Blood pressure (BP) control in hypertensive patients is crucial for reducing the risk of heart failure development and may be particularly important in elderly subjects, who have an especially high prevalence of hypertension and risk of heart failure (1). Left ventricular (LV) global longitudinal strain (GLS) is an echocardiographic measure of LV systolic function that can be an indicator of early subclinical cardiac dysfunction, even when LV ejection fraction is normal. The association of BP control with early subclinical LV dysfunction according to GLS has not been extensively studied, and it is also unknown whether assessing BP control with ambulatory blood pressure (ABP) monitoring is superior to using office BP measurements in this regard. Therefore, we investigated the association of BP control with GLS by using ABP and office BP criteria in a community-based, predominantly elderly cohort with normal LV ejection fraction

Di Tullio, Marco R.

Elkind, Mitchell S.

Homma, Shunichi

Jin, Zhezhen

Lee, Edward S.

Rundek, Tatjana

Russo, Cesare

Sacco, Ralph L.

Schwartz, Joseph E.

Sera, Fusako

English

PubMed

Elkind, Mitchell S.V.

Elsevier - Publisher Connector 

FIGURE 1 Associati
Uncontrolled
Uncontrolled 
Uncontrolled day
Uncontrolled night
*Adjusted for age, dia
index. ABP ¼ ambula
strain.
J O U R N A L O F T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y V O L . 6 6 , N O . 1 2 , 2 0 1 5
ª 2 0 1 5 B Y T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N I S S N 0 7 3 5 - 1 0 9 7 / $ 3 6 . 0 0
P U B L I S H E D B Y E L S E V I E R I N C .LettersAmbulatory Blood
Pressure Control and
Subclinical Left Ventricular
Dysfunction in Treated
Hypertensive SubjectsBlood pressure (BP) control in hypertensive patients
is crucial for reducing the risk of heart failure devel-
opment and may be particularly important in elderly
subjects, who have an especially high prevalence
of hypertension and risk of heart failure (1). Left
ventricular (LV) global longitudinal strain (GLS) is an
echocardiographic measure of LV systolic function
that can be an indicator of early subclinical cardiac
dysfunction, even when LV ejection fraction is
normal. The association of BP control with early
subclinical LV dysfunction according to GLS has not
been extensively studied, and it is also unknown
whether assessing BP control with ambulatory
blood pressure (ABP) monitoring is superior to us-
ing ofﬁce BP measurements in this regard. There-
fore, we investigated the association of BP control
with GLS by using ABP and ofﬁce BP criteria in aon of Uncontrolled Ofﬁce BP and ABP With Abnormal GLS
*Adjusted odds ratio (95% CI) for abnormal GLS
0.1 1 10
 office BP
24-h ABP
time ABP
time ABP
1.31 (0.78-2.21)
2.38 (1.39-4.08)
2.62 (1.53-4.50)
2.50 (1.40-4.45)
betes mellitus, coronary artery disease, and left ventricular mass
tory blood pressure; BP ¼ blood pressure; GLS ¼ global longitudinalcommunity-based, predominantly elderly cohort with
normal LV ejection fraction.
The study cohort consisted of 394 treated hyper-
tensive patients (mean age 72  9 years; 63% women)
with LV ejection fraction$50% from the CABL (Cardiac
Abnormalities and Brain Lesion) study. The patients
underwent transthoracic echocardiography and ABP
monitoring. Uncontrolled ofﬁce BP was deﬁned as of-
ﬁce systolic blood pressure (SBP) $140 mm Hg and/or
diastolic blood pressure (DBP) $90 mm Hg; uncon-
trolled 24-h ABP as mean 24-h SBP$130 mmHg and/or
DBP $80 mm Hg; uncontrolled daytime ABP as mean
daytime SBP$135 mmHg and/or DBP$85 mmHg; and
uncontrolled night-time ABP as mean night-time
SBP $120 mm Hg and/or DBP $70 mm Hg (2).
Speckle-tracking analysis was performed on digital
echocardiographic images by using commercially
available software (QLAB Advanced Quantiﬁcation
Software version 8.1, Philips, Andover, Massachu-
setts). The GLS was calculated by averaging the nega-
tive peak of longitudinal strain of 12 LV segments from
the apical 4- and 2-chamber views. Abnormal GLS was
deﬁned as a GLS more than –14.7%, which is the 95th
percentile of the GLS distribution in the healthy
normotensive subjects from the CABL cohort (3).
Seventy-seven subjects (19.5%) had abnormal GLS.
Ofﬁce BP was uncontrolled in 188 subjects (47.7%),
and 24-h ABP was uncontrolled in 162 (41.1%).
Concordant classiﬁcation of BP control between ofﬁce
BP and 24-h ABP was identiﬁed only in 230 subjects
(58.4%; kappa ¼ 0.16; 95% conﬁdence interval [CI]:
0.06 to 0.26). Uncontrolled daytime and night-time
ABP were identiﬁed in 36.6% and 53.0% of partici-
pants, respectively.
In univariable logistic regression analyses, uncon-
trolled 24-h ABP was signiﬁcantly associated with
abnormal GLS (odds ratio: 2.95; 95% CI: 1.76 to 4.93;
p < 0.0001), whereas uncontrolled ofﬁce BP was not
(odds ratio: 1.41; 95% CI: 0.85 to 2.32; p ¼ 0.18). After
adjustment for age, diabetes mellitus, coronary artery
disease, and LV mass index, uncontrolled 24-h ABP
remained signiﬁcantly associated with abnormal GLS
(Figure 1). A signiﬁcant association with abnormal GLS
was also found by using either daytime or night-time
criteria (Figure 1).
