| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1997;96:442-447.)
© 1997 American Heart Association, Inc.
Articles |
Effects of Ramipril on Plasma Fibrinolytic Balance in Patients With Acute Anterior Myocardial Infarction
From the Departments of Medicine and Pharmacology, Vanderbilt University Medical Center and Nashville Veterans Affairs Medical Center, Nashville, Tenn (D.E.V.); Montreal Heart Institute, Montreal, Quebec, Canada (J.-L.R.); the Cardiovascular Division (P.M.R., M.A.P.) and Division of Preventive Medicine (P.M.R.), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Victoria Hospital, London, Ontario, Canada (J.M.O.A.); and Geisinger Medical Center, Danville, Pa (F.J.M.).
Correspondence to Douglas E. Vaughan, MD, Vanderbilt University School of Medicine, Division of Cardiology, Room 315, MRB II, 2220 Pierce Ave, Nashville, TN 37232-6300. E-mail Doug.Vaughan{at}mcmail.vanderbilt.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background The long-term administration of ACE inhibitors to selected patients with left ventricular dysfunction appears to reduce the incidence of recurrent myocardial infarction (MI) and unstable angina pectoris. The mechanisms responsible for the reduction in ischemic events are unknown, but likely candidates include effects on the atherosclerotic process, thrombosis, and/or vascular tone.
Methods and Results The effects of ACE inhibitor therapy with ramipril on plasma fibrinolytic variables were assessed in 120 subjects participating in the Healing and Early Afterload Reduction Therapy (HEART) study, a double-blind, placebo-controlled trial of acute anterior MI patients who were randomly assigned within 24 hours of the onset of symptoms to receive low-dose ramipril (0.625 mg daily), full-dose ramipril (1.25 mg titrated to 10 mg/d), or placebo for 14 days. Plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity and PAI-1 antigen and tissue plasminogen activator (TPA) antigen were measured before randomization and on day 14. Clinical characteristics of the three study groups were similar, as were the prerandomization plasma levels of PAI-1 antigen, PAI-1 activity, and TPA antigen. Compared with the placebo group, PAI-1 antigen levels were 44% lower (P=.004) at day 14 in the ramipril-treated patients, and PAI-1 activity levels were 22% lower (P=.02). In contrast, plasma TPA levels were not significantly different between the placebo-treated and ramipril-treated groups.
Conclusions Treatment with ramipril has a significant impact on plasma fibrinolytic variables during the recovery phase after acute MI. The renin-angiotensin system appears to play an important role in the regulation of vascular fibrinolysis, and interruption of this regulatory pathway may contribute to the clinical benefits of ACE inhibitors.
Key Words: angiotensin • bradykinin • fibrinolysis • plasminogen activators • renin • myocardial infarction • thrombolysis
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The fibrinolytic system serves as one of the major endogenous defense mechanisms against intravascular thrombosis. Vascular fibrinolytic activity is to a large part determined by the balance between plasminogen activators, primarily TPA, and plasminogen activator inhibitors, predominantly PAI-1.1 Both of these essential fibrinolytic components are synthesized locally in the vascular wall (in endothelial and smooth muscle cells), have short half-lives, and circulate in trace concentrations in plasma.
Epidemiological data have linked PAI-1 with increased risk of MI.2 Elevated levels of PAI-1 are seen in youthful survivors of acute MI compared with age-matched control subjects,3 and elevated levels of PAI-1 appear to be a risk factor for recurrent MI.4 Recently, a common single 4/5 guanine (4G/5G) polymorphism located 675 bp upstream from the transcription start site of the PAI-1 gene has been described, with the 4G allele associated with higher plasma PAI-1 activity.5 The prevalence of the 4G allele is significantly higher in white patients with MI under the age of 45 years than in population-based control subjects (allele frequencies of 0.63 versus 0.53).6
We and others have recently shown that Ang II stimulates PAI-1 expression in cultured endothelial cells7 8 and can induce rapid, specific, dose-dependent increases in plasma PAI-1 levels in vivo in humans.9 More recent evidence from this laboratory indicates that the induction of PAI-1 expression in endothelial cells may also be mediated by the hexapeptide Ang IV, which acts through a pharmacologically and biochemically distinct angiotensin receptor.10 ACE, which is responsible for converting Ang I to Ang II, is also responsible for the degradation of bradykinin.11 We have recently found that bradykinin induces dose-dependent increases in plasma TPA levels in ACE inhibitor–treated human subjects.12 This confirms and extends previous observations that bradykinin is one of the most potent stimuli for the release of TPA in vivo.13 14 Thus, by virtue of its endothelial localization and its dual functional role in activating angiotensin and degrading bradykinin, ACE is strategically poised to regulate vascular fibrinolytic balance.
ACE inhibitor therapy has been shown to reduce the incidence of MI in patients with left ventricular dysfunction.15 16 The mechanisms responsible for this newly appreciated property of ACE inhibitors are unclear but may include effects on the atherosclerotic process, coronary artery tone, and thrombosis.17 Since angiotensin and bradykinin appear to have divergent regulatory effects on plasma fibrinolysis, we hypothesized that ACE inhibition would improve fibrinolytic balance and that this mechanism may contribute to the reduced incidence of coronary events in patients treated with these agents. In this study, we examined the effects of ACE inhibitor therapy with ramipril on plasma levels of TPA and PAI-1 in patients with an acute anterior MI. Our findings indicate that ramipril reduces plasma PAI-1 after acute MI and that ACE inhibitor therapy helps maintain the balance of the endogenous regulators of plasminogen activation toward thrombolysis.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patients and Study Design
The Healing and Early Afterload Reducing Therapy (HEART) Study was a randomized, double-blind, placebo-controlled multicenter trial of 352 anterior MI patients with systolic blood pressure >100 mm Hg.18 The HEART Study was designed to examine the effects of dosage and timing of ACE inhibitor therapy on ventricular remodeling after anterior MI. In brief, subjects were randomized within 24 hours to placebo or low-dose (0.625 mg/d) or full-dose (1.25 mg titrated to 10 mg/d) ramipril. At day 14 after randomization, the placebo phase ended and those subjects initially treated with placebo were crossed over into the full-dose ramipril group.
