Mendelian randomization study of the relation between adiponectin and heart function, unravelling the paradox.
Peptides
; 146: 170664, 2021 12.
Article
in En
| MEDLINE
| ID: mdl-34597752
ABSTRACT
High adiponectin concentrations are generally regarded as beneficial with regard to cardiometabolic health, but have been paradoxically associated with increased cardiovascular disease risk, specifically heart failure, in individuals at high cardiovascular risk. We aimed to investigate the association between adiponectin and heart function parameters, and inversely, we estimated the effect of genetically-determined heart function and NT-proBNP as the main marker of heart failure on adiponectin using Mendelian randomisation. Observational analyses between adiponectin and measures of heart function, i.e. E/A ratio, left, and right ventricular ejection fraction, were performed in participants of the Netherlands Epidemiology of Obesity (NEO) study, assessed by MRI of the heart (n = 1,138). Two-sample Mendelian randomisation analyses were conducted to estimate the effect of NT-proBNP and heart function on adiponectin concentrations using publicly-available summary statistics (ADIPOGen; the PLATO trial). The mean (standard deviation) age was 56 (6) years and mean body mass index was 26 (4) kg/m2. Per five µg/mL higher adiponectin, the E/A ratio was -0.05 (95 % CI -0.10, -0.01) lower, left ventricle ejection fraction was -0.5 % (95 % CI -1.1, 0.1) lower, and right ventricle ejection fraction was 0.5 % (95 % CI -0.1, 1.2) higher. Genetically-determined NT-proBNP was causally related to adiponectin concentrations in ADIPOGen per doubling of genetically-determined NT-proBNP, adiponectin concentrations were 11.4 % (95 % CI 1.7, 21.6) higher. With causal MR methods we showed that NT-proBNP affects adiponectin concentrations, while adiponectin is not associated with heart function parameters. Therefore, reverse causation may explain the adiponectin paradox observed in previous studies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adiponectin
/
Mendelian Randomization Analysis
/
Heart
Type of study:
Clinical_trials
/
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Peptides
Year:
2021
Document type:
Article