Intrafamilial Aggregation and Heritability of Left Ventricular Geometric Remodeling Is Independent of Cardiac Mass in Families of African Ancestry

As acknowledged by all guidelines, left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular events independent of conventional risk factors and coronary artery disease. In addition, compared to a normal LV geometry, concentric LV remodeling (an increased relative wall thickness (RWT) without an increase in LV mass (LVM)) is associated with a worse prognosis.1–4 Although LVM rather than concentric LV remodeling predicts incident heart failure,3 concentric LV remodeling without LVH is associated with the development of diastolic dysfunction, and concentric rather than eccentric LVH is associated with greater increases in indices of LV filling pressures.5 Thus, the extent of concentric LV remodeling may determine whether progression from LVH to heart failure with a preserved rather than reduced systolic chamber function occurs. The factors that determine LV remodeling are therefore of considerable interest. Although the impact of age, sex, blood pressure, and obesity on LV geometric remodeling has been well described, there is nevertheless uncertainty as to the role of genetic factors independent of LVM, a major determinant of LV wall thickness, and a change that itself is well recognized as being inherited.6–14 Compared to age-, and sex-matched controls, siblings of those with LVH have a greater risk of concentric, but not eccentric LVH.9 However, in that study,9 whether siblings were also at risk for concentric LV remodeling is uncertain and hence LVM may have made a major contribution to the inheritance of concentric LVH. Moreover, in the Framingham Heart Study, the risk for concentric LV remodeling was only modestly increased in related compared to unrelated individuals, whereas the risk for concentric LVH was markedly augmented.15 Hence, again, LVM may have been the major determinant of the inheritance of LV remodeling. Although alternative studies indicate that RWT is indeed inherited,10–12,16 none of these studies reported on the inheritance of RWT independent of LVM. To address the aforementioned uncertainty as to the extent to which genetic factors contribute toward concentric LV remodeling beyond LVM, in the present study, we aimed to evaluate the intrafamilial aggregation and heritability of RWT independent of LVM and additional confounders. We hypothesized that RWT would show intrafamilial aggregation and heritability independent of LVM and additional confounders.