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• W4387138061 abstract "Abstract Importance Apolipoprotein B (apoB), low-density lipoprotein cholesterol (LDL-C), and possibly triglycerides (TG) play causal roles in the aetiology of coronary artery disease (CAD). However, trial evidence for effects of intensive LDL-C lowering and TG lowering on mortality is less definitive. Objectives To investigate dose-response relations of apoB, LDL-C, and TG with CAD and mortality overall, by sex, and by age. Design We performed linear Mendelian randomization (MR) analyses to assess the associations of genetically-predicted apoB, LDL-C, and TG with CAD, all-cause mortality, and cause-specific mortality. We also performed non-linear MR analyses, dividing the population into 10 strata, to assess stratum-specific estimates and characterise the shape of these associations. Setting UK Biobank. Participants 347,797 European ancestry participants (23,818 CAD cases and 23,848 deaths). Exposures Genetically-predicted apoB, LDL-C, and TG. Main outcomes and measures CAD, all-cause mortality, cardiovascular mortality, cancer mortality, and non-cardiovascular/cancer mortality. Results Genetically-predicted apoB was positively associated with CAD (odds ratio (OR) 1.65 per standard deviation increase [95% confidence interval 1.57, 1.73]), all-cause mortality (hazard ratio (HR) 1.11 [1.06, 1.16]), and cardiovascular mortality (HR 1.36 [1.24, 1.50]), with some evidence for stronger associations in men than women. Findings were similar for LDL-C. Genetically-predicted TG was positively associated with CAD (OR 1.60 [1.52, 1.69]), all-cause mortality (HR 1.08 [1.03, 1.13]), and cardiovascular mortality (HR 1.21 [1.09, 1.34]); however, sensitivity analyses suggested evidence of pleiotropy. The association of genetically-predicted TG with CAD persisted but its associations with mortality outcomes were attenuated towards the null after controlling for LDL-C. Non-linear MR suggested the shapes of all these associations were monotonically increasing across the whole observed distribution of each lipid trait, with no diminution at low lipid levels. Such patterns were observed irrespective of sex or age. Conclusions and relevance Our findings suggest that apoB (or equivalently LDL-C) increases CAD risk, all-cause mortality, and cardiovascular mortality all in a dose-dependent way. TG likely increases CAD risk, although the possible presence of pleiotropy is a limitation. These insights highlight the importance of LDL-C lowering for reducing cardiovascular morbidity and mortality across its whole distribution. Key points Question Do apolipoprotein B (apoB), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) increase risk of coronary artery disease (CAD), all-cause mortality, or cause- specific mortality, and if so, what are the shapes of these relations? Findings In this Mendelian randomization study including 347,797 European ancestry participants from UK Biobank, genetically-predicted apoB and LDL-C were positively associated with CAD, all- cause mortality, and cardiovascular mortality all in a dose-dependent way. Genetically-predicted TG was positively associated with CAD, although the presence of pleiotropy was suggested. Meaning ApoB (or equivalently LDL-C) lowering reduces cardiovascular morbidity and mortality across its whole observed distribution." @default.
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• W4387138061 date "2023-09-27" @default.
• W4387138061 modified "2023-10-05" @default.
• W4387138061 title "Assessing dose-response relations of lipid traits with coronary artery disease, all-cause mortality, and cause-specific mortality: a linear and non-linear Mendelian randomization study" @default.
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• W4387138061 doi "https://doi.org/10.1101/2023.09.27.23296203" @default.
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