Circulating Dimethylguanidino Valeric Acid, Dietary Factors, and Risk of Coronary Heart Disease
Background
Coronary Heart Disease (CHD) is one of the leading causes of death globally, with a complex pathogenesis involving multiple metabolic and dietary factors. In recent years, the development of metabolomics has provided new perspectives for studying CHD, particularly through the analysis of blood metabolites to uncover potential disease risk markers. Dimethylguanidino Valeric Acid (DMGV) is a newly discovered metabolite associated with cardiorespiratory fitness and metabolic abnormalities. Existing research suggests that DMGV levels may be modulated by diet, but its specific relationship with CHD-related food/nutrient intake has not been fully explored. Therefore, this study aimed to investigate the association between plasma DMGV levels and the risk of CHD, as well as its relationship with dietary intake.
Source of the Paper
This study was conducted by Yoriko Heianza, Xuan Wang, Minghao Kou, and other authors from renowned research institutions such as Tulane University, University of California San Diego, and Brigham and Women’s Hospital. The paper was published online on September 7, 2024, in the journal Cardiovascular Research, titled “Circulating Dimethylguanidino Valeric Acid, Dietary Factors, and Risk of Coronary Heart Disease.”
Research Process and Details
Study Subjects and Design
This study employed a nested case-control design, with participants drawn from two independent cohorts: the Nurses’ Health Study (NHS) and the Women’s Lifestyle Validation Study (WLVS). The NHS cohort included 1520 women, of whom 760 were CHD cases and 760 were controls. The WLVS cohort included 724 women, used to assess the relationship between plasma DMGV levels and dietary intake as well as metabolic abnormalities.
Data Collection and Processing
In the NHS cohort, blood samples were collected from participants in 1989-1990 and 2000-2002, with long-term follow-up until 2016. CHD cases were defined as non-fatal myocardial infarction or fatal CHD, confirmed through medical records and death certificates. In the WLVS cohort, participants provided two blood samples and completed 7-day Dietary Records (7DDRs) to assess their dietary intake.
Metabolite Measurement
Plasma DMGV was measured using Liquid Chromatography-Mass Spectrometry (LC-MS). All samples were analyzed in the same batch, with technicians blinded to the case-control status of the samples. Quality control results showed high reproducibility in DMGV measurement (average coefficient of variation: 15.1%).
Statistical Analysis
The study used conditional logistic regression models to evaluate the relationship between DMGV levels and CHD risk, adjusting for dietary intake and metabolic factors. To assess the association between DMGV and dietary intake, the researchers calculated the effect (β value) of each 1-standard deviation (SD) increase in dietary intake on DMGV levels and further estimated the corresponding relative risk (RR) of CHD.
Main Findings
DMGV and CHD Risk
The study found a linear positive correlation between plasma DMGV levels and CHD risk (p = 0.006). Each 1-SD increase in DMGV levels was associated with a 26% increase in CHD risk (RR = 1.26, 95% CI 1.13-1.40). After adjusting for diet and lifestyle factors, the highest quartile (Q4) of DMGV levels was significantly associated with CHD risk (RR = 1.60, 95% CI 1.17-2.18). However, this association was attenuated after further adjustment for metabolic factors such as obesity and hypertension (RR = 1.29, 95% CI 0.93-1.79).
DMGV and Dietary Intake
The study also found that higher sodium intake, energy-dense foods, and processed/red meat consumption were associated with higher DMGV levels. For example, each 1-SD increase in sodium intake was associated with a 0.13 increase in DMGV levels (p = 0.007), corresponding to a 3.1% increase in CHD risk (RR = 1.031, 95% CI 1.016-1.046). On the other hand, higher intakes of potassium, dietary fiber, nuts, and fruits were associated with lower DMGV levels, and these dietary factors were linked to reduced CHD risk.
DMGV and Metabolic Abnormalities
In both independent cohorts, higher DMGV levels were significantly associated with greater obesity and more adverse metabolic status. For example, DMGV levels were positively correlated with Body Mass Index (BMI), body fat mass, blood lipids, HbA1c, and other metabolic markers (p < 0.0001).
Conclusion and Significance
This study demonstrates that plasma DMGV levels, as a metabolite reflecting unfavorable dietary intake, are associated with an increased long-term risk of CHD in women. This unfavorable association was partially attenuated by metabolic risk factors such as obesity and hypertension. The findings highlight the potential of DMGV as an early biomarker, which could be targeted through dietary interventions to reduce CHD risk. Additionally, the study reveals a strong link between DMGV and metabolic abnormalities, providing new directions for exploring the biological mechanisms of DMGV in cardiovascular diseases.
Research Highlights
- Novel Biomarker: DMGV, as a newly discovered metabolite, was first confirmed to be associated with CHD risk, revealing its close relationship with dietary intake.
- Long-Term Follow-Up Data: The study is based on long-term follow-up data from two large cohorts, NHS and WLVS, providing robust epidemiological evidence.
- Comprehensive Analysis of Diet and Metabolism: The study not only analyzed the association between DMGV and diet but also explored its relationship with metabolic abnormalities, offering new insights into the multifactorial pathogenesis of CHD.
Additional Valuable Information
The study also found that DMGV was significantly associated with insulin secretion-related markers (e.g., insulin, C-peptide), suggesting that DMGV may play an important role in metabolic regulation. Furthermore, the findings provide important clues for further exploration of the biological mechanisms and potential intervention strategies related to DMGV.
Through this study, we have deepened our understanding of CHD risk factors and provided scientific evidence for future prevention and intervention strategies. DMGV, as a potential early biomarker, is expected to play a significant role in clinical practice in the future.