Lipoprotein(a), abbreviated Lp(a), is a genetically determined atherogenic particle that elevates cardiovascular and cerebrovascular risk independently of standard lipid panels. Approximately 20-25% of the population has elevated Lp(a) (defined typically as greater than 50 mg/dL or greater than 125 nmol/L), and the elevation is largely fixed across the lifespan — determined by genetics, modifiable only minimally by lifestyle, and unaffected by statin therapy. Despite this, Lp(a) is among the most underordered tests in primary care and longevity medicine.
The clinical case for measuring Lp(a) once in every adult patient is straightforward. The test is widely available, inexpensive, and informative. The result does not change across the lifespan, so the test needs to be ordered only once. The result identifies a substantial subgroup of patients at meaningfully elevated cardiovascular and cerebrovascular risk independent of their other risk factors, including some patients who appear low-risk on standard assessment. Patients with family history of early-onset cardiovascular disease or stroke have particularly high pretest probability of elevated Lp(a) being part of the picture.
Elevated Lp(a) is associated with elevated risk of myocardial infarction, ischemic stroke, calcific aortic stenosis, and (relevant to this volume) vascular contributions to cognitive decline. The risk is independent of LDL, apoB, and other standard risk markers — meaning that a patient with otherwise excellent lipid management can still have elevated Lp(a)-driven risk that is invisible to standard panels. The clinical conversation often surfaces the question of family history that explains a patient's concern: "My father had a heart attack at 50 and my brother had a stroke at 55, but my LDL is fine — what is happening?" Lp(a) is frequently the answer.
The clinical actions when Lp(a) is elevated have historically been limited, but the landscape is changing. Standard intervention has been more aggressive management of modifiable risk factors — tighter LDL/apoB targets, more aggressive blood pressure control, more aggressive metabolic optimization — to compensate for the inherited risk. Aspirin has been considered for some patients with elevated Lp(a) and additional risk factors, though its role is less clear in primary prevention now than previously. PCSK9 inhibitors lower Lp(a) modestly (15-25%). Niacin lowers it modestly but has fallen out of favor due to side effect profile. The Lp(a)-specific pharmacological pipeline is the most exciting development: pelacarsen and other Lp(a)-targeted agents are in advanced clinical trials, with results expected in the next several years. If effective, they will represent the first targeted treatment for what has been an unmanaged risk factor.
The longevity-psychiatry implication of Lp(a) testing is to incorporate it as a once-in-lifetime measurement in every patient and to use the result to calibrate the aggressiveness of other vascular interventions. A patient with Lp(a) of 200 mg/dL deserves tighter apoB targets, more aggressive blood pressure control, more rigorous attention to other modifiable factors than a patient with Lp(a) of 20 mg/dL — even if their other risk factors are similar. The test reframes the risk picture and the clinical urgency in a way that nothing else does.