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Editorial Comment−−Left Ventricular Hypertrophy: An Unseemly Risk Factor for
Stroke?
Osvaldo Fustinoni
Stroke. 2003;34:2385-2386; originally published online September 18, 2003;
doi: 10.1161/01.STR.0000094582.60549.25
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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Left Ventricular Mass and Geometry and the Risk of
Ischemic Stroke
Marco R. Di Tullio, MD; Donna R. Zwas, MD; Ralph L. Sacco, MD;
Robert R. Sciacca, EngScD; Shunichi Homma, MD
Background and Purpose—Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular events, but its effect on
ischemic stroke risk is established mainly in whites. The effect of LV geometry on stroke risk has not been defined. The
aim of the present study was to evaluate whether LVH and LV geometry are independently associated with increased
ischemic stroke risk in a multiethnic population.
Methods—A population-based case-control study was conducted on 394 patients with first ischemic stroke and 413 age-,
sex-, and race-ethnicity–matched community control subjects. LV mass was measured by transthoracic echocardiography. LV geometric patterns (normal, concentric remodeling, concentric or eccentric hypertrophy) were identified.
Stroke risk associated with LVH and different LV geometric patterns was assessed by conditional logistic regression
analysis in the overall group and age, sex, and race-ethnic strata, with adjustment for established stroke risk factors.
Results—Concentric hypertrophy carried the greatest stroke risk (adjusted odds ratio [OR], 3.5; 95% confidence interval
[CI], 2.0 to 6.2), followed by eccentric hypertrophy (adjusted OR, 2.4; 95% CI, 2.0 to 4.3). Concentric remodeling
carried slightly increased stroke risk (adjusted OR, 1.7; 95% CI, 1.0 to 2.9). Increased LV relative wall thickness was
independently associated with stroke after adjustment for LV mass (OR, 1.6; 95% CI, 1.1 to 2.3).
Conclusions—LVH and abnormal LV geometry are independently associated with increased stroke risk. LVH is strongly
associated with ischemic stroke in all age, sex, and race-ethnic subgroups. Increased LV relative wall thickness imparts
an increased stroke risk after adjustment for LV mass and is of additional value in stroke risk prediction. (Stroke. 2003;
34:2380-2386.)
Key Words: echocardiography 䡲 heart ventricle 䡲 hypertrophy, left ventricular 䡲 stroke
L
eft ventricular hypertrophy (LVH), or increased LV
mass, is a risk factor for cardiovascular diseases.1–9
Echocardiographic LVH is associated with cardiovascular
morbidity and mortality, as well as all-cause mortality.4 –9 The
risk increase is independent of other cardiovascular risk
factors, including arterial hypertension.4 – 6,8,9 Recently, there
have been reports of incremental risk associated with abnormal LV geometry beyond the simple LV mass increase. From
LV mass and relative wall thickness (RWT), 3 abnormal
geometric patterns— concentric hypertrophy, eccentric hypertrophy, and concentric remodeling10—are identified that
appear to carry different risks for cardiovascular events.
Concentric hypertrophy (increase in both LV mass and RWT)
carries the highest risk,4,11 followed by eccentric hypertrophy
(increased LV mass, normal RWT4,11). The independent risk
of an isolated RWT increase (concentric remodeling) is
controversial.11–14
LVH is also independently associated with risk of ischemic
stroke.15–20 This association, identified in ECG studies,14 –17
was confirmed with more sensitive echocardiographic tech-
See Editorial Comment, page 2385
niques.19,20 Increased stroke risk was shown mainly in
whites,15–19 with fewer data available in blacks13,20 and
Hispanics.21 The role of abnormal LV geometry in stroke risk
has received little attention. In hypertensive patients, concentric and eccentric hypertrophy was associated with an ⬇2fold increase in stroke incidence, whereas concentric remodeling did not carry increased risk.4 However, the small
number of strokes precluded definitive conclusions in this
and similar studies.4,13
The aim of the present study was to evaluate the role of
LVH and abnormal LV geometry as independent risk factors
for ischemic stroke in the multiethnic population of the
Northern Manhattan Stroke Study (NOMASS).