Blood Sampling
A prospective analysis of the effects of ramipril on
fibrinolytic variables was designed into the study. The subjects
participating in this portion of the study provided informed consent
for the additional blood samples and analysis. Baseline blood
samples were drawn before randomization and again on study day 14.
Venous blood (4.5 mL) was collected into 0.5 mL trisodium citrate
(0.13 mmol/L, pH 5.5). Samples were thoroughly mixed and
briefly stored on ice before centrifugation and
isolation of the plasma supernatant. All samples were stored at
-70°C until assayed. Baseline blood samples were drawn after
informed consent was obtained; therefore the timing of these samples
was uncontrolled. The day 14 samples were all drawn between 8 and 10
AM to minimize the confounding effects of diurnal variation
in the fibrinolytic system.19 20
Determination of Plasma PAI-1 and TPA Levels
PAI-1 activity levels were measured with an assay based on the
methods of Veheijen et al,21 with standardized commercial
kits purchased from Biopool Inc and results expressed as units/mL
(U/mL). PAI-1 and TPA antigens were measured with the use of specific
enzyme-linked immunosorbent assays as previously
described22 23 with kits purchased from Biopool Inc;
results are expressed as nanograms per milliliter. The PAI-1 and TPA
mass ratio was determined by dividing plasma concentrations
(ng/mL) by the molecular weights of the two proteins, with a
value of 70 000 g/mol used for TPA and a value of 50 000
g/mol used for PAI-1. All measurements were performed on coded
samples without knowledge of randomization status.
Statistical Analysis
Means and proportions for clinical characteristics and
concurrent medications at study entry were computed for those patients
randomly assigned to placebo therapy and for those assigned to low-dose
and full-dose ramipril. The significance of any differences in means
was tested by the Student's t test, whereas the
significance of any difference in proportions was tested by the
2 statistic. The significance of differences
between study groups in terms of mean levels of TPA antigen, PAI-1
antigen, PAI-1 activity, and the PAI-1/TPA molar ratio at baseline and
at day 14 was similarly tested with the Student's t test.
All tests of significance were repeated with the use of
nonparametric methods to ensure that our observed effects
were not simply due to deviation from normality. Mean±SEM values are
shown unless otherwise indicated.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Characteristics of the Study Group
Of the 352 patients randomized into the HEART study, paired plasma samples from baseline (before randomization) and day 14 were available for analysis from 120 (34%) of the subjects enrolled in the trial. The clinical and demographic characteristics of the subjects are shown in Table 1
.
|
Fibrinolytic Parameters
Baseline levels of PAI-1 activity and PAI-1 and TPA antigen are
shown in Table 2. PAI-1 activity was
24.0±1.7 U/mL in the placebo group, 25.3±1.6 U/mL in the low-dose
group, and 22.2±1.9 U/mL in the full-dose group (P=NS).
PAI-1 antigen levels were also similar between the groups with values
of 58.8±4.6, 61.2±5.2, and 51.2±5.9 ng/mL for the placebo
group, low-dose group, and full-dose group, respectively
(P=NS). Each of these treatment groups was found to have
comparable TPA antigen levels at baseline, with values of 27.7±3.8
ng/mL for the placebo group, 23.1±1.3 ng/mL for the
low-dose group, and 29.2±4.8 ng/mL for the full-dose group
(P=NS).
|
There were marked differences between baseline values and those
measured at day 14, with PAI-1 activity and antigen and TPA antigen
levels reduced in all treatment groups. Comparative values for each of
the three treatment groups on study day 14 are shown in Table 3. PAI-1 antigen levels showed the
greatest effect of treatment, with significantly lower values observed
in the low-dose (P<.05) and full-dose ramipril
(P<.005) groups when compared with placebo. There were no
significant differences in any of the three fibrinolytic variables
between the low-dose and full-dose ramipril groups. A comparison of
fibrinolytic measures for the placebo group compared with combined
ramipril-treated patients is shown in Fig 1. PAI-1 activity levels were
on average 22% lower in the ramipril-treated subjects (14.9±1.0 U/mL)
compared with the placebo group (placebo, 19.2±1.7 U/mL;
P=.02). PAI-1 antigen levels were 44% lower in the subjects
receiving ramipril, with a value of 44.3±5.7 ng/mL in the
placebo group versus 25.0±3.1 ng/mL in the ramipril-treated
subjects (P=.004). Plasma TPA antigen showed a similar trend
with treatment, with values of 12.7±1.3 ng/mL in the
placebo-treated group versus 10.1 ±0.8 ng/mL in the
ramipril-treated subjects (P=.08).
