Clinical correlates and heritability of cardiac mechanics: The HyperGEN study

Sadiya S. 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 J. Rasmussen-Torvik; Sanjiv J. Shah

doi:10.1016/j.ijcard.2018.07.057

Clinical correlates and heritability of cardiac mechanics: The HyperGEN study

Sadiya S. 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 J. Rasmussen-Torvik, Sanjiv J. Shah

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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 language	English
Pages (from-to)	208-213
Number of pages	6
Journal	International Journal of Cardiology
Volume	274
DOIs	https://doi.org/10.1016/j.ijcard.2018.07.057
State	Published - Jan 1 2019

Bibliographical note

Funding Information:
No relationships or disclosures with industry. This study was funded by the National Institutes of Health (NIH) R01 HL107577 and HL127028 (to SJS); HL55673 (to DKA); and HL54471 , HL54472 , HL54473 , HL54495 , HL54496 , HL54497 , HL54509 , and HL54515 (HyperGEN parent study). SJS is also supported by American Heart Association grants 16SFRN28780016 and 15CVGPSD27260148 . SSK is supported by NIH F32 HL129695 and KL2TR001424 .

Funding Information:
Research reported in this publication was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences , Grant Number KL2TR001424 (SSK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

Cardiac mechanics
Echocardiography
Genetics
Heritability
Strain

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.ijcard.2018.07.057

Cite this

Khan, S. S., Kim, K. Y. A., Peng, J., Aguilar, F. G., Selvaraj, S., Martinez, E. E., Baldridge, A. S., Sha, J., Irvin, M. R., Broeckel, U., Arnett, D. K., Rasmussen-Torvik, L. J., & Shah, S. J. (2019). Clinical correlates and heritability of cardiac mechanics: The HyperGEN study. International Journal of Cardiology, 274, 208-213. https://doi.org/10.1016/j.ijcard.2018.07.057

@article{f60e213da2ee466d95d2123b692d9711,

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.",

keywords = "Cardiac mechanics, Echocardiography, Genetics, Heritability, Strain",

author = "Khan, {Sadiya S.} 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 J.} and Shah, {Sanjiv J.}",

note = "Funding Information: No relationships or disclosures with industry. This study was funded by the National Institutes of Health (NIH) R01 HL107577 and HL127028 (to SJS); HL55673 (to DKA); and HL54471 , HL54472 , HL54473 , HL54495 , HL54496 , HL54497 , HL54509 , and HL54515 (HyperGEN parent study). SJS is also supported by American Heart Association grants 16SFRN28780016 and 15CVGPSD27260148 . SSK is supported by NIH F32 HL129695 and KL2TR001424 . Funding Information: Research reported in this publication was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences , Grant Number KL2TR001424 (SSK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",

year = "2019",

month = jan,

day = "1",

doi = "10.1016/j.ijcard.2018.07.057",

language = "English",

volume = "274",

pages = "208--213",

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TY - JOUR

T1 - Clinical correlates and heritability of cardiac mechanics

T2 - The HyperGEN study

AU - Khan, Sadiya S.

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 J.

AU - Shah, Sanjiv J.

N1 - Funding Information: No relationships or disclosures with industry. This study was funded by the National Institutes of Health (NIH) R01 HL107577 and HL127028 (to SJS); HL55673 (to DKA); and HL54471 , HL54472 , HL54473 , HL54495 , HL54496 , HL54497 , HL54509 , and HL54515 (HyperGEN parent study). SJS is also supported by American Heart Association grants 16SFRN28780016 and 15CVGPSD27260148 . SSK is supported by NIH F32 HL129695 and KL2TR001424 . Funding Information: Research reported in this publication was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences , Grant Number KL2TR001424 (SSK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: © 2018 Elsevier B.V.

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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DO - 10.1016/j.ijcard.2018.07.057

M3 - Article

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AN - SCOPUS:85050121734

SN - 0167-5273

VL - 274

SP - 208

EP - 213

JO - International Journal of Cardiology

JF - International Journal of Cardiology

ER -

Clinical correlates and heritability of cardiac mechanics: The HyperGEN study

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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