Methods
Study Population
Subjects were drawn from NOMASS, a community-based epidemiological study that evaluates stroke incidence, risk factors, and
Received January 10, 2003; final revision received May 20, 2003; accepted June 4, 2003.
From the Departments of Medicine (M.R. Di T., D.R.Z., R.R.S., S.H.), Neurology (R.L.S.,) and Public Health (Epidemiology) (R.L.S.), Sergievsky
Center, Columbia-Presbyterian Medical Center, New York, NY.
Correspondence to Marco R. Di Tullio, MD, Division of Cardiology, PH 3-342, Columbia-Presbyterian Medical Center, 630 W 168th St, New York,
NY 10032. E-mail [email protected]
© 2003 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org
DOI: 10.1161/01.STR.0000089680.77236.60
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Di Tullio et al
TABLE 1.
Left Ventricular Geometry and Ischemic Stroke
Demographics of the Study Group
Stroke Patients (n⫽394)
Echocardiographic Evaluation
Transthoracic echocardiography was performed according to the
guidelines of the American Society of Echocardiography23 with
Hewlett-Packard Sonos 1000 and 2500 ultrasound equipment
(Hewlett-Packard Imaging Systems Division).
LV end-diastolic diameter (LVDD), LV end-systolic diameter
(LVSD), interventricular septum (IVS), and posterior wall (PW) thickness at end diastole were measured. LV mass (LVM) was calculated
from the corrected American Society of Echocardiography method24:
LVM⫽0.8(1.04[(IVS⫹LVDD⫹PW)3⫺LVDD3]⫹0.6).
LV mass (log transformed to increase normality) was then
regressed on height and sex. LVH was defined as adjusted LV mass
greater than the 90th percentile of the control subjects without
conditions associated with LVH such as arterial hypertension,
diabetes mellitus, obesity, and cardiovascular diseases. RWT was
calculated according to this formula10: 2(PW/LVDD).
The 90th percentile of the control population described above
(RWT: 0.60 for women, 0.54 for men) was used as the upper limit of
normal. Four LV geometric patterns10 were identified on the basis of
LV mass and RWT: normal (normal LV mass, normal RWT),
concentric remodeling (normal LV mass, abnormal RWT), eccentric
hypertrophy (abnormal LV mass, normal RWT), and concentric
hypertrophy (abnormal LV mass, abnormal RWT).
Echocardiographic studies were interpreted by researchers blinded
to case-control status and other clinical characteristics. Interobserver
variability for the variables measured ranged between 8% and 10%.
Control Subjects (n⫽413)
Age*
Men/
Women
Age*
Men/
Women
Overall group
68.6⫾12.2
183/211
68.3⫾11.5
185/228
Whites
75.2⫾12.8
35/32
74.5⫾11.1
37/33
Blacks
69.4⫾10.6
38/71
69.9⫾10.5
41/75
Hispanics
66.3⫾12.0
105/107
65.6⫾11.3
102/119
*Mean⫾SD.
prognosis in northern Manhattan. Recruitment modalities have been
published previously.21,22 Briefly, patients ⬎39 years of age residing
in northern Manhattan who were admitted at the Presbyterian
Hospital with a first ischemic stroke were eligible. The race-ethnic
distribution in this community is ⬇20% black, 63% Caribbean
Hispanic, and 15% white residents. Race-ethnicity was defined by
self-identification in response to a questionnaire modeled after the
US census. Stroke-free subjects were identified by random-digit
dialing of northern Manhattan households. Control subjects were
matched to cases by age (within 5 years), sex, and race-ethnicity.
From May 1993 through December 1998, 431 patients with first
ischemic stroke and 434 stroke-free control subjects underwent
2-dimensional transthoracic echocardiography. All necessary echocardiographic measurements were obtainable in 394 stroke patients
(91.4%) and in 413 control subjects (95.2%). Written informed
consent was obtained from all subjects. The study was approved by
the Institutional Review Board of Columbia-Presbyterian Medical
Center.
Statistical Analysis
Data are reported as mean⫾SD for continuous variables and as
frequency for categorical variables. Differences between proportions
were assessed by ␹2 test or Fisher’s exact test; differences between
mean values, by unpaired Student’s t test. A 2-tailed value of
P⬍0.05 was considered significant.
