(Circulation. 1995;91:948-950.)
© 1995 American Heart Association, Inc.
Articles |
Rapid Angiographic Progression of Coronary Artery Disease in Patients With Elevated Lipoprotein(a)
From the Department of Cardiology (W. Terres, E. Tatsis, C.W.H.) and Lipid Laboratory, the Department of Medicine (B.P., F.U.B., U.B.), University Hospital Eppendorf, Hamburg, Germany.
Correspondence to Wolfram Terres, MD, Department of Cardiology, Medical Clinic, University Hospital Eppendorf, Martinistr 52, 20246 Hamburg, FRG.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background The mechanisms underlying rapid angiographic progression of coronary artery disease are still unknown. Intravascular thrombosis with or without plaque rupture may be involved.
Methods and Results In a prospective study in 79 patients
with coronary artery disease and at least one coronary diameter
stenosis 
50%, possible risk factors for rapid progression were
investigated. Quantitative coronary angiography was performed twice at
a mean time interval of 66±25 days. Rapid progression of coronary
disease defined as (1) an increase >10% in stenosis severity in at
least one stenosis 50%, (2) occurrence of a new stenosis 50%, or
(3) occlusion of a formerly patent vessel was found in 21 patients
(27%). Between patients with rapid progression and those without,
there were no significant differences in sex distribution, age, smoking
history, frequency of hypertension or diabetes mellitus, and serum LDL
cholesterol, HDL cholesterol, and apolipoprotein B concentrations. In
contrast, serum lipoprotein(a) [Lp(a)] concentrations 25 mg/dL
were
found in 14 of 21 patients (67%) with rapid progression of coronary
artery disease but in only 19 of 58 (33%) in the group without
progression (P=.007). The respective median Lp(a)
concentrations were 66 mg/dL (range, 2 to 139) and 13 mg/dL (range, 2
to 211; P=.01).
Conclusions Lp(a) appears to be a risk factor for the rapid angiographic progression of coronary artery disease. The pathophysiological link between Lp(a) and rapid progression may be an interference with thrombolysis through the partial structural homology of Lp(a) with plasminogen.
Key Words: lipoproteins • coronary disease • stenosis • risk factors • angiography
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Angiographic progression of coronary artery disease is frequently encountered in patients undergoing repeated coronary angiographies at short intervals.1 2 Studies in patients with acute coronary syndromes suggest that intravascular thrombosis or plaque rupture with superimposed thrombosis may occur.3 Acute thrombosis or plaque rupture and subsequent remodeling of thrombus or plaque may present angiographically as progressive narrowing of the vessel.4 Little is known about factors associated with or causative for rapid progression of coronary disease. The present prospective study investigated the role of smoking, blood pressure, diabetes mellitus, and serum lipids including lipoprotein(a) [Lp(a)] as risk factors for the progression of coronary artery disease in patients restudied at a mean (±SD) of 66±25 days after diagnostic coronary angiography before performing elective coronary angioplasty.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Seventy-nine consecutive patients with at least one coronary diameter stenosis
50% on angiography who fulfilled the following
criteria were included into the study: indication and patient consent
for elective percutaneous transluminal coronary angioplasty (PTCA) of
at least one stenosis; no prior PTCA or coronary artery bypass surgery,
no known interfering acute or chronic illness, and written informed
consent for participation in the study. Indication for PTCA was based
on the presence of exercise-induced anginal symptoms and/or the
detection of ischemia on stress test (ECG or 201-thallium myocardial
scintigraphy). On the occasion of PTCA after 66±25 days of waiting
time for elective procedures, a second left and right coronary
angiography was performed immediately before intervention. Both
angiographies were effected through a femoral approach obtaining the
same standardized views. Patients were maintained on an identical
chronic therapy, and no additional vasoactive drugs were given before
or during the procedures.
All pairs of angiograms were analyzed independently by two experienced
observers blinded for any information on the patients. In each coronary
angiogram, all stenoses 50% of the vessel diameter were identified
and quantified in the single projection where they appeared to be most
severe. For this purpose, selected cine frames at end diastole were
projected on a screen, and the stenosed arterial segment was traced
from the projected view. The projected image then was digitized and
corrected for pincushion distortion. For each image, a centerline was
constructed, with its perpendiculars intersecting at any point both
vessel edges at equal distances from itself. The extent of stenosis was
defined by comparison of the most narrow part of the segment with both
the normal proximal and distal portions of the vessel.5
With this method, the intraobserver variability of repeated
measurements for a given lesion is <5% in our laboratory.
Rapid progression of coronary artery disease was defined as (1) an
increase >10% in stenosis severity in at least one stenosis 50%,
(2) occurrence of a new stenosis 50%, or (3) occlusion of a formerly
patent vessel.
