Clinical correlates and heritability of cardiac mechanics

The HyperGEN study

Sadiya Sana Khan, Kwang-Youn A Kim, Jie Peng, Frank G. Aguilar, Senthil Selvaraj, Eva E. Martinez, Abigail S. Baldridge, Jin Sha, Marguerite R. Irvin, Ulrich Broeckel, Donna K. Arnett, Laura Jarmila Rasmussen-Torvik, Sanjiv J Shah*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)208-213
Number of pages6
JournalInternational Journal of Cardiology
Volume274
DOIs
StatePublished - Jan 1 2019

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Molecular Epidemiology
Mechanics
Hypertension
African Americans
Social Adjustment
Fasting
Analysis of Variance
Heart Failure
Blood Pressure
Glucose
Population

Keywords

  • Cardiac mechanics
  • Echocardiography
  • Genetics
  • Heritability
  • Strain

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Khan, Sadiya Sana ; Kim, Kwang-Youn A ; Peng, Jie ; Aguilar, Frank G. ; Selvaraj, Senthil ; Martinez, Eva E. ; Baldridge, Abigail S. ; Sha, Jin ; Irvin, Marguerite R. ; Broeckel, Ulrich ; Arnett, Donna K. ; Rasmussen-Torvik, Laura Jarmila ; Shah, Sanjiv J. / Clinical correlates and heritability of cardiac mechanics : The HyperGEN study. In: International Journal of Cardiology. 2019 ; Vol. 274. pp. 208-213.
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title = "Clinical correlates and heritability of cardiac mechanics: The HyperGEN study",
abstract = "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.",
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author = "Khan, {Sadiya Sana} and Kim, {Kwang-Youn A} and Jie Peng and Aguilar, {Frank G.} and Senthil Selvaraj and Martinez, {Eva E.} and Baldridge, {Abigail S.} and Jin Sha and Irvin, {Marguerite R.} and Ulrich Broeckel and Arnett, {Donna K.} and Rasmussen-Torvik, {Laura Jarmila} and Shah, {Sanjiv J}",
year = "2019",
month = "1",
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Khan, SS, Kim, K-YA, Peng, J, Aguilar, FG, Selvaraj, S, Martinez, EE, Baldridge, AS, Sha, J, Irvin, MR, Broeckel, U, Arnett, DK, Rasmussen-Torvik, LJ & Shah, SJ 2019, 'Clinical correlates and heritability of cardiac mechanics: The HyperGEN study', International Journal of Cardiology, vol. 274, pp. 208-213. https://doi.org/10.1016/j.ijcard.2018.07.057

Clinical correlates and heritability of cardiac mechanics : The HyperGEN study. / Khan, Sadiya Sana; Kim, Kwang-Youn A; Peng, Jie; Aguilar, Frank G.; Selvaraj, Senthil; Martinez, Eva E.; Baldridge, Abigail S.; Sha, Jin; Irvin, Marguerite R.; Broeckel, Ulrich; Arnett, Donna K.; Rasmussen-Torvik, Laura Jarmila; Shah, Sanjiv J.

In: International Journal of Cardiology, Vol. 274, 01.01.2019, p. 208-213.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clinical correlates and heritability of cardiac mechanics

T2 - The HyperGEN study

AU - Khan, Sadiya Sana

AU - Kim, Kwang-Youn A

AU - Peng, Jie

AU - Aguilar, Frank G.

AU - Selvaraj, Senthil

AU - Martinez, Eva E.

AU - Baldridge, Abigail S.

AU - Sha, Jin

AU - Irvin, Marguerite R.

AU - Broeckel, Ulrich

AU - Arnett, Donna K.

AU - Rasmussen-Torvik, Laura Jarmila

AU - Shah, Sanjiv J

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Cardiac mechanics

KW - Echocardiography

KW - Genetics

KW - Heritability

KW - Strain

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