Univariate and multivariate conditional logistic regression analyses (PROC PHREG, SAS 8.2) were used to test the association
between LVH/geometric patterns and ischemic stroke. Unadjusted
odds ratios (ORs) were calculated for the entire study group and age,
sex, and race-ethnic subgroups. Multivariate analysis was used to
determine the adjusted OR for stroke of LVH and each LV geometric
pattern after adjustment for variables significantly associated with
ischemic stroke by univariate analysis (arterial hypertension, diabetes mellitus, atrial fibrillation, coronary artery disease, congestive
heart failure). Adjusted ORs and 95% confidence intervals (CIs)
were calculated.
To assess the effect of age (41 to 59, ⱖ60 years), sex, and
race-ethnicity on the association between LVH/geometric patterns
and stroke, separate variables were fit in the model to quantify the
effect of LVH/geometric patterns independently for each strata.
Differences between strata were tested with Wald’s ␹2.
To assess the effect of RWT above that of LV mass on stroke risk,
multivariate analysis was performed after adjustment for LV mass as
Diagnostic Evaluation
Stroke risk factors were collected by direct interview or medical
record review. Arterial hypertension was defined by history or
antihypertensive treatment or by blood pressure ⬎140/90 mm Hg
(average of 2 measurements). Hypercholesterolemia was defined as
total serum cholesterol ⬎240 mg/dL or the presence of appropriate
treatment. Diabetes mellitus was defined as abnormal fasting blood
sugar, positive history, or presence of oral or insulin treatment.
Coronary artery disease included history of myocardial infarction or
typical angina, a positive diagnostic test (stress test, coronary
angiography), or appropriate treatment. Atrial fibrillation was documented on a current or past ECG or Holter monitoring. Congestive
heart failure was diagnosed on the basis of clinical signs, symptoms,
and/or appropriate medical treatment.
Neurological workup in stroke patients included head CT or MRI,
carotid and vertebral artery duplex Doppler ultrasonography, and
transcranial Doppler examination of the middle and anterior cerebral
arteries or basilar artery.
TABLE 2.
2381
Stroke Risk Factors Distribution in the Entire Study Group and by Race-Ethnicity
Entire Group
Whites
Blacks
P
Cases
(n⫽67),
%
Arterial hypertension
78
67
0.001
70
54
0.06
82
61
0.05
79
70
0.03
Diabetes mellitus
31
16
0.001
16
9
0.2
34
11
0.001
34
21
0.002
Cigarette smoking
20
16
0.2
5
13
0.09
35
20
0.01
16
15
0.6
Hypercholesterolemia
36
42
0.1
26
40
0.08
36
43
0.3
40
43
Atrial fibrillation
10
2
0.001
21
3
0.001
8
4
0.1
8
1
0.001
CAD
35
20
0.001
54
29
0.003
26
17
0.1
34
20
0.001
CHF
12
5
0.001
15
1
0.004
6
3
0.3
15
8
0.02
Cases, Controls,
%
%
Controls
(n⫽70),
%
P
Cases
Controls
(n⫽109), (n⫽116),
%
%
Hispanics
P
Cases
Controls
(n⫽212), (n⫽221),
%
%
CAD indicates coronary artery disease; CHF, congestive heart failure.
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P
0.6
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October 2003
TABLE 4. Association Between LV Hypertrophy and
Ischemic Stroke
LVH
Unadjusted OR
(95% CI)
LV geometric patterns in the study population. 䡺 Indicates normal; o, concentric remodeling; 1, concentric hypertrophy; and
u, eccentric hypertrophy.
a continuous variable and for other stroke risk factors described
above.
Results
Demographics of the study population are shown in Table 1.
Interracial differences existed in traditional stroke risk factors
(Table 2).
LVH, LV Geometry, and Risk of Ischemic Stroke
The distribution of LV geometric patterns is summarized in
the Figure. Normal pattern was more frequent in control
subjects than in stroke patients (65% versus 43%;
P⫽0.0001). Stroke patients had significantly higher frequencies of concentric hypertrophy (13% versus 6%; P⫽0.0001)
and eccentric hypertrophy (33% versus 20%; P⫽0.0001).
