Springer - Publisher Connector

DOI 10.1007/s11789-017-0088-x
Clin Res Cardiol Suppl (2017) (Suppl) 12:18–21
Lipoprotein (a) and coronary heart disease – is there an efficient
secondary prevention?
Klaus-Peter Mellwig1 · Dieter Horstkotte1 · Frank van Buuren1
Published online: 23 February 2017
© The Author(s) 2017. This article is available at SpringerLink with Open Access.
Abstract Lipoprotein (a) (Lp (a)) is one risk factor for
the development of cardiovascular diseases. Several studies
have shown that Lp (a) hyperlipoproteinaemia has a partic-
ular influence on the development of coronary heart disease
(CHD). A retrospective single-centre observation study was
performed to evaluate the effectiveness of lipid apheresis on
the basis of consecutively performed percutaneous coronary
interventions (PCI) in patients with high Lp (a) values and
angiographically documented CHD.
In 23 pts (male 18, age 60.04 ± 0.58 years) with
angiographically documented CHD (first manifestation
48.00 ± 9.41 years), elevated LDL cholesterol (144.39 ±
92.01 mg/dl) and Lp (a) (133.04 ± 39.68 mg/dl), 49 PCI
and 3 coronary artery bypass grafting (CABG) procedures
had been performed prior to the initiation of lipid aphere-
sis. Following the initiation of weekly lipid apheresis, LDL
cholesterol was 99.43 ± 36.53 mg/dl and Lp (a) 91.13 ±
33.02 mg/dl. In a time interval of 59.87 ± 49.49 months
(median 51.00, range 1–153 months) 15 pts did not re-
quire an additional PCI. In 8 pts (7 pts 3-vessel disease,
1 pt 2-vessel disease) 14 PCI – no CABG – were per-
formed after 69.38 ± 71.67 months (median: 32.50, range
17–232 months). The incidence of PCI could thus be
reduced by 71.43%.
This article is part of the special issue “Lp(a) – the underestimated
cardiovascular risk factor”
 Klaus-Peter Mellwig
kpmellwig@hdz-nrw.de
1 Clinic for Cardiology, Herz- und Diabeteszentrum NRW,
Ruhr-Universität Bochum, Georgstr. 11, 32545 Bad
Oeynhausen, Germany
Keywords Lipoprotein (a) · Lp (a) · Coronary heart
disease (CHD) · Acute coronary syndrome · Intervention ·
Lipid apheresis · Prevention
Introduction
Lipoprotein (a) (Lp (a)) is one of the most atherogenous
lipoproteins and its impact on atherogenesis has become of
increasing scientific interest during recent years [1]. Many
studies have shown that elevated Lp (a) concentrations have
an important influence on the development of coronary
heart disease (CHD) [2–4]. The structure of Lp (a) con-
sisting of the Lp (a)-specific glycoprotein apolipoprotein-
a (APO (a)) implies the pro-atherogenous and pro-throm-
bogenous characteristics [3] with increased risk of myocar-
dial infarction and heart failure [5].
Our retrospective study in 31,734 patients over a 5-year
period documented that an increasing Lp (a) concentration
is associated with a higher incidence of CHD and severity
of vascular disease (Table 1) as well as more myocardial
infarctions, interventions and surgical myocardial revascu-
larizations (Table 2).
Current options of drug therapy are very limited. A sig-
nificant reduction of Lp (a) concentrations is neither
achieved by statins or ezetimibe nor by PCSK9 inhibitors
[6, 7]. In contrast, high doses of nicotinic acid (niacin)
(2–4 g) significantly reduce Lp (a) [8]. However, since
2013 this substance is not available any more in Europe
due to its side effects.
Lipid apheresis seems to be the only therapeutic option
providing a favourable effect on cardiac events and the pro-
gression of coronary heart disease.
K
Lipoprotein (a) and coronary heart disease – is there an efficient secondary prevention? 19
