The impact of Niacin on Lp(a) might also differ depending on what type of apolipoprotein phenotype a person has and/or LPA genetics:
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This might help stratify the risk/reward decision for someone with high Lp(a) further.
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we recommend genetic testing for patients with elevated Lp(a) and to consider Niacin therapy in a patient-to-patient case based on genetic profile
Lowering of lipoprotein(a) level under niacin treatment is dependent on apolipoprotein(a) phenotype
Abstract
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.
Conclusion
High-dose ER niacin declines elevated Lp(a) level in male subjects with low- but not high-molecular weight apo(a) phenotype.
https://www.sciencedirect.com/science/article/abs/pii/S1567568815000094#:~:text=Niacin%20is%20effective%20not%20only,7]%2C%20[8].
Niacin decreases Lpa(a) by 20%. However, there has been cases reported in the literature with 60-80% reduction in Lp(a) levels by Niacin alone based on Lp(a) isoform. The following case presents a patient with reduction of Lp(a) levels by 68% with Niacin.
62-year-old male with past medical history of CAD with elevated calcium score 254 and elevated Lp(a). Patient presented to the cardiologist office to establish care and at that time Lp(a) was 325.7 nmol/L not on any lipid reducing agents. Patient was started on high dose Rosuvastatin and 6 months later, repeat Lp(a) level was persistently high 313 nmol/L (3.9% reduction). Patient was started on Niacin 500 mg daily and 5 months later Lp(a) levels significantly reduced to 115 nmol/L (63% reduction).
Recent studies have shown that reduction of Lp(a) by Niacin could be related to Apolipoprotein(a) isoform size, which normally confers rate of Lp(a) anabolism and catabolism as well as structural and functional properties of Lp(a). However, apart from apo(a) isoform size, Niacin also binds to the LPA gene promoter region. Our patient underwent genetic testing, he had rs3798220 variant in LPA gene.Research has shown that the presence of such sequence variants near the promoter region, can affect niacin regulation and furthermore can explain the difference of Niacin effectivity among patients.
Conclusion
Based on these findings, we recommend genetic testing for patients with elevated Lp(a) and to consider Niacin therapy in a patient-to-patient case based on genetic profile.
https://www.jacc.org/doi/10.1016/S0735-1097(23)03757-9
