A Test With No Drug Yet: Ordering Lipoprotein(a) Before Any Therapy Targets It
A 46-year-old woman with a family history of early coronary disease and normal LDL asks whether to check her lipoprotein(a) — a heritable risk factor with no FDA-approved targeted therapy yet, testable today for reasons that have nothing to do with a future drug.
Mireille K., a 46-year-old translator who works from a converted sunroom stacked with dictionaries in four languages, has spent the past two weeks unable to shake a phone call from her older sister, 51, who was told after a first heart attack that her cholesterol had 'looked fine on paper for years.' Mireille came in today not for a complaint of her own, but because that phone call turned an ordinary annual physical into something with a much sharper edge. Mireille's own labs, drawn as part of a routine physical two months ago, are genuinely unremarkable by the numbers that usually drive this conversation — an LDL of 118mg/dL and a calculated 10-year ASCVD risk under 3%. What brought her in today was a single question, asked with more urgency than the numbers on her own chart would suggest: is there a test her sister should have had that might have caught this earlier, and should Mireille have it herself before she finds out the same way?
The honest answer involves a test that measures something LDL doesn't: lipoprotein(a), a largely genetically fixed particle that current guidelines recognize as an independent, causal contributor to cardiovascular risk regardless of how favorable someone's LDL looks. The complicating layer, and the reason this isn't a simple yes, is that no Lp(a)-specific lowering therapy is FDA-approved yet — the furthest-along candidate completed its outcomes-trial follow-up this year without public results so far, and a second remains in an ongoing trial expected to read out later this year. Ordering a test with no matching drug on the other end of an abnormal result isn't automatically the wrong call, but it isn't automatically the right one either, and Mireille's actual question — whether her sister's story could repeat itself in her own chart — is exactly what's in front of the room now.
In clinic, a test with no matching drug yet
I'd hold off ordering it. There is currently no FDA-approved, Lp(a)-specific lowering therapy — pelacarsen's own outcomes trial completed its follow-up this year and the results still haven't been made public, olpasiran's outcomes trial doesn't read out until later this year at the earliest. Telling a 46-year-old with a normal LDL and no personal cardiovascular history that she has an elevated, largely unmodifiable genetic risk factor, with nothing specific to offer her for it yet, risks manufacturing anxiety without changing what I'd actually do differently today.
I'd order it, and I don't think 'nothing to offer her' is quite right even before an Lp(a)-specific drug exists. A markedly elevated Lp(a) is itself a risk-enhancing factor in the current guidelines, one that would justifiably lower my threshold for treating her LDL more aggressively than her risk calculator alone suggests, and it would change how hard I push on every other modifiable risk factor she has — blood pressure, weight, smoking status if that ever becomes relevant.
The 'nothing to offer her' framing treats Lp(a) as useful only once a drug exists to lower it directly, which misses that it already changes the intensity of everything else we're doing for the risk factors we can modify.
There's a second reason to test that neither of you has named yet: this is a one-time, largely genetically fixed measurement, unlike LDL, which needs to be checked periodically. If it's elevated, it has direct implications for her first-degree relatives, since Lp(a) follows a co-dominant inheritance pattern and her siblings and children carry a real chance of sharing it — a cascade-testing argument that has nothing to do with whether a targeted drug exists yet for her specifically.
I'd frame the result to her honestly if it comes back elevated: it sharpens how aggressively we manage everything we can already act on, and it's worth knowing for her family's sake, even while the drugs built to target it directly are still investigational.
Agreed: order the one-time lipoprotein(a). All three physicians ultimately converged on testing, though for different weighted reasons — the risk-enhancer argument and the family-cascade argument together outweighed the internal medicine physician's actionability concern, who explicitly conceded the point once those two framings were on the table.
Not agreed: exactly how much the result should change her management if it comes back elevated but not extreme. The preventive cardiologist would treat any meaningfully elevated value as sufficient to start a statin despite her low calculated risk; the internal medicine physician would want a more clearly elevated threshold before overriding an otherwise reassuring risk score. That specific cutoff was left for the result itself to force, rather than settled in the abstract today.