CLINICAL STUDIES
Lipoprotein(a) is a risk factor for occurrence of acute myocardial infarction in patients with coronary vasospasm
Kunihisa Miwa, MDa,
Keiko Nakagawa, MDa,
Naohiro Yoshida, MDa,
Yoshiharu Taguchi, MDa and
Hiroshi Inoue, MD, FACCa
a The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Manuscript received October 21, 1998;
revised manuscript received November 9, 1999,
accepted December 29, 1999.
Reprint requests and correspondence: Dr. Kunihisa Miwa, The Second Department of Internal Medicine, Kansai Electric Power Hospital, 2-1-7 Fukushima, Fukushima-ku, Osaka 553-0003, Japan
k-21568{at}kepco.co.jp
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Abstract
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OBJECTIVES
The purpose of this study is to determine whether lipoprotein(a) (Lp[a]) is an independent risk factor for coronary spasm and occurrence of acute myocardial infarction (AMI) in patients with coronary spasm.
BACKGROUND
Although elevated serum Lp(a) levels are known to be associated with coronary atherosclerosis and AMI, the association between the elevated level of this lipoprotein and coronary spasm remains to be elucidated.
METHODS
Serum Lp(a) levels were measured using a latex immunoassay in 77 patients with coronary spasm but without a significant (>75%) fixed coronary stenosis, including 16 with prior myocardial infarction (MI), in 177 patients with a fixed stenosis but without rest angina, including 114 with prior MI and in 81 control subjects without coronary artery disease.
RESULTS
The serum Lp(a) level in patients with coronary spasm (median; 17 mg/dl) was higher (p < 0.01) than in control subjects (12 mg/dl) but lower (p < 0.01) than in patients with a fixed stenosis (23 mg/dl). The incidence of subjects with higher (>25 mg/dl) serum Lp(a) levels was higher in patients with a fixed stenosis (46%, p < 0.01) but not in patients with coronary spasm (27%), compared with control subjects (21%). Among the patients with coronary spasm, the incidence of higher Lp(a) levels was higher in patients with than in those without a history of prior MI (56% vs. 21%, p < 0.05). The patients with higher Lp(a) levels had a higher incidence of prior MI than those without (41% vs. 13%, p < 0.05). The multivariate analysis confirmed that higher serum Lp(a) level is an independent determinant for prior MI in these patients (odds ratio, 4.19; 95%, confidence interval, 1.03 to 17.00).
CONCLUSIONS
Elevated serum level of Lp(a) was found to be associated with a history of prior MI in patients with coronary spasm, suggesting that Lp(a) may play an important role in the genesis of thrombotic coronary occlusion and the occurrence of AMI subsequent to coronary spasm.
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Abbreviations and Acronyms
| | AMI | = acute myocardial infarction | | apo(a) | = apolipoprotein(a) | | HDL | = high-density lipoprotein | | LDL | = low-density lipoprotein | | Lp(a) | = lipoprotein(a) | | MI | = myocardial infarction | | PAI | = plasminogen activator inhibitor | | t-PA | = tissue-type plasminogen activator |
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Coronary artery spasm plays an important role in the entire spectrum of acute ischemic events, although the exact pathophysiologic mechanisms by which coronary artery spasm is triggered remain to be elucidated (1,2). Coronary spasm can be the primary event in the pathophysiology of acute myocardial infarction (AMI) (3,4). Thrombin activation and fibrin formation have been shown to be induced by coronary spasm (5,6). Also, impaired fibrinolytic activity, which is lowest in the early morning, was reported in patients with variant angina (7). These reports suggest that coronary spasm may trigger thrombus formation in coronary arteries and that the reduction of fibrinolytic activity may slow the removal of thrombus, ultimately leading to AMI in some patients. However, differences in the prevalence of risk factors or predisposing conditions between subjects with coronary spasm who develop and those who do not develop AMI are unknown, whereas both a high incidence of current smoking and a lower level of serum high-density lipoprotein (HDL) cholesterol without an elevation of low-density lipoprotein (LDL) cholesterol level have been identified in patients with coronary vasospasm (8–13).