|
|
To generate an index of relative changes in the plasma concentrations
of PAI-1 and TPA, the molar ratios of these two proteins were compared
(Fig 2). In 178 healthy subjects studied
in this laboratory, the PAI-1/TPA molar ratio averaged 3.9±0.2
(mean±SEM). In the placebo-treated group, the PAI-1/TPA ratio
increased from 4.1±0.5 at baseline to 9.8±2.3 on day 14
(P=.02). In contrast, the PAI-1/TPA ratio was stable over
the 2-week study period in the ramipril-treated subjects (3.6±0.3
versus 4.9±0.9, P=NS). The statistical significance of all
the relationships described above was confirmed in analyses
with nonparametric tests.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Before this study, we hypothesized that ACE inhibitor therapy would improve plasma fibrinolytic balance by reducing the Ang II–dependent production and secretion of PAI-1 while promoting the bradykinin- dependent secretion of TPA. The results presented here indicate that the ACE inhibitor ramipril is associated with selective, statistically significant reductions in PAI-1 activity and antigen, whereas the concomitant effects on plasma TPA antigen are marginal. Overall, ramipril appears to shift fibrinolytic balance toward lysis in patients after MI, a finding that may provide a mechanism for the beneficial effect of ACE inhibitors on the observed incidence of MI in several prior randomized clinical trials.
At the time of presentation, plasma levels of TPA and PAI-1 were elevated in all groups. This confirms previous work demonstrating that plasma PAI-1 activity increases during the acute phase of MI.24 Basal TPA antigen levels were approximately two to three times higher than normal in the patients.23 25 This may be explained partially by the effects of catecholamine release during the acute phase of MI.26 Furthermore, 66% of the subjects enrolled in this study were treated with thrombolytic therapy at the time of presentation; many received recombinant TPA (rTPA). Although this drug has a short half-life in plasma,27 the elevated basal TPA levels may reflect residual circulating rTPA.
Between the time of enrollment and day 14, there were marked reductions in plasma TPA and PAI-1 levels in all patients. In the ramipril-treated patients, however, there were additional selective reductions in plasma PAI-1 activity and antigen levels. This suggests that the RAS may play an important role in the regulation of plasma PAI-1 levels in patients during the recovery phase after acute MI. Alternatively, since increased PAI-1 levels are consistently seen after acute MI as a manifestation of the acute-phase response, the reduced PAI-1 levels in the ramipril-treated subjects may represent a more rapid attenuation of that response. Ramipril treatment was also associated with a similar reduction in plasma TPA antigen levels. However, in the aggregate, these changes in PAI-1 and TPA antigen would lead to a relative decrease in plasma PAI activity in view of the stoichiometric inhibitory relationship between PAI-1 and TPA on a molar basis. The relative sparing of TPA mass seen in this study merits further consideration in view of the evidence that plasma TPA antigen directly reflects PAI-1 levels.28 29 The discordant reduction in PAI-1 antigen compared with TPA antigen in ramipril-treated subjects suggests that ACE inhibitor therapy may influence TPA secretion. In recent studies from this laboratory, we have found that ACE inhibitor therapy markedly potentiates the ability of bradykinin to induce TPA secretion humans.12 This interpretation is further supported by our examination of the effects of therapy on the molar ratios of PAI-1 to TPA in plasma. The molar ratio of PAI-1/TPA more than doubled in the placebo-treated subjects, whereas the ratio was essentially stable in the ramipril-treated subjects. These findings differ from those of Wright et al,30 who reported nearly proportional reductions in TPA and PAI-1 in infarct survivors treated with captopril. The reasons for these divergent findings are unclear but may reflect differences in patient population, study design, and treatment protocols.
The reductions in plasma PAI-1 and apparent improvement in fibrinolytic balance observed in this trial may be clinically significant. The magnitude of the reduction in PAI-1 that was observed in ramipril-treated subjects is generally proportional to the differences in plasma PAI-1 activity that are associated with increased risk of MI.4 Furthermore, no other drugs have been demonstrated to have such an impact on plasma fibrinolytic balance after MI in humans. A comparison of the day 14 fibrinolytic parameters between the low-dose and full-dose ramipril-treated subjects failed to identify any significant differences. The absence of a dose-dependent effect suggests that both low-dose and full-dose ramipril influenced PAI-1 and TPA production to a comparable extent. We suggest that this observation represents the cumulative effects of ACE inhibitors on bradykinin degradation and angiotensin production. The possibility that ACE inhibitor therapy affects plasma PAI-1 and TPA levels through an attenuation of the acute-phase response or indirectly through an effect on left ventricular function cannot be excluded.