We show, for the ﬁrst time, the superiority of ABP
control over ofﬁce BP control for the risk stratiﬁcation
J A C C V O L . 6 6 , N O . 1 2 , 2 0 1 5 Letters
S E P T E M B E R 2 2 , 2 0 1 5 : 1 4 0 8 – 1 3
1409of treated hypertensive subjects for the presence of
subclinical LV systolic dysfunction. In a hypertensive
animal model, impairment of GLS occurred in parallel
with the accumulation of ﬁbrosis induced by pressure
overload in the LV subendocardium in the early
stage of hypertensive heart failure (4). Therefore, we
speculate that consistent reduction of LV pressure
overload throughout the 24 h by antihypertensive
medications might be important in delaying the
progression of LV systolic dysfunction and that ABP
control may be a better indicator of the effective
reduction of LV pressure overload than ofﬁce BP
control. Of note, inadequate ABP control was more
frequent at night than during the day in this cohort,
further underlining how ofﬁce BP does not provide an
adequate representation of BP values in a critical
period of the day.
Evaluating BP control by use of ABP monitoring,
but not by ofﬁce BP, may identify patients with
hypertension at higher risk of early LV systolic
dysfunction. Whether achieving BP control according
to ABP criteria may help decrease the risk of devel-
oping subclinical LV systolic dysfunction, and
possibly slow its progression to clinical heart failure,
is a hypothesis that deserves further investigation.Fusako Sera, MD
Zhezhen Jin, PhD
Cesare Russo, MD
Edward S. Lee, MD
Joseph E. Schwartz, PhD
Tatjana Rundek, MD, PhD
Mitchell S.V. Elkind, MD, MS
Shunichi Homma, MD
Ralph L. Sacco, MD, MS
*Marco R. Di Tullio, MD
*Division of Cardiology, Columbia University
College of Physicians and Surgeons
622 West 168th Street
New York, New York 10032
E-mail: md42@cumc.columbia.edu
http://dx.doi.org/10.1016/j.jacc.2015.05.083
Please note: This study was supported by grants from the National Institute of
Neurological Disorders and Stroke (R01 NS36286 and R37 NS29993). The authors
have reported that they have no relationships relevant to the contents of this
paper to disclose.
RE F E RENCE S
1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—
2014 update: a report from the American Heart Association. Circulation 2014;
129:e28–292.
2. Pickering TG, Hall JE, Appel LJ, et al. Recommendations for blood
pressure measurement in humans and experimental animals: part 1: blood
pressure measurement in humans: a statement for Professionals from the
Subcommittee of Professional and Public Education of the American Heart
Association Council on High Blood Pressure Research. Hypertension 2005;45:
142–61.3. Russo C, Jin Z, Elkind MS, et al. Prevalence and prognostic value of sub-
clinical left ventricular systolic dysfunction by global longitudinal strain in a
community-based cohort. Eur J Heart Fail 2014;16:1301–9.
4. Ishizu T, Seo Y, Kameda Y, et al. Left ventricular strain and transmural
distribution of structural remodeling in hypertensive heart disease. Hyper-
tension 2014;63:500–6.Aortic Dissection After
Previous Aortic Valve
Replacement for Bicuspid
Aortic Valve DiseaseThe effect of bicuspid aortic valve (BAV) phenotype on
the future risk of type A aortic dissection is unknown.
On the basis of previous data (1), we hypothesized that
the risk of post–aortic valve replacement (AVR) aortic
dissection might be different in BAV insufﬁciency
versus BAV stenosis.
A meta-analysis was performed in accordance with
published guidelines (2). We conducted a systematic
search on PubMed, Embase, Ovid, and Google Scholar
by using the terms “aortic dissection,” “bicuspid
aortic valve,” “aortic valve replacement,” “previous
cardiac surgery,” and “bicuspid aortopathy.” The
search was limited to original adult human studies of
type A aortic dissection occurring after previous iso-
lated AVR surgery in patients with BAV disease and
known functional phenotype (i.e., insufﬁciency vs.
stenosis). Reports on post-AVR dissection in patients
with tricuspid aortic valve disease and after combined
procedures were excluded. Papers reporting aortic
dissection within 14 days of AVR were also excluded.
The primary endpoint was the risk of post-AVR
dissection in BAV insufﬁciency versus BAV stenosis.
All analyses were conducted using Comprehensive
Meta-Analysis version 2 (Biostat, Englewood, New
Jersey). Events were compared as odds ratios by us-
ing a 95% conﬁdence interval. A random effects
model was used to derive pooled estimates. Study-
speciﬁc estimates were calculated on the assump-
tion that type A dissection develops in 0.6% of
patients after AVR (3) and that patients undergoing
surgery for BAV disease are 6 to 8 times more likely to
present with aortic stenosis than with insufﬁciency
(4). Heterogeneity was evaluated, and a sensitivity
analysis was performed. Fixed-effect meta-regression
was performed to determine the modulating effect of
arterial hypertension/aortic diameters. Publication
bias was evaluated using a funnel plot and Begg and
Mazumdar’s rank correlation test.
The keyword-based search revealed 17,068 poten-
tial publications. After removal of 3,056 duplicate