Intracoronary thrombus formation has been thought to play an important role in the genesis of AMI (14). A number of recent studies have shown that increased plasma concentrations of lipoprotein(a) (Lp[a]) are associated with coronary atherosclerosis and also the evolution of AMI (15–17). This lipoprotein has been suggested to be an independent risk factor for the development of cardiovascular and cerebrovascular diseases (17,18). Lipoprotein(a) consists of an LDL bound by a disulfide bond to apolipoprotein(a) (apo[a]). Apolipoprotein(a) is a hydrophilic glycoprotein of the plasminogen family. It acts as a competitive inhibitor of the tissue-type plasminogen activator (t-PA) and inhibits the generation of thrombolytic enzyme plasmin because of its structural similarity to plasminogen (19). These unique features give Lp(a) potential atherogenic and thrombogenic roles, and they have generated considerable interest in this lipoprotein. However, the possible significance of Lp(a) in patients with coronary vasospasm has not been clarified.
The purpose of this study is to determine whether the elevation of serum Lp(a) levels is a risk factor for coronary spasm and also whether it is a risk factor for the development of AMI in patients with coronary spasm.
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Methods
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Study patients.
Seventy-seven consecutive patients (65 men and 12 women: mean age 57 ± 11 years; range, 15 to 74 years) with coronary spastic angina but without significant (>75% of luminal diameter) organic coronary arterial stenosis (Spasm group), in whom electrocardiographic ST-segment shift was confirmed during attacks occurring spontaneously, were studied for the determination of serum level of Lp(a). In all the patients, coronary artery spasm was angiographically demonstrated in at least one of the major coronary arteries during spontaneous or induced attacks by intracoronary injection of acetylcholine (20–22). Another 177 patients (142 men and 35 women: mean age, 61 ± 9 years; range, 36 to 82 years) with a significant organic narrowing of either coronary artery documented by coronary angiographic study, who had abnormal treadmill exercise stress test results but no rest angina (Stenosis group), were also subjected to the study. Coronary artery stenosis was quantitated with a computer-assisted analysis system. For the control group, 81 age- and sex-matched subjects (65 men and 16 women: mean age, 57 ± 12 years; range, 26 to 73 years) without any significant systemic disease, who had normal treadmill exercise stress test results with the standard Bruce protocol (Control group), were selected. No patient was receiving estrogen therapy. Clinical and angiographic characteristics of the study groups are listed in Table 1. A history of previous myocardial infarction (MI) had been diagnosed based on typical chest pain lasting for more than 30 min with ST-T segment deviation on a standard 12-lead electrocardiogram and an increase in creatine kinase to at least twice the normal upper limit. Written informed consent was obtained from all the study patients, and the study protocol followed the guidelines of the ethics committee at our institution.
Serum analysis.
Venous samples were obtained in the fasting state when the subjects were free of any acute illness. Samples were not obtained within four weeks of the onset of AMI (23). The total cholesterol level was measured directly in the serum, and HDL cholesterol was measured after precipitation of very-low-density lipoprotein cholesterol and LDL cholesterol with dextran sulfate-magnesium chloride by an enzymatic method. The concentration of triglyceride in serum was determined by measuring glycerol after an enzymatic hydrolysis with lipase-esterase. The LDL-cholesterol concentration was calculated according to the following formula: LDL cholesterol = (total cholesterol) – (HDL cholesterol) – (triglyceride/5). Lipoprotein(a) was measured by the method of latex-enhanced turbidimetric immunoassay (24).
Assessment of coronary risk factors.
Smoking was considered to be present if the patient had smoked more than three cigarettes a day for at least one year. Diabetes mellitus was diagnosed either clinically or by a 75-g oral glucose tolerance test according to World Health Organization criteria (25). Hypertension was defined as a persistent resting blood pressure exceeding 140 mm Hg (systolic) or 90 mm Hg (diastolic). Body mass index was calculated as weight (kg)/height (cm)2.
Statistical analysis.
Baseline characteristics of the study patients were compared using the chi-square test. Lipoprotein(a) data were expressed as medians (interquartile or 25th to 75th percentile range) because of the known skewed distribution of these levels. Other data are presented as mean ± standard deviation. The Mann-Whitney U test was used for two-group comparison of Lp(a). An overall test for differences among the three groups was performed using the Kruskall-Wallis test. Comparisons of serum lipid levels and age among the three groups were performed with one-way analysis of variance followed by Scheffé’s test. To determine whether serum Lp(a) level is an independent risk factor for AMI in patients with coronary vasospasm, multivariate logistic regression analyses were performed using software (SPSS Professional Statistics 7.5 for Windows; SPSS Japan Inc.). The dependent variable was a history of previous MI. The results of the multivariate analysis are expressed as odds ratios for the comparison of risk between the 10% and 90% percentiles (with 95% confidence intervals). The level of significance was set as p < 0.05.
