HI JeffN,
I too find Lp(a) fascinating. I have learned alot from cardiologist Sam Tsimikas @Lpa_Doc from
https://twitter.com/Lpa_Doc.
For instance, in the placebo arms of this trial, intra-individual variation up to +25% .
Temporal variability in lipoprotein(a) levels in patients enrolled in the placebo arms of IONIS-APO(a) Rx and IONIS-APO(a)-L Rx antisense oligonucleotide clinical trials
Santica M Marcovina 1, Nicholas J Viney 2, Steven G Hughes 2, Shuting Xia 2, Joseph L Witztum 3, Sotirios Tsimikas 4
https://pubmed.ncbi.nlm.nih.gov/29174389/ DOI: 10.1016/j.jacl.2017.10.024
Abstract
Background: Lipoprotein(a) [Lp(a)] levels are primarily genetically determined, but their natural variability is not well known.
Objective: The aim of the study was to evaluate the short-term temporal variability in Lp(a) in 3 placebo groups from the IONIS-APO(a)Rx and IONIS-APO(a)-LRx trials.
Methods: The placebo groups comprised 3 studies: Study 1 with 10 subjects with any Lp(a) concentration; Study 2 with 13 subjects with Lp(a) ≥75 nmol/L (∼30 mg/dL); and Study 3 with 29 patients with Lp(a) ≥125 nmol/L (≥∼50 mg/dL). Lp(a) was measured in serial blood samples (range 7-12 samples up to 190 days of follow-up) and analyzed as absolute change and mean percent change from baseline. Outliers were defined as having a > ±25% difference in Lp(a) from baseline at any future time point.
Results: No significant temporal differences in mean absolute Lp(a) levels were present in any group. However, among individuals, the mean change in absolute Lp(a) levels at any time point ranged from -16.2 to +7.0 nmol/L in Study 1, -15.8 to +9.8 nmol/L in Study 2, and -60.2 to +16.6 nmol/L in Study 3. The mean percent change from baseline ranged from -9.4% to +21.6% for Study 1, -13.1% to 2.8% for Study 2, and -12.1% to +4.9% in Study 3. A total of 21 of 52 subjects (40.4%) were outliers, with 13 (62%) >25% up and 8 (38%) >25% down. Significant variability was also noted in other lipid parameters, but no outliers were noted with serum albumin.
Conclusion: In subjects randomized to placebo in Lp(a) lowering trials, modest intra-individual temporal variability of mean Lp(a) levels was present. Significant number of subjects had > ±25% variation in Lp(a) in at least 1 time point. Although Lp(a) levels are primarily genetically determined, further study is required to define additional factors mediating short-term variability.