Ambulatory Blood Pressure Control and Subclinical Left Ventricular Dysfunction in Treated Hypertensive Subjects 

Sera, Fusako

Jin, Zhezhen

Russo, Cesare

Lee, Edward S

Schwartz, Joseph E

Rundek, Tatjana

Elkind, Mitchell S.V

Homma, Shunichi

Sacco, Ralph L

Di Tullio, Marco R

University of Miami: Scholarship Miami

Journal of the American College of Cardiology

Ambulatory Blood Pressure Control and Subclinical Left Ventricular Dysfunction in Treated Hypertensive Subjects

Columbia University Academic Commons

Ambulatory Blood Pressure Control and Subclinical Left Ventricular Dysfunction in Treated Hypertensive SubjectsFusako Sera, MD*, Zhezhen Jin, PhD†, Cesare Russo, MD*, Edward S. Lee, MD*, Joseph E. Schwartz, PhD*,‡, Tatjana Rundek, MD, PhD§, Mitchell S.V. Elkind, MD, MS∥, Shunichi Homma, MD*, Ralph L. Sacco, MD, MS§,¶, and Marco R. Di Tullio, MD**Department of Medicine, Columbia University, New York, NY, USA†Department of Biostatistics, Columbia University, New York, NY, USA‡Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA§Departments of Neurology and Public Health Sciences, University of Miami, Miami, FL, USA∥Departments of Neurology and Epidemiology, Columbia University, New York, NY, USA¶Department of Human Genetics, University of Miami, Miami, FL, USABlood pressure (BP) control in hypertensive patients is crucial for reducing the risk of heart failure (HF) development, and may be of particular importance in the elderly, who have especially high prevalence of hypertension and risk of HF (1). Left ventricular (LV) global longitudinal strain (GLS) is an echocardiographic measure of LV systolic function that can be an indicator of early subclinical cardiac dysfunction, even when LV ejection fraction (LVEF) is normal. The association of BP control with early subclinical LV dysfunction by GLS has not been extensively studied, and it is also unknown whether assessing BP control with ambulatory BP (ABP) monitoring may be superior to using office BP measurements in this regard. Therefore, we investigated the association of BP control with GLS using ABP and office BP criteria in a community-based, predominantly elderly cohort with normal LVEF.The study cohort consisted of 394 treated hypertensive subjects (mean age 72±9 years; 63% women) with LVEF ≥50% from the Cardiac Abnormalities and Brain Lesion (CABL) study who underwent transthoracic echocardiography and ABP monitoring. Uncontrolled office BP was defined as office systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg; uncontrolled 24-hour ABP as mean 24-hour SBP ≥130 mmHg and/or DBP ≥80 mmHg; uncontrolled daytime ABP as mean daytime SBP ≥135 mmHg and/or DBP ≥85 mmHg; uncontrolled nighttime ABP as mean nighttime SBP ≥120 mmHg and/or DBP ≥70 mmHg (2).Address for correspondence: Marco R. Di Tullio, MD, Division of Cardiology, Columbia University, College of Physicians & Surgeons, 622 West 168th Street, New York, NY 10032, Phone: +1-212-305-8805 /Fax: +1-212-305-9049, ; Email: md42@cumc.columbia.edu Conflicts of Interest: NoneHHS Public AccessAuthor manuscriptJ Am Coll Cardiol. Author manuscript; available in PMC 2016 September 22.Published in final edited form as:J Am Coll Cardiol. 2015 September 22; 66(12): 1408–1409. doi:10.1016/j.jacc.2015.05.083.