A woman who had a stroke, then a myocardial infarction
Authors: Chris Ciesielski-Carlucci, Bryon K Lee, Linda M Boxer, Lawrence LK Leung
Journal: The Lancet (1997)

A 36-year-old woman had a right-sided hemiparesis due to a stroke in 1994. Carotid ultrasound showed a thrombus in her left internal carotid artery. An echocardiogram was normal. Her erythrocyte sedimentation rate, anticardiolipin antibody, proteins C and S, antithrombin III, and random serum homocysteine concentration were also normal. She had had two normal pregnancies and no spontaneous abortions. She had had an injection of depoprovera 3 months before admission. She smoked 40 cigarettes per day and denied intravenous drug use. She had no family history of hypercoagulability, early cardiovascular disease, or of elevated lipoproteins or homocysteine. Cocaine was found on a toxicology screen and was thought to have been the cause of her stroke. She was anticoagulated with coumadin until March, 1996. In November, 1996, she had an acute myocardial infarction. She was taken immediately to the catheterisation laboratory and found to have a large thrombus in her left anterior descending coronary artery extending into her left main coronary artery; other vessels appeared disease free. After unsuccessful attempts at angioplasty, she had ventricular fibrillation and cardiac arrest. She was cardioverted into sinus rhythm and had an emergency coronary artery bypass graft. During her hospital admission she had these laboratory results cholesterol 6·6 mmol/L, prothrombin time 11·8 s, international normalised ratio 1·1, partial thromboplastin time 29 s, and a creatinekinase peak of 8777 U/L with an MB fraction of 11%. Postoperative echocardiogram showed an apical thrombus and severe left ventricular dysfunction. She denied any use of cocaine after her stroke and had a negative toxicology screen on admission Investigation for a hypercoagulable state showed negative factor V Leiden, a lipoprotein(a) concentration of 66·9 mg/dL, and a homocysteine concentration 4 h after methionine challenge of 61 μmol/L. She was diagnosed as having hyperhomocysteinaemia and elevated lipoprotein(a) and discharged on digoxin, aspirin, coumadin, captopril, niacin, pyridoxine, and folic acid. When last seen in March, 1997, she was doing fine. This patient had two major arterial thrombotic events. The cause is presumed to be her elevated lipoprotein(a) and heterozygosity for hyperhomocysteinaemia since both abnormalities are independent risk factors for accelerated cardiovascular disease.1Bostom A Cupples A Jenner J et al.Elevated plasma lipoprotein (a) and coronary heart disease in men aged 55 years and younger.JAMA. 1996; 276: 544-548Crossref PubMed Google Scholar, 2Clarke R Daly L Robinson K et al.Hyperhomocysteinemia: an independent risk factor for vascular disease.N Engl J Med. 1991; 324: 1149-1155Crossref PubMed Scopus (2047) Google Scholar The combined prevalence of these two disorders is conservatively estimated to be less than 0·5% in women of this age group. Lipoprotein(a) is homologous with plasminogen and may compete for binding sites on fibrin clots, inhibiting fibrinolysis.3Palabrica T Liu A Aronovitz M Furie B Lawn R Furie B Antifibrinolytic activity of apolipoprotein (a) in vivo: human apolipoprotein (a) transgenic mice are resistant to tissue plasminogen activator-mediated thrombolysis.Nat Med. 1995; 1: 256-259Crossref PubMed Scopus (133) Google Scholar Homocysteine is a reactive aminoacid and may damage endothelium by oxidation of lipoproteins and generation of free radicals.4McCully K Homocysteine and vascular disease.Nat Med. 1996; 2: 386-389Crossref PubMed Scopus (693) Google Scholar There is in-vitro evidence suggesting that these abnormalities are synergistic in enhancing atherogenesis and thrombogenesis because homocysteine augments the affinity of lipoprotein(a) for fibrin.5Harpel P Chang V Borth W Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein (a) to fibrin: a potential biochemical link between thrombosis, atherogenesis, and sulfhydryl compound metabolism.Proc Natl Acad Sci USA. 1992; 89: 10193-10197Crossref PubMed Scopus (267) Google Scholar This case is a possible in-vivo example of the combination of raised lipoprotein(a) and hyperhomocysteinaemia leading to serious cardiovascular and cerebrovascular morbidity. Niacin has been shown to lower lipoprotein(a), and pyridoxine and folic acid have been shown to lower homocysteine. It is not known whether lowering serum concentrations reduces the risk of disease. The availability of transgenic and knock-out mice for lipoprotein(a) and hyperhomocysteinemia offers an opportunity to study the interaction of these two risk factors. DEPARTMENT OF ERRORA woman who had a stroke, then a myocardial infarction−In this Case Report by Ciesielski-Carlucci and colleagues (April 26, p 1218) the second author's name should read Byron K Lee. Full-Text PDF