Arterial hypertension frequency and duration and blood
pressure values are listed in Table 3. Blood pressure was
significantly higher in abnormal geometry compared with
normal geometry groups (P⬍0.01). Hypertension duration
was longest in the concentric hypertrophy group, but not
significantly (P⫽0.1). Of patients with LVH, 15% had no
diagnosis of hypertension.
LVH was associated with increased stroke risk (adjusted
OR, 2.5; 95% CI, 1.7 to 3.5; Table 4). This was observed in
all age, sex, and race-ethnic strata. No significant interaction
between LVH and arterial hypertension or other stroke risk
factors on stroke risk was found.
Concentric hypertrophy carried the greatest stroke risk
(Table 5), followed by eccentric hypertrophy. Concentric
remodeling was associated with a modest risk increase.
Increase in risk was independent of the presence of arterial
hypertension and other risk factors.
Effect of Age, Sex, and Race-Ethnicity
Concentric and eccentric hypertrophy was associated with
ischemic stroke across all sex and age strata, with adjusted
TABLE 3.
Adjusted OR*
(95% CI)
Entire group
2.9 (2.1–4.1)
2.5 (1.7–3.5)
Men
3.3 (2.0–5.5)
2.8 (1.7–4.9)
Women
2.6 (1.7–4.1)
2.2 (1.4–3.6)
Age 41–59 y
3.5 (1.8–7.1)
2.9 (1.4–6.0)
Age ⱖ60 y
2.7 (1.9–4.0)
2.4 (1.6–3.5)
White
5.3 (2.0–13.8)
4.6 (1.7–12.2)
Black
2.4 (1.3–4.3)
2.1 (1.1–4.0)
Hispanic
2.8 (1.7–4.3)
2.3 (1.4–3.8)
*Adjusted for arterial hypertension, diabetes mellitus, atrial fibrillation,
coronary artery disease, and congestive heart failure.
ORs ranging from 2.3 to 6.0 (Table 5). Concentric remodeling was not associated with increased stroke risk in any
subgroup.
The effect of concentric hypertrophy on stroke risk appeared stronger in Hispanics (adjusted OR, 4.3; 95% CI, 1.9
to 9.8), although differences were not statistically significant
(Hispanics versus blacks, P⫽0.37; Hispanics versus whites,
P⫽0.93). Eccentric hypertrophy was associated with stroke
in whites and Hispanics but less so in blacks. Interracial
differences were not statistically significant (whites versus
blacks, P⫽0.18; Hispanics versus blacks, P⫽0.76). Concentric remodeling was not associated with an increased stroke
risk in any race-ethnic subgroups.
RWT and Risk of Stroke
After adjustment for LV mass as a continuous variable,
abnormal RWT was found to significantly increase stroke
risk in both univariate (OR, 1.5; 95% CI, 1.03 to 2.2) and
multivariate (OR, 1.6; 95% CI, 1.1 to 2.3) analyses. No
interaction on stroke risk was detected between RWT and LV
mass (P⫽0.47 unadjusted, P⫽0.68 adjusted).
Geometric Patterns and Stroke Subtype
Of 392 strokes, 65 (16.6%) were large-vessel disease, 91
(23.2%) were lacunar, 72 (18.4%) were cardioembolic, 13
(3.3%) were other mechanisms, and 151 (38.5%) were
cryptogenic. Concentric LVH tended to have more lacunar
(32.7%) and fewer cryptogenic (23.1%) strokes than other
geometries. Eccentric hypertrophy was associated with a
Prevalence and Duration of Hypertension and Blood Pressure Values in Different Geometric Patterns
Normal
Prevalence of
hypertension, %
Hypertension duration, y*
Concentric Hypertrophy
Eccentric Hypertrophy
Concentric Remodeling
Cases
Controls
Cases
Controls
Cases
Controls
Cases
Controls
68.5
59.3
86.5
75.0
84.1
86.3
85.7
76.9
10.9⫾10.6
12.7⫾13.5
15.8⫾15.3
18.7⫾17.0
14.4⫾12.3
12.0⫾10.4
13.7⫾13.0
12.0⫾7.8
SBP, mm Hg
139.6⫾16.7
138.6⫾20.7
150.9⫾22.7
153.2⫾28.7
144.8⫾20.1
153.4⫾22.8
148.9⫾22.4
144.2⫾21.8
DBP, mm Hg
80.7⫾10.4
81.7⫾11.2
86.1⫾13.2
86.0⫾13.3
84.2⫾11.3
84.7⫾12.6
85.0⫾15.1
86.2⫾11.1
SBP indicates systolic blood pressure; DBP, diastolic blood pressure.
