{"id":"76a86b1be3e9","type":"article","url":"https://hartvaat.nl/2019/09/17/ldl-cholesterol-en-micro-versus-macrovasculaire-ziekte-mendeliaanse-randomisatie/","title":"LDL-cholesterol en micro- versus macrovasculaire ziekte: Mendeliaanse randomisatie","title_en":"Impact of LDL Cholesterol on Microvascular Versus Macrovascular Disease: A Mendelian Randomization Study.","category":"cholesterol","category_label":"Cholesterol","professions":["cardioloog","internist"],"tags":["dyslipidemie","ezetimibe","ldl-cholesterol","lipide-aferese","lipidenverlaging","statines"],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2019.07.037","source_url":"https://doi.org/10.1016/j.jacc.2019.07.037","authors":["Frida Emanuelsson","Børge G Nordestgaard","Anne Tybjærg-Hansen","Marianne Benn"],"significance":6,"published":"2019-09-17","source_date":"2019-09-17","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/"],"congress":"","summary_en":"This Mendelian randomization study examined whether genetically determined LDL cholesterol affects microvascular disease (retinopathy, nephropathy) in addition to macrovascular atherosclerosis, exploring the breadth of LDL's causal role.","created":"2026-07-03T10:28:09Z","updated":"2026-07-03T13:27:20Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Mendeliaanse randomisatiestudie naar de differentiële impact van LDL-cholesterol op microvasculaire versus macrovasculaire ziekte.","abstract_original":"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."}