Key result
Family history of early-onset CHD linked to 38 inflammatory and vascular plasma proteins.
Why the study?
What plasma protein profile is associated with a family history of early-onset coronary heart disease?
Observational (n=4,521)
Yes
What plasma protein profile is associated with a family history of early-onset coronary heart disease?
Answers are grounded in this paper and cite their sources.
A family history of early-onset CHD is associated with a distinct plasma protein profile, including novel associations with follistatin, highlighting potential new mechanisms for heritable atherosclerosis.
BACKGROUND: Proteins linked to heritable coronary heart disease (CHD) could uncover new pathophysiological mechanisms of atherosclerosis. We report on the protein profile associated with a family history of early-onset CHD and whether the relation between proteins and coronary atherosclerotic burden differs according to family history status, as well as inferences from Mendelian randomization. METHODS: Data on coronary atherosclerotic burden from computed tomography angiography and Olink proteomics were retrieved for 4521 subjects, free of known CHD, from SCAPIS (the Swedish Cardiopulmonary Bioimage Study). Records of myocardial infarction and coronary revascularization therapies in any parent or sibling of subjects were retrieved from national registers. Linear associations between family history and proteins were adjusted for age, sex, and study site. Statistical interactions between proteins and family history for the association between proteins and the coronary atherosclerotic burden were also studied. Mendelian randomization for causal associations between proteins and CHD was performed with genome-wide association study summary data from UKB-PPP (UK Biobank Pharma Proteomics Project), CARDIoGRAMplusC4D, and FinnGen. RESULTS: Of 4251 subjects, family history of early-onset CHD was present in 9.5%. Thirty-eight proteins, with biological features of inflammation, lipid metabolism, and vascular function, were associated with family history using a false discovery rate of 0.05. The strongest associations were observed with cathepsin D, paraoxonase 3, renin andfollistatin, neither of which was attenuated by adjusting for cardiovascular risk factors. Eighteen proteins were statistical interactors with family history in the association between each protein and the coronary atherosclerotic burden, most notably the LDL (low-density lipoprotein) receptor, transferrin receptor protein 1, and PECAM1 (platelet endothelial cell adhesion molecule 1). In 2-sample Mendelian randomization, a novel association was found for follistatin and myocardial infarction, and previous associations for PCSK9 (proprotein convertase subtilisin/kexin type 9) and PECAM1 were repeated. CONCLUSIONS: These findings highlight new potential mechanisms for heritable and general atherosclerosis.
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Wahrenberg et al. (2025) conducted an observational in Coronary heart disease (n=4,521). Family history of early-onset CHD vs. No family history of early-onset CHD was evaluated on Plasma protein profile associated with family history of early-onset CHD. A family history of early-onset CHD was present in 9.5% of subjects and was associated with 38 plasma proteins related to inflammation, lipid metabolism, and vascular function (FDR 0.05).
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