J Gram1, E M Bladbjerg, L Møller, A Sjøl, J Jespersen. 1. Department of Clinical Biochemistry, Ribe County Hospital, South Jutland University Centre, Esbjerg, Denmark. JGR@ribeamt.DK
Abstract
OBJECTIVES: To study the importance of inflammation and fibrinolysis for evolution of ischaemic heart disease in a cohort of initially healthy subjects. DESIGN: Nested case-control study. Follow-up periods 7-15 years. SUBJECTS: Included in the study were 133 cases with coronary heart disease and 258 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Subjects with ischaemic heart disease identified in 1991 by the Danish National Hospital Register. Protein concentration of C-reactive protein (CRP) and tissue-type plasminogen activator (t-PA) were measured with ELISA methods in stored serum samples. RESULTS: CRP and t-PA concentrations were both significantly higher in cases than in controls (P < 0.001 and P < 0. 001). This difference between cases and controls for CRP and t-PA was present in both men (CRP: P = 0.022; t-PA: P = 0.001) and women (CRP: P = 0.013; t-PA: P = 0.005) and it was present in both the 7-9 years follow-up cohort (CRP: P = 0.014; t-PA: P = 0.001) and the 15 years follow-up cohort (CRP: P = 0.027; t-PA: P = 0.012). The best predictor of CRP was t-PA, whilst the best predictor of t-PA was triglycerides. In a logistic regression analysis model, t-PA still came out as independent predictor of coronary heart disease, whilst such a significance disappeared for CRP. With the use of ROC curves we determined that AUC for t-PA was 0.62, and for CRP 0.59, indicating that none of these two analytes has a high prognostic power in predicting future coronary events in an initially healthy population. CONCLUSION: We conclude that moderate increases in serum concentrations of CRP and t-PA are present for up to 15 years before the presence of clinical overt coronary heart disease; that a low-grade inflammation is determined by other risk factors and that t-PA is an independent risk factor for evolution of coronary heart disease.
OBJECTIVES: To study the importance of inflammation and fibrinolysis for evolution of ischaemic heart disease in a cohort of initially healthy subjects. DESIGN: Nested case-control study. Follow-up periods 7-15 years. SUBJECTS: Included in the study were 133 cases with coronary heart disease and 258 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Subjects with ischaemic heart disease identified in 1991 by the Danish National Hospital Register. Protein concentration of C-reactive protein (CRP) and tissue-type plasminogen activator (t-PA) were measured with ELISA methods in stored serum samples. RESULTS:CRP and t-PA concentrations were both significantly higher in cases than in controls (P < 0.001 and P < 0. 001). This difference between cases and controls for CRP and t-PA was present in both men (CRP: P = 0.022; t-PA: P = 0.001) and women (CRP: P = 0.013; t-PA: P = 0.005) and it was present in both the 7-9 years follow-up cohort (CRP: P = 0.014; t-PA: P = 0.001) and the 15 years follow-up cohort (CRP: P = 0.027; t-PA: P = 0.012). The best predictor of CRP was t-PA, whilst the best predictor of t-PA was triglycerides. In a logistic regression analysis model, t-PA still came out as independent predictor of coronary heart disease, whilst such a significance disappeared for CRP. With the use of ROC curves we determined that AUC for t-PA was 0.62, and for CRP 0.59, indicating that none of these two analytes has a high prognostic power in predicting future coronary events in an initially healthy population. CONCLUSION: We conclude that moderate increases in serum concentrations of CRP and t-PA are present for up to 15 years before the presence of clinical overt coronary heart disease; that a low-grade inflammation is determined by other risk factors and that t-PA is an independent risk factor for evolution of coronary heart disease.
Authors: J Danesh; S Erqou; M Walker; S G Thompson; R Tipping; C Ford; S Pressel; G Walldius; I Jungner; A R Folsom; L E Chambless; M Knuiman; P H Whincup; S G Wannamethee; R W Morris; J Willeit; S Kiechl; P Santer; A Mayr; N Wald; S Ebrahim; D A Lawlor; J W G Yarnell; J Gallacher; E Casiglia; V Tikhonoff; P J Nietert; S E Sutherland; D L Bachman; J E Keil; M Cushman; B M Psaty; R P Tracy; A Tybjaerg-Hansen; B G Nordestgaard; R Frikke-Schmidt; S Giampaoli; L Palmieri; S Panico; D Vanuzzo; L Pilotto; L Simons; J McCallum; Y Friedlander; F G R Fowkes; A J Lee; F B Smith; J Taylor; J Guralnik; C Phillips; R Wallace; D Blazer; K T Khaw; J H Jansson; C Donfrancesco; V Salomaa; K Harald; P Jousilahti; E Vartiainen; M Woodward; R B D'Agostino; P A Wolf; R S Vasan; M J Pencina; E M Bladbjerg; T Jorgensen; L Moller; J Jespersen; R Dankner; A Chetrit; F Lubin; A Rosengren; L Wilhelmsen; G Lappas; H Eriksson; C Bjorkelund; P Cremer; D Nagel; R Tilvis; T Strandberg; B Rodriguez; L M Bouter; R J Heine; J M Dekker; G Nijpels; C D A Stehouwer; E Rimm; J Pai; S Sato; H Iso; A Kitamura; H Noda; U Goldbourt; V Salomaa; J T Salonen; K Nyyssönen; T-P Tuomainen; D Deeg; J L Poppelaars; T Meade; J Cooper; B Hedblad; G Berglund; G Engstrom; A Döring; W Koenig; C Meisinger; W Mraz; L Kuller; R Selmer; A Tverdal; W Nystad; R Gillum; M Mussolino; S Hankinson; J Manson; B De Stavola; C Knottenbelt; J A Cooper; K A Bauer; R D Rosenberg; S Sato; Y Naito; I Holme; H Nakagawa; H Miura; P Ducimetiere; X Jouven; C Crespo; M Garcia-Palmieri; P Amouyel; D Arveiler; A Evans; J Ferrieres; H Schulte; G Assmann; J Shepherd; C Packard; N Sattar; B Cantin; B Lamarche; J-P Després; G R Dagenais; E Barrett-Connor; D Wingard; R Bettencourt; V Gudnason; T Aspelund; G Sigurdsson; B Thorsson; M Trevisan; J Witteman; I Kardys; M Breteler; A Hofman; H Tunstall-Pedoe; R Tavendale; G D O Lowe; Y Ben-Shlomo; B V Howard; Y Zhang; L Best; J Umans; A Onat; T W Meade; I Njolstad; E Mathiesen; M L Lochen; T Wilsgaard; J M Gaziano; M Stampfer; P Ridker; H Ulmer; G Diem; H Concin; F Rodeghiero; A Tosetto; E Brunner; M Shipley; J Buring; S M Cobbe; I Ford; M Robertson; Y He; A M Ibanez; E J M Feskens; D Kromhout; R Collins; E Di Angelantonio; S Kaptoge; S Lewington; L Orfei; L Pennells; P Perry; K Ray; N Sarwar; M Scherman; A Thompson; S Watson; F Wensley; I R White; A M Wood Journal: Eur J Epidemiol Date: 2007-09-18 Impact factor: 8.082
Authors: Peter Willeit; Alexander Thompson; Thor Aspelund; Ann Rumley; Gudny Eiriksdottir; Gordon Lowe; Vilmundur Gudnason; Emanuele Di Angelantonio Journal: PLoS One Date: 2013-02-07 Impact factor: 3.240