Atherosclerosis Supplements 18 (2015) 163e169

www.elsevier.com/locate/atherosclerosis

Specific Lipoprotein(a) apheresis attenuates progression of carotid

intima-media thickness in coronary heart disease patients with high
lipoprotein(a) levels
M.V. Ezhov a,*,1, M.S. Safarova a,1, O.I. Afanasieva b, O.A. Pogorelova c, M.I. Tripoten c,
I.Y. Adamova b, G.A. Konovalov d, T.V. Balakhonova c, S.N. Pokrovsky b
a
Atherosclerosis Department, Institute of Clinical Cardiology named after A.L. Myasnikov, Federal State Institution “Russian Cardiology Research and
Production Center” of Ministry of Health of the Russian Federation, 15A, 3d Cherepkovskaya Street, Moscow 121552, Russia
b
Laboratory of Atherosclerosis, Institute of Experimental Cardiology, Federal State Institution “Russian Cardiology Research and Production Center” of
Ministry of Health of the Russian Federation, 15A, 3d Cherepkovskaya Street, Moscow 121552, Russia
c
Ultrasound Laboratory, Institute of Clinical Cardiology named after A.L. Myasnikov, Federal State Institution “Russian Cardiology Research and
Production Center” of Ministry of Health of the Russian Federation, 15A, 3d Cherepkovskaya Street, Moscow 121552, Russia
d
Center of Extracorporeal Therapies, MEDSI Clinic, 3A, Georgian Lane, Moscow 123056, Russia

Abstract

Background: To date, there have been no studies evaluating the effect of isolated lipoprotein(a) (Lp(a)) lowering therapy on carotid
atherosclerosis progression.
Methods: We enrolled 30 patients who had coronary heart disease (CHD) verified by angiography, Lp(a) level
50 mg/dL, and low density
lipoprotein cholesterol (LDL-C) level 2.6 mmol/L (100 mg/dL) on chronic statin therapy. Subjects were allocated in a 1:1 ratio to receive
apheresis treatment on a weekly basis with immunoadsorption columns (“Lp(a) Lipopak”Ò, POCARD Ltd., Russia) added to atorvastatin,
or atorvastatin monotherapy. The primary efficacy end-point was the change from baseline in the mean intima-media thickness (IMT) of the
common carotid arteries.
Results: After one month run-in period with stable atorvastatin dose, LDL-C level was 2.3  0.3 mmol/L and Lp(a) e 105  37 mg/dL. As
a result of acute effect of specific Lp(a) apheresis procedures, Lp(a) level decreased by an average of 73  12% to a mean of 29  16 mg/
dL, and mean LDL-C decreased by 17  3% to a mean of 1.8  0.2 mmol/L. In the apheresis group, changes in carotid IMT at 9 and 18
months from baseline were 0.03  0.09 mm (p ¼ 0.05) and 0.07  0.15 mm (p ¼ 0.01), respectively. In the atorvastatin group no
significant changes in lipid and lipoprotein parameters as well as in carotid IMT were received over 18-month period. Two years after study
termination carotid IMT increased by an average of 0.02  0.08 mm in apheresis group and by 0.06  0.10 mm in the control group
(p ¼ 0.033).
Conclusion: Isolated extracorporeal Lp(a) elimination over an 18 months period produced regression of carotid intimaemedia thickness in
stable CHD patients with high Lp(a) levels. This effect was maintained for two years after the end of study.
Trial Registration: Clinicaltrials.gov (NCT02133807).
Ó 2015 Elsevier Ireland Ltd. All rights reserved.

Keywords: Lipoprotein(a); Lp(a) apheresis; Immunoadsorption; Carotid intima-media thickness; Atherosclerosis; Regression

* Corresponding author. Tel.: þ7 (495) 414 6067, þ7 (910) 413 7499 (mobile); fax: þ7 (495) 414 6067.
