHD was registered during 21-year follow-ups.

Results: Of 739 participants, 97 men (13.1%) developed an IHD event. For time to first occurrence of IHD, univariable analyses showed that elevated levels of high sensitivity troponin T (hs-TNT), high sensitivity-C reactive protein (hs-CRP) and interleukin-6 (IL-6) were significant predictors of IHD. In addition, a high number of biomarkers with elevated levels (hs-TNT > 10 ng/L, hs-CRP > 1 mg/L, IL-6 > 8 ng/L and N-terminal pro b-type natriuretic peptide (NT-proBNP) > 100 pg/mL) increased predictive ability. In univariable and multivariable analysis high-density lipoprotein-cholesterol (HDL-C) had the highest predictive ability. Hs-TNT provided better predictive ability than smoking, body mass index and glucose, and was an independent significant predictor when adjusted for HDL-C, total cholesterol and hypertension. Addition of biomarkers on top of clinical risk factors provided significantly better prediction as tested by likelihood ratio test (p = 0.033), but did not significantly enhance the model's discriminative ability However, it appeared contributing to higher sensitivity in the late phase of follow-up.

Conclusion: In this random, middle-aged male population sample, the addition of biomarker hs-TNT was an independent significant predictor of IHD and significantly improved prediction, indicating the probability of a better prediction of long-term risk of IHD in a low-risk population.

Trial registration: The study is registered at Clinical Identifier number: NCT03138122.

Keywords: Ischaemic heart disease; Prevention; Risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cholesterol, HDL / blood*
  • Early Diagnosis
  • Follow-Up Studies
  • Humans
  • Incidence
  • Interleukin-6 / blood
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood*
  • Myocardial Ischemia / diagnosis
  • Myocardial Ischemia / epidemiology
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Sweden / epidemiology
  • Time Factors
  • Troponin T / blood*


  • Biomarkers
  • Cholesterol, HDL
  • IL6 protein, human
  • Interleukin-6
  • Peptide Fragments
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • C-Reactive Protein

Associated data