From all patients, standardized clinical information was obtained with the help of a specific questionnaire. The day before the second angiography, blood was collected and blood pressure was measured after 5 minutes of rest in a supine position. Total cholesterol, HDL cholesterol, and triglyceride concentrations were determined in serum, and LDL cholesterol concentration was calculated according to Friedewald.6 Apolipoprotein B was determined by radial immunodiffusion (Immuno) and Lp(a) by radioimmunoassay (Pharmacia).
Continuous variables were tested for normal distribution with the
Kolmogorov-Smirnov test. Between-group comparisons of normally
distributed variables were performed using the Student's t
test for unpaired data. Variables not normally distributed were
compared by the Mann-Whitney test, and frequencies were compared using
the 
2 test. For all statistical evaluations, a
two-sided P value of .05 or less was considered to be
statistically significant.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Rapid angiographic progression of coronary artery disease during a mean time interval of 66 days occurred in 21 of 79 patients (27%). Of these 21 patients, 14 had an increase >10% in the severity of a stenosis, 4 had a new stenosis
50%, and 1 had a new occlusion. Two
patients had an increase in stenosis severity in conjunction with
either a new stenosis or a new occlusion.
There were no significant differences in age, sex distribution, number
of vessels diseased, or time interval between angiographies between
patients with or without rapid progression of coronary artery disease.
Rapid angiographic progression tended to be more frequently associated
with worsening of angina pectoris from first to second angiography, but
the difference between the groups did not reach statistical
significance (Table 1
).
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Smoking behavior and the proportion of patients with elevated blood
pressure or diabetes mellitus were similar in the two groups. There
were no significant differences in serum LDL cholesterol, HDL
cholesterol, triglyceride, or apolipoprotein B concentrations (Table
2).
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In contrast, the serum Lp(a) concentrations were significantly higher
in patients with rapid progression of coronary artery disease than in
those without progression (Figure), with median values
of 66 mg/dL (range, 2 to 139) and 13 mg/dL (range, 2 to 211),
respectively (P=.01). Serum Lp(a) concentrations 25 mg/dL
were found in 14 of 21 patients (67%) with rapid progression of
coronary artery disease but in only 19 of 58 patients (33%) in the
group without progression (P=.007).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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Lp(a) is a plasma lipoprotein composed of apolipoprotein B-100, which is also the major component of LDL and apolipoprotein(a), linked covalently through a disulfide bridge.7 8 Apolipoprotein(a) has been shown to share a high degree of structural homology with plasminogen.9 10 In contrast to plasminogen, however, apolipoprotein(a) is not a zymogen and cannot be converted to an active fibrinolytic protease. It has been shown that Lp(a) attenuates the activation of plasminogen by streptokinase11 and tissue plasminogen activator12 in vitro and that there is competition between Lp(a) and plasminogen for binding sites on endothelial cells,13 platelets,14 and fibrinogen and fibrin.15 16 It has been postulated that the increased risk of myocardial infarction and cerebrovascular disease associated with elevated levels of Lp(a) may be explained by this antifibrinolytic action of Lp(a).13 16
The frequency of rapid angiographic progression of coronary artery disease is not low in clinical practice, but the reported rates vary largely, depending on the selection of patients, the definition of progression, and the method of angiographic assessment.1 2 In the present study, 27% of patients scheduled for elective PTCA had rapid angiographic progression of coronary artery disease according to predefined criteria after a mean time interval of 66 days.
The causes underlying rapid progression are unknown. Possible mechanisms include intracoronary plaque rupture and thrombosis, which may be encountered angiographically in early stages or after a period of remodeling of the inner vessel surface.4 In addition, accelerated proliferation of vascular wall cells also may lead to the angiographic picture of progressive narrowing.
In the present study, smoking, hypertension, and diabetes mellitus were similarly frequent in the two groups of patients with and without rapid progression of coronary artery disease. In addition, the serum concentrations of LDL cholesterol, HDL cholesterol, triglycerides, and apolipoprotein B were also similar. Thus, the classic cardiovascular risk factors did not appear to be risk factors for rapid progression. In contrast, serum Lp(a) concentrations were clearly elevated in patients with rapid angiographic progression compared with patients without progression. Lp(a) concentrations in the study group as a whole were higher than in healthy subjects and are typical for patients with manifest coronary disease.17
The possible pathophysiological link between elevated levels of Lp(a) and rapid progression of coronary artery disease may be the inhibitory effect of Lp(a) on fibrinolysis. With inhibition of fibrinolysis, intravascular thrombus formation may be enhanced in both the presence and the absence of a ruptured plaque. In a recent study, survivors of myocardial infarction whose infarct artery failed to recanalize were shown to have higher plasma Lp(a) concentrations than those with a patent infarct artery.18
Enhanced local thrombus formation may additionally translate into an enhanced reparative proliferative response of the vascular wall. This proliferative response may be increased by Lp(a), which was shown to stimulate the proliferation of human smooth muscle cells, probably by inhibiting the activation through plasmin of latent transforming growth factor-ß, an inhibitor of smooth muscle cell growth.19
Received October 17, 1994; revision received December 7, 1994; accepted December 18, 1994.
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