There are several important limitations to this study. First, this trial was designed to compare the effects of 2 weeks of therapy with ramipril versus placebo on fibrinolytic balance. It is not known how quickly the beneficial changes in plasma fibrinolysis occur. However, a recent meta-analysis of four large-scale clinical trials that examined the impact of ACE inhibitor therapy in evolving MI31 found a significant reduction in mortality within 24 to 48 hours in patients who present with acute MI. We speculate that some of this benefit may be due to a reduced incidence of infarct extension accompanying improved fibrinolytic function. Second, this study was designed to provide information on the short-term effects of ramipril on fibrinolytic balance. In light of the previously reported long-term beneficial effects of ACE inhibitor after MI,15 16 the placebo treatment phase of the trial was terminated after 14 days, and those patients were crossed over to full-dose ramipril. Therefore, no additional comparisons of the chronic effects of ramipril versus placebo on fibrinolytic balance were possible. Although we speculate that the reduced incidence of recurrent MI associated with the administration of ACE inhibitors is mechanistically linked to effects on fibrinolytic balance, this trial lacked an adequate number of ischemic end points to establish such a relationship. Additional large-scale clinical studies designed to quantify clinical and laboratory end points will be required to confirm or reject this mechanistic interaction. Finally, although the present findings indicate a directionally consistent reduction in PAI-1 antigen and activity levels in the ramipril-treated subjects, there was a greater treatment effect on PAI-1 antigen. The reasons for this are unclear but may be explained partially by the relative instability of PAI-1 activity.28 We are unaware of any mechanism that could explain an effect of ramipril on plasma PAI-1 mass to a greater extent than PAI-1 activity. The measurements performed in this study do not permit a direct estimation of TPA/PAI-1 complex formation or other potential functional alterations secondary to interactions between TPA and PAI-1 and other inhibitors.32
There is a substantial body of evidence in support of the hypothesis that activation of the RAS increases the risk of ischemic cardiovascular events independent of the effects of the RAS on blood pressure.33 34 35 Additional links between PAI-1 and activation of the RAS have been reported. Patients with ischemic heart disease treated with diuretics have significantly higher levels of PAI-1 antigen compared with patients not receiving diuretics.36 We have also reported that plasma PAI-1 antigen levels correlate with plasma aldosterone and plasma renin activity.37 There are other clinical populations that may benefit from this apparent interaction. Plasma PAI-1 is increased in patients with diabetes mellitus38 and has been linked to the development of renal and vascular disease in diabetics. We have recently shown that ACE inhibition reduces local renal PAI-1 expression and the development of glomerulosclerosis in rats after radiation injury,39 and we speculate that a similar mechanism may contribute to the renoprotective effects of ACE inhibitor therapy in diabetes.40 This suggests that ACE inhibition therapy may have some theoretical advantages in the treatment of hypertensive diabetics, and this hypothesis merits further investigation. Conversely, there is evidence that interruption of the RAS system by administration of ACE inhibitors can reduce the incidence of MI in selected populations.15 16 Recent experimental evidence indicates that ACE inhibitor therapy can reduce PAI-1 expression in normal and balloon-injured aortic wall of rats.41 The data presented in this study indicate that the RAS plays an important role in the regulation of fibrinolytic balance after MI and suggest that this mechanistic linkage may in fact contribute to the ability of ACE inhibitors to reduce the incidence of ischemic coronary events in patients with left ventricular dysfunction.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
The HEART study and this ancillary trial were supported by a grant from Hoechst-Roussel Pharmaceuticals, Inc, which was not involved in the acquisition or analysis of data presented in this study. Dr Vaughan is the recipient of a Clinical Investigator Award from the Research Service of the United States Veterans Administration. This work was also supported by National Institutes of Health grant R01 HL-51387 (D.E.V.). The authors are grateful for the assistance of Jacqueline Haynes for the preparation of the manuscript.
Received November 4, 1996; revision received February 25, 1997; accepted February 28, 1997.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Saksela O, Rifkin DB. Cell-associated plasminogen activation: regulation and physiologic functions. Am Rev Cell Biol. 1988;4:93-126.
2. Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischemic heart disease in the Northwick Park Heart study. Lancet. 1993;342:1076-1079.[Medline] [Order article via Infotrieve]
3. Hamsten A, Wiman B, deFaire U, Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med. 1985;313:1557-1563.[Abstract]
4. Hamsten A, Walldius G, Szamosi A, Blombäck M. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet. 1987;2:3-9.[Medline] [Order article via Infotrieve]
5.
Dawson SJ, Wiman B, Hamsten A, Green F, Humphries S,
Henney A. The two allele sequences of a common
polymorphism in the promoter of the plasminogen
activator inhibitor-1 (PAI-1) gene respond
differently to interleukin-1 in HepG2 cells. J Biol
Chem. 1993;268:10739-10745.
6.
Eriksson P, Kallin B, Hooft FM, Bavenholm P, Hamsten
A. Allele-specific increase in basal transcription of the
plasminogen activator inhibitor-1
gene is associated with myocardial infarction. Proc Natl
Acad Sci U S A. 1995;92:1851-1855.
7. Vaughan DE, Lazos SA, Tong K. Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. J Clin Invest. 1995;95:995-1001.
8. Feener EP, Northrup JM, Aiello LP, King GL. Angiotensin II induces plasminogen activator inhibitor-1 and -2 expression in vascular endothelial and smooth muscle cells. J Clin Invest. 1995;95:1353-1362.
9.
Ridker PM, Gaboury CL, Conlin PR, Seely EW, Williams
GH, Vaughan DE. Stimulation of plasminogen
activator inhibitor in vivo by infusion of
angiotensin II. Circulation. 1993;87:1969-1973.
10. Kerins DM, Hao Q, Vaughan DE. Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV. J Clin Invest. 1995;96:2515-2520.
11. Erdos E, Skidgel RA. The angiotensin I converting enzyme. Lab Invest. 1987;56:345-348.[Medline] [Order article via Infotrieve]
12. Brown NJ, Nadeau J, Vaughan DE. Stimulation of tissue-type plasminogen activator in vivo by infusion of bradykinin. Thromb Haemost. 1997;77:522-525.[Medline] [Order article via Infotrieve]
13.
Smith D, Gilbert M, Owen WG. Tissue
plasminogen activator release in vivo in
response to vasoactive agents. Blood. 1985;66:835-839.
14. Emeis JJ, Tranquille N. On the role of bradykinin in secretion from vascular endothelial cells. Agents Actions. 1992;38:285-291.
15. Pfeffer MA, Braunwald LA, Moye L, Basta EJ, Drown EJ, Cuddy TE, on behalf of the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1992;327:669-677.[Abstract]
16. Yusuf S, Pepine CJ, Garces C, Pouleur H. Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions. Lancet. 1992;340:1173-1178.[Medline] [Order article via Infotrieve]
17.