E-mail address: Marat_Ezhov@mail.ru (M.V. Ezhov).
1
MV Ezhov and MS Safarova contributed equally to this work. These authors are joint first authors.

http://dx.doi.org/10.1016/j.atherosclerosissup.2015.02.025
1567-5688/Ó 2015 Elsevier Ireland Ltd. All rights reserved.
164 M.V. Ezhov et al. / Atherosclerosis Supplements 18 (2015) 163e169
1. Introduction
Large epidemiological and genetic studies determine
lipoprotein(a) (Lp(a)) as an independent cardiovascular risk
factor [1], associated with accelerated coronary athero-
sclerosis progression [2], increased risk of coronary death,
myocardial infarction (MI) and ischemic stroke [3,4].
However, there are controversial data on the relationship
between Lp(a) level and course of carotid atherosclerosis
[5e7].
Generally accepted therapeutic approaches for lowering
Lp(a) are limited to niacin and lipoprotein apheresis [1].
Until now, there are few data showing that substantial
decrease in Lp(a) of less than 30 mg/dL would affect course
of atherosclerosis and diminish the risk of subsequent
vascular events. At present, the prognostic evidence is
based on results from two multicenter studies. In 2009,
Jaeger et al. demonstrated that lowering Lp(a) level from
the mean of 108 to 30 mg/dL with the use of lipoprotein
apheresis in severe CHD patients (n ¼ 120) resulted in the
reduction of coronary event rate by 86% during mean of 5
years [8]. Notably, different commercially available lipo-
protein apheresis systems were used in that study, and all of
them had a significant impact on lipid profile of the
included patients. In 2013, Leebman et al. demonstrated
a decreased incidence rate of atherosclerotic events by 78%
within two years of non-specific lipoprotein apheresis in
170 patients with elevated Lp(a) (104.9  45.7 mg/dL),
progressive cardiovascular disease, and maximally toler-
ated lipid-lowering drug-therapy [9]. However, neither
study could elucidate the impact of Lp(a) lowering on
cardiac outcomes beyond lipoprotein apheresis effect. The
only study investigating the ability of isolated Lp(a)
lowering treatment to achieve coronary disease regression
as compared to standard medical approach was performed
by our group [10]. The purpose of the present sub-study
was to evaluate the impact of specific Lp(a) apheresis
added to optimal medical therapy of stable CHD patients
with elevated Lp(a) level on carotid atherosclerosis.
2. Materials and methods
The design of LaRCA (Specific Lp(a) Apheresis for
Regression of Coronary and Carotid Atherosclerosis) study
has been previously described [10]. Briefly, this prospec-
tive, open-label controlled 18-month study was designed
for stable CHD patients with clinical indications for coro-
nary angiography. All participants had Lp(a) levels of more
than 50 mg/dL, and low density lipoprotein cholesterol
(LDL-C) 2.6 mmol/L (100 mg/dL). With regard to the
extent of limitation on daily activities and the kind of
physical activity that provokes the anginal episode, the
patients were classified according to the Canadian Cardio-
vascular Society (CCS) Classification of angina pectoris
[11]. This study was conducted according to the principles
of the Declaration of Helsinki and the Institutional Ethics
Committee. All patients provided written informed consent.
After a one-month run-in period with open-label ator-
vastatin in a stable dose, eligible subjects were allocated
into two groups in a 1:1 ratio. The dose of atorvastatin
ranged from 20 to 80 mg per day. At screening participants
were evaluated for the evidence of traditional atheroscle-
rotic risk factors, history of MI and/or revascularization.
Functional class of angina was assessed, and a stress test
was performed in order to verify myocardial ischemia.
Patients of the main group received specific Lp(a) apheresis
with immunoadsorption “Lp(a) Lipopak”Ò columns
(POCARD Ltd., Moscow, Russia) on a weekly basis in
addition to the optimal medical therapy. The detailed
protocol of extracorporeal procedure as well as character-
istics of used immunoadsorption columns are described
elsewhere [10].
