Relationship between sex, shape, and substrate in hypertrophic cardiomyopathy

J. Martijn Bos, Jeanne L. Theis, A. Jamil Tajik, Bernard J. Gersh, Steve R. Ommen, Michael John Ackerman

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Hypertrophic cardiomyopathy (HCM) is a disease characterized by substantial genetic, morphologic, and prognostic heterogeneity. Recently, sex-related differences in HCM were reported, with women being older at diagnosis and exhibiting greater left ventricular outflow tract obstruction than men. We sought to evaluate the influence of sex on the HCM phenotype in a large cohort of unrelated patients with genetically and morphologically classified HCM. Methods: Comprehensive genotyping of 13 HCM-susceptibility genes encoding myofilament and Z-disc proteins of the cardiac sarcomere was performed previously on 382 unrelated patients with HCM. Blinded to the genotype, the septal morphology was graded as reverse-curvature, sigmoidal, apical, or neutral-contour HCM by echocardiography. Results: Overall, women (a) were significantly older at diagnosis (45.1 ± 20 vs 35.8 ± 17 years, P < .001), (b) had greater left ventricular outflow tract obstruction (53.5 ± 45 vs 41.7 ± 42 mm Hg, P = .009), (c) were more likely to have concomitant hypertension (19% vs 11%, P = .02), and (d) had a higher rate of surgical myectomy (49% vs 36%, P = .01) than men. Interestingly, these sex-based differences were apparent only among patients with sigmoidal HCM (P < .001). Conclusions: In this largest cohort of comprehensively genotyped and morphologically classified patients with clinically diagnosed HCM, we observed that the striking sex-related differences in the clinical phenotype are confined largely to the subset of mutation-negative sigmoidal HCM. Whereas mutations within the sarcomere appear to dominate the disease process, in their absence, sex has a significant modifying effect, specifically noted in cases of sigmoidal HCM.

Original languageEnglish (US)
Pages (from-to)1128-1134
Number of pages7
JournalAmerican Heart Journal
Volume155
Issue number6
DOIs
StatePublished - Jun 2008

Fingerprint

Hypertrophic Cardiomyopathy
Sex Characteristics
Ventricular Outflow Obstruction
Sarcomeres
Phenotype
Mutation
Myofibrils
Echocardiography
Genotype
Hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Relationship between sex, shape, and substrate in hypertrophic cardiomyopathy. / Bos, J. Martijn; Theis, Jeanne L.; Tajik, A. Jamil; Gersh, Bernard J.; Ommen, Steve R.; Ackerman, Michael John.

In: American Heart Journal, Vol. 155, No. 6, 06.2008, p. 1128-1134.

Research output: Contribution to journalArticle

Bos, J. Martijn ; Theis, Jeanne L. ; Tajik, A. Jamil ; Gersh, Bernard J. ; Ommen, Steve R. ; Ackerman, Michael John. / Relationship between sex, shape, and substrate in hypertrophic cardiomyopathy. In: American Heart Journal. 2008 ; Vol. 155, No. 6. pp. 1128-1134.
@article{e686b65a8fbe4b4c8235beed32aad662,
title = "Relationship between sex, shape, and substrate in hypertrophic cardiomyopathy",
abstract = "Background: Hypertrophic cardiomyopathy (HCM) is a disease characterized by substantial genetic, morphologic, and prognostic heterogeneity. Recently, sex-related differences in HCM were reported, with women being older at diagnosis and exhibiting greater left ventricular outflow tract obstruction than men. We sought to evaluate the influence of sex on the HCM phenotype in a large cohort of unrelated patients with genetically and morphologically classified HCM. Methods: Comprehensive genotyping of 13 HCM-susceptibility genes encoding myofilament and Z-disc proteins of the cardiac sarcomere was performed previously on 382 unrelated patients with HCM. Blinded to the genotype, the septal morphology was graded as reverse-curvature, sigmoidal, apical, or neutral-contour HCM by echocardiography. Results: Overall, women (a) were significantly older at diagnosis (45.1 ± 20 vs 35.8 ± 17 years, P < .001), (b) had greater left ventricular outflow tract obstruction (53.5 ± 45 vs 41.7 ± 42 mm Hg, P = .009), (c) were more likely to have concomitant hypertension (19{\%} vs 11{\%}, P = .02), and (d) had a higher rate of surgical myectomy (49{\%} vs 36{\%}, P = .01) than men. Interestingly, these sex-based differences were apparent only among patients with sigmoidal HCM (P < .001). Conclusions: In this largest cohort of comprehensively genotyped and morphologically classified patients with clinically diagnosed HCM, we observed that the striking sex-related differences in the clinical phenotype are confined largely to the subset of mutation-negative sigmoidal HCM. Whereas mutations within the sarcomere appear to dominate the disease process, in their absence, sex has a significant modifying effect, specifically noted in cases of sigmoidal HCM.",
author = "Bos, {J. Martijn} and Theis, {Jeanne L.} and Tajik, {A. Jamil} and Gersh, {Bernard J.} and Ommen, {Steve R.} and Ackerman, {Michael John}",
year = "2008",
month = "6",
doi = "10.1016/j.ahj.2008.01.005",
language = "English (US)",
volume = "155",
pages = "1128--1134",
journal = "American Heart Journal",
issn = "0002-8703",
publisher = "Mosby Inc.",
number = "6",

}

TY - JOUR

T1 - Relationship between sex, shape, and substrate in hypertrophic cardiomyopathy

AU - Bos, J. Martijn

AU - Theis, Jeanne L.

AU - Tajik, A. Jamil

AU - Gersh, Bernard J.

AU - Ommen, Steve R.

AU - Ackerman, Michael John

PY - 2008/6

Y1 - 2008/6

N2 - Background: Hypertrophic cardiomyopathy (HCM) is a disease characterized by substantial genetic, morphologic, and prognostic heterogeneity. Recently, sex-related differences in HCM were reported, with women being older at diagnosis and exhibiting greater left ventricular outflow tract obstruction than men. We sought to evaluate the influence of sex on the HCM phenotype in a large cohort of unrelated patients with genetically and morphologically classified HCM. Methods: Comprehensive genotyping of 13 HCM-susceptibility genes encoding myofilament and Z-disc proteins of the cardiac sarcomere was performed previously on 382 unrelated patients with HCM. Blinded to the genotype, the septal morphology was graded as reverse-curvature, sigmoidal, apical, or neutral-contour HCM by echocardiography. Results: Overall, women (a) were significantly older at diagnosis (45.1 ± 20 vs 35.8 ± 17 years, P < .001), (b) had greater left ventricular outflow tract obstruction (53.5 ± 45 vs 41.7 ± 42 mm Hg, P = .009), (c) were more likely to have concomitant hypertension (19% vs 11%, P = .02), and (d) had a higher rate of surgical myectomy (49% vs 36%, P = .01) than men. Interestingly, these sex-based differences were apparent only among patients with sigmoidal HCM (P < .001). Conclusions: In this largest cohort of comprehensively genotyped and morphologically classified patients with clinically diagnosed HCM, we observed that the striking sex-related differences in the clinical phenotype are confined largely to the subset of mutation-negative sigmoidal HCM. Whereas mutations within the sarcomere appear to dominate the disease process, in their absence, sex has a significant modifying effect, specifically noted in cases of sigmoidal HCM.

AB - Background: Hypertrophic cardiomyopathy (HCM) is a disease characterized by substantial genetic, morphologic, and prognostic heterogeneity. Recently, sex-related differences in HCM were reported, with women being older at diagnosis and exhibiting greater left ventricular outflow tract obstruction than men. We sought to evaluate the influence of sex on the HCM phenotype in a large cohort of unrelated patients with genetically and morphologically classified HCM. Methods: Comprehensive genotyping of 13 HCM-susceptibility genes encoding myofilament and Z-disc proteins of the cardiac sarcomere was performed previously on 382 unrelated patients with HCM. Blinded to the genotype, the septal morphology was graded as reverse-curvature, sigmoidal, apical, or neutral-contour HCM by echocardiography. Results: Overall, women (a) were significantly older at diagnosis (45.1 ± 20 vs 35.8 ± 17 years, P < .001), (b) had greater left ventricular outflow tract obstruction (53.5 ± 45 vs 41.7 ± 42 mm Hg, P = .009), (c) were more likely to have concomitant hypertension (19% vs 11%, P = .02), and (d) had a higher rate of surgical myectomy (49% vs 36%, P = .01) than men. Interestingly, these sex-based differences were apparent only among patients with sigmoidal HCM (P < .001). Conclusions: In this largest cohort of comprehensively genotyped and morphologically classified patients with clinically diagnosed HCM, we observed that the striking sex-related differences in the clinical phenotype are confined largely to the subset of mutation-negative sigmoidal HCM. Whereas mutations within the sarcomere appear to dominate the disease process, in their absence, sex has a significant modifying effect, specifically noted in cases of sigmoidal HCM.

UR - http://www.scopus.com/inward/record.url?scp=44149114286&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44149114286&partnerID=8YFLogxK

U2 - 10.1016/j.ahj.2008.01.005

DO - 10.1016/j.ahj.2008.01.005

M3 - Article

C2 - 18513529

AN - SCOPUS:44149114286

VL - 155

SP - 1128

EP - 1134

JO - American Heart Journal

JF - American Heart Journal

SN - 0002-8703

IS - 6

ER -