Lonn EM, Yusuf S, Jha P, Montague TJ. Emerging
role of angiotensin-converting enzyme
inhibitors in cardiac and vascular protection.
Circulation. 1994;90:2056-2069.
18. Pfeffer MA, LaMotte FS, Arnold JM, Rouleau JL. Titration of angiotensin converting enzyme inhibition in acute anterior infarction: the Healing and Early Afterload Reducing Therapy (HEART) study. Circulation. 1995;92(suppl I):I-19. Abstract.
19.
Angleton P, Chandler WL, Schmer G. Diurnal
variation of tissue-type plasminogen activator
and its rapid inhibitor. Circulation. 1989;79:101-106.
20. Grimaudo V, Hauert J, Backmann F, Kruithof EKO. Diurnal variation of the fibrinolytic system. Thromb Haemost. 1988;59:495-499.[Medline] [Order article via Infotrieve]
21. Verheijen JH, Chang GTG, Kluff C. Evidence for the occurrence of a fast acting inhibitor of tissue-type plasminogen activator in plasma. Thromb Haemost. 1984;51:392-395.[Medline] [Order article via Infotrieve]
22.
Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Shen C,
Newcomer L, Goldhaber SZ, Hennekens CH. Baseline fibrinolytic
state and the risk of future venous thrombosis: a prospective study of
endogenous tissue plasminogen
activator and plasminogen activator
inhibitor. Circulation. 1992;85:1822-1827.
23. Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen activator and the risk of future myocardial infarction. Lancet. 1993;341:1165-1168.[Medline] [Order article via Infotrieve]
24. Almer LO, Ohlin H. Elevated levels of the rapid inhibitor of plasminogen activator (t-PA) in acute myocardial infarction. Thromb Res. 1987;47:335-339.[Medline] [Order article via Infotrieve]
25. Ridker PM, Hennekens CH, Stampfer MJ, Manson JE, Vaughan DE. A prospective study of tissue-type plasminogen activator and the risk of stroke. Lancet. 1994;343:940-943.[Medline] [Order article via Infotrieve]
26. Chandler WL, Veita RC, Fellingham GW, Levy WC. Fibrinolytic response during exercise and epinephrine infusion in the same subjects. J Am Coll Cardiol. 1992;92:1412-1420.
27. Garabedian HD, Gold HK, Leinbach RC. Comparative properties of two clinical preparations of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction. J Am Coll Cardiol. 1987;9:599-607.[Abstract]
28. Wiman B. Plasminogen activator inhibitor 1 (PAI-1) in plasma: its role in thrombotic disease. Thromb Haemost. 1995;74:71-76.[Medline] [Order article via Infotrieve]
29. Fujii S, Abendschein DR, Sobel BE. Augmentation of plasminogen activator inhibitor type I activity by thrombosis and by thrombolysis. J Am Coll Cardiol. 1991;18:1547-1554.[Abstract]
30. Wright RA, Flapan AD, Alberti KGMM, Ludlam CA, Fox KAA. Effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction. J Am Coll Cardiol. 1994;24:67-73.[Abstract]
31. Zuanetti G, Maggioni AP, Latini R, Franzosi MG. The early beneficial effect of treatment with oral ACE-inhibitors in patients with acute MI. Circulation. 1995;92(suppl I):I-24. Abstract.
32.
Lucore CL, Sobel BE. Interactions of tissue-type
plasminogen activator with plasma
inhibitors and their pharmacologic implications.
Circulation. 1988;77:660-669.
33. Alderman MH, Madhavan S, Ooi WL, Cohen H, Sealey JE, Laragh JH. Association of renin-sodium profile with risk of myocardial infarction in patients with hypertension. N Engl J Med. 1991;324:1098-1104.[Abstract]
34. Cambien F, Poirer O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 1992;359:641-644.[Medline] [Order article via Infotrieve]
35.
Ludwig E, Corneli PS, Anderson JL, Marshall HW, Lalouel
JM, Ward RH. Angiotensin-converting enzyme gene
polymorphism is associated with myocardial infarction but not with
development of coronary stenosis.
Circulation. 1995;91:2120-2124.
36. Pedersen OD, Gram JJ, Baggar H, Keller N, Jespersen J. Regulation of tissue-type plasminogen activator-mediated fibrinolysis by plasminogen activator inhibitor-1 in patients with ischemic heart disease: possible unfavorable effects of diuretics. Coron Artery Dis. 1994;5:617-623.[Medline] [Order article via Infotrieve]
37. Vaughan DE, Rouleau JL, Pfeffer MA. Role of fibrinolytic system in preventing myocardial infarction. Eur Heart J. 1995;16(K):31-36.
38. McGill JB, Schneider DJ, Arfken CL, Lucore CL, Sobel BE. Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients. Diabetes. 1994;43:104-109.[Abstract]
39. Oikawa T, Freeman M, Lo W, Vaughan DE, Fogo A. Modulation of plasminogen activator inhibitor-1 (PAI-1) in vivo: a new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition. Kidney Int. 1997;51:164-172.[Medline] [Order article via Infotrieve]
40.
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The
effect of angiotensin-converting-enzyme inhibition on
diabetic nephropathy: the Collaborative Study
Group. N Engl J Med. 1993;329:1456-1462.
41.
Hamdan AD, Quist WC, Gagne JB, Feener EP.
Angiotensin-converting enzyme inhibition suppresses
plasminogen activator inhibitor-1
expression in the neointima of balloon-injured rat
aorta. Circulation. 1996;93:1073-1078.
