Eva E. Martinez

Association of Low-Grade Albuminuria With Adverse Cardiac Mechanics Findings From the Hypertension Genetic Epidemiology Network (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 attributable to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction. Methods and Results— 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). Conclusions— Albuminuria, even at low levels, is associated with adverse cardiac mechanics and higher E/e′ ratio.

Archeological Echocardiography: Digitization and Speckle Tracking Analysis of Archival Echocardiograms in the HyperGEN Study

Several large epidemiologic studies and clinical trials have included echocardiography, but images were stored in analog format and these studies predated tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE). We hypothesized that digitization of analog echocardiograms, with subsequent quantification of cardiac mechanics using STE, is feasible, reproducible, accurate, and produces clinically valid results.

Association of Central Adiposity With Adverse Cardiac Mechanics Findings From the Hypertension Genetic Epidemiology Network Study

Background— Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s′] and early diastolic [e′] tissue velocities). Methods and Results— We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m2, waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s′ velocity, and e′ velocity ( P <0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status. Conclusions— In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics.Background—Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s′] and early diastolic [e′] tissue velocities). Methods and Results—We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m2, waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s′ velocity, and e′ velocity (P<0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status. Conclusions—In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics.

Phenomapping for the Identification of Hypertensive Patients with the Myocardial Substrate for Heart Failure with Preserved Ejection Fraction

We sought to evaluate whether unbiased machine learning of dense phenotypic data (“phenomapping”) could identify distinct hypertension subgroups that are associated with the myocardial substrate (i.e., abnormal cardiac mechanics) for heart failure with preserved ejection fraction (HFpEF). In the HyperGEN study, a population- and family-based study of hypertension, we studied 1273 hypertensive patients utilizing clinical, laboratory, and conventional echocardiographic phenotyping of the study participants. We used machine learning analysis of 47 continuous phenotypic variables to identify mutually exclusive groups constituting a novel classification of hypertension. The phenomapping analysis classified study participants into 2 distinct groups that differed markedly in clinical characteristics, cardiac structure/function, and indices of cardiac mechanics (e.g., phenogroup #2 had a decreased absolute longitudinal strain [12.8 ± 4.1 vs. 14.6 ± 3.5%] even after adjustment for traditional comorbidities [p < 0.001]). The 2 hypertension phenogroups may represent distinct subtypes that may benefit from targeted therapies for the prevention of HFpEF.

Association of Central Adiposity With Adverse Cardiac MechanicsCLINICAL PERSPECTIVE

Background— Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s′] and early diastolic [e′] tissue velocities). Methods and Results— We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m2, waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s′ velocity, and e′ velocity ( P <0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status. Conclusions— In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics.Background—Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s′] and early diastolic [e′] tissue velocities). Methods and Results—We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m2, waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s′ velocity, and e′ velocity (P<0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status. Conclusions—In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics.

Association of Central Adiposity With Adverse Cardiac MechanicsCLINICAL PERSPECTIVE: Findings From the Hypertension Genetic Epidemiology Network Study

Background— Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s′] and early diastolic [e′] tissue velocities). Methods and Results— We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m2, waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s′ velocity, and e′ velocity ( P <0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status. Conclusions— In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics.Background—Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s′] and early diastolic [e′] tissue velocities). Methods and Results—We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m2, waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s′ velocity, and e′ velocity (P<0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status. Conclusions—In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics.