Lowering of lipoprotein(a) level under niacin treatment is dependent on apolipoprotein(a) phenotype.
BACKGROUND
Lipoprotein(a) [Lp(a)] is a cardiovascular risk factor; in addition to being a low-density lipoprotein (LDL)-like particle, it contains highly heterogeneous apolipoprotein(a) [apo(a)]. No prior studies have evaluated extended-release (ER) niacin effect on Lp(a) level depending on apo(a) phenotype.


METHODS
For this 24-week, prospective, open-label clinical trial we recruited 30 men (mean age 46.2 ± 7.5 years) with Lp(a) levels >20 mg/dL. No participant had previously received lipid lowering therapy, and started ER niacin 500 mg with stepwise dose increasing up to 1.5-2.0 g. Subjects were evaluated for Lp(a), lipids, high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 (Lp-PLA2), and fibrinolytic markers (plasminogen activator inhibitor-1, tissue plasminogen activator/plasminogen activator inhibitor-1 complex, plasmin-antiplasmin complex). Patients were divided into two groups with major low- (LMW) or high-molecular weight (HMW) apo(a) isoforms determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of plasma under reducing conditions followed by immunoblotting.


RESULTS
At baseline, groups were comparable in age, lipid, inflammatory and fibrinolytic biomarkers levels. There was a significant difference in baseline Lp(a) concentrations: 92 ± 29 mg/dL versus 54 ± 46 mg/dL in LMW and HMW apo(a) groups, respectively, p < 0.01. During the course of niacin treatment Lp(a) decreased by 28% (p < 0.003), Lp-PLA2 by 22% (p < 0.001), C-reactive protein by 24% (p = 0.07) in LMW apo(a) group, whereas no changes in Lp(a) and biomarkers levels were obtained in HMW apo(a) group.


CONCLUSIONS
High-dose ER niacin declines elevated Lp(a) level in male subjects with low- but not high-molecular weight apo(a) phenotype.
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. Electronic address: artemevanv@gmail.com.
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Artemeva
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.
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Safarova
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.
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Ezhov
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.
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Afanasieva
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.
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Dmitrieva
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.
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Pokrovsky
D000328:Adult; D053241:Apoprotein(a) / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015536:Down-Regulation; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009525:Niacin / Q000627:therapeutic use*; D018579:Patient Selection; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012426:Russia; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D000960:Hypolipidemic Agents; D017270:Lipoprotein(a); D009525:Niacin; D053241:Apoprotein(a)
Apolipoprotein(a) phenotype; Lipoprotein(a); Niacin