Blood cell traits on cardiovascular morpho-functional phenotypes: evidence from Mendelian randomization analysis

The causal relationships between blood cell traits and cardiac and aortic structure and function remain unclear. In this 2-sample Mendelian randomization study, we investigated the causal genetic relationships between 15 blood cell traits and 100 cardiovascular magnetic resonance imaging traits. instrumental variables comprised independent genetic variants significantly associated with 7 red blood cell traits, 6 white blood cell traits, and 2 platelet traits. The cardiovascular magnetic resonance traits, derived from 7 distinct genome-wide association studies, served as preclinical endophenotypes characterizing aortic segment and cardiac chamber structure and function. Primary effects were estimated using the inverse-variance weighted method, with sensitivity analyses addressing horizontal pleiotropy. Multivariable and reverse Mendelian randomization analyses were also performed. Genetically predicted elevations in red blood cell count, hemoglobin concentration, and hematocrit (HCT) were associated with reduced volumes across various heart chambers and aortic diameters. Elevated hemoglobin and HCT levels correlate with diminished ventricular volumes and masses. Conversely, genetically predicted higher lymphocyte count was predominantly associated with reduced aortic diameter. Additionally, increased HCT was linked to enhanced left ventricular global longitudinal strain, whereas red cell distribution width was positively associated with aortic and thoracic aortic diameters. This study suggests potential causal relationships between blood cell traits and cardiac and aortic remodeling. These findings indicate that risk assessment and monitoring strategies incorporating blood cell traits may represent novel approaches for cardiovascular disease prevention.