Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Impact of LDL cholesterol on microvascular versus macrovascular disease: A Mendelian Randomization Study

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Age-Related Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Prevalence of Infective Endocarditis in Enterococcus faecalis Bacteremia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Association of Carpal Tunnel Syndrome With Amyloidosis, Heart Failure, and Adverse Cardiovascular Outcomes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Low LDL cholesterol by PCSK9 variation reduces cardiovascular mortality

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Shared heritability and functional enrichment across six solid cancers

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Prevalence and risk factors of prolonged QT interval and electrocardiographic abnormalities in persons living with HIV

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Publisher Correction: Shared heritability and functional enrichment across six solid cancers

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is causally associated with a high risk of coronary artery disease. Whether this also holds for a spectrum of peripheral vascular diseases is unknown.

OBJECTIVES: The purpose of this study was to determine whether high LDL-C causally relates to risk of retinopathy, neuropathy, chronic kidney disease (CKD), and peripheral arterial disease (PAD) in the general population.

METHODS: One-sample Mendelian randomization (MR) of 116,419 Danish individuals, 2-sample MR on summary-level data from the Global Lipid Genetics Consortium (GLGC) (n = 94,595) and the UK Biobank (n = 408,455), and meta-analysis of randomized statin trials (n = 64,134) were performed.

RESULTS: Observationally, high LDL-C did not associate with high risk of retinopathy or neuropathy. There were stepwise increases in risk of CKD and PAD with higher LDL-C (both p for trend <0.001), with hazard ratios of 1.05 (95% confidence interval [CI]: 0.97 to 1.13) for CKD, and 1.41 (95% CI: 1.23 to 1.62) for PAD in individuals with LDL-C above the 95th percentile versus below the 50th percentile. In genetic, causal analyses in the Copenhagen studies, the risk ratio of disease for a 1 mmol/l higher LDL-C was 1.06 (95% CI: 0.24 to 4.58) for retinopathy, 1.05 (95% CI: 0.64 to 1.72) for neuropathy, 3.83 (95% CI: 2.00 to 7.34) for CKD, and 2.09 (95% CI: 1.30 to 2.38) for PAD. Summary-level data from the GLGC and the UK Biobank for retinopathy, neuropathy, and PAD gave similar results. For CKD, a 1-mmol/l lower LDL-C conferred a higher eGFR of 1.95 ml/min/1.73 m2 (95% CI: 1.88 to 2.02 ml/min/1.73 m2) observationally, 5.92 ml/min/1.73 m2 (95% CI: 4.97 to 6.86 ml/min/1.73 m2) genetically, and 2.69 ml/min/1.73 m2 (95% CI: 1.48 to 3.94 ml/min/1.73 m2) through statin therapy.

CONCLUSIONS: High LDL-C was not causally associated with risk of retinopathy and neuropathy; however, high LDL-C was observationally and genetically associated with high risks of PAD and CKD, suggesting that LDL-C is causally involved in the pathogenesis of these diseases.

OriginalsprogEngelsk
TidsskriftJournal of the American College of Cardiology
Vol/bind74
Udgave nummer11
Sider (fra-til)1465-1476
Antal sider12
ISSN0735-1097
DOI
StatusUdgivet - 17 sep. 2019

Bibliografisk note

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

ID: 58287943