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptSpeckle-tracking analysis was performed on digital echocardiographic images using commercially available software (QLAB Advanced Quantification Software version 8.1, Philips, Andover, MA). GLS was calculated by averaging the negative peak of longitudinal strain of 12 LV segments from the apical four-chamber and two-chamber views. Abnormal GLS was defined as a GLS ≥14.7%, which is the 95th percentile of the GLS distribution in the healthy normotensive subjects from the CABL cohort (3).Seventy-seven subjects (19.5%) had abnormal GLS. Office BP was uncontrolled in 188 subjects (47.7%), while 24-hour ABP was uncontrolled in 162 (41.1%). Concordant classification of BP control between office BP and 24-hour ABP was identified only in 230 subjects (58.4%; kappa=0.16, 95% CI, 0.06–0.26). Uncontrolled daytime and nighttime ABP was identified in 36.6% and 53.0% of participants, respectively.In univariable logistic regression analyses, uncontrolled 24-hour ABP was significantly associated with abnormal GLS (odds ratio [OR] = 2.95; 95% confidence interval [CI], 1.76 to 4.93; p<0.0001), whereas uncontrolled office BP was not (OR=1.41; 95% CI, 0.85 to 2.32; p=0.18). After adjustment for age, diabetes mellitus, coronary artery disease, and LV mass index, uncontrolled 24-hour ABP remained significantly associated with abnormal GLS (Figure 1). A significant association with abnormal GLS was also found using either daytime or nighttime criteria (Figure 1).We demonstrate for the first time the superiority of ABP control over office BP control for the risk stratification of treated hypertensive subjects for presence of subclinical LV systolic dysfunction. In a hypertensive animal model, impairment of GLS occurred in parallel with the accumulation of fibrosis induced by pressure overload in the LV subendocardium in the early stage of hypertensive HF (4). Therefore, we speculate that consistent reduction of LV pressure overload throughout the 24 hours by antihypertensive medications might be important to delay the progression of LV systolic dysfunction, and that ABP control might be a better indicator of the effective reduction of LV pressure overload than office BP control. Of note, inadequate ABP control was more frequent at night than during the day in this cohort, further underlining how office BP does not provide an adequate representation of BP values in a critical period of the day.Evaluating BP control by ABP monitoring, but not by office BP, may identify hypertensive patients at higher risk of early LV systolic dysfunction. Whether achieving BP control by ABP criteria may help decrease the risk of developing subclinical LV systolic dysfunction, and possibly slow its progression to clinical HF, is a hypothesis that deserves further investigation.AcknowledgmentsSources of Funding: R01 NS36286 and R37 NS29993 from the National Institute of Neurological Disorders and Stroke (NINDS).References1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014; 129:e28–e292. [PubMed: 24352519] Sera et al. Page 2J Am Coll Cardiol. Author manuscript; available in PMC 2016 September 22.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscript2. Pickering TG, Hall JE, Appel LJ, et al. Recommendations for blood pressure measurement in humans and experimental animals: Part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension. 2005; 45:142–61. [PubMed: 15611362] 3. Russo C, Jin Z, Elkind MS, et al. Prevalence and prognostic value of subclinical left ventricular systolic dysfunction by global longitudinal strain in a community-based cohort. Eur J Heart Fail. 2014; 16:1301–9. [PubMed: 25211239] 4. Ishizu T, Seo Y, Kameda Y, et al. Left ventricular strain and transmural distribution of structural remodeling in hypertensive heart disease. Hypertension. 2014; 63:500–6. [PubMed: 24396022] Sera et al. Page 3J Am Coll Cardiol. Author manuscript; available in PMC 2016 September 22.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptFigure 1. Association of Uncontrolled Office and Ambulatory BP with Abnormal GLSBP indicates blood pressure; ABP, ambulatory BP; GLS, global longitudinal strain.Sera et al. Page 4J Am Coll Cardiol. Author manuscript; available in PMC 2016 September 22.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscript

Fusako Sera

Zhezhen Jin

Cesare Russo

Edward S. Lee

Joseph E. Schwartz

Tatjana Rundek

Mitchell S.V. Elkind

Shunichi Homma

Ralph L. Sacco

Marco R. Di Tullio

Crossref

Ambulatory Blood Pressure Control and Subclinical Left Ventricular Dysfunction in Treated Hypertensive Subjects

Background:
Blood pressure (BP) control in hypertensive patients is crucial to reducing the risk of future cardiovascular events and heart failure. Left ventricular (LV) global longitudinal strain (GLS) can detect early subclinical cardiac dysfunction, even when LV ejection fraction (EF) is normal, and is an important prognostic indicator. It is not known whether poor BP control is associated with subclinical dysfunction by GLS, and whether ambulatory BP (ABP) is superior to office BP measurements in this regard.
Methods:
Two-dimensional speckle tracking echocardiography and 24-hour ABP monitoring were performed in 394 treated hypertensive subjects (mean age 72 ± 9 years; 63% women) with LVEF ≥50% from the Cardiovascular Abnormalities and Brain Lesions (CABL) study. Uncontrolled office BP was defined as systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg; uncontrolled ABP as mean 24-hour systolic BP ≥130 mmHg and/or diastolic BP ≥80 mmHg. Abnormal GLS was defined as a value above the 95% percentile of healthy normotensive subjects from the CABL cohort.
Results:
Office BP was uncontrolled in 188 subjects (47.7%), and ABP in 162 (41.1%). Agreement between these two categorization was low [kappa = 0.16, 95% confidence interval (CI), 0.06-0.26; concordant classification in only 58.4% of subjects]. Subjects with uncontrolled ABP showed significantly worse GLS compared to those with controlled ABP (-16.3 ± 3.0% vs -17.7 ± 2.9%, p<0.0001), whereas GLS was not significantly different between those with uncontrolled vs controlled office BP (-16.8 ± 3.1% vs -17.4 ± 3.0%, p=0.07). After adjustment for pertinent covariates (age, sex, race-ethnicity, body mass index, diabetes mellitus, coronary artery disease and LV mass index), uncontrolled ABP was associated with a higher risk of abnormal GLS (odds ratio = 2.32; 95% CI, 1.33-4.03; p=0.003), while uncontrolled office BP was not (odds ratio = 1.30; 95% CI, 0.76-2.22; p=0.35).
Conclusions:
Uncontrolled 24-hour ABP is strongly associated with LV subclinical dysfunction in hypertensive subjects with normal LVEF. Assessing BP control with ABP monitoring may refine the risk stratification of treated hypertensive patients for early LV dysfunction

Elkind, Mitchell S

Circulation

Abstract 15836: Blood Pressure Control and Subclinical Left Ventricular Dysfunction in Treated Hypertensive Subjects

http://dx.doi.org/10.1016/j.jacc.2015.05.083

Ambulatory Blood Pressure Control and Subclinical Left Ventricular Dysfunction in Treated Hypertensive Subjects

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Elsevier - Publisher Connector

Columbia University Academic Commons

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University of Miami: Scholarship Miami