title: Estimating the Population Impact of Lp(a) Lowering on the Incidence of Myocardial Infarction and Aortic Stenosis-Brief Report.
abstract: OBJECTIVE
  High lipoprotein(a) (Lp[a]) is the most common genetic dyslipidemia and is a causal factor for myocardial infarction (MI) and aortic stenosis (AS). We sought to estimate the population impact of Lp(a) lowering that could be achieved in primary prevention using the therapies in development.
  
  
  RESULTS
  We used published data from 2 prospective cohorts. High Lp(a) was defined as ≥50 mg/dL (≈20th percentile). Relative risk, attributable risk, the attributable risk percentage, population attributable risk, and the population attributable risk percentage were calculated as measures of the population impact. For MI, the event rate was 4.0% versus 2.8% for high versus low Lp(a) (relative risk, 1.46; 95% confidence interval [CI], 1.45-1.46). The attributable risk was 1.26% (95% CI, 1.24-1.27), corresponding to 31.3% (95% CI, 31.0-31.7) of the excess MI risk in those with high Lp(a). The population attributable risk was 0.21%, representing a population attributable risk percentage of 7.13%. For AS, the event rate was 1.51% versus 0.78% for high versus low Lp(a) (relative risk, 1.95; 95% CI, 1.94-1.97). The attributable risk was 0.74% (95% CI, 0.73-0.75), corresponding to 48.8% (95% CI, 48.3-49.3) of the excess AS risk in those with high Lp(a). The population attributable risk was 0.13%, representing a population attributable risk percentage of 13.9%. In sensitivity analyses targeting the top 10% of Lp(a), the population attributable risk percentage was 5.2% for MI and 7.8% for AS.
  
  
  CONCLUSIONS
  Lp(a) lowering among the top 20% of the population distribution for Lp(a) could prevent 1 in 14 cases of MI and 1 in 7 cases of AS, suggesting a major impact on reducing the burden of cardiovascular disease. Targeting the top 10% could prevent 1 in 20 MI cases and 1 in 12 AS cases.
authors.affiliation: From the Department of Medicine, McGill University, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark (P.R.K., B.G.N.); KenAnCo Biostatistics, San Antonio, TX (K.W.); Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark (B.G.N.); and Department of Clinical Epidemiology, McGill University Health Center, Montreal, Québec, Canada (G.T.).
authors.forename: Mehdi
authors.initials: M
authors.lastname: Afshar
authors.affiliation: From the Department of Medicine, McGill University, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark (P.R.K., B.G.N.); KenAnCo Biostatistics, San Antonio, TX (K.W.); Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark (B.G.N.); and Department of Clinical Epidemiology, McGill University Health Center, Montreal, Québec, Canada (G.T.).
authors.forename: Pia R
authors.initials: PR
authors.lastname: Kamstrup
authors.affiliation: From the Department of Medicine, McGill University, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark (P.R.K., B.G.N.); KenAnCo Biostatistics, San Antonio, TX (K.W.); Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark (B.G.N.); and Department of Clinical Epidemiology, McGill University Health Center, Montreal, Québec, Canada (G.T.).
authors.forename: Ken
authors.initials: K
authors.lastname: Williams
authors.affiliation: From the Department of Medicine, McGill University, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark (P.R.K., B.G.N.); KenAnCo Biostatistics, San Antonio, TX (K.W.); Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark (B.G.N.); and Department of Clinical Epidemiology, McGill University Health Center, Montreal, Québec, Canada (G.T.).
authors.forename: Allan D
authors.initials: AD
authors.lastname: Sniderman
authors.affiliation: From the Department of Medicine, McGill University, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark (P.R.K., B.G.N.); KenAnCo Biostatistics, San Antonio, TX (K.W.); Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark (B.G.N.); and Department of Clinical Epidemiology, McGill University Health Center, Montreal, Québec, Canada (G.T.).
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: From the Department of Medicine, McGill University, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, Montreal, Québec, Canada (M.A., A.D.S., G.T.); Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark (P.R.K., B.G.N.); KenAnCo Biostatistics, San Antonio, TX (K.W.); Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark (B.G.N.); and Department of Clinical Epidemiology, McGill University Health Center, Montreal, Québec, Canada (G.T.). george.thanassoulis@mcgill.ca.
authors.forename: George
authors.initials: G
authors.lastname: Thanassoulis
mesh_terms: D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D003718:Denmark / Q000453:epidemiology; D015536:Down-Regulation; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D017270:Lipoprotein(a) / Q000097:blood*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D011446:Prospective Studies; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D000960:Hypolipidemic Agents; D017270:Lipoprotein(a)
keywords: aortic valve stenosis; atherosclerosis; coronary disease; epidemiology; genetics; lipoproteins; prevention and control