Ultrasound duplex scanning of both common carotid
arteries was performed four times for each included patient:
at baseline, after 9 and 18 months of active period, and two
years after completion of the protocol-specific procedures.
Patients underwent B-mode carotid ultrasonography with
the use of Philips IU22 ultrasound system with 9e13 MHz
linear array transducer (Philips Electronics Ltd., Germany).
Depth and gain were chosen to give optimal image quality
with the best visualization of “intima-lumen” interface and
all three layers of posterior wall. Real-time images of
common carotid artery (CCA) were synchronized with R-
wave of ECG. Intima-media thickness (IMT) of the right
and left CCA in anterior plane was measured at a distance
of one cm proximal to the carotid bifurcation. Measure-
ments were performed three times during consecutive heart
cycles. Mean far wall IMT of the right and left CCA was
measured with Qlab (Philips) automated system (according
to Mannheim carotid IMT and plaque consensus 2011 and
recommendations of American Society of Echocardiog-
raphy 2008) [12,13]. The values of carotid IMT (CIMT)

1.5 mm were excluded from analysis. Two independent
operators with 4.8% intra- and 5.1% interobserver repro-
ducibility of automatic CIMT measurement were blinded to
the treatment allocation. The primary efficacy end-point for
this sub-study was the absolute change from baseline
through 18 months of the mean posterior wall IMT of the
left and right CCA. As shown earlier, the average rate of
increase in CIMT for the similar category of patients was
0.015 mm per year [14], so we defined criterion for stabi-
lization and regression of CIMT as change in
0.02 mm in
comparison with baseline at the scheduled visits.
Blood samples were drawn after 8e12 h of fasting at
each appointment for carotid duplex scan. In patients
receiving specific Lp(a) apheresis, levels of total choles-
terol (TC), triglycerides (TG), high-density lipoprotein
(HDL-C), and Lp(a) were additionally measured before and
after each immunoadsorption procedure. Lp(a) concentra-
tion was determined by enzyme-linked immunosorbent
assay using monospecific polyclonal sheep anti-human-
 M.V. Ezhov et al. / Atherosclerosis Supplements 18 (2015) 163e169 165

Table 1
Baseline characteristics of studied patients.
Variable, n (%) Lp(a) apheresis N ¼ 15 Atorvastatin N ¼ 15 P Value
Age, years 51.4  9.3 55.6  6.8 0.17
Male sex 11 (73) 10 (67) 1.0
Body mass index, kg/m2 27.5  4.0 28.3  7.3 0.72
Body mass index >30 kg/m2 4 (27) 3 (20) 1.0
Hypertension 9 (60) 9 (60) 1.0
Current smoking 4 (27) 3 (20) 1.0
Diabetes mellitus 3 (20) 1 (7) 0.60
Family history of coronary heart disease 7 (47) 8 (53) 1.0
History of coronary heart disease
Angina pectoris III-IV class 7 (47) 4 (27) 0.45
Myocardial infarction 12 (80) 10 (67) 0.68
Percutaneous coronary revascularization 11 (73) 8 (53) 0.45
Coronary bypass surgery 1 (7) 1 (7) 1.0
Concomitant medications
Antiplatelets 15 (100) 15 (100) 1.0
Beta-blockers 13 (87) 12 (80) 1.0
Angiotensin-converting enzyme inhibitors 6 (40) 10 (67) 0.27
Angiotensin receptor antagonists 7 (47) 2 (13) 0.11
Calcium antagonists 5 (33) 6 (40) 1.0
Organic nitrates 7 (47) 6 (40) 1.0
Mean atorvastatin dose, mg 34  13 32  10 0.69
Biochemical values
Lipoprotein(a), mg/dL 103  23 101  52 0.88
TC, mmol/L 4.6  0.5 4.5  0.5 0.41
LDL-C, mmol/L 2.2  0.2 2.3  0.3 0.38
LDL-Ccorr, mmol/L 2.0  0.6 1.9  0.4 0.60
HDL-C, mmol/L 1.2  0.3 1.4  0.3 0.06
Triglycerides, mmol/L 1.4  0.5 1.4  0.5 0.85
Pluseminus values are means  SD. The body-mass index is the weight in kilograms divided by the square of the height in meters. To convert the values for
lipoprotein(a) to mmol/L multiply by 0.0357. To convert the values for cholesterol to mg/dL, divide by 0.0259. To convert the values for triglycerides to mg/
dL, divide by 0.0113. LDL denotes low-density lipoprotein, and HDL high-density lipoprotein.

