High Lipoprotein(a) and Low Risk of Major Bleeding in Brain and Airways in the General Population: a Mendelian Randomization Study

TY - JOUR

T1 - High Lipoprotein(a) and Low Risk of Major Bleeding in Brain and Airways in the General Population

T2 - a Mendelian Randomization Study

AU - Langsted, Anne

AU - Kamstrup, Pia R

AU - Nordestgaard, Børge G

N1 - © 2017 American Association for Clinical Chemistry.

PY - 2017/11

Y1 - 2017/11

N2 - BACKGROUND: The physiological role of lipoprotein(a) is unclear; however, lipoprotein(a) may play a role in hemostasis and wound healing. We tested the hypothesis that high lipoprotein(a) concentrations are associated with low risk of major bleeding in the brain and airways both observationally and causally (from human genetics).METHODS: We examined 109169 individuals from the Copenhagen City Heart Study and the Copenhagen General Population study, 2 similar prospective studies conducted in the Danish general population. Individuals had information on plasma lipoprotein(a) concentrations (n = 59980), LPA kringle-IV type 2 (KIV-2) number of repeats (n = 98965), and/or LPA single-nucleotide polymorphism rs10455872 associated with high lipoprotein(a) concentrations (n = 109 169), and information on hospital contacts or death due to major bleeding in brain and airways from registers.RESULTS: Using extreme phenotypes or genotypes, the multifactorially adjusted hazard ratio for major bleeding in the brain and airways was 0.84 (95%CI: 0.71-0.99) for lipoprotein(a), >800 mg/L vs <110 mg/L; 0.83 (0.73-0.96) for KIV-2, <24 vs >35 number of repeats; and 0.89 (0.81-0.97) for rs10455872 carriers (heterozygotes + homozygotes) vs noncarriers. The corresponding hazard ratios were 0.89 (0.82-0.98) for heterozygotes and 0.59 (0.36-0.98) for homozygotes separately vs rs10455872 noncarriers. Also, for a 1 standard deviation higher lipoprotein(a) (= 310 mg/L), the hazard ratio for major bleeding in the brain and airways was 0.95 (95%CI: 0.91-1.00) observationally, 0.89 (0.80-0.98) causally based on LPA KIV-2 number of repeats, and 0.94 (0.87-1.02) causally based on LPA rs10455872.CONCLUSIONS: High lipoprotein(a) concentrations were associated with lower risk of major bleeding in the brain and airways observationally and causally. This indicates that lipoprotein(a) may play a role in hemostasis and wound healing.

AB - BACKGROUND: The physiological role of lipoprotein(a) is unclear; however, lipoprotein(a) may play a role in hemostasis and wound healing. We tested the hypothesis that high lipoprotein(a) concentrations are associated with low risk of major bleeding in the brain and airways both observationally and causally (from human genetics).METHODS: We examined 109169 individuals from the Copenhagen City Heart Study and the Copenhagen General Population study, 2 similar prospective studies conducted in the Danish general population. Individuals had information on plasma lipoprotein(a) concentrations (n = 59980), LPA kringle-IV type 2 (KIV-2) number of repeats (n = 98965), and/or LPA single-nucleotide polymorphism rs10455872 associated with high lipoprotein(a) concentrations (n = 109 169), and information on hospital contacts or death due to major bleeding in brain and airways from registers.RESULTS: Using extreme phenotypes or genotypes, the multifactorially adjusted hazard ratio for major bleeding in the brain and airways was 0.84 (95%CI: 0.71-0.99) for lipoprotein(a), >800 mg/L vs <110 mg/L; 0.83 (0.73-0.96) for KIV-2, <24 vs >35 number of repeats; and 0.89 (0.81-0.97) for rs10455872 carriers (heterozygotes + homozygotes) vs noncarriers. The corresponding hazard ratios were 0.89 (0.82-0.98) for heterozygotes and 0.59 (0.36-0.98) for homozygotes separately vs rs10455872 noncarriers. Also, for a 1 standard deviation higher lipoprotein(a) (= 310 mg/L), the hazard ratio for major bleeding in the brain and airways was 0.95 (95%CI: 0.91-1.00) observationally, 0.89 (0.80-0.98) causally based on LPA KIV-2 number of repeats, and 0.94 (0.87-1.02) causally based on LPA rs10455872.CONCLUSIONS: High lipoprotein(a) concentrations were associated with lower risk of major bleeding in the brain and airways observationally and causally. This indicates that lipoprotein(a) may play a role in hemostasis and wound healing.

KW - Journal Article

U2 - 10.1373/clinchem.2017.276931

DO - 10.1373/clinchem.2017.276931

M3 - Journal article

C2 - 28877919

SN - 0009-9147

VL - 63

SP - 1714

EP - 1723

JO - Clinical Chemistry

JF - Clinical Chemistry

IS - 11

ER -