*Mean⫾SD.
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Di Tullio et al
TABLE 5.
Left Ventricular Geometry and Ischemic Stroke
2383
Association Between LV Geometric Patterns and Ischemic Stroke
Concentric Hypertrophy
Eccentric Hypertrophy
Concentric Remodeling
Unadjusted OR
(95% CI)
Adjusted OR*
(95% CI)
Unadjusted OR
(95% CI)
Adjusted OR*
(95% CI)
Unadjusted OR
(95% CI)
Adjusted OR*
(95% CI)
Entire group
3.8 (2.2–6.5)
3.5 (2.0–6.2)
2.9 (2.0–4.3)
2.4 (1.6–3.7)
1.7 (1.0–2.8)
1.7 (1.0–2.9)
Men
3.9 (1.7–8.9)
4.3 (1.8–10)
3.4 (1.9–6.0)
2.7 (1.4–5.0)
1.5 (0.7–2.9)
1.6 (0.8–3.3)
Women
3.6 (1.8–7.5)
2.9 (1.4–6.3)
2.7 (1.7–4.4)
2.3 (1.3–3.8)
2.0 (1.0–4.1)
1.8 (0.9–3.8)
Age 41–59 y
5.8 (1.2–27)
6.0 (1.2–31)
3.2 (1.5–6.7)
2.5 (1.1–5.4)
1.5 (0.4–5.4)
1.6 (0.4–5.9)
Age ⱖ60 y
3.5 (1.9–6.4)
3.2 (1.7–6.0)
2.9 (1.9–4.4)
2.4 (1.5–3.9)
1.7 (1.0–2.9)
1.5 (0.8–2.7)
White
4.0 (0.7–21)
4.0 (0.8–20)
6.1 (2.2–17)
5.0 (1.7–15)
2.0 (0.5–8.2)
2.2 (0.4–11)
Black
2.5 (1.1–6.1)
2.5 (1.0–6.2)
2.3 (1.1–4.8)
2.0 (0.9–4.4)
1.2 (0.5–2.7)
1.2 (0.5–2.8)
Hispanic
4.8 (2.2–10)
4.3 (1.9–9.8)
2.8 (1.7–4.6)
2.3 (1.3–4.0)
2.0 (1.0–4.0)
2.0 (1.0–4.1)
All comparisons were with normal LV geometry.
*Adjusted for arterial hypertension, diabetes mellitus, atrial fibrillation, coronary artery disease, and congestive heart failure.
slight excess of cardioembolic strokes (26.5%), as was
concentric remodeling for lacunar strokes (26.2%).
Discussion
LVH and Stroke Risk
LVH is an established risk factor for cardiovascular diseases1–9 and ischemic stroke, the latter demonstrated mainly in
whites.15–19 Fewer data are available in black populations,
mainly regarding the combined end point of cardiovascular
events and stroke.13,20 Little information is available in
Hispanics, especially of Caribbean origin.21 In our study,
LVH was associated with a 2.5-fold increase in stroke risk
after adjustment for other stroke risk factors. LVH was
independently associated with stroke across all the raceethnic subgroups studied, suggesting that its effect on stroke
risk may be similar across races, even in the presence of
different stroke risk factors profiles.
The mechanisms of the association between LVH and
ischemic stroke are not clear. LVH might be a marker of
subclinical disease25 or predispose to other conditions directly
involved in stroke etiology. LV mass correlates with carotid
wall thickness and luminal diameter26,27 and predicts carotid
atherosclerosis.28,29 LVH has been linked to cerebrovascular
disease in blacks30 and predisposes to developing hypertension31 and atrial fibrillation.32 Alternatively, LVH could
represent a time-integrated indicator of exposure to other risk
factors33 such as hypertension and obesity, which affect the
risk of stroke and cardiovascular disease.
