The following is a summary of “Association Between Whole Blood–Derived Mitochondrial DNA Copy Number, Low‐Density Lipoprotein Cholesterol, and Cardiovascular Disease Risk,” published in the October 2023 issue of Cardiology by Liu et al.

The investigation delved into the intricate association between mitochondrial DNA copy number (mtDNA CN) and cardiovascular disease, seeking clarity on this relationship. Across 8 cohorts encompassing 27,316 participants from diverse racial and ethnic backgrounds, cross‐sectional and prospective analyses were conducted to evaluate blood-derived mtDNA CN and its correlation with cardiovascular disease outcomes. Employing whole-genome sequencing, the study also utilized Mendelian randomization to explore potential causal links between mtDNA CN and coronary heart disease (CHD) alongside various cardiometabolic risk factors like obesity, diabetes, hypertension, and hyperlipidemia. Significance was determined at P<0.01. 

The study validated numerous previously reported associations between mtDNA CN and cardiovascular disease outcomes. Specifically, a reduction of 1 standard deviation in mtDNA CN was linked to a 1.08 times higher hazard (95% CI, 1.04–1.12; P<0.001) for developing incident CHD, adjusted for covariates. However, Mendelian randomization analyses failed to indicate any causal effect from lower mtDNA CN levels to increased CHD risk (β=0.091; P=0.11) or vice versa (β=−0.012; P=0.076). Additionally, bidirectional Mendelian randomization analyses unveiled that while low‐density lipoprotein cholesterol had a causal impact on mtDNA CN (β=−0.084; P<0.001), the reverse direction lacked significance (P=0.059). Notably, no causal relationships were observed between mtDNA CN and obesity, diabetes, or hypertension in either direction. Furthermore, multivariable Mendelian randomization analyses suggested no causal effect of CHD on mtDNA CN when controlling for low‐density lipoprotein cholesterol levels (P=0.52). However, a pronounced direct causal effect was observed where higher levels of low‐density lipoprotein cholesterol were associated with lower mtDNA CN, even after adjusting for CHD status (β=−0.092; P<0.001). 

These findings suggest a potential link between elevated low‐density lipoprotein cholesterol and the intricate interplay of mtDNA CN and vascular atherosclerosis.

Source: ahajournals.org/doi/10.1161/JAHA.122.029090