apolipoprotein(a) antibodies as previously reported [15]. As
in all patients TG were <4.5 mmol/L, LDL-C concentra-
tion was determined with Friedewald formula. The level of
LDL-C corrected for Lp(a) cholesterol was estimated with
modified Friedewald equation: LDL-Ccorr ¼ TC  HDL-
C  TG/2.2  0.3  Lp(a)/38.7 (mmol/L). The interval
mean was calculated using the A. Kroon’s equation [16]
Cmean ¼ Cmin þ 0.73  (Cmax  Cmin), where Cmin was
cholesterol level immediately after an apheresis, Cmax e at
the start of the subsequent procedure.
STATISTICA (version 10, StatSoft Inc., USA) software
was used to perform all analyses. For continuous variables
mean  standard deviation and/or a median and inter-
quartile interval were applied. The normality of the distri-
bution was assessed with the Shapiro-Wilkes test. Cate-
gorical parameters were presented as absolute values and
percentages. The Wilcoxon test was used in assessing the
change of CIMT and biomarkers with the baseline; for the
estimation of the between-group differences comparison
was performed with the ManneWhitney U-test. Estimation
of changes from baseline (X1) to nine or 18 months, or two
years of follow-up after the end-of-study visit (X2) were
presented as absolute (D) values with the following equa-
tion: Y2eY1. Categorical variables were summarized
using frequencies and compared using the chi-square test or
Fisher’s exact test, as appropriate. Spearman rank-order
correlation coefficient was used to test a relationship
between CIMT change and biomarkers over the whole
study period. For the correlation analysis for the patients
from the apheresis group we used blood tests drawn at the
scheduled visits at 9 and 18 months after at least one week
after the procedure was performed. A simple linear
regression model was created to describe the relationship
between Lp(a) level and changes in CIMT. A two-sided P
value <0.05 was considered to indicate statistical
significance.
3. Results
3.1. Patient characteristics
Of the 32 eligible patients, 30 underwent coronary
angiography and intravascular ultrasound at baseline and
follow-up; therefore, we present carotid duplex imaging
data for these patients. Mean age was 53.5  8.1 years,
70% were men, one-half of patients had positive CHD
history, about 70% had either a prior history of MI or
coronary revascularization, 13% had diabetes mellitus, and
23% were current smokers. Baseline characteristics are
presented in Table 1. In LaRCA cohort after one month of
166 M.V. Ezhov et al. / Atherosclerosis Supplements 18 (2015) 163e169
stable atorvastatin dose, LDL-C level was 2.3  0.3 mmol/
L, Lp(a) was 105  37 mg/dL, In specific Lp(a) apheresis
group, difference before and immediately after procedures
in Lp(a) level was 73  12%, resulting in a mean of
29  16 mg/dL; LDL-C decreased by 17  3% to a mean
of 1.8  0.2 mmol/L, corrected LDL-C decreased by
7  3%, producing a final mean of 1.9  0.2 mmol/L. The
final change in Lp(a) level in the immunoadsoption group
was 31.7  22.3 mg/dL, as compared with
4.8  10.8 mg/dL in the atorvastatin monotherapy group
(p < 0.0001). According to Kroon’s equation, the interval
mean values for Lp(a) were 73.3  13.2 mg/dL. The final
change in LDL-C level in the apheresis group was
0.1  0.4 mmol/L, as compared with 0.1  0.3 mmol/L
in the control group (p ¼ 0.96). LDL-C level corrected for
Lp(a) cholesterol statistically unchanged: 0.2  0.6 and
0.1  0.6 (mmol/L) for apheresis and control groups,
respectively (p ¼ 0.65).
