Suchergebnisse

Lipoprotein(a) (Lp[a]) is a circulating lipoprotein with proatherogenic, proinflammatory, and possibly prothrombotic properties. Circulating Lp(a) levels are largely genetically determined, in particular, by the LPA gene. As such, genetic variants at the LPA locus can serve as instrumental variables for investigating the clinical effects of circulating Lp(a) levels. Mendelian randomization (MR) studies have shown that elevated Lp(a) levels are associated with a higher risk of coronary artery disease1–3 and aortic valve stenosis.2–4 Evidence on the causal role of elevated Lp(a) levels for other atherosclerotic and specific valvular diseases is limited, although there are MR data supporting a positive association between genetically predicted Lp(a) levels and peripheral artery disease.2,3 Whether Lp(a) is causally related to thrombotic disease and cerebrovascular disease remains unclear.2,3,5 In this study, we used the UK Biobank cohort to perform an MR investigation into the causal effects of circulating Lp(a) levels on atherosclerotic, cerebrovascular, thrombotic, and valvular diseases. Because a recent MR study provided evidence of an inverse association of Lp(a) levels with Alzheimer disease,5 we additionally explored whether genetically predicted Lp(a) levels are associated with Alzheimer disease and dementia. ; Dr Larsson receives support from the Swedish Heart-Lung Foundation (Hjärt-Lungfonden, grant number 20190247), the Swedish Research Council (Vetenskapsrådet, grant number 2019-00977), and the Swedish Research Council for Health, Working Life and Welfare (Forte, grant number 2018-00123). Dr Gill is funded by the Wellcome 4i Clinical PhD Program at Imperial College London. Dr Burgess is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (award number 204623/Z/16/Z). Drs Burgess and Butterworth report funding from Novartis relating to the investigation of lipoprotein(a). The funder had no influence on the content of the investigation or the decision to publish. This work was supported by core funding from the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946), the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust] and Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome.