Association of Low-Grade Albuminuria with Adverse Cardiac Mechanics: Findings from the HyperGEN Study

: Background —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 due to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction. Methods and Results —In the 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 (GLS, GCS, and GRS, respectively), and early diastolic (e’) tissue velocities. We used E/e’ ratio as a marker of increased LV 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 African-American. Comorbidities were increasingly prevalent among higher UACR quartiles. Albuminuria was associated with GLS, GCS, GRS, e’ velocity, and E/e’ ratio on unadjusted analyses. After adjustment for covariates, UACR was independently associated with lower absolute GLS (multivariable-adjusted mean GLS [95% CI] for UACR Quartile 1 = 15.3 [15.0-15.5]% vs. 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] vs. Q4 = 29.0 [27.0-31.0], P= 0.003). The association between UACR and GLS was present even in participants with UACR < 30 mg/g (P<0.001 after multivariable adjustment). ratio. diastolic (e’) tissue velocities. We used E/e’ ratio as a marker of increased LV fifilllllinining g g prprpresesessususurereress.s We used multivariable-adjusted linear mixed effect models to determine independent asasssosocciciatatioonsnss bbbetweweenen UUACACR R anand d caardiaicc mechhananiiicss. Thehe mmean agagagee wawass 4 yeyears,, 559%% were feefemmmale, and 46%%% wwwereee AAAfriciccannn-AAmemeriricacann. CCCommmorrbbiidittieieis s s wwwerrre inncncrreasiiingglglyy y pprrevalallennnt t amamamonggg hihighghhererer UUUACACACRR quququararartititlelelesss. AAAlblumumminininuururiaia wawawasss asasassososociciciatatatededed wwwititith h h GLGLGLSS,S, GGGCCSCS,, GGGRRSRS, e’e’e’ vvvelelelococitittyyy, EEE/e/e/’ atio on unaadjdjdjususustetetedd d anananalalalysyseseses. AfAffteteerr adadajujuustststmemementntnt fffororo cccovovovarariaiaiatetesss, UUUACACACRRR wawawasss ininidedeepeppendndndenenently y ooof ttisisisuuue ee vevevelololocicititiiesess aandndd myyoyoccardddiaaal sttrtraaiain,n,, reesesppeeccttivivelelely.y. TThhhesesse e ininndidiicececsss ofofof ccaaardddiac memeechchchanananicicss arararee seseensssititivivve inindidiccacatototorsrsrs ooof f mymymyocococyyyte ee ininijjujuryryry aaandndd mmmalllfufufunnnctititionono, , , ccacann n prprprovovovidideee nnonoveveel pppotototenenetititialalal rrrisisisk k fafafactctctororrs,s,s ssucucuch asasa aaalblblbumumumininnurururiaiai ((ii.i.e.e.e.,, enenendododothtteleleliaiaall dydydysfsfsfununnctctctioioion)n)n), pppeaaak basal wall early (e’) E/e’ aaa oo aaabbsolute vaalulueees (i.e.e., lololongngngititituduudininnalalal aanndnd circcucummfeererentiaaal l ststraraiinn vvalaluueues wewewerere cccoononvevertrrededed fffrooommm nenegagagatititivevev tto oo popopsisittiivvee vvaaaluueues)s. LoLoLowewewer r r ababsososolululutetete sstrtrtraiainnn vvvalllueueess,s, lllowwwererr ee’ tititsssssueee vveelelocococititieieiess,s, aanndnd hhigiggheeer r n E/e’ wererreee ususuededed tto o o ininididiicacacatete wwworororseses cccararardididiacacac fffunununctctcioioion.n. AAA vvvalalaidididatatatiooon nn ofofof tthehehe ddigiggitittizizizatatatioioon diastolic (e’) tissue velocity; and (E) E/e’ ratio are shown by UACR quartile for all subjects and 3 subgroups after adjustment for speckle-tracking analyst, study site, image quality, age, sex, body mass index, estimated glomerular filtration rate, diabetes mellitus, coronary artery disease, systolic blood pressure, use of antihypertensive medication, history of smoking, left ventricular mass index, and ejection fraction. LVH = left ventricular hypertrophy; DM = diabetes mellitus; HTN = hypertension. Tissue velocities by speckle tracking are lower than values observed using tissue Doppler. Thus e’ tissue velocity is lower and E/e’ is higher than observed with tissue Doppler.