chest pain to a single coronary care unit were studied. .... CCU=coronary care unit; Lp(a) = lipoprotein(a); accelerated angina = increasing angina in the 48 h ...
European Heart Journal (1997) 18, 603-607
A prospective study of the role of lipoprotein(a) in the pathogenesis of unstable angina P. Stubbs, M. Seed, D. Moseley*, B. O'Connor, P. Collinsonf and M. Noble$ Charing Cross and Westminster Medical School, London; * West Middlesex University Hospital, London; tMayday University Hospital, London, U.K.
Aim Lipoprotein(a) is considered to be a risk factor for atherothrombotic diseases. The aim of the study was to examine the potential role of lipoprotein(a) concentrations in patients admitted with unstable angina with particular reference to their cardiac Troponin T concentrations, which identifies a subgroup at high risk of subsequent cardiac events.
Introduction High concentrations of lipoprotein(a) may be a risk factor for arteriosclerotic diseases1'"31. This lipoprotein contains apolipoprotein B-100 (the apolipoprotein of low density lipoprotein) and a large heterogenous hydrophilic glycoprotein named apolipoprotein(a)'4'51, bound together by a disulphide linkage'6'. The gene for apolipoprotein(a) has close structural homology with that of plasminogen'71. In vitro and animal studies have suggested that this close homology can cause competitive inhibition of the fibrinolytic properties of plasminogen18""1 by lipoprotein(a), leading to a more prothrombotic state and an increased risk of arteriosclerotic disease. There have been a number of clinical case controlled and epidemiological studies in man examining the role of lipoprotein(a) as a risk factor for myocardial infarction. Whilst the majority of studies have shown a Revision submitted 11 June 1996, and accepted 12 June 1996. JGarfield Weston Professor of Cardiovascular Medicine. Correspondence: Dr Peter John Stubbs, Academic Unit of Cardiovascular Medicine, Charing Cross and Westminster Medical School, Fifth Floor South Wing, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, U.K. 0195-668X/97/040603 + 05 $18.00/0
Conclusion This study provides the first evidence in man of a significant role for lipoprotein(a) in unstable angina. The correlation between lipoprotein(a) concentration and cardiac Troponin T concentration suggests that lipoprotein(a) may be significantly involved in the early failure of plaque rupture stabilization. (Eur Heart J 1997; 18: 603-^07)
Key Words: Lipoprotein(a), unstable angina, biochemical markers, Troponin T, pathogenesis.
significant correlation between lipoprotein(a) and myocardial infarction'12"16', the findings have not been universal[17-181 and so there is no absolute consensus as to its importance as an independent risk factor for myocardial infarction. The role of lipoprotein(a) in patients admitted with the other major acute coronary syndrome, unstable angina pectoris, has been relatively underestimated by comparison'19'201. This syndrome represents a critical phase of ischaemic heart disease and is associated with a significant risk of subsequent myocardial infarction or death'21"271. At a pathophysiological level, plaque rupture commonly occurs but does not inevitably progress to myocardial infarction. The outcome depends upon the severity of the plaque rupture and the ability of the homeostatic thrombotic, fibrinolytic and repair mechanisms to stabilize and heal the plaque'281. Identification of patients at risk of an adverse prognosis remains a continuing clinical problem'291. It has recently been demonstrated that approximately one third of patients admitted with unstable angina have raised levels of the cardiac-specific protein Troponin T in their serum in the early admission period'30"331. This protein is a 37-kDa polypeptide subunit of the myofibrillar regulatory troponin complex'341. It is mainly intracellular in its structurally bound form, is not present in the serum of the 1997 The European Society of Cardiology
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Methods and results Consecutive patients admitted with chest pain to a single coronary care unit were studied. One hundred and sixty-seven patients had a final diagnosis of unstable angina, of whom 56 were cardiac Troponin T-positive. Admission lipoprotein(a) concentrations were significantly higher in the cardiac Troponin T-positive unstable angina group as compared to the cardiac Troponin T-negative unstable angina group: median and
interquartile ranges 22-25 mg. d l " ' (625, 320) vs 60mg . dl" ' (2-22, 14-8) respectively) P=00004. A highly significant correlation was also found between the level of cardiac Troponin T at diagnosis and the lipoprotein(a) concentration: rs=0-2798, P= 0-0001.
