Circulating dimethylguanidino valeric acid, dietary factors, and risk of coronary heart disease.

Aims: Circulating dimethylguanidino valeric acid (DMGV) was identified as a novel metabolite related to cardiorespiratory fitness and cardiometabolic abnormalities. Circulating DMGV levels are subjective to dietary modulation; however, studies on its associations with intakes of coronary heart disease (CHD)-related foods/nutrients are limited. We investigated whether plasma DMGV was related to risk of incident CHD. We tested associations of DMGV with CHD-related dietary intakes measured by 7-day dietary records and estimated corresponding disease risk.

Methods and results: This nested case-control study on the incidence of CHD included 1520 women (760 incident cases of fatal CHD and nonfatal myocardial infarction and 760 controls) from the Nurses' Health Study. Separately, plasma DMGV and CHD-related dietary intakes and cardiometabolic abnormalities were assessed in the Women's Lifestyle Validation Study (WLVS; n=724). Higher plasma DMGV was related to a greater risk of CHD (relative risk [RR] per 1-SD: 1.26 [95% CI: 1.13, 1.40]; P-for-linearity=0.006). Greater intakes of sodium, energy dense-foods, and processed/red meat were related to higher DMGV levels; every 1-SD intake of sodium was associated with β 0.13 (SE 0.05; p=0.007) for DMGV-Z-scores, which corresponded to a RR of 1.031 [1.016, 1.046] for CHD. High DMGV (the top quartile, Q4) showed a significant RR of 1.60 [1.17, 2.18] after adjusting for diet and lifestyle factors; the RR further adjusting for obesity and hypertension was 1.29 [0.93, 1.79] as compared with the lowest quartile. In both cohorts, greater adiposity and adverse cardiometabolic factor status were significantly related to higher DMGV levels.

Conclusion: Higher levels of plasma DMGV, a metabolite reflecting unfavorable CHD-related dietary intakes, were associated with an increased risk of CHD. The unfavorable association was attenuated by cardiometabolic risk factor status. Our study underscores the potential importance of plasma DMGV as an early biomarker associated with diet and the long-term risk of CHD among women.