Lp(a) Can Vary Over Time in ASCVD Patients With High Baseline Levels: OCEAN(a)-DOSE

Serial measurements of lipoprotein(a) can change by as much as 10% over time for about one in five patients with atherosclerotic cardiovascular disease (ASCVD) and high Lp(a) concentration at baseline, according to new data from the placebo arm of OCEAN(a)-DOSE.

With the general consensus now being to measure Lp(a) only once over a person’s lifetime due to the key role genetics usually play in this characteristic, the authors say the data suggest that some patients may need additional measurements over time if this information is being used to guide treatment decisions.

“The intent here was just to highlight that there is a fair amount of variability that is observed when serial Lp(a) values are obtained over what was a relatively short time frame,” senior author Michelle L. O’Donoghue, MD, MPH (Brigham and Women’s Hospital, Boston, MA), told TCTMD. “There is clinical relevance for looking at people with high values at baseline, because ultimately these are really the patients that we're going to be considering initially for some of these Lp(a)-lowering therapies.”

Placebo-Arm Findings

For the study, published as a brief report this week in the Journal of the American College of Cardiology, Prakriti Gaba, MD, MPH (Brigham and Women’s Hospital), O’Donoghue, and colleagues included the 53 patients with ASCVD and elevated baseline Lp(a) from the randomized OCEAN(a)-DOSE trial who were assigned to placebo. Patients had a median of 16 Lp(a) measurements taken over approximately a 1.7-year follow-up period, with a median Lp(a) value of 257 nmol/L across all follow-up visits.

Overall, Lp(a) concentrations varied across study visits, with a median of 16.4 nmol/L (6.2%) absolute variability observed compared with an individual’s mean Lp(a) value and a maximum absolute difference of 135 nmol/L (49%).

One-quarter of patients had a relative change in Lp(a) in either direction of at least 25%, and just over half had an absolute change of at least 50 nmol/L. Almost one-third of patients saw their baseline Lp(a) value change by 5%-10%, and 19% had a change of at least 10%.

Notably, Lp(a) concentration remained constant over the study period for the entire placebo arm, the researchers noted a 10% rate of intraindividual variation which only dropped to 9.5% when two outliers were removed from the analysis. This rate of intraindividual variation was smaller than those observed for LDL-cholesterol (15.6%; P = 0.005) and triglycerides (22%; P < 0.001), but comparable to what was observed with apolipoprotein B (10.8%; P = 0.60).

‘Fair Amount of Fluctuation’

The idea behind the trial came from anecdotes that O’Donoghue heard about “people who had very high Lp(a) values when measured in a local clinic but then when they were brought in to be considered for one of the Lp(a)-lowering therapeutic trials, they were finding a much different value than had been initially measured through a local lab.”

While assays can and do vary, she said, the findings confirm that “we were still seeing a fair amount of fluctuation over time in those values” using a single assay.

The notion that Lp(a) can vary with time is not new, but “that's not something that people often talk about,” O’Donoghue said. The data reinforce this idea, she added, giving examples of how both pregnancy and menopause as well as liver, thyroid, and renal disease are known to alter Lp(a).

The take home message from the study is that “the value you obtain when you measure Lp(a) may not be the same on a subsequent draw,” she said. “The reasons for that are not completely understood but might highlight more biologic variability than we had previously appreciated.”

Progress on getting Lp(a) measured, at least in the US, has been slow, according to O’Donoghue. “I think it would be a step forward if everybody had their value measured at least once, let alone more than once,” she said. But looking forward, as more Lp(a)-lowering therapies come to market, “consideration could be given to measuring Lp(a) value more than once for people with high values at baseline as you consider eligibility.”