This article has been cited by other articles:
 |
|
 |
|
  C. L. Lau, Y. Zhao, J. Kim, I. L. Kron, A. Sharma, Z. Yang, V. E. Laubach, J. Linden, G. Ailawadi, and D. J. Pinsky Enhanced fibrinolysis protects against lung ischemia-reperfusion injury. J. Thorac. Cardiovasc. Surg., May 1, 2009; 137(5): 1241 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Van Guilder, M. Pretorius, J. M. Luther, J. B. Byrd, K. Hill, J. V. Gainer, and N. J. Brown Bradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition Hypertension, February 1, 2008; 51(2): 454 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. S. Packard and P. Libby Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction Clin. Chem., January 1, 2008; 54(1): 24 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Arndt, S. K. Young, K. R. Poch, J. A. Nick, S. Falk, R. W. Schrier, and G. S. Worthen Systemic Inhibition of the Angiotensin-Converting Enzyme Limits Lipopolysaccharide-Induced Lung Neutrophil Recruitment through Both Bradykinin and Angiotensin II-Regulated Pathways J. Immunol., November 15, 2006; 177(10): 7233 - 7241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Festa, K. Williams, R. P. Tracy, L. E. Wagenknecht, and S. M. Haffner Progression of Plasminogen Activator Inhibitor-1 and Fibrinogen Levels in Relation to Incident Type 2 Diabetes Circulation, April 11, 2006; 113(14): 1753 - 1759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown, J. A.S. Muldowney III, and D. E. Vaughan Endogenous NO Regulates Plasminogen Activator Inhibitor-1 During Angiotensin-Converting Enzyme Inhibition Hypertension, March 1, 2006; 47(3): 441 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pretorius, J. M. Luther, L. J. Murphey, D. E. Vaughan, and N. J. Brown Angiotensin-Converting Enzyme Inhibition Increases Basal Vascular Tissue Plasminogen Activator Release in Women But Not in Men Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2435 - 2440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Verdecchia, G. Reboldi, F. Angeli, R. Gattobigio, M. Bentivoglio, L. Thijs, J. A. Staessen, and C. Porcellati Angiotensin-Converting Enzyme Inhibitors and Calcium Channel Blockers for Coronary Heart Disease and Stroke Prevention Hypertension, August 1, 2005; 46(2): 386 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Daly, K. M. Fox, W. J. Remme, M. E. Bertrand, R. Ferrari, M. L. Simoons, and on behalf of the EUROPA investigators The effect of perindopril on cardiovascular morbidity and mortality in patients with diabetes in the EUROPA study: results from the PERSUADE substudy Eur. Heart J., July 2, 2005; 26(14): 1369 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Goligorsky Endothelial cell dysfunction: can't live with it, how to live without it Am J Physiol Renal Physiol, May 1, 2005; 288(5): F871 - F880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamamoto, K. Takeshita, T. Kojima, J. Takamatsu, and H. Saito Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly Cardiovasc Res, May 1, 2005; 66(2): 276 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw Biochemical risk markers: a novel area for better prediction of renal risk? Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508. [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Lazar Role of Angiotensin-Converting Enzyme Inhibitors in the Coronary Artery Bypass Patient Ann. Thorac. Surg., March 1, 2005; 79(3): 1081 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Sokol, E. L. Portnay, J. P. Curtis, M. A. Nelson, P. R. Hebert, J. F. Setaro, and J. M. Foody Modulation of the renin-angiotensin-aldosterone system for the secondary prevention of stroke Neurology, July 27, 2004; 63(2): 208 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Roncal, J Orbe, J.A Rodriguez, M Belzunce, O Beloqui, J Diez, and J.A Paramo Influence of the 4G/5G PAI-1 genotype on angiotensin II-stimulated human endothelial cells and in patients with hypertension Cardiovasc Res, July 1, 2004; 63(1): 176 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19. [Full Text] [PDF]
|
|
|
|
|
|
E. Svarstad and B. M. Iversen Reply Nephrol. Dial. Transplant., March 1, 2004; 19(3): 748 - 749. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Takeshita, M. Hayashi, S. Iino, T. Kondo, Y. Inden, M. Iwase, T. Kojima, M. Hirai, M. Ito, D. J. Loskutoff, et al. Increased Expression of Plasminogen Activator Inhibitor-1 in Cardiomyocytes Contributes to Cardiac Fibrosis after Myocardial Infarction Am. J. Pathol., February 1, 2004; 164(2): 449 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Tsikouris, J. A. Suarez, G. E. Meyerrose, M. Ziska, D. Fike, and J. Smith Questioning a Class Effect: Does ACE Inhibitor Tissue Penetration Influence the Degree of Fibrinolytic Balance Alteration following an Acute Myocardial Infarction? J. Clin. Pharmacol., February 1, 2004; 44(2): 150 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pretorius, L. J. Murphey, J. A. McFarlane, D. E. Vaughan, and N. J. Brown Angiotensin-Converting Enzyme Inhibition Alters the Fibrinolytic Response to Cardiopulmonary Bypass Circulation, December 23, 2003; 108(25): 3079 - 3083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Vaughan Plasminogen Activator Inhibitor-1 and the Calculus of Mortality After Myocardial Infarction Circulation, July 29, 2003; 108(4): 376 - 377. [Full Text] [PDF]
|
|
|
|
|
|