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Results
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Clinical variables in study patients.
The baseline characteristics, including conventional coronary risk factors and coronary arteriographic findings in study patients, are shown in Table 1. Smoking, hypertension and diabetes mellitus were all significantly more prevalent in the Spasm group than in the Control group. Both a history of previous MI and diabetes mellitus were significantly less prevalent in the Spasm group than in the Stenosis group, although no significant differences were found in the incidence of other conventional risk factors. No significant differences were noted in the incidence of hypercholesterolemia among the groups, although 22% of the Stenosis group were receiving lipid-lowering treatment.
Lp(a) levels in study patients.
Serum Lp(a) concentrations in the study patients are summarized in Table 2 and Figure 1. The serum Lp(a) level was significantly (p < 0.01) higher in the Stenosis group (median: 23 mg/dl) than in either the Control group (12 mg/dl) or the Spasm group (17 mg/dl). The incidence of patients with serum Lp(a) levels higher than 25 mg/dl was significantly (p < 0.01) greater in the Stenosis group (46%) than in either the Control group (21%) or the Spasm group (27%). As a whole, the serum Lp(a) level was significantly (p < 0.01) higher in the Spasm group than in the Control group. However, the incidence of higher (>25 mg/dl) serum Lp(a) level in the Spasm group was not significantly different from that in the Control group. In the 51 patients in the Spasm group with a fixed stenosis below 50%, both the serum Lp(a) level (16 mg/dl) and the incidence of higher serum Lp(a) level (25%) were not significantly different from those in the Control group.
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Figure 1 Box plots with the 10th, 25th, 50th, 75th and 90th percentiles. The serum Lp(a) level was significantly higher in the stenosis group than in the Control and Spasm groups. The level was also significantly higher in the Spasm group than in the Control group. Control = control subjects without coronary artery disease. Spasm = patients with coronary spasm but without a significant fixed coronary stenosis. Stenosis = patients with a significant fixed coronary stenosis but without rest angina; m = median.
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The comparative data of the incidence of various risk factors between the patients with, and those without, prior MI in the Spasm group are shown in Table 3. In the Spasm group, there were no significant differences in the incidence of smoking, hypertension, hypercholesterolemia, diabetes mellitus and obesity between the patients with, and those without, prior MI. However, the serum level of Lp(a) was significantly higher in those patients with than in those without prior MI (29 vs. 16 mg/dl, p < 0.05) (Figure 2). By contrast, the serum level of Lp(a) was comparable—not significantly different—between the patients with, and those without, prior MI in the Stenosis group (Figure 3). The incidence of prior MI was compared between the patients with, and those without, higher (>25 mg/dl) serum Lp(a) level. As shown in Table 4, the incidence of patients with higher levels of Lp(a) (>25 mg/dl) was significantly greater in the patients with, than in those without, prior MI in the Spasm group (56% vs. 21%, p < 0.05). However, this was not the case in the Stenosis group. When the incidence of prior MI was compared between the patients with higher (>25 mg/dl) and lower ( 25 mg/dl) levels of serum Lp(a) in each group, a significantly greater incidence of prior MI was noted in patients with higher, than in those with lower, serum Lp(a) level in the Spasm group (41% vs. 13%, p < 0.05), but not in the Stenosis group (Table 5).
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Table 3 Comparative Data of Risk Factors and Serum Lipid Profiles in Study Patients With Coronary Spasm With and Without Prior MI
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Figure 2 Box plots with the 10th, 25th, 50th, 75th and 90th percentiles. The serum Lp(a) level was significantly higher in patients with than in those without a history of previous myocardial infarction among the Spasm group. Spasm = patients with coronary spasm but without a significant fixed coronary stenosis. MI = previous myocardial infarction; m = median.
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Figure 3 Box plots with the 10th, 25th, 50th, 75th and 90th percentiles. The serum Lp(a) level was not significantly different between patients with and without a history of previous myocardial infarction among the Stenosis group. Stenosis = patients with a significant fixed coronary stenosis but without rest angina. MI = previous myocardial infarction; m = median.
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Table 4 Comparison of the Incidence of Patients With Higher (>25 mg/dl) Serum Level of Lipoprotein(a) in Study Patients With and Without a History of Prior MI
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Table 5 Comparison of the Incidence of a History of Previous MI in Patients With Higher (>25 mg/dl) and Lower Serum Level of Lipoprotein(a) in Study Patients
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Multivariate analysis.
