Abstract
Abstract Background Identification of lifestyle modifiable metabolic pathways related to cardiometabolic disease risk is essential for improvement of primary prevention in susceptible individuals. It was recently shown that plasma dimethylguanidino valerate (DMGV) levels are associated with incident type 2 diabetes (T2DM). Our aims were to investigate if plasma DMGV is related to risk of future coronary artery disease (CAD) and with cardiovascular mortality and to replicate the association with T2DM and to pinpoint candidate lifestyle interventions susceptible to modulate DMGV levels. Methods Plasma DMGV levels were measured using liquid chromatography-mass spectrometry (LC-MS) in a total of 5768 participants from the Malmö Diet and Cancer Study – Cardiovascular Cohort (MDC), the Malmö Preventive Project (MPP) and the Malmö Offspring Study (MOS). Dietary intake assessment was performed in MOS. Results Baseline levels of DMGV associated with incident CAD in both MDC (HR=1.29, C.I= 1.16–1.43, P=3.3e-6) and MPP (OR=1.25, C.I=1.08–1.44, P=2.4e-3). In MDC, DMGV was associated with cardiovascular mortality and incident CAD, independently of traditional risk factors. Furthermore, the association between DMGV and incident T2DM was replicated in both MDC (HR=1.83, C.I=1.63–2.05, P=8.7e-25) and MPP (OR=1.65, C.I=1.38–1.98, P=8.7e-8). Intake of sugar-sweetened beverages (SSB) associated with increased levels of DMGV, while intake of vegetables and level of physical activity associated with lower DMGV. Conclusions We discovered novel independent associations between plasma DMGV and incident CAD and cardiovascular mortality, while replicating the previously reported association with incident T2DM. Additionally, strong associations with SSB, vegetable intake and physical activity suggest the potential to modify DMGV levels using lifestyle interventions. Acknowledgement/Funding Knut and Alice Wallenberg Foundation, Göran Gustafsson Foundation, the Swedish Heart- and Lung Foundation, the Swedish Research Council
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