Table 1 Incidence of coronary vessel disease associated with increasing Lp (a) levels
Group 1 VD (%; n) 2 VD (%; n) 3 VD (%; n)
Lp (a)  2 mg/dl 10.3%; 22 8.5%; 18 9.9%; 21
Lp (a) 23–29 mg/dl 15.7%; 50 12.2%; 39 25.1%; 80
Lp (a) 30–60 mg/dl 15.6%; 35 9.8%; 22 27.1%; 61
Lp (a) 61–90 mg/dl 23.1%; 53 17.5%; 40 40.2%; 92
Lp (a) 91–110 mg/dl 19.2%; 30 19.9%; 31 38.5%; 60
Lp (a) > 110 mg/dl 14.0%; 37 18.2%; 48 50.4%; 133
VD vessel disease
Table 2 Incidence of myocardial infarction, PCI and CABG under increasing Lp (a) levels
Group Myocardial infarction (%; n) PCI (%; n) CABG (%; n)
Lp (a)  2 mg/dl 11.8%; 25 22.2%; 47 9.0%; 19
Lp (a) 23–29 mg/dl 16.6%; 53 33.6%; 107 20.8%; 66
Lp (a) 30–60 mg/dl 18.2%; 38 56.6%; 125 26.4%; 58
Lp (a) 61–90 mg/dl 26.9%; 61 78.5%; 179 33.5%; 76
Lp (a) 91–110 mg/dl 35.7%; 55 72.3%; 112 30.1%; 47
Lp (a) > 110 mg/dl 34.4%; 90 54.8%; 144 40.5%; 107
Fig. 1 Interventions (PCI/
myocardial revascularization)
before and after the initiation of
lipid apheresis
Patients and methods
In a retrospective, single-centre observation study, the ef-
fectiveness of lipid apheresis in patients with high Lp (a)
levels and angiographically documented coronary heart dis-
ease was evaluated on the basis of percutaneous coronary
intervention (PCI). All patients undergoing lipid apheresis
during the observation period with Lp (a) > 60 mg/dl prior
to the first procedure were included. All patients fulfilled
the criteria of the German federal authority to be eligible
for lipid apheresis, and reimbursement had been approved
by committees of regional associations of statutory health
insurance physicians. Furthermore, all patients gave their
informed consent to the scientific analysis of their data.
Twenty-three patients (male 18, age 60.04 ± 10.58 years)
fulfilled the above criteria and were included in the study
(Table 3). Apheresis was performed applying the heparin-
induced extracorporeal LDL precipitation (HELP) (Plas-
mat-Futura®, B. Braun, Melsungen, Germany) and the poly-
acrylate adsorption of whole blood or plasmapheresis by
means of double filtration (DALI® and MONET®, Frese-
nius Medical Care, Bad Homburg, Germany). During the
weekly procedures, lipid status (Lp (a), total cholesterol,
HDL cholesterol, LDL cholesterol, triglycerides) was ob-
K
20 K. Mellwig et al.
Table 3 Patient characteristics
Patients (n) 23
Men (n) 18
Women (n) 5
Age (y) (at the time of the study) 60.04 ± 10.58
Men (y) 61.11 ± 8.45
Women(y) 54.75 ± 14.72
Age (y) (first manifestation of CHD) 48.00 ± 9.20
Men (y) 50.00 ± 7.81
Women (y) 40.80 ± 10.19
BMI (kg.m–2) 26.33 ± 4.08
Coronary status Pat (n/%)
0-vessel disease 1/4.34
1-vessel disease 5/21.73
2-vessel disease 3/13.04
3-vessel disease 14/60.87
Vascular morphology (segm. occlu-
sion)
Pat (n/%)
1 vessel 5/21.73
2 vessels 2/8.68
3 vessels 1/4.34
PCI pre 49
Number of PCI Pat (n/%)
5 x PCI 1/4.34
4 x PCI 2/8.68
3 x PCI 5/21.73
2 x PCI 7/30.43
1 x PCI 7/30.43
0 x PCI 1/4.34
CABG prior to lipid apheresis 3/13.04
PCI post 14
Number of PCI Pat (n/%)
1 x PCI 5/21.73
2 x PCI 1/4.34
3 x PCI 1/4.34
4 x PCI 1/4.34
CABG following lipid apheresis 0
LV dysfunction Pat (n)
LV-EF: <0.50 5/21.7
Peripheral arterial occlusive disease Pat (n/%)
Angiographically proven 5/21.7
Intervention 3/13.0
Cerebral atherosclerosis Pat (n/%)
Symptomatic Insult 1/4.3
Carotid stenosis
(haemodynamically not relevant)
5/21.7
Arterial hypertension Pat (n/%)
Drug therapy 16/69.6
Chronic renal insuffiency (eGFR) Pat (n/%)
≥90 (ml/min) 13/56.52
60–89 (ml/min) 8/34.78
30–59 (ml/min) 2/8.69
tained before and after the procedure. Reduction of LDL
