Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity, and resistance to activated protein C.
Our specific aim was to examine the interface between risk factors for atherosclerosis, thrombosis, and hypofibrinolysis in a previously healthy 35-year-old male who had sustained a recent myocardial infarction. By angiography, the right, left main, and left anterior descending coronary arteries were smooth-walled, widely patent, and free of significant obstruction; the circumflex exhibited total, probably thrombotic occlusion of the distal large second marginal branch. The patient was found to have prothrombotic high homocysteine (46.4 mumol/L), prothrombotic resistance to activated protein C (ratio, 1.47), and hypofibrinolytic high plasminogen activator inhibitor (PAI-Fx) activity (54 U/mL). He was homozygous for the 677C-->T; A-->V mutation in the methylenetetrahydrofolate reductase (MTHFR) gene causing homocysteinemia, heterozygous for the mutant factor V Leiden gene causing resistance to activated protein C, and heterozygous for the 4G/5G polymorphism in the PAI-1 promoter gene causing high PAI-Fx. Other major risk factors for coronary artery disease included previously undiagnosed adult-onset diabetes, high triglycerides (291 mg/dL), and low high-density lipoprotein (HDL) cholesterol (26 mg/dL). The patient's prothrombotic status (homocysteinemia and resistance to activated protein C) and hypofibrinolysis (high PAI-Fx) apparently facilitated occlusive coronary artery thrombus formation and retention. Prothrombotic factors and hypofibrinolysis appear to play important pathogenetic roles in premature myocardial infarction. In patients with severe premature coronary artery disease, we suggest that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention. Moreover, in patients with heritable prothrombotic factors or hypofibrinolysis, it should be important to optimize lipid and lipoprotein cholesterol levels with the goal of stabilizing coronary plaques to reduce the likelihood of plaque rupture and thrombosis.
Glueck
C J
CJ
Cholesterol Center, Jewish Hospital, Cincinnati, OH 45229, USA.
Fontaine
R N
RN
Gupta
A
A
Alasmi
M
M
D000328:Adult; D001161:Arteriosclerosis / Q000453:epidemiology / Q000503:physiopathology; D008076:Cholesterol, HDL / Q000097:blood; D005165:Factor V / Q000235:genetics; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D009154:Mutation; D009203:Myocardial Infarction / Q000097:blood* / Q000503:physiopathology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D015849:Plasminogen Inactivators / Q000097:blood*; D011486:Protein C / Q000502:physiology*; D012307:Risk Factors; D013927:Thrombosis / Q000453:epidemiology / Q000503:physiopathology; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D017395:Plasminogen Activator Inhibitor 1; D015849:Plasminogen Inactivators; D011486:Protein C; D014280:Triglycerides; C095381:factor V Leiden; D006710:Homocysteine; D005165:Factor V