Premature Coronary Artery Disease, Association with Relative Blood Number of Mitochondrial DNA Copies in Mexican Population—Results of GEA Study

Figures

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  Figure 1. Flow chart representing the distribution of the participants in the study.

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  Figure 2. Relative blood mtDNA-CN in the study population stratified by sex (a) and studied groups (b). Data is expressed as median [interquartile range]. Comparisons between groups were made with Mann–Whitney U test.

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  Figure 3. Relative blood mtDNA-CN in women and men stratified by studied groups. Data is expressed as median [interquartile range]. Comparisons between groups were made with Mann–Whitney U test.

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  Figure 4. Association between pCAD and relative blood mtDNA-CN in the study population. Model 1: Adjusted for age and sex; Model 2: Adjusted for model 1 + body mass index; Model 3: Adjusted for model 2 + current smoking; Model 4: Adjusted for model 3 + LDL-cholesterol; Model 5: Adjusted for model 4 + type 2 diabetes mellitus and hypertension; Model 6: Adjusted for model 5 + physical activity.

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  Figure 5. Association between pCAD and relative blood mtDNA-CN in the study population stratified by sex. Model 1: Adjusted for age; Model 2: Adjusted for model 1 + body mass index; Model 3: Adjusted for model 2 + current smoking; Model 4: Adjusted for model 3 + LDL-cholesterol; Model 5: Adjusted for model 4 + type 2 diabetes mellitus and hypertension; Model 6: Adjusted for model 5 + physical activity.

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  Figure 6. Spearman correlation between relative blood mtDNA-CN and adiposity measurements in the premature coronary patients. TAF = total abdominal fat, SAF = subcutaneous abdominal fat, VAF = visceral abdominal fat. The p values were not adjusted for multiple comparisons because these were simple bivariate correlations testing specific predefined hypotheses.

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  Figure 7. Conceptual hypothesis. An inverse correlation between relative blood mtDNA-CN and both total abdominal adiposity and, more specifically, visceral adipose tissue (VAT), was observed. VAT is known to secrete proinflammatory cytokines while simultaneously reducing the production of adiponectin, an adipokine with protective effects on mitochondrial function. These inflammatory signals interfere with mitochondrial biogenesis, thereby promoting mitochondrial dysfunction. Such dysfunction leads to increased generation of reactive oxygen species (ROS) and elevated oxidative stress, which further contribute to a reduction in mitochondrial mass, greater mitochondrial alterations, and a subsequent decrease in relative blood mtDNA-CN. These interconnected processes may contribute to visceral fat accumulation, although this proposed relationship cannot be established from the present study. Our findings demonstrate that reduced relative blood mtDNA-CN is significantly associated with pCAD and correlates inversely with total and visceral abdominal fat depots. Consequently, we propose that relative blood mtDNA-CN may warrant further evaluation as a useful indicator associated with the presence…