Lipoprotein(a) — Lp(a)
The most underrated genetic cardiovascular risk factor — affects 20% of the population
Definition
Lipoprotein(a) — Lp(a), pronounced 'lipoprotein little a' — is an inherited LDL variant in which apolipoprotein B-100 is covalently bound to apolipoprotein(a), a protein unique to the plasminogen family. Approximately 20% of the world population has elevated Lp(a) (>50 mg/dL or >125 nmol/L) for genetic reasons (LPA gene on chromosome 6), making it an independent risk factor for heart attack, stroke, calcified aortic stenosis, and peripheral arterial disease.
Detailed explanation
Unique features of Lp(a):
Genetic and lifelong: the Lp(a) level is 80-90% inheritable; a value obtained at age 18 remains essentially the same throughout adult life. A single lifetime measurement is sufficient. Dual risk mechanism: atherogenic (like LDL) + prothrombotic (apolipoprotein(a) competes with plasminogen, inhibiting fibrinolysis). Resistant to conventional treatment: statins do not significantly lower it (may even raise it 10-20%); diet and exercise minimal reduction.
Available interventions to lower Lp(a): Extended-release niacin (1-2 g/day): reduces 25-30%, but tolerance limited. LDL-apheresis: for patients with very high Lp(a) and premature cardiovascular events — mechanical plasma removal every 1-2 weeks. PCSK9 inhibitors (Evolocumab, Alirocumab): reduce Lp(a) by 25%. New drugs in phase 3: pelacarsen (antisense RNA against ApoA, reduces Lp(a) >80%) — HORIZON and OCEAN(a) trials are in development and will be the first treatments specifically targeting Lp(a).
Current clinical strategy: measure Lp(a) once in life in all adults; in carriers of elevated Lp(a), be more aggressive with all other risk factors (ApoB <50 mg/dL, optimal blood pressure, no tobacco, regular exercise, strict Mediterranean diet) until new drugs are available.
Scientific sources
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