Thread by @PeterWyrtz

Coronary artery disease and lower extremity artery disease represent atherosclerosis in different vascular beds. We compared blood biomarker signatures for these 2 types of CVD: new preprint medrxiv.org/content/10.110…
based on @NgaleHealth metabolomics in @THLBiopankki Thread 👇

Peripheral artery disease (PAD) is understudied, and biomarkers analyses are commonly limited to classical risk factors. We used @NgaleHealth NMR metabolomics to study lipids and polar metabolites with the risk for future PAD events in 5 prospective Finnish cohorts (n=31,657).

This led to discovery of a range of novel biomarkers for future PAD risk, including circulating fatty acids, glycolysis metabolites, amino acids and inflammation markers. Many were stronger than corresponding biomarkers associations for future CAD risk.

LDL cholesterol, HDL cholesterol and apolipoproteins were not predictive of PAD events, but were robust predictors of CAD events, showing limitations of current risk factors for PAD prediction. This extend results from Women’s Health Study pubmed.ncbi.nlm.nih.gov/30021845/

Here are the lipid associations for CAD (in red) and absence of associations for PAD (blue). Triglycerides in all lipoprotein fractions were directly predictive of both PAD and CAD

The biomarker signature for PAD risk was distinct to that for CAD risk. This may represent pathophysiological differences. Thus, detailed metabolic profiling in large cohorts can uncover different molecular signatures for vascular diseases with seemingly similar pathogenesis.

Differential metabolic biomarker signatures have previously been observed for ischemic stroke and intracerebral hemorrhage pubmed.ncbi.nlm.nih.gov/29420958/ in China Kadoorie Biobank

Thanks to @emmitiki for leading the study and to @mvholmes @mak_sysepi @MarkusPerola @thlorg and others for the collaboration. We welcome feedback

Soon-to-be-released @NgaleHealth metabolomics data for @uk_biobank will enable such studies across all common diseases, and inform prediction.

Can we expect to see similar strong prediction as for severe infectious diseases? (cf medrxiv.org/content/10.110…) - stay tuned!