Multi-modality biomarkers in the early prediction of ischaemic heart disease in middle-aged men during a 21-year follow-up.
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
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
Ischaemic heart disease
Prevention
Risk factors
Journal
BMC cardiovascular disorders
ISSN: 1471-2261
Titre abrégé: BMC Cardiovasc Disord
Pays: England
ID NLM: 100968539
Informations de publication
Date de publication:
02 02 2021
02 02 2021
Historique:
received:
10
10
2020
accepted:
21
01
2021
entrez:
3
2
2021
pubmed:
4
2
2021
medline:
16
6
2021
Statut:
epublish
Résumé
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. 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. "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. 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. 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. The study is registered at Clinical Trials.gov Identifier number: NCT03138122.
Sections du résumé
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 Trials.gov Identifier number: NCT03138122.
Identifiants
pubmed: 33530933
doi: 10.1186/s12872-021-01886-x
pii: 10.1186/s12872-021-01886-x
pmc: PMC7851898
doi:
Substances chimiques
Biomarkers
0
Cholesterol, HDL
0
IL6 protein, human
0
Interleukin-6
0
Peptide Fragments
0
Troponin T
0
pro-brain natriuretic peptide (1-76)
0
Natriuretic Peptide, Brain
114471-18-0
C-Reactive Protein
9007-41-4
Banques de données
ClinicalTrials.gov
['NCT03138122']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
65Commentaires et corrections
Type : ErratumIn
Références
Rafieian-Kopaei M, Setorki M, Doudi M, Baradaran A, Nasri H. Atherosclerosis: process, indicators, risk factors and new hopes. Int J Prev Med. 2014;5(8):927–46.
pubmed: 25489440
pmcid: 25489440
Kaptoge S, Seshasai SR, Gao P, Freitag DF, Butterworth AS, Borglykke A, et al. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J. 2014;35(9):578–89.
doi: 10.1093/eurheartj/eht367
Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med. 2011;17(11):1410–22.
doi: 10.1038/nm.2538
Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2010;56(25):e50-103.
doi: 10.1016/j.jacc.2010.09.001
de Lemos JA, Morrow DA, Bentley JH, Omland T, Sabatine MS, McCabe CH, et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med. 2001;345(14):1014–21.
doi: 10.1056/NEJMoa011053
Chrysohoou C, Georgiopoulos G, Kosyfa H, Kotsopoulou Haritou I, Kouvari M, Filippou A, et al. Brain Natriuretic Peptide mediates the prognostic role of renal function toward 10-year cardiovascular mortality in patients with Acute Coronary Syndrome: the HHF study (2006–2016). Hellenic J Cardiol. 2018;59(2):110–8.
doi: 10.1016/j.hjc.2017.07.001
Tapanainen JM, Lindgren KS, Makikallio TH, Vuolteenaho O, Leppaluoto J, Huikuri HV. Natriuretic peptides as predictors of non-sudden and sudden cardiac death after acute myocardial infarction in the beta-blocking era. J Am Coll Cardiol. 2004;43(5):757–63.
doi: 10.1016/j.jacc.2003.09.048
Jorgensen PG, Jensen JS, Appleyard M, Jensen GB, Mogelvang R. Plasma pro-brain natriuretic peptide and electrocardiographic changes in combination improve risk prediction in persons without known heart disease. Int J Cardiol. 2015;201:104–9.
doi: 10.1016/j.ijcard.2015.07.100
Daniels LB, Laughlin GA, Clopton P, Maisel AS, Barrett-Connor E. Minimally elevated cardiac troponin T and elevated N-terminal pro-B-type natriuretic peptide predict mortality in older adults: results from the Rancho Bernardo Study. J Am Coll Cardiol. 2008;52(6):450–9.
doi: 10.1016/j.jacc.2008.04.033
Kim HC, Greenland P, Rossouw JE, Manson JE, Cochrane BB, Lasser NL, et al. Multimarker prediction of coronary heart disease risk: the Women’s Health Initiative. J Am Coll Cardiol. 2010;55(19):2080–91.
doi: 10.1016/j.jacc.2009.12.047
Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006;355(25):2631–9.
doi: 10.1056/NEJMoa055373
Zethelius B, Berglund L, Sundstrom J, Ingelsson E, Basu S, Larsson A, et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med. 2008;358(20):2107–16.
doi: 10.1056/NEJMoa0707064
Saltin B, Grimby G. Physiological analysis of middle-aged and old former athletes. Comparison with still active athletes of the same ages. Circulation. 1968;38(6):1104–15.
Framingham Heart Study. The Framingham Risk Score. https://framinghamheartstudy.org/fhs-risk-functions/hard-coronary-heart-disease-10-year-risk/ . Accessed 3 Jan 2021.
D’Agostino RB Sr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743–53.
doi: 10.1161/CIRCULATIONAHA.107.699579
Conroy RM, Pyorala K, Fitzgerald AP, Sans S, Menotti A, De Backer G, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24(11):987–1003.
doi: 10.1016/S0195-668X(03)00114-3
Hippisley-Cox J, Coupland C, Robson J, Brindle P. Derivation, validation, and evaluation of a new QRISK model to estimate lifetime risk of cardiovascular disease: cohort study using QResearch database. BMJ. 2010;341:c6624.
doi: 10.1136/bmj.c6624
Zhong Y, Rosengren A, Fu M, Welin L, Welin C, Caidahl K, et al. Secular changes in cardiovascular risk factors in Swedish 50-year-old men over a 50-year period: The study of men born in 1913, 1923, 1933, 1943, 1953 and 1963. Eur J Prev Cardiol. 2017;24(6):612–20.
de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010;304(22):2503–12.
doi: 10.1001/jama.2010.1768
Parikh RH, Seliger SL, de Lemos J, Nambi V, Christenson R, Ayers C, et al. Prognostic significance of high-sensitivity cardiac troponin T concentrations between the limit of blank and limit of detection in community-dwelling adults: a metaanalysis. Clin Chem. 2015;61(12):1524–31.
doi: 10.1373/clinchem.2015.244160
Cesari M, Penninx BW, Newman AB, Kritchevsky SB, Nicklas BJ, Sutton-Tyrrell K, et al. Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation. 2003;108(19):2317–22.
doi: 10.1161/01.CIR.0000097109.90783.FC
Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation. 2003;107(3):391–7.
doi: 10.1161/01.CIR.0000055014.62083.05
Yamashita H, Shimada K, Seki E, Mokuno H, Daida H. Concentrations of interleukins, interferon, and C-reactive protein in stable and unstable angina pectoris. Am J Cardiol. 2003;91(2):133–6.
doi: 10.1016/S0002-9149(02)03097-7
Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004;350(14):1387–97.
doi: 10.1056/NEJMoa032804
Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375(9709):132–40.
doi: 10.1016/S0140-6736(09)61717-7