Multiple logistic regression analysis, including age, gender, hypertension, smoking, body mass index, diabetes mellitus and lipid variables (total, LDL and HDL cholesterol, triglycerides and Lp[a]) was performed to define the presence of prior MI. When all patients in the Spasm group were included in this analysis, Lp(a) concentration >25 mg/dl was the only variable independently predictive for prior MI (odds ratio, 4.19; 95%, confidence interval, 1.03 to 17.00; p < 0.05).
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Discussion
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Relation between Lp(a) levels and prior MI in patients with coronary spasm.
It has been well documented that plasma levels of Lp(a) vary widely between individuals in a population while remaining remarkably constant throughout life in a given individual (19). Lipoprotein(a) has been shown to be an independent risk factor for atherosclerosis of coronary and cerebral arteries (17,18). In the present study, a significantly elevated serum Lp(a) level was confirmed in patients with a significant fixed coronary artery stenosis. Also, on the whole, the serum Lp(a) level of patients with coronary spasm, but without significant fixed stenosis, was significantly higher than that found in the control subjects. Most of our patients with vasospasm had a mild stenosis or irregularity in the coronary arteries. However, the incidence of subjects with higher serum Lp(a) levels (>25 mg/dl) was found to be not significantly different between the patients with coronary spasm and the control patients, suggesting that it is difficult to discriminate by serum Lp(a) levels between subjects with, and those without, coronary artery spasm. The incidence was significantly greater in the patients with a significant fixed coronary stenosis than in either the control subjects or the patients with coronary spasm. Thus, the relation of elevated serum Lp(a) levels to coronary spasm appears to be weak, if any. By contrast, the incidence of subjects with higher serum Lp(a) levels (>25 mg/dl) was found to be significantly different between the patients with, and those without, previous MI among patients with coronary spasm. Coronary spastic patients with prior MI had a significantly higher level of serum Lp(a) than those without prior MI. The incidence of no other convenient risk factors differed between patients with, and those without, prior MI. Also in patients with coronary vasospasm, a significantly higher incidence of prior MI was noted in the subgroup with, than in the subgroup without, serum levels of Lp(a) higher than 25 mg/dl. These results indicate that an elevated serum level of Lp(a) is a risk factor for the occurrence of acute MI in patients with coronary vasospasm. The multivariate analysis confirmed that serum Lp(a) level is an independent determinant for prior MI in patients with coronary spasm.
Possible mechanisms of AMI in patients with high Lp(a) levels.
It is now established that intracoronary thrombus formation is usually an essential event in the pathogenesis of AMI (14). Coronary artery spasm is known to play an important role in the occurrence of AMI in some patients (17,18). It is not known whether coronary spasm, in itself, can cause sufficiently severe and prolonged ischemia to precipitate AMI or whether coronary spasm may predispose to the formation of fibrin or platelet aggregates, which then leads to prolonged total coronary obstruction and subsequent AMI. It is reported that the coagulation system was activated after coronary spasm (5,26). However, turnover of thrombus depends not only on formation but also on lysis. Recently impaired fibrinolytic activity was demonstrated in patients with variant angina (6,7). Both plasma plasminogen activator inhibitor (PAI) activity and t-PA antigen concentrations were found to be significantly higher in patients with variant angina than in patients with stable effort angina or the control subjects (7). The main component of the fibrinolytic system is plasmin, which dissolves fibrin or thrombus and which is converted from plasminogen by t-PA. Fibrinolysis is initiated by the release of t-PA from the endothelium (27). Thus, t-PA promotes fibrinolysis, whereas its specific inhibitor, PAI, rapidly inhibits t-PA by complexing it. It has been postulated that high concentrations of Lp(a) may hinder fibrinolysis. In in vitro studies, Lp(a) has been shown to interfere with several steps in the fibrinolytic pathway, including the binding of plasminogen to endothelial cells and platelets, plasminogen activation on the endothelial surface and the lysis of platelet-rich thrombi, the binding of plasminogen and t-PA to fibrin and the binding of plasminogen to its activator (28–31). A similar interaction may occur in vivo. A significant relation of Lp(a) to infarct artery patency and also vein graft stenosis has been reported, suggesting an impaired fibrinolytic system in patients with higher Lp(a) levels (32,33). Thus, the structural similarity of Lp(a) and plasminogen may allow the former to compete with the latter for cellular receptors, fibrin and t-PA, thereby diminishing plasminogen activation, plasmin production and, ultimately, fibrinolysis. Even though, following coronary artery spasm, the coagulation system is activated and fibrinolytic system is inhibited, resulting in initiation of thrombus formation, the thrombotic coronary obstruction may not be completed if the spasm is of short duration and fibrinolytic activity is restored. By contrast, if the fibrinolytic activation is extremely impaired by high concentrations of Lp(a), thrombotic occlusion secondary to severe coronary spasm may be established and persist for long enough to cause AMI in some patients with coronary vasospasm. Then the occluded infarct-related artery may become patent in these patients, probably because of delayed fibrinolysis after resolved spasm.
