Aortic stenosisLandmark
A test in context: Lp(a) diagnosis, prognosis, controversies and emerging therapies (Tsimikas, JACC 2017)
Original title: A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies
The review clinicians reached for before the RNA era: isoform-independent assays plus genetic and epidemiological evidence make Lp(a) an independent, genetic and likely causal risk factor for cardiovascular disease and calcific aortic stenosis across patient groups, statins tend to raise Lp(a), PCSK9 inhibitors and mipomersen lower it 20 to 30 percent, and RNA-targeted therapies lower it by more than 80 percent, finally allowing the Lp(a) hypothesis to be tested.
Original abstract
Evidence that elevated lipoprotein(a) (Lp[a]) levels contribute to cardiovascular disease (CVD) and calcific aortic valve stenosis (CAVS) is substantial. Development of isoform-independent assays, in concert with genetic, epidemiological, translational, and pathophysiological insights, have established Lp(a) as an independent, genetic, and likely causal risk factor for CVD and CAVS. These observations are consistent across a broad spectrum of patients, risk factors, and concomitant therapies, including patients with low-density lipoprotein cholesterol <70 mg/dl. Statins tend to increase Lp(a) levels, possibly contributing to the "residual risk" noted in outcomes trials and at the bedside. Recently approved proprotein convertase subtilisin/kexin-type 9 inhibitors and mipomersen lower Lp(a) 20% to 30%, and emerging RNA-targeted therapies lower Lp(a) >80%. These approaches will allow testing of the "Lp(a) hypothesis" in clinical trials. This review summarizes the current landscape of Lp(a), discusses controversies, and reviews emerging therapies to reduce plasma Lp(a) levels to decrease risk of CVD and CAVS.
aortic stenosisepidemiologygeneticstestingtherapy
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.