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Arterioscler Thromb Vasc Biol. 2019 Oct 3:ATVBAHA119312951. doi: 10.1161/ATVBAHA.119.312951. [Epub ahead of print]

Lp(a) (Lipoprotein[a])-Lowering by 50 mg/dL (105 nmol/L) May Be Needed to Reduce Cardiovascular Disease 20% in Secondary Prevention: A Population-Based Study.

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From the Department of Clinical Biochemistry, Copenhagen University Hospital, Denmark (C.M.M.).
The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark (C.M.M., P.R.K., A.L., A.V., B.G.N.).
Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (C.M.M., A.L., A.V., B.G.N.).
The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark (B.G.N.).



High Lp(a) (lipoprotein[a]) cause cardiovascular disease (CVD) in a primary prevention setting; however, it is debated whether high Lp(a) lead to recurrent CVD events. We tested the latter hypothesis and estimated the Lp(a) lowering needed for 5 years to reduce CVD events in a secondary prevention setting. Approach and Results: From the CGPS (Copenhagen General Population Study; 2003-2015) of 58 527 individuals with measurements of Lp(a), 2527 aged 20 to 79 with a history of CVD were studied. The primary end point was major adverse cardiovascular event (MACE). We also studied 1115 individuals with CVD from the CCHS (Copenhagen City Heart Study; 1991-1994) and the CIHDS (Copenhagen Ischemic Heart Disease Study; 1991-1993). During a median follow-up of 5 years (range, 0-13), 493 individuals (20%) experienced a MACE in the CGPS. MACE incidence rates per 1000 person-years were 29 (95% CI, 25-34) for individuals with Lp(a)<10 mg/dL, 35 (30-41) for 10 to 49 mg/dL, 42 (34-51) for 50 to 99 mg/dL, and 54 (42-70) for ≥100 mg/dL. Compared with individuals with Lp(a)<10 mg/dL (18 nmol/L), the multifactorially adjusted MACE incidence rate ratios were 1.28 (95% CI, 1.03-1.58) for 10 to 49 mg/dL (18-104 nmol/L), 1.44 (1.12-1.85) for 50 to 99 mg/dL (105-213 nmol/L), and 2.14 (1.57-2.92) for ≥100 mg/dL (214 nmol/L). Independent confirmation was obtained in individuals from the CCHS and CIHDS. To achieve 20% and 40% MACE risk reduction in secondary prevention, we estimated that plasma Lp(a) should be lowered by 50 mg/dL (95% CI, 27-138; 105 nmol/L [55-297]) and 99 mg/dL (95% CI, 54-273; 212 nmol/L [114-592]) for 5 years.


High concentrations of Lp(a) are associated with high risk of recurrent CVD in individuals from the general population. This study suggests that Lp(a)-lowering by 50 mg/dL (105 nmol/L) short-term (ie, 5 years) may reduce CVD by 20% in a secondary prevention setting.High Lp(a) (Lipoprotein[a]) is associated with high risk of incident cardiovascular disease (CVD) in observational studies of individuals without CVD at baseline1, 2, that is, in a primary prevention setting. Mendelian randomization studies with genetic variants affecting the concentration of Lp(a) strongly support Lp(a) as a direct cause of incident CVD in the form of especially coronary artery disease, but also aortic valve stenosis, heart failure, and peripheral atherosclerotic stenosis.3-7.


atherosclerosis; cardiovascular disease; cholesterol; population secondary prevention


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