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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.

SUBMITTER: Katz DH

PROVIDER: S-EPMC3888488 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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

Katz Daniel H DH Selvaraj Senthil S Aguilar Frank G FG Martinez Eva E EE Beussink Lauren L Kim Kwang-Youn A KY Peng Jie J Sha Jin J Irvin Marguerite R MR Eckfeldt John H JH Turner Stephen T ST Freedman Barry I BI Arnett Donna K DK Shah Sanjiv J SJ

Circulation 20130927 1

<h4>Background</h4>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.<h4>Methods and results</h4>In the Hypertension Genetic Epidemiology Network (HyperGEN) Study, a population- and family-based study of hypertension, we examined the relationship between urine albumin-to-creatin ...[more]

PMID: 24077169

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Project description:BACKGROUND:Indices of cardiac mechanics are sensitive markers of subclinical myocardial dysfunction. Improved understanding of the clinical correlates and heritability of cardiac mechanics could result in novel insight into the acquired and genetic risk factors for myocardial dysfunction. Therefore, we sought to determine the clinical correlates and heritability of indices of cardiac mechanics in whites and African Americans (AAs). METHODS:We examined 2058 participants stratified by race (1104 whites, 954 AA) in the Hypertension Genetic Epidemiology Network (HyperGEN), a population- and family-based study, and performed digitization of analog echocardiograms with subsequent speckle-tracking analysis. We used linear mixed effects models to determine the clinical correlates of indices of cardiac mechanics (longitudinal, circumferential, radial strain; early diastolic strain rate; and early diastolic tissue velocities). Heritability estimates for cardiac mechanics were calculated using maximum-likelihood variance component analyses in Sequential Oligogenic Linkage Analysis Routine (SOLAR), with adjustment for clinical and echocardiographic covariates. RESULTS:Several clinical characteristics and conventional echocardiographic parameters were found to be associated with speckle-tracking traits of cardiac mechanics. Male sex, blood pressure, and fasting glucose were associated with worse longitudinal strain (LS) (P?<?0.05 for all) after multivariable adjustment. After adjustment for covariates, LS, e' velocity, and early diastolic strain rate were found to be heritable; LS and e' velocity had higher heritability estimates in AAs compared to whites. CONCLUSIONS:Indices of cardiac mechanics are heritable traits even after adjustment for clinical and conventional echocardiographic correlates. These findings provide the basis for future studies of genetic determinants of these traits that may elucidate race-based differences in heart failure development.

Project description:BACKGROUND:The optimal level of sodium intake remains controversial. OBJECTIVES:This study sought to determine whether examination of left ventricular longitudinal strain (LS), circumferential strain, and e' velocity can provide insight into thresholds for the detrimental effects of estimated sodium intake (ESI) on subclinical cardiovascular disease. METHODS:We performed speckle-tracking analysis on HyperGEN (Hypertension Genetic Epidemiology Network) study echocardiograms with available urinary sodium data (N = 2,996). We evaluated the associations among ESI and LS, circumferential strain, and e' velocity using multivariable-adjusted linear mixed-effects models (to account for relatedness among subjects) with linear splines (spline 1: ESI ?3.7 g/day, spline 2: ESI >3.7 g/day based on visual inspection of fractional polynomial plots of the association between ESI and indices of strain and e' velocity). We performed mediation analysis to understand the indirect effects of systolic blood pressure and serum aldosterone on the relationship between ESI and strain and e' velocity. RESULTS:Mean age of participants was 49 ± 14 years, 57% were female, 50% were African American, and 54% had hypertension. The median ESI was 3.73 (interquartile range: 3.24, 4.25) g/day. ESI >3.7 g/day was associated with larger left atrial and left ventricular dimensions (p < 0.05). After adjusting for speckle-tracking analyst, image quality, study site, age, sex, smoking status, alcohol use, daily blocks walked, diuretic use, estimated glomerular filtration rate, left ventricular mass, ejection fraction, and wall motion score index, ESI >3.7 g/day was associated with both strain parameters and e' velocity (p < 0.05 for all comparisons), but ESI ?3.7 g/day was not (p > 0.05 for all comparisons). There were significant interactions by potassium excretion for circumferential strain. Mediation analysis suggested that systolic blood pressure explained 14% and 20% of the indirect effects between ESI and LS and e' velocity, respectively, whereas serum aldosterone explained 19% of the indirect effects between ESI and LS. CONCLUSIONS:ESI >3.7 g/day is associated with adverse cardiac remodeling and worse systolic strain and diastolic e' velocity.

Project description:Hypertension is an important contributor to global burden of disease and mortality, and is a growing public health problem in sub-Saharan Africa. However, most sub-Saharan African countries lack detailed countrywide data on hypertension and other non-communicable diseases (NCD) risk factors that would provide benchmark information for design of appropriate interventions. We analyzed blood pressure data from Uganda's nationwide NCD risk factor survey conducted in 2014, to describe the prevalence and distribution of hypertension in the Ugandan population, and to identify the associated factors.The NCD risk factor survey drew a countrywide sample stratified by the four regions of the country, and with separate estimates for rural and urban areas. The World Health Organization's STEPs tool was used to collect data on demographic and behavioral characteristics, and physical and biochemical measurements. Prevalence rate ratios (PRR) using modified Poison regression modelling was used to identify factors associated with hypertension.Of the 3906 participants, 1033 were classified as hypertensive, giving an overall prevalence of 26.4%. Prevalence was highest in the central region at 28.5%, followed by the eastern region at 26.4%, western region at 26.3%, and northern region at 23.3%. Prevalence in urban areas was 28.9%, and 25.8% in rural areas. The differences between regions, and between rural-urban areas were not statistically significant. Only 7.7% of participants with hypertension were aware of their high blood pressure. The prevalence of pre-hypertension was also high at 36.9%. The only modifiable factor found to be associated with hypertension was higher body mass index (BMI). Compared to participants with BMI less than 25 kg/m2, prevalence was significantly higher among participants with BMI between 25 to 29.9 kg/m2 with an adjusted PRR = 1.46 [95% CI = 1.25-1.71], and even higher among obese participants (BMI ≥ 30 kg/m2) with an adjusted PRR = 1.60 [95% CI = 1.29-1.99]. The un-modifiable factor found to be associated with hypertension was older age with an adjusted PRR of 1.02 [95% CI = 1.02-1.03] per yearly increase in age.The prevalence of hypertension in Uganda is high, with no significant differences in distribution by geographical location. Only 7.7% of persons with hypertension were aware of their hypertension, indicating a high burden of undiagnosed and un-controlled high blood pressure. Thus a big percentage of persons with hypertension are at high risk of hypertension-related cardiovascular NCDs.

Dataset Information

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

Publications

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

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