cholesterol and Lp (a) was 60–65% per procedure.
Lipid status
Prior to the initiation of lipid apheresis, LDL cholesterol
was 144.39 ± 92.01 mg/ld and Lp (a) 133.04 ± 39.68 mg/dl.
18 patients received the highest tolerated dosage of statins,
8 patients of them ezetimibe in addition. 5 patients had
a statin intolerance.
Cardiovascular status
Fourteen of 23 patients had a coronary 3-vessel disease (3-
VD), 3 patients a 2-VD, 5 patients a 1-VD. One patient
with a history of a TIA turned out to suffer from coro-
nary sclerosis (0-VD). In 5 patients, CHD was associated
with segmental occlusions and another 5 patients showed
an additional involvement of the vascular periphery and
the cerebrovascular region (Table 3). Patient age at first
disease manifestation was low with 48.00 ± 9.41 years, in
10 patients first manifestation was accompanied by an acute
coronary syndrome (ACS).
Prior to lipid apheresis, 49 PCI and 3 CABG procedures
had been performed in patients with a haemodynamically
relevant coronary stenosis. Lipid apheresis was initiated af-
ter a mean duration of 4.30 ± 4.95 years following first
manifestation of CHD. Thereafter, all patients underwent
non-invasive diagnosis on a routine basis every year and in-
vasive diagnostic procedure every 2 years followed by PCI
in case of a haemodynamically relevant stenosis (Table 3).
Results
At the time of the study, LDL cholesterol was 99.43 ±
36.53 mg/dl and Lp (a) 91.13 ± 33.02 mg/dl. In a time
interval of 59.87 ± 49.49 months (median 51.00, range
1–153 months) 15 patients did not require a PCI. For
the first time after initiation of lipid apheresis, 8 patients
(7 pat 3-VD, 1 pat 2-VD) underwent PCI after 69.38 ±
71.67 months (median: 32.50, range 17–232 months) the
total number of PCI being 14. Two of 3 patients with re-
current stenosis and multiple interventions had an in-stent
restenosis. CABG was not necessary (Fig. 1).
Discussion
The present study was intended to document the influence
of lipid apheresis on the incidence of PCI. The patient co-
hort with a high Lp (a) concentration was characterized by
a diffuse, advanced CHD with a high proportion of segmen-
K
Lipoprotein (a) and coronary heart disease – is there an efficient secondary prevention? 21
tal coronary occlusions. The additional high proportion of
patients with cerebrovascular and peripheral vascular dete-
rioration shows the vascular manifestations to be expected.
Regular lipid apheresis significantly reduced LDL
cholesterol and Lp (a). In contrast to the multicentre
prospective study evaluating cardiac events (MACE) after
the initiation of lipid apheresis [9], our collective underwent
PCI after documentation of a haemodynamically relevant
stenosis as a sign of major disease progression. The sig-
nificant decline in PCI procedures (71.43%) indicates the
impact on the atherosclerotic process mainly induced by
Lp (a) hyperlipoproteinaemia. This is of particular impor-
tance as it is a diffuse vascular disease of different vascular
origin with a strong tendency to progression. At present,
lipid apheresis has to be regarded as the most effective
therapeutic procedure in secondary prevention.
Conclusion
Our single centre observation study in patients with
markedly increased LDL cholesterol and Lp (a) values
accompanied by an early manifestation of coronary heart
disease and consecutive PCI or surgical myocardial revas-
cularization showed that lipid apheresis reduced the inci-
dence of PCI or surgical myocardial revascularization by
71.43%. This therapeutic option has to be part of secondary
prevention.