LV Geometry and Stroke Risk
The value of LV geometry in the prediction of cardiovascular
risk is controversial.11,12,14 Moreover, its role as a risk factor
for ischemic stroke has been minimally investigated. We
demonstrate that abnormal LV geometry is associated with an
increased ischemic stroke risk and that RWT adds information not contained in LV mass. Although RWT per se did not
increase stroke risk to a significant extent, it did so after
adjustment for LV mass. This suggests that LV geometry may
contribute to stroke in ways not necessarily related to LV
mass. Determination of RWT may be useful for further stroke
risk stratification, especially among patients with LVH.
The observation that abnormal LV geometry may affect
stroke risk has precedents in the literature. Asymptomatic
lacunar lesions are more frequent in patients with abnormal
LV geometry, and both LV mass and RWT predict them.34
Arterial structure and function are abnormal in patients with
concentric LVH35 and may partly explain its excess morbidity. Neurohormonal changes such as aldosterone and atrial
natriuretic peptide elevation are associated with abnormal LV
geometry36 and might be involved in both its development
and its adverse prognostic effect. In our study, increased
RWT tended to be more frequently associated with lacunar
infarcts, suggesting a possible role of RWT as a marker of
small-vessel disease. Cryptogenic stroke was less frequent in
patients with concentric hypertrophy, which may be a marker
of more extensive cardiovascular disease, leading to development of identifiable sources for stroke. Eccentric hypertrophy tended to be associated with cardioembolism, suggesting
a role for LV dilatation as a possible embolic source. Further
studies are needed to elucidate the complex relationship
between LV mass, LV geometry, and stroke and potential
strategies for decreasing stroke risk.
Study Strengths and Limitations
This is the first study to address the effect of LV mass and
geometry on ischemic stroke risk in a community-based
multiethnic population and in age, sex, and race-ethnic
subgroups. Furthermore, it provides data on Hispanics of
Caribbean origin, information that is scarce in the literature.
The case-control design has limitations, including potential
selection bias. This bias was minimized by recruitment of
cases and controls from the same community, randomization
of control subject selection, and individual case-control
matching. However, differences between cases and controls
may have existed in variables not measured. Moreover, the
study did not have power to address the association between
LV mass and geometry and different stroke subtypes, and its
power for detecting interracial differences was suboptimal.
Finally, definitions of race-ethnicity are problematic because
ethnicity is heterogeneous and its categorization may lead to
assumptions of biological differences while masking other
differences, such as cultural and socioeconomic variables,
which may affect disease.
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2384
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October 2003
Clinical Implications
Our data suggest that assessment of LV mass and RWT
should be included in stroke risk evaluation. Treatment is
available to promote regression of LVH, possibly associated
with reduction in the incidence of cardiovascular events,
including stroke.37 Angiotensin-converting enzyme inhibitors
were shown to decrease RWT in hypertensive patients even
in the absence of LVH.38 The possibility that pharmacological
treatment affecting LV mass and geometry may also reduce
the risk of ischemic stroke deserves further investigation.
Acknowledgments
This project was supported in part by grants from the National
Institute of Neurological Disorders and Stroke (R01 NS29993, ROI
NS33248, T32 NS07153). Dr Di Tullio is the recipient of a
Mid-Career Award in Patient-Oriented Research by the National
Institutes of Neurological Disorders and Stroke (K24 NS02241). We
gratefully acknowledge the support of J.P. Mohr, MD, Director of
Cerebrovascular Research. We also wish to thank Bernadette BodenAlbala, PhD, for her assistance in the preparation of the manuscript;
Drs Renee Weslow, Maria Teresa Savoia, Tamanna Nahar, and Rui
Liu for the interpretation of the echocardiographic studies; and
Lynette M. De Los Santos, BS, Inna Titova, BS, and Gabrielle
Gaspard, BS, for their assistance in the collection of the data.
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Di Tullio et al
Left Ventricular Geometry and Ischemic Stroke
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Editorial Comment
Left Ventricular Hypertrophy: An Unseemly Risk Factor for Stroke?
Left ventricular hypertrophy (LVH) has been increasingly
recognized in the last decade as a risk factor for cardiovascular disease and stroke. However, at least in this guest
editor’s experience, LVH is seldom or never mentioned, in
everyday practice, among the risk factors considered
relevant in a patient with cerebrovascular disease, whether
because it is forgotten, neglected, or even despised. Why is
this so?