An elevated Lp(a) level is associated with coronary artery disease in most but not all studies, which has caused investigators to disagree about its importance (34). High Lp(a) levels have been shown to promote events in subjects with other coronary risk factors (16,35). It is possible that the significant elevation of Lp(a) in patients with coronary vasospasm and prior MI might be acting synergistically with one or more other risk factors to produce the infarction.
By contrast to the patients with coronary spasm, no significant differences in serum Lp(a) levels were found between patients having a fixed coronary stenosis with prior MI and those without prior MI. The Lp(a) appears to play no significant role in the evolution of AMI or thrombotic occlusion following plaque rupture in the advanced stage of atherosclerotic coronary artery disease, even if this lipoprotein may be an important risk factor for the development or initiation of coronary atherosclerosis.
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Conclusions
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The incidence of elevated serum Lp(a) level was not significantly different between patients with coronary vasospasm and control subjects, suggesting that this lipoprotein may not play an important role in the pathogenesis of coronary spasm. However, among the patients with coronary spasm, a significantly higher level of serum Lp(a) was noted in patients with, than in those without, prior MI, suggesting that Lp(a) is a risk factor for the occurrence of AMI in patients with coronary vasospasm.
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References
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1. Yasue H, Omote S, Takizawa A, Nagao M. Coronary arterial spasm and its pathogenesis: a review. Circ Res. 1983;52(suppl I):I147–I152[Medline]
2. Maseri A, Severi S, De Nes M, et al. ‘Variant’ angina: one aspect of continuous spectrum of vasospastic myocardial ischemia. Am J Cardiol. 1978;42:1019–1035[CrossRef][Medline]
3. Oliva PB, Breckinridge JC. Arteriographic evidence of coronary arterial spasm in acute myocardial infarction. Circulation. 1977;56:366–374[Abstract/Free Full Text]
4. Maseri A, L’Abbate A, Baroldi G, et al. Coronary vasospasm as a possible cause of myocardial infarction: a conclusion derived from the study of ‘preinfarction’ angina. N Engl J Med. 1978;299:1271–1277[Abstract]
5. Oshima S, Yasue H, Ogawa H, et al. Fibrinopeptide A is released into the coronary circulation after coronary spasm. Circulation. 1990;82:2222–2225[Abstract/Free Full Text]
6. Masuda T, Yasue H, Ogawa H, et al. Plasma plasminogen activator inhibitor activity and tissue plasminogen activator levels in patients with unstable angina and those with coronary spastic angina. Am Heart J. 1992;124:314–319[CrossRef][Medline]
7. Masuda T, Ogawa H, Miyao Y, et al. Circadian variation in fibrinolytic activity in patients with variant angina. Br Heart J. 1994;71:156–161[Abstract/Free Full Text]
8. Nobuyoshi M, Abe M, Nosaka H, et al. Statistical analysis of clinical risk factors for coronary artery spasm: identification of the most important determinant. Am Heart J. 1992;124:32–38[CrossRef][Medline]
9. Sugiishi M, Takatsu F. Cigarette smoking is a major risk factor for coronary spasm. Circulation. 1993;87:76–79[Abstract/Free Full Text]
10. Miwa K, Fujita M, Miyagi Y, et al. High-density lipoprotein cholesterol level and smoking modify the prognosis of patients with coronary vasospasm. Clin Cardiol. 1995;18:267–272[Medline]
11. Miwa K, Yoshida N, Nakagawa K, Inoue H. High-density lipoprotein particles are large in patients with variant angina. Cardiovasc Res. 1998;37:729–737[Abstract/Free Full Text]
12. Miwa K, Miyagi Y, Fujita M. Susceptibility of plasma low-density lipoprotein to cupric ion-induced peroxidation in patients with variant angina. J Am Coll Cardiol. 1995;26:632–638[Abstract]
13. Miwa K, Miyagi Y, Igawa A, et al. Vitamin E deficiency in variant angina. Circulation. 1996;94:14–18[Abstract/Free Full Text]
