Association of low-grade albuminuria with adverse cardiac mechanics: findings from the hypertension genetic epidemiology network (HyperGEN) study.

Abstract

Albuminuria is a marker of endothelial dysfunction and has been associated with adverse cardiovascular outcomes. The reasons for this association are unclear but may be attributable to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction. In the Hypertension Genetic Epidemiology Network (HyperGEN) Study, a population- and family-based study of hypertension, we examined the relationship between urine albumin-to-creatinine ratio (UACR) and cardiac mechanics (n=1894, all of whom had normal left ventricular ejection fraction and wall motion). We performed speckle-tracking echocardiographic analysis to quantify global longitudinal, circumferential, and radial strain, and early diastolic (e') tissue velocities. We used E/e' ratio as a marker of increased left ventricular filling pressures. We used multivariable-adjusted linear mixed effect models to determine independent associations between UACR and cardiac mechanics. The mean age was 50±14 years, 59% were female, and 46% were black. Comorbidities were increasingly prevalent among higher UACR quartiles. Albuminuria was associated with global longitudinal strain, global circumferential strain, global radial strain, e' velocity, and E/e' ratio on unadjusted analyses. After adjustment for covariates, UACR was independently associated with lower absolute global longitudinal strain (multivariable-adjusted mean global longitudinal strain [95% confidence interval] for UACR Quartile 1 = 15.3 [15.0-15.5]% versus UACR Q4 = 14.6 [14.3-14.9]%, P for trend <0.001) and increased E/e' ratio (Q1 = 25.3 [23.5-27.1] versus Q4 = 29.0 [27.0-31.0], P=0.003). The association between UACR and global longitudinal strain was present even in participants with UACR < 30 mg/g (P<0.001 after multivariable adjustment). Albuminuria, even at low levels, is associated with adverse cardiac mechanics and higher E/e' ratio.