J.P. Collet, G. Montalescot, E. Vicaut, A. Ankri, F. Walylo, C. Lesty, R. Choussat, F. Beygui, M. Borentain, N. Vignolles, et al. Acute Release of Plasminogen Activator Inhibitor-1 in ST-Segment Elevation Myocardial Infarction Predicts Mortality Circulation, July 29, 2003; 108(4): 391 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.J. Remme Reconsider the management of all coronary artery disease patients: Importance of the EUROPA trial Eur. Heart J. Suppl., July 1, 2003; 5(suppl_E): E23 - E30. [Abstract] [PDF]
|
|
|
|
|
|
M. Pretorius, D. Rosenbaum, D. E. Vaughan, and N. J. Brown Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin Circulation, February 4, 2003; 107(4): 579 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Murphey, D. Vaughan, and N. Brown Contribution of bradykinin to the cardioprotective effects of ACE inhibitors Eur. Heart J. Suppl., January 1, 2003; 5(suppl_A): A37 - A41. [Abstract] [PDF]
|
|
|
|
|
|
N. J. Brown, S. Kumar, C. A. Painter, and D. E. Vaughan ACE Inhibition Versus Angiotensin Type 1 Receptor Antagonism: Differential Effects on PAI-1 Over Time Hypertension, December 1, 2002; 40(6): 859 - 865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. L Ruberg and J. Loscalzo Prothrombotic determinants of coronary atherothrombosis Vascular Medicine, November 1, 2002; 7(4): 289 - 299. [Abstract] [PDF]
|
|
|
|
 |
|
 D Rimar, E Crystal, A Battler, S Gottlieb, D Freimark, H Hod, V Boyko, L Mandelzweig, S Behar, and J Leor Improved prognosis of patients presenting with clinical markers of spontaneous reperfusion during acute myocardial infarction Heart, October 1, 2002; 88(4): 352 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Barua, J. A. Ambrose, D. C. Saha, and L.-J. Eales-Reynolds Smoking Is Associated With Altered Endothelial-Derived Fibrinolytic and Antithrombotic Factors: An In Vitro Demonstration Circulation, August 20, 2002; 106(8): 905 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. McMurray and M. A. Pfeffer New Therapeutic Options in Congestive Heart Failure: Part I Circulation, April 30, 2002; 105(17): 2099 - 2106. [Full Text] [PDF]
|
|
|
|
|
|
E. Svarstad, D. Hultstrom, D. Jensen, G. Jenssen, and B. M. Iversen Renal artery thrombosis with acute renal failure after withdrawal of angiotensin converting enzyme inhibitor: a case report Nephrol. Dial. Transplant., April 1, 2002; 17(4): 687 - 689. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Festa, R. D'Agostino Jr, R. P. Tracy, and S. M. Haffner Elevated Levels of Acute-Phase Proteins and Plasminogen Activator Inhibitor-1 Predict the Development of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study Diabetes, April 1, 2002; 51(4): 1131 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pahor, L. V. Franse, S. R. Deitcher, W. C. Cushman, K. C. Johnson, R. I. Shorr, K. Kottke-Marchant, R. P. Tracy, G. W. Somes, and W. B. Applegate Fosinopril Versus Amlodipine Comparative Treatments Study: A Randomized Trial to Assess Effects on Plasminogen Activator Inhibitor-1 Circulation, January 29, 2002; 105(4): 457 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown, A. Abbas, D. Byrne, J. A. Schoenhard, and D. E. Vaughan Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women Circulation, January 22, 2002; 105(3): 304 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fava, J. Azzopardi, S. Ellard, and A. T. Hattersley ACE Gene Polymorphism as a Prognostic Indicator in Patients With Type 2 Diabetes and Established Renal Disease Diabetes Care, December 1, 2001; 24(12): 2115 - 2120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kennon, K. Barakat, G. A. Hitman, C. P. Price, P. G. Mills, K. Ranjadayalan, J. Cooper, H. Clark, and A. D. Timmis Angiotensin-converting enzyme inhibition is associated with reduced troponin release in non-ST-elevation acute coronary syndromes J. Am. Coll. Cardiol., September 1, 2001; 38(3): 724 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kaikita, A. B. Fogo, L. Ma, J. A. Schoenhard, N. J. Brown, and D. E. Vaughan Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition Circulation, August 14, 2001; 104(7): 839 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. M. T. Zaman, S. Fujii, H. Sawa, D. Goto, N. Ishimori, K. Watano, T. Kaneko, T. Furumoto, T. Sugawara, I. Sakuma, et al. Angiotensin-Converting Enzyme Inhibition Attenuates Hypofibrinolysis and Reduces Cardiac Perivascular Fibrosis in Genetically Obese Diabetic Mice Circulation, June 26, 2001; 103(25): 3123 - 3128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown, L. J. Murphey, N. Srikuma, N. Koschachuhanan, G. H. Williams, and D. E. Vaughan Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen Arterioscler Thromb Vasc Biol, June 1, 2001; 21(6): 1071 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Minai, T. Matsumoto, H. Horie, N. Ohira, H. Takashima, H. Yokohama, and M. Kinoshita Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: effects of angiotensin-converting enzyme inhibitors J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1565 - 1570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Skurk, Y.-M. Lee, and H. Hauner Angiotensin II and Its Metabolites Stimulate PAI-1 Protein Release From Human Adipocytes in Primary Culture Hypertension, May 1, 2001; 37(5): 1336 - 1340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-C. Chen, J. L. Bouchie, A. S. Perez, A. C. Clermont, S. Izumo, J. Hampe, and E. P. Feener Role of the Angiotensin AT1 Receptor in Rat Aortic and Cardiac PAI-1 Gene Expression Arterioscler Thromb Vasc Biol, October 1, 2000; 20(10): 2297 - 2302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C Felmeden and G. Y. Lip The renin-angiotensin-aldosterone system and fibrinolysis Journal of Renin-Angiotensin-Aldosterone System, September 1, 2000; 1(3): 240 - 244. [PDF]