14. DeWood MA, Spores J, Notsuke R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med. 1980;303:897–902[Abstract]
15. Nguyen TT, Ellefson R, Hodge DO, et al. Predictive value of electrophoretically detected lipoprotein(a) for coronary heart disease and cerebrovascular disease in a community-based cohort of 9,936 men and women. Circulation. 1997;96:1390–1397[Abstract/Free Full Text]
16. Cobbaert D, Jukena JW, Zwinderman AH, et al. Modulation of lipoprotein(a) atherogenicity by high density lipoprotein cholesterol levels in middle-aged men with symptomatic coronary artery disease and normal to moderately elevated serum cholesterol. J Am Coll Cardiol. 1997;30:1491–1499[Abstract]
17. Schwartzman RA, Cox ID, Poloniecki J, et al. Elevated plasma lipoprotein(a) is associated with coronary artery diseases in patients with chronic stable angina pectoris. J Am Coll Cardiol. 1998;31:1260–1266[Abstract/Free Full Text]
18. Murai A, Miyahara T, Fujimoto N, et al. Lp(a) lipoprotein as a risk factor for coronary heart disease and cerebral infarction. Atherosclerosis. 1986;59:199–204[CrossRef][Medline]
19. Utterman G. The mysteries of lipoprotein(a). Science. 1989;246:904–910[Abstract/Free Full Text]
20. Miwa K, Goto M, Lee JD, et al. Supersensitivity of coronary arteries in variant angina to spasm induced by intracoronary acetylcholine. Am J Cardiol. 1988;61:77–82[CrossRef][Medline]
21. Okumura K, Yasue H, Matsuyama K, et al. Sensitivity and specificity of intracoronary injection of acetylcholine for the induction of coronary artery spasm. J Am Coll Cardiol. 1988;12:883–888[Abstract]
22. Miwa K, Fujita M, Ejiri M, Sasayama S. Comparative sensitivity of intracoronary injection of acetylcholine for the induction of coronary artery spasm in patients with various types of angina pectoris. Am Heart J. 1990;120:544–550[CrossRef][Medline]
23. Maeda S, Abe M, Seishima K, et al. Transient changes of serum lipoprotein(a) as an acute phase protein. Atherosclerosis. 1989;78:145–150[CrossRef][Medline]
24. Abe A, Yoshimura Y, Sekine T, et al. Fully mechanized latex immunoassay for serum lipoprotein(a). Clin Chim Acta. 1994;225:105–113[CrossRef][Medline]
25. WHO Expert Committee in Diabetes Mellitus. Second report. WHO Tech Rep Ser 1980;646:1–80.
26. Ogawa H, Yasue H, Oshima S, et al. Circadian variation of plasma fibrinopeptide A level in patients with variant angina. Circulation 1989;80:1617–108.
27. Aoki N. Fibrinolysis. Semin Thromb Hemost. 1984;10:1–108[Medline]
28. Miles LA, Fless GM, Levin EG, et al. A potential basis for the thrombotic risks associated with lipoprotein(a). Nature. 1989;339:301–303[CrossRef][Medline]
29. Hajjar KA, Gavish D, Breslow JL, Nachman RL. Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature. 1989;339:303–305[CrossRef][Medline]
30. Harpel PC, Gordon BR, Parker TS. Plasmin catalyzes binding of lipoprotein(a) to immobilized fibrinogen and fibrin. Proc Natl Acad Sci USA. 1989;86:3847–3851[Abstract/Free Full Text]
31. Loscalzo J, Weinfeld M, Fless GM, Scanu AM. Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis. 1990;10:240–245[Abstract/Free Full Text]
32. Hoff HF, Beck GJ, Skibinski CI, et al. Serum Lp(a) level as a predictor of vein graft stenosis after coronary artery bypass surgery in patients. Circulation. 1988;77:1238–1244[Abstract/Free Full Text]
33. Moliterno DJ, Lange RA, Meidel RS, et al. Relation of plasma lipoprotein(a) to infarct artery patency in survivors of myocardial infarction. Circulation. 1998;88:935–940
34. Ridker PM, Hennekens CH, Stampfer MJ. A prospective study a lipoprotein(a) and the risk of myocardial infarction. JAMA. 1993;270:2195–2199[Abstract/Free Full Text]
35. Maher VMG, Brown BG, Marcovina SM, et al. Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a). JAMA. 1995;274:1771–1774[Abstract/Free Full Text]
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Abstract
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