Metabolic and inflammatory biomarkers associated with incident heart failure
Incident heart failure occurs as result of changes in heart metabolism as well as with low-grade, chronic inflammation. The most common heart diseases underlying incident heart failure are known to be elevated blood pressure, coronary artery disease and especially previous myocardial infarction. Some incident heart failure is also caused by cardiomyopathy or valvular heart disease. In addition, diabetes, systolic blood pressure, age, overweight, high insulin levels, declining kidney function and microalbuminuria are well established risk factors for heart failure that are considered to be associated with the development of incident heart failure. Studies have shown that these changes are present even years before any sign of heart failure. Despite the progresses made in the clinical studies, the prognosis of incident heart failure is still considered very poor. Therefore, it is important to identify and treat high-risk patients well before the disease develops. Previous studies conducted in this direction mostly used animal models that showed that disturbed metabolism of the heart muscle precedes, initiates and maintains unfavorable changes in the heart. Researchers in Finland in a newly published study showed for the first time that biomarkers of energy metabolism predict the development of incident heart failure in humans. They published their research in ESC Heart Failure (Novel biomarkers associated with incident heart failure in 10 106 Finnish men. ESC Heart Failure, 2020; DOI: 10.1002/ehf2.13132).
Researchers showed that by measuring biomarkers indicative of heart failure, it could be possible to better identify people with an elevated risk of developing incident heart failure. In their study, they discovered several new biomarkers that were associated with incident heart failure. In this study, several inflammatory biomarkers and cell energy metabolites were linked to an increased risk of incident heart failure. The study employed a random selection of 10,106 men participating in the Metabolic Syndrome in Men (METSIM) study. These men at baseline did not have a diagnosis of incident heart failure. Researchers then measured elevated levels of inflammatory biomarkers and several biomarkers associated with heart metabolism by NMR analysis that were associated with the development of incident heart failure in a follow-up that lasted for 8.8 years.
The new biomarkers that were discovered included adiponectin, high sensitivity C- reactive protein, the chronic inflammation biomarker GlycA, the amino acids alanine and phenylalanine, as well as glycerol and pyruvate. These biomarkers are used by the heart muscle for energy. Researchers then adjustment for age, BMI, diabetes and statin medication, adiponectin, pyruvate and urinary albumin excretion rate. They were subsequently identified with the development of incident heart failure.
Incident heart failure associated risk factors and biomarkers into components were classified by using principal component analysis. The analysis revealed that could possibly be linked to different courses of the disease. Four of these components were found to be statistically significant for the development of incident heart failure. Three of the components contained a different inflammatory biomarker and one contained cell energy metabolites. This study is expected to pave the way to further breakthroughs in drugs targeting inflammatory and metabolic pathways to prevent the development of incident heart failure.