|
|
|
|
 |
|
 H. L. White and A. S. Hall 'ACE inhibitors are better than AT1 receptor blockers (ARBs)' -- controversies in heart failure Eur J Heart Fail, September 1, 2000; 2(3): 237 - 240. [Full Text] [PDF]
|
|
|
|
|
|
C. Labinjoh, D. E. Newby, P. Dawson, N. R. Johnston, C. A. Ludlam, N. A. Boon, and D. J. Webb Fibrinolytic actions of intra-arterial angiotensin II and bradykinin in vivo in man Cardiovasc Res, September 1, 2000; 47(4): 707 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tarnow, C. D. A. Stehouwer, J. J. Emeis, O. Poirier, F. Cambien, B. V. Hansen, and H.-H. Parving Plasminogen activator inhibitor-1 and apolipoprotein E gene polymorphisms and diabetic angiopathy Nephrol. Dial. Transplant., May 1, 2000; 15(5): 625 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Bouchie, H.-C. Chen, R. Carney, J. C. Bagot, P. A. Wilden, and E. P. Feener P2Y Receptor Regulation of PAI-1 Expression in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 2000; 20(3): 866 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J. Brown, K.-S. Kim, Y.-Q. Chen, L. S. Blevins, J. H. Nadeau, S. G. Meranze, and D. E. Vaughan Synergistic Effect of Adrenal Steroids and Angiotensin II on Plasminogen Activator Inhibitor-1 Production J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 336 - 344. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. A. Bavry, D. Li, D. S. Zander, M. I. Phillips, and J. L. Mehta Inhibition of Arterial Thrombogenesis by Quinapril but Not Losartan Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(2): 121 - 127. [Abstract] [PDF]
|
|
|
|
|
|
J. P.M Cleutjens, W.M. Blankesteijn, M. J.A.P Daemen, and J. F.M Smits The infarcted myocardium: Simply dead tissue, or a lively target for therapeutic interventions Cardiovasc Res, November 1, 1999; 44(2): 232 - 241. [Full Text] [PDF]
|
|
|
|
|
|
H. Soejima, H. Ogawa, H. Yasue, K. Kaikita, K. Takazoe, K. Nishiyama, K. Misumi, S. Miyamoto, M. Yoshimura, K. Kugiyama, et al. Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction J. Am. Coll. Cardiol., October 1, 1999; 34(4): 983 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Raizada, M. J. Katovich, H. Wang, K. H. Berecek, and C. H. Gelband Is antisense gene therapy a step in the right direction in the control of hypertension? Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H423 - H432. [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown, M. Agirbasli, and D. E. Vaughan Comparative Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Antagonism on Plasma Fibrinolytic Balance in Humans Hypertension, August 1, 1999; 34(2): 285 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Gustafsson, C. Torp-Pedersen, L. Kober, F. Gustafsson, P. Hildebrandt, and on behalf of the Trace Study Group Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction J. Am. Coll. Cardiol., July 1, 1999; 34(1): 83 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Zurbano, I. Anguera, M. Heras, E. Roig, M. Lozano, G. Sanz, and G. Escolar Captopril Administration Reduces Thrombus Formation and Surface Expression of Platelet Glycoprotein IIb/IIIa in Early Postmyocardial Infarction Stage Arterioscler Thromb Vasc Biol, July 1, 1999; 19(7): 1791 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. R. Goodfield, D. E. Newby, C. A. Ludlam, and A. D. Flapan Effects of Acute Angiotensin II Type 1 Receptor Antagonism and Angiotensin Converting Enzyme Inhibition on Plasma Fibrinolytic Parameters in Patients With Heart Failure Circulation, June 15, 1999; 99(23): 2983 - 2985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Brunner-La Rocca, G. Vaddadi, and M. D. Esler Recent insight into therapy of congestive heart failure: focus on ACE inhibition and angiotensin-II antagonism J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1163 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pahor, M. B. Elam, R. J. Garrison, S. B. Kritchevsky, and W. B. Applegate Emerging Noninvasive Biochemical Measures to Predict Cardiovascular Risk Arch Intern Med, February 8, 1999; 159(3): 237 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Sayer, C. Gutteridge, D. Syndercombe-Court, P. Wilkinson, and A. D. Timmis Circadian activity of the endogenous fibrinolytic system in stable coronary artery disease: effects of beta-adrenoreceptor blockers and angiotensin-converting enzyme inhibitors J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1962 - 1968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown, M. A. Agirbasli, G. H. Williams, W. R. Litchfield, and D. E. Vaughan Effect of Activation and Inhibition of the Renin-Angiotensin System on Plasma PAI-1 Hypertension, December 1, 1998; 32(6): 965 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Bouchie, H. Hansen, and E. P. Feener Natriuretic Factors and Nitric Oxide Suppress Plasminogen Activator Inhibitor-1 Expression in Vascular Smooth Muscle Cells : Role of cGMP in the Regulation of the Plasminogen System Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1771 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Nesto and S. Zarich Acute Myocardial Infarction in Diabetes Mellitus : Lessons Learned From ACE Inhibition Circulation, January 13, 1998; 97(1): 12 - 15. [Full Text] [PDF]
|
|
|
|
|
|
H. Tomiyama, Y. Kimura, H. Mitsuhashi, T. Kinouchi, H. Yoshida, T. Kushiro, and N. Doba Relationship Between Endothelial Function and Fibrinolysis in Early Hypertension Hypertension, January 1, 1998; 31(1): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||