3.2. Common carotid intima-media thickness
measurements
Fig. 1 describes the baseline and follow-up changes in
CIMT findings. In patients on regular Lp(a) apheresis
treatment, carotid atherosclerosis regressed significantly by
Fig. 1. Changes in the mean carotid intima-media thickness over 18 month-
study period and in 2 years follow-up in apheresis group (A; 30 segments)
and control group (B; 30 segments). Red line denotes the resulting one by
mean.
an absolute change in CIMT of 0.03  0.09 mm
(p ¼ 0.05) at 9 months, and 0.07  0.15 mm (p ¼ 0.01) at
18 months. Two years after the last procedure was finished
for each patient, CIMT increased on average by
0.02  0.08 mm (p ¼ 0.12 in comparison with the baseline,
p ¼ 0.3 versus end of study) (Fig. 1a). Over the active study
period, no significant changes in CIMT were observed in
the control group. However, two years after the end of
study CIMT increased by up to 0.06  0.10 mm (p ¼ 0.18
versus baseline, p ¼ 0.0006 versus end of study; p ¼ 0.033
for between-group comparison) (Fig. 1b). After 18 months
of regular immunoadsorption treatment, regression of
CIMT occurred in 56% (17/30) of the carotid segments,
whereas in the control group CIMT declined in only 26%
(8/30) of segments, c2 ¼ 5.57, p ¼ 0.06 (Fig. 2a). Two
years after study concluded, visits were conducted for all
patients, but one patient from the apheresis group had
inappropriate imaging quality of CIMT. Mostly carotid
segments fulfilling regression/stabilization criteria were
met in patients who received active treatment strategy: 64%
(20 of 28) in comparison with 37% (11 of 30) in control
group participants, c2 ¼ 5.32, p ¼ 0.07 (Fig.2b). Direct
relationship was observed between decrease in Lp(a)
concentration at the scheduled visits and reduction in mean
CIMT (r ¼ 0.29, p < 0.05).
Fig. 2. Number of carotid segments with and without intima-media
thickness progression, stabilization or regression at 18 months (A) and 2
years after study termination (B).
 M.V. Ezhov et al. / Atherosclerosis Supplements 18 (2015) 163e169
After the 18-month course of apheresis treatment, most
patients (6 of 7) improved in CCS angina class from III-IV
to II (p ¼ 0.06). Furthermore, there was a decrease in the
number of positive stress-tests from 90% (11 of 12) to 50%
(6 of 12), p < 0.01. In the control group, the number of
subjects with angina class III increased from 27% (4 of 15)
to 47% (7 of 15) and the number of positive stress-tests
remained unchanged (12 of 14 to 11 of 14); the differ-
ence from baseline was non-significant. Moreover, three
cases of coronary artery stenting were reported in this
group during the study. Two years after active study period,
there was no angina progression in patients treated earlier
with specific Lp(a) apheresis, whereas in control group
eight subjects remained at CCS class III (p ¼ 0.01).
Myocardial revascularization was performed in one case
from group initially treated with immunoadsorption and in
two patients from control group. It should be noted that
after completion of 18 months of study noncompliance with
statin therapy was observed in one and three patients,
respectively. These data support the fact that patients
allocated to apheresis treatment were more likely to strictly
follow investigators’ recommendations. Moreover, during
the follow-up period, mean atorvastatin dose had
a tendency to be higher in the main group in comparison
with control: 44  30 mg versus 27  24 mg per day
(p ¼ 0.09).
