Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Low LDL cholesterol by PCSK9 variation reduces cardiovascular mortality

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Smartphone Activation of Citizen Responders to Facilitate Defibrillation in Out-of-Hospital Cardiac Arrest

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Natural History of Subclinical Atrial Fibrillation Detected by Implanted Loop Recorders

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Effects of Interatrial Shunt on Pulmonary Vascular Function in Heart Failure With Preserved Ejection Fraction

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Reply: Enterococcus faecalis Infective Endocarditis

    Publikation: Bidrag til tidsskriftKommentar/debatForskningpeer review

  1. Genetic variation at PPP1R3B increases hepatic CT attenuation and interacts with prandial status on plasma glucose

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Impact of glucose on risk of dementia: Mendelian randomisation studies in 115,875 individuals

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Repositioning of the global epicentre of non-optimal cholesterol

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Peripheral Neuropathy - time for better biomarkers?

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Type-2 diabetes and risk of dementia: observational and Mendelian randomisation studies in 1 million individuals

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

BACKGROUND: Reduced low-density lipoprotein (LDL) cholesterol due to inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) reduces cardiovascular events and may therefore also reduce cardiovascular and all-cause mortality.

OBJECTIVES: This study tested the hypothesis that genetically low LDL cholesterol due to PCSK9 variation is causally associated with low cardiovascular and all-cause mortality in the general population.

METHODS: A total of 109,566 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were genotyped for PCSK9 R46L (rs11591147), R237W (rs148195424), I474V (rs562556), and E670G (rs505151). During a median follow-up of 10 years (range 0 to 42 years) and 1,247,225 person-years, there were 3,828 cardiovascular deaths and 16,373 deaths from any cause. Results were validated using data on 431,043 individuals from the UK Biobank.

RESULTS: An increasing number of weighted PCSK9 alleles were associated with stepwise lower LDL cholesterol of up to 0.61 mmol/l (24 mg/dl; 18.2%; p for trend <0.001) and with lower cardiovascular mortality (p = 0.001), but not with lower all-cause mortality (p = 0.11). In causal, genetic analyses, a 0.5-mmol/l (19.4-mg/dl) lower LDL cholesterol was associated with risk ratios for cardiovascular and all-cause mortality of 0.79 (95% confidence interval [CI]: 0.63 to 0.99; p = 0.04) and 1.02 (95% CI: 0.94 to 1.12; p = 0.63) in the Copenhagen studies, 0.79 (95% CI: 0.58 to 1.08; p = 0.14) and 0.98 (95% CI: 0.87 to 1.10; p = 0.75) in the UK Biobank, and of 0.79 (95% CI: 0.65 to 0.95; p = 0.01) and 1.01 (95% CI: 0.94 to 1.08; p = 0.85), respectively, in studies combined.

CONCLUSIONS: Genetically low LDL cholesterol due to PCSK9 variation was causally associated with low risk of cardiovascular mortality, but not with low all-cause mortality in the general population.

OriginalsprogEngelsk
TidsskriftJournal of the American College of Cardiology
Vol/bind73
Udgave nummer24
Sider (fra-til)3102-3114
Antal sider13
ISSN0735-1097
DOI
StatusUdgivet - 25 jun. 2019

Bibliografisk note

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

ID: 58288652