604 P. Stubbs et al. normal population and is highly cardiac specific'35"371. An enzyme-linked immunosorbent assay (ELISA) specific for cardiac Troponin T has recently been developed1381. The presence of this marker in patients with unstable angina appears to identify a very high risk subgroup that have an excess of cardiac events (nonfatal myocardial infarction or cardiac death) both as inpatients[3O~331 and on short-term follow-up'39^"1. This study aimed to examine the atherothrombotic role of lipoprotein(a) in unstable angina by comparing lipoprotein(a) concentrations in the high and low unstable angina risk groups identified according to the Troponin T status.
Methods
Eur Heart J, Vol. 18, April 1997
Analytical methods Biochemical markers of myocyte damage The Troponin T immunoassay is based on a single-step sandwich principle, with streptavidin-coated tubes as the solid phase and two monoclonal anti-human cardiac Troponin T antibodies. Troponin T is bound on different epitopes by the capture and signal antibodies. The capture antibody is biotinylated, binds completely and reproducibly to the streptavidin-coated tube, and is 99% specific for cardiac troponin'301. Samples for Troponin T estimation were measured using the ES-300 Immunoassay analyzer (Boehringer Mannheim, Lewes, Sussex, U.K.). The within-run coefficient of variation was 12-3%, 7-7% and 4-2% at mean Troponin T levels of 0-13 ng . m l " ' , 1-6 ng . ml" ' and 71 ng . ml" ', respectively. The between-run coefficient of variation was 20% and 1-9% at mean Troponin T values of 1-7 ng . m l " ' and 70 ng . ml" ' respectively. Aspartate transaminase and HBD were measured at 37 °C on a Perspective analyser (American Monitor, Burgess Hill, West Sussex, U.K.) following the manufacturer's recommended methods. The manufacturer's reagents were used for AST and commercially supplied reagents used for HBD (Merckotest HBDH, BDH Diagnostics, Poole, Dorset). Total creatine kinase was measured at 30 °C using commercially supplied reagents (CK NAC opt., BCL, Lewes, Sussex, U.K.). All determinations were made using an RA 1000 analyser (Bayer Technicon, Basingstoke, U.K.).
Lipid variables Admission lipoprotein(a) concentrations were determined by an enzyme-linked immunosorbent assay using sheep polyclonal monospecific antibodies against purified human lipoprotein(a) (Biopool AB, Umea, Sweden). The standard calibration curve was linear in the range 0-60 mg . dl ~'. If serum samples were of higher concentration, separate aliquots were diluted with sample buffer and analysed. The within-run coefficient of variation was 3-2%, and the between-run coefficient of variation was 6%. The reference median lipoprotein(a) concentration for the laboratory was 7-9 mg . d l " ' . All samples were batch assayed in duplicate with the mean value reported, by a single experienced operator. Admission cholesterol concentrations (reference interval 3-5—6-5 mmol. 1"') were measured using a cholesterol oxidase method and a Technicon Axon (Bayer Technicon, Basingstoke Hampshire, U.K.). The manufacturer's recommended method was followed (withinrun coefficient of variation 2-2%, between-run coefficient of variation 5%). Admission triglyceride concentrations (reference interval 0-9-2-0 mmol. 1~ ') were measured
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This was a single centre study of patients admitted with chest pain to a hospital coronary care unit. The hospital's routine cardiac enzyme protocol was used and patients underwent daily sampling for 3 days. Daily creatine kinase (reference interval