Conflict of interest K.-P. Mellwig received honoraria for lectures
and travel reimbursement from B. Braun and Fresenius Medical Care.
F. van Buuren received honoraria for lectures from Daiichi Sankyo,
Amgen and Fresenius Medical Care and travel reimbursement from
Biotronik. D. Horstkotte declares that he has no competing interests.
Open Access This article is distributed under the terms of the
Creative Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted
use, distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
made.
References
1. Bennet A, Di Angelantonio E, Erqou S et al (2008) Lipoprotein(a)
levels and risk of future coronary heart disease: large-scale prospec-
tive data. Arch Intern Med 168:598–608
2. Berg K, Dahlen G, Christophersen B et al (1997) Lp (a) lipoprotein
level predicts survival and major coronary events in the Scandina-
vian Simvastatin Survival Study. Clin Genet 52:254–261
3. Clarke R, Peden JF, Hopewell JC et al (2009) Genetic variants as-
sociated with Lp (a) lipoprotein level and coronary disease. N Engl
J Med 361:2518–2528
4. Luc G, Bard JM, Arveiler D et al (2002) Lipoprotein (a) as a pre-
dictor of coronary heart disease: the PRIME Study. Atherosclerosis
163:377–384
5. Kamstrup PR, Benn M, Tybjaerg-Hansen A (2008) Extreme
lipoprotein(a) levels and risk of myocardial infarction: th Copen-
hagen City HEART sTUDY. Circulation 117:176–184
6. Boffa MB (2016) Emerging therapeutic options for lowering of
lipoprotein(a): implications for prevention of cardiovascular dis-
ease. Curr Atheroscler Rep 18:69
7. Raal FJ, Giugliano RP, Sabatine MS et al (2016) PCSK9 inhibi-
tion-mediated reduction in Lp (a) with evolocumab: an analysis
of 10 clinical trials and the LDL receptor’s role. J Lipid Res
57:1086–1096
8. Sahebkar A, Reiner Z, Simental-Mendia LE et al (2016) Effect of
extended-release niacin on plasma lipoprotein(a) levels: a system-
atic review and meta-analysis of randomized placebo-controlled tri-
als. Metabolism 65:1664–16786
9. Leebmann J, Roeseler E, Julius U et al (2013) Lipoprotein aphere-
sis in patients with maximally tolerated lipid-lowering therapy,
lipoprotein(a)-hyperlipoproteinemia, and progressive cardiovascu-
lar disease: prospective observational multicenter study. Circulation
128:2567–2576
K


Lipoprotein (a) and coronary heart disease – is there an efficient secondary prevention?

Remla Miftah

Weyzer Tilahun

Atsde Fantahun

Seid Adulkadir

Kahsu Gebrekirstos

Knowledge and factors associated with pain management for hospitalized children among nurses working in public hospitals in Mekelle City, North Ethiopia: cross sectional study

Hai Liu

Guoxing Jing

Yueming Jiang

Fuying Luo

Zaifeng Li

The effect of carbamic acid, (1,2,3-thiadiazole-4-ylcarbonyl)-hexyl ester on Peronophythora litchii infection, quality and physiology of postharvest litchi fruits

Long-term outcomes of children undergoing video-assisted gastrostomy

An SQP method for mathematical programs with vanishing constraints with strong convergence properties

Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells

Genome-wide identification of conserved intronic non-coding sequences using a Bayesian segmentation approach

Systematic review of the health-related quality of life issues facing adolescents and young adults with cancer

Genetic variability within  Syd.- a pathogen of caraway  L

The Self-help Online against Suicidal thoughts (SOS) trial: study protocol for a randomized controlled trial

Not a member yet

Lipoprotein (a) and coronary heart disease – is there an efficient secondary prevention?