Top Things to Know: Next Generation Cardiometabolic Biomarkers: Early, Mechanistic and Modifiable
Published: October 30, 2023
- Clinical manifestations of cardiometabolic risks (CMR) typically occur late during dysmetabolism, at which point currently available therapies may only mitigate but not reverse progression to type 2 diabetes, cardiovascular, renal, and hepatic diseases.
- Research advances in multi-omic technologies are broadening our understanding of the molecular mechanisms that underpin metabolic health across the lifespan.
- ‘Omic’ biomarkers promise to identify the earliest departure from healthy metabolism, which may be very early in life when therapeutic interventions may prove more successful.
- Alterations in the somatic and mitochondrial epigenome in response to environmental stressors are associated with heritable CMR. However, it is unclear whether adverse epigenetic alterations can be reversed to confer cardiometabolic health.
- The intestinal microbiome is well-established as early as 3 to 5 years of age yet remains modifiable across the lifespan. For example, short-chain fatty acid butyrate production reflects favorable dietary-microbiome interactions, sustains gut wall integrity, attenuates inflammation, and promotes functional mitochondria and cardiometabolic health.
- Metabolomic small molecule biomarkers reflect genetic, epigenetic, transcriptomic, and proteomic environmental interactions. As one example, branched-chain amino acids reflect impaired mitochondrial function and associate with CMR across the lifespan.
- Lipidomic sphingolipid ceramides build up in ectopic adipose depots in the face of caloric excess, particularly saturated fat and refined carbohydrate calories, impair mitochondrial function, and predict cardiometabolic disease.
- Ether glycerophospholipid plasmalogens sourced from essential fatty acids in breast milk and across the lifespan in cold water fish provide mitochondrial support, inhibit ectopic adiposity, and attenuate CMR.
- Chronic and excessive inflammation triggers inflammasome activation, predisposing to insulin resistance, lipotoxicity, and CMR that can be attenuated with an anti-inflammatory diet.
- Strong evidence supports a lifestyle approach to optimize functional mitochondria and cardiometabolic health. Successful implementation of preventive nutrition, activity, and environmental strategies will benefit from more deliberate community engagement in omics research and a clear focus on implementation science.
Citation
Mietus-Snyder M, Perak AM, Cheng S, Hayman LL, Haynes N, Meikle PJ, Shah SH, Suglia SF; on behalf of the American Heart Association Atherosclerosis, Hypertension and Obesity in the Young Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Cardiovascular and Stroke Nursing. Next generation, modifiable cardiometabolic biomarkers: mitochondrial adaptation andmetabolic resilience: a scientific statement from the American Heart Association [published online aheadof print October 30, 2023]. Circulation. doi: 10.1161/CIR.0000000000001185