4. Discussion
In this study we compared the effect of the conventional
treatment strategy with addition of specific extracorporeal
Lp(a) removal approach on subclinical carotid atheroscle-
rosis burden assessed by duplex scan. The analyzed cohort
of CHD patients was unique for high Lp(a) levels and
reached target LDL-C goals on the background of chronic
statin therapy. During the active study phase, the classical
atherosclerotic risk factors were under strict control: proper
use of antihypertensive drugs with targeting blood pressure,
HDL-C exceeded 1.1 mmol/L, TG was less than 1.7 mmol/
L, reaching LDLeC at 2.3  0.3 mmol/L, LDL-C adjusted
to the Lp(a) level was less than 2.0 mmol/L. The impor-
tance of low-fat diet and smoking cessation were empha-
sized at each visit during active follow-up of study
participants. Thus, we consider that the main underlying
cause of atherosclerosis disease progression in these
patients was substantial excess in Lp(a) levels. Our results
further support recently introduced new indication for
lipoprotein apheresis for the purpose of ischemic events
prevention and elevated Lp(a) levels that was accepted by
several medical communities [17].
To the best of our knowledge, this research is the first
interventional evidence demonstrating causal relationship
between diminishing of high Lp(a) concentration and
carotid atherosclerosis regression. We showed a decrease in
CIMT during the course of specific Lp(a) apheresis by
0.03 mm at 9 months and by 0.07 mm at 18 months.
167
Importantly, the effect sustained over the next two years
with mean increase in CIMT by 0.01 mm per year. In the
control group CIMT remained unchanged over the active
study period but increased by 0.06 mm after two years of
follow-up. Throughout the whole study period there was no
significant change in lipid parameters in the control group
that was attributed to the fact that patients were on chronic
statin therapy.
As an acute effect of immunoadsorption procedures,
Lp(a) decreased by an average of 73  12%, resulting in
29  16 mg/dL (mean value that was measured after the
procedures in 15 patients during the whole active study
period). In the active treatment group, after 9 and 18
months Lp(a) was reduced by an average of 26% (28 mg/
dL to mean of 79 mg/dL) and 28% (33 mg/dL; 74 mg/
dL), respectively. This finding corresponds well to previous
studies showing acute decrease in Lp(a) level by 70e85%
with specific immunoadsorption columns, and sustained
moderate decrease in Lp(a) as a result of regular long-term
treatment [18e20].
There is no doubt that among available therapies lipo-
protein apheresis is the most effective method for reducing
Lp(a) concentration in plasma. However, concomitant
elimination of other atherogenic lipoproteins should also be
taken into account [8,9,21]. The primary hypothesis of our
study was to prove the pathogenic role of Lp(a) in the
atherosclerotic disease progression. Thus, an agent that
specifically eliminates Lp(a) from the blood can serve as an
ideal tool for testing this hypothesis. As is known, during
immunoadsorption procedures the degree of Lp(a) reduc-
tion is directly related to the volume of treated plasma.
Therefore, for each patient an individual treatment regimen
was worked out, that took into account baseline Lp(a) level,
its recovery curve, and characteristics of metabolism.
Importantly, actual LDL-C level did not change signifi-
cantly: correcting for Lp(a) cholesterol LDL-C level
confirmed the stability of this parameter.
Epidemiological studies show that carotid atheroscle-
rosis progression is an independent risk factor for cardio-
vascular complications [22]. In particular, increase in
CIMT by
0.03 mm per year was associated with
progressive increase in incidence of adverse events in
familial hypercholesterolemia (FH) patients [23]. Accord-
ing to a meta-analysis of eight large-scale studies with
a total of 37,197 subjects enrolled, an increase in CIMT by
0.1 mm was related to the increase in risk of MI by 15%
and stroke e by 18% [24]. It was demonstrated that in
untreated FH patients estimated progression of CIMT is
about 0.05 mm/year [25], and in individuals with LDL-C
level in the range of 4.8e5.0 mmol/L this value reached
0.03 mm/year [26]. In this study we have shown that in
patients with high Lp(a) levels without specific treatment
rate of CIMT progression was 0.03 mm per year.
