Serum metabolite signatures of cardiac function and morphology in individuals from a population-based cohort
Background: Changes in serum metabolites in individuals with subclinical cardiovascular disease (CVD) can provide important information about pathway dysregulation and potential risk factors. We aimed to explore associations of markers of cardiac morphology and function, evaluated using magnetic resonance imaging (MRI) with a large panel of serum metabolites.
Methods: Cross-sectional data from 399 individuals (mean age 56.3 years; 41.9% female) without CVD from the population-based KORA cohort were analyzed. Associations between MRI-derived left ventricular function and morphology parameters (e.g., volumes, mass, filling rates, wall thickness) and markers of carotid plaque with metabolite profile clusters and single metabolites were assessed by multinomial logistic regression models with metabolite profile clusters as the outcome.
Results: 146 serum metabolites clustered into three distinct profiles that reflected high-, intermediate- and low-CVD risk. Higher stroke volume (RRR: 0.53, 95%-CI[0.37; 0.76], p-value<0.001) and early diastolic filling rate (RRR: 0.51, CI:[0.37; 0.71], p-value<0.001) were most strongly associated with the high-risk profile compared to the low-risk profile after adjusting for traditional CVD risk factors. Moreover, imaging markers were associated with 10 metabolites in single metabolite models using linear regression. Notable were the negative associations of stroke volume and early diastolic filling rate with acylcarnitine C5, and the positive association of function parameters with lysophosphatidylcholines, diacylphosphatidylcholines, and acylalkylphosphatidylcholines. Furthermore, there was a negative association of LV wall thickness segments with alanine, creatinine and symmetric dimethylarginine. We found no significant associations with carotid plaque.
Conclusions: Serum metabolite signatures are associated with cardiac morphology and function even in individuals without a clinical indication of CVD.