LVH is usually considered a consequence of arterial
hypertension: the left ventricle increases its mass and wall
thickness to oppose a rise in the pressure load. Patients with
LVH whose blood pressure is normal are thought to be
“probably hypertensive,” albeit with “nonsustained hypertension.” In this line of reasoning, the relevant risk factor is
hypertension and not the “secondary” consequence of LVH.
In other instances, LVH is dismissed as a phenomenon linked
to “aging,” akin to the “sclerosis” of the aortic valve or the
“stiffness” of the arterial vessels often found in ultrasound
studies of the elderly. Embolism is considered the necessary
mechanism to ascribe a stroke to cardiac disease, and LVH is
not regarded as a cardiac source of embolism. In myocardial
diseases, it is dilated and not hypertrophic cardiomyopathy
that is deemed liable to cause stroke.
However, after adjusting for hypertension and other
recognized factors, LVH remains an independent risk
factor for stroke. Different patterns of LVH have now been
described, and a coherent picture seems to be slowly
emerging. In the current issue of Stroke, Di Tullio and
coworkers present further evidence relating LVH to stroke,
and new evidence relating LV geometric patterns to stroke
risk and stroke subtypes in a tri-ethnic population. The
authors did not find statistically significant differences
between the groups they studied. LVH appeared thus to be
independently associated with stroke, across age, sex, and
ethnicity.
Although 38.5% of the cases in their series were
cryptogenic, concentric remodeling and concentric hypertrophy were associated more with lacunar than with other
stroke subtypes, and eccentric hypertrophy with an excess
of cardioembolic strokes (26.5%). Concentric remodeling,
in which the LV mass index remains normal and only
changes in relative wall thickness (RWT) occur, was
associated with 26.2% of lacunar strokes. Overall, concentric remodeling carried only a slight increase in stroke risk,
but RWT was independently associated with stroke after
adjusting for LV mass. Lacunar strokes were more prevalent in the concentric hypertrophy group (32.7%), which
carried the highest stroke risk. The increased risk was
independent of the presence of hypertension. In a previous
article, RWT was found to be a predictor for asymptomatic
lacunar lesions. 1 Therefore, concentric remodeling
emerges as a marker for stroke risk, small-vessel disease,
and lacunar stroke, and as a predictor of concentric
hypertrophy and stroke recurrence. Recently, concentric
hypertrophy has also been shown to be related to asymptomatic cerebrovascular disease.2
Concentric remodeling occurs in elderly nonhypertensive
subjects. It has been linked to aging and shown to parallel
age-related arterial stiffening and elevation of systolic blood
pressure.3 These factors may be associated with lacunar
strokes. Concentric remodeling is associated with carotid
intima-media thickening in hypertensive patients.4 Patients
with concentric hypertrophy also show an increase in arterial
wall thickness, even in general population studies.5,6 Concentric remodeling has even mysteriously been linked to insulin
resistance in elderly men, suggesting as yet unknown disease
mechanisms connecting the myocardium to metabolic
disturbances.7
It is not yet entirely clear whether LVH represents “a
marker, a limited adaptative process or a pathological process,”8 amenable to different therapeutic strategies. But it
seems clear that it responds to treatment. The same group
reporting the present data has found that physical activity
decreases stroke risk in patients with increased left ventricular mass.9 Antihypertensive treatment reduces LV mass and
RWT,10 and concentric remodeling often goes untreated.11
And if eccentric hypertrophy is confirmed as a risk factor for
cardioembolism in future studies, a rationale for antithrombotic treatment would reasonably follow.
Perhaps we may now understand better why also normotensive patients showed a reduction in stroke risk in recent
trials with antihypertensive agents12: they may have decreased LVH. It looks as if physicians should now do well to
think again before dismissing LVH as irrelevant for cerebrovascular disease.
Osvaldo Fustinoni, MD, Guest Editor
Instituto de Neurociencias Buenos Aires (INEBA)
and Cátedra de Neurología
Facultad de Medicina
Universidad de Buenos Aires
Buenos Aires, Argentina
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October 2003
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