In the unblinded randomized study of male subjects with
hypercholesterolemia (n ¼ 21) an addition of lipoprotein
apheresis on top of simvastatin 40 mg over two years
168 M.V. Ezhov et al. / Atherosclerosis Supplements 18 (2015) 163e169
resulted in CIMT decrease by 0.05  0.34 mm, whereas in
the control group (n ¼ 21) of monotherapy with simvastatin
40 mg there was an opposite effect e increase in CIMT by
0.06  0.38 mm (p < 0.001) [25]. There were following
changes in lipoproteins: mean LDL-C level was reduced
from mean of 7.8 to 3.0 mmol/L, Lp(a) e from 57.0 to
44.5 mg/dL (19%) in patients from the main group,
whereas in the control group LDL-C was decreased from
7.9 mmol/L to 4.1 mmol/L, and Lp(a) was increased from
38.4 to 44.5 mg/dL (þ15%). Multiple regression analysis
highlighted significant association between progression of
carotid atherosclerosis and changes in Lp(a) and apoAI
levels. In our cohort of patients treated with atorvastatin as
a background we also revealed a direct relationship
between changes in CIMT and Lp(a) level (r ¼ 0.29,
p < 0.05). Previously, we have shown that in similar
category of patients with CHD and elevated Lp(a) levels
combination treatment with niacin and atorvastatin resulted
in a 23% reduction in Lp(a) level and CIMT decrease by
0.06 mm over six-months study period [27]. A correlation
analysis demonstrated that changes in CIMT were directly
related to the changes in Lp(a) (r ¼ 0.42, p ¼ 0.04) and TG
(r ¼ 0.37, p ¼ 0.02) concentration, but not to the changes in
LDL-C and HDL-C levels. The effect of specific Lp(a)
apheresis on CIMT confirmed the clinical importance of
Lp(a) correction.
Several limitations of the present study should be noted.
First, LaRCA design was unblinded and nonrandomized;
however, subjects from the control group were clinically
comparable to the patients from the active group. More-
over, to minimize bias in data interpretation, sonographers
and laboratory technicians were blinded to the participants’
treatment assignment. Second, this was a pilot small sample
size study that was not aimed to assess frequency of
cardiovascular events. Third, the approval of the study
protocol and enrollment of the subjects were completed
before the publication of the new version of the European
guidelines on management of dyslipidemia, in which LDL-
C goal of less than 1.8 mmol/L for very high risk patients
was emphasized [28]. It should be mentioned that LDL-C
corrected for Lp(a) was less than 2.0 mmol/L in this
cohort during the active study period. Finally, our study
used surrogate end-point and encompasses the experience
at a single center; therefore the generalizability of our
findings may not extend to all clinics performing lipopro-
tein apheresis in CHD patients.
5. Conclusion
The addition of specific Lp(a) apheresis for 18 months to
guidelines-supported medical therapy of CHD patients
resulted in carotid intima-media thickness regression.
Moreover, clinical effect of specific Lp(a) apheresis was
maintained up to two years after Lp(a) apheresis termina-
tion. These results provide evidence for Lp(a) as a cardio-
vascular trait. Further large trials are essential to elucidate
insights into the mechanisms of protective effects of Lp(a)
reduction in cerebrovascular disease prevention.
Conflict of interest statement
All authors report no financial relationships or conflicts
of interest regarding the content herein.
Acknowledgments
The study was supported by the research grant No 8/3-
284n-10 from the Moscow State Government.
The authors acknowledge the help of Kathy Eisenhofer
in preparation of this paper.
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