Download Relation of insulin to left ventricular geometry and function in African

AJH
2002; 15:1029 –1035
Relation of Insulin to Left Ventricular Geometry
and Function in African American and White
Hypertensive Adults: The HyperGEN Study
Richard B. Devereux, Giovanni de Simone, Vittorio Palmieri, Albert Oberman,
Paul Hopkins, Dalane W. Kitzman, Dabeeru C. Rao, and Donna K. Arnett
Background: It has been suggested that the trophic
effects of insulin may contribute to left ventricular (LV)
hypertrophy in hypertension, but few population-based
data exist to assess the potential impact of insulin level on
LV structure or systolic function.
Methods: Fasting plasma insulin levels (log-transformed) in 1542 nondiabetic African American or white
hypertensive participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study were compared to
indices of LV geometry and function, with adjustment for
potential confounders (age, sex, ethnicity, blood pressure
(BP), body mass index, height and antihypertensive
drugs).
Results: In simple correlation analysis, a weak positive
relation (r ⫽ 0.078, P ⫽ .002) was found between LV
mass and insulin, principally due to positive correlations (r
⫽ 0.22 and 0.50) of both variables to body mass index.
Multivariate analysis, adjusting for age, sex, ethnicity,
body size, systolic BP, and antihypertensive drugs revealed a modest negative relation between insulin and LV
mass (r ⫽ ⫺0.08, P ⫽ .001) due to a negative relationship
between insulin with LV chamber size (r ⫽ ⫺ 0.10, P ⬍
.001) and no significant relation to LV wall thicknesses.
I
These results were confirmed in additional analysis controlling for a positive relation (r ⫽ .19, P ⬍ .0001) of
insulin to heart rate, and the relation with insulin became
slightly more negative when LV mass was indexed for
height2.7 (r ⫽ ⫺0.13, P ⬍ .001). After adjustment for
covariates, there were no significant relations of insulin to
LV ejection fraction or stress-corrected midwall shortening; however, insulin was negatively related to stroke
volume (r ⫽ ⫺0.12, p ⬍ 0.001) and was weakly related
positively to relative wall thickness (r ⫽ .053) (P ⫽ .04).
Conclusions: After adjustment for body mass index
and other covariates, insulin in nondiabetic hypertensive
individuals has weak negative relations to LV chamber
size, mass, and stroke volume, and also has weak positive
relations to relative wall thickness but not to measures of
LV systolic function. Thus, native plasma insulin level
may not play a major independent role in the pathogenesis
of hypertensive LV hypertrophy or dysfunction. Am J
Hypertens 2002;15:1029 –1035 © 2002 American Journal
of Hypertension, Ltd.
Key Words: Echocardiography, hypertension, insulin,
left ventricle.
nsulin has been shown in human and animal experiments to have cardiovascular effects that are
characterized by increased renal sodium retention,1
increased sympathetic stimulation2,3 and reduced peripheral vascular resistance.2,3 The fact that as much as half of
the interindividual variability in LV mass among adults
remains unexplained after standard demographic and he-
modynamic factors are taken into account4 has stimulated
investigation of the potential cardiac effects of a variety of
hormones and growth factors. A number of previous studies have evaluated relations between fasting or postchallenge plasma insulin levels and measures of LV structure
and function, with variably positive or negative results.5–22
However, the effects of insulin on the cardiovascular sys-
Received March 29, 2002. First decision May 11, 2002. Accepted
July 23, 2002.
From Weill Medical College of Cornell University (RBD, GdS, VP),
New York, New York; Department of Preventive Medicine (AO), University of Alabama at Birmingham, Birmingham, Alabama; Department
of Medicine (PH), University of Utah, Salt Lake City, Utah; Department
of Medicine (DWK), Wake Forest University, Winston-Salem, North
Carolina; Department of Biostatistics (DCR), Washington University, St.
Louis, Missouri; and Department of Epidemiology (DKA), University of
Minnesota, Minneapolis, Minnesota.
This work was supported by grants 5 R01 HL55673 and cooperative
agreement grants 5 U10 HL54471, HL 54472, HL54473, HL54496,
HL54509 and HL 54515 from the National Heart, Lung and Blood
Institute, Bethesda, MD, and grant M10RR0047-34 (GCRC) from the
National Institutes of Health, Bethesda, MD.
© 2002 by the American Journal of Hypertension, Ltd.
Published by Elsevier Science Inc.
Address correspondence and reprint requests to Dr. Richard B. Devereux, Division of Cardiology, Box 222, Weill Medical College of
Cornell University, 1300 York Avenue, New York, NY 10021; e-mail:
[email protected]
0895-7061/02/$22.00
PII S0895-7061(02)03080-7
1030
INSULIN AND THE HEART IN HYPERTENSION
tem have not been previously studied in a large population-based sample of nondiabetic hypertensive adults.
Accordingly, the present study was undertaken to assess relations of plasma insulin levels with various parameters of LV structure and function in hypertensive adults
without diabetes from the biethnic population– based sample of the Hypertension Genetic Epidemiology Network
(HyperGEN) Study.
Methods
Study Population
The HyperGEN Study is part of the National Heart, Lung
and Blood Institute (NHLBI) Family Blood Pressure Program that was funded in 1995 to assess the genetic basis of
hypertension in population-based samples.23 HyperGEN
primarily relied on a sib-pair design that recruited hypertensive members of sibships. Hypertension was defined as
being on antihypertensive treatment or having recorded
blood pressure (BP) measurements on at least two occasions ⱖ140 mm Hg systolic or ⱖ90 mm Hg diastolic. To
be eligible, hypertensive subjects were required to have
onset of hypertension by age 60 years and at least one
hypertensive sibling willing to participate. Individuals
with type 1 diabetes were excluded because of their high
risk of hypertension due to nephropathy. Four field centers
in HyperGEN participated in the ancillary echocardiographic study. Study participants were recruited from existing populations that were previously defined, including
the Atherosclerosis Risk in Communities study (Minneapolis, MN, and Forsyth County, NC), the Minnesota Heart
Study, and the Utah Healthy Family Tree Study. Selected
participants from these parent studies previously participated in the NHLBI Family Heart Study,24 from which a
large proportion of the hypertensive sibships were sampled for HyperGEN. Many of the Birmingham patients (all
African American) were selected from the community.
The target population was 50% each African American
and white in Winston-Salem, and was 100% white in
Minnesota and Utah. Informed consent was obtained from
participants at Field Centers, and approval was obtained
from Institutional Review Boards in all centers.
The first HyperGEN examination began in 1996 to
obtain standardized measurements of BP at rest as well as
reactivity of BP to several stimuli. Standardized anthropometric measurements included body mass index, body
surface area, and waist/hip ratio. Fasting serum glucose,
insulin, lipid, and lipoprotein concentrations were obtained. Diabetes mellitus was diagnosed by American Diabetes Association criteria25 (fasting glucose ⱖ126 mg/dL
or use of hypoglycemic medication). Insulin levels were
assessed by immunoassay (Sanofi Access, Chaska, MN,
reference range 1.9 to 23 ␮U/mL). History of myocardial
infarction, coronary bypass, and percutaneous coronary
angioplasty were identified by participant reports.
Clinical and echocardiographic information were available on 2170 hypertensive subjects. From these were ex-
AJH–December 2002–VOL. 15, NO. 12
cluded individuals without technically satisfactory LV
measurements, those with diabetes, and those who lacked
necessary insulin measurements.
Echocardiographic Methods
Echocardiography was performed by previously described
methods4,26,27 using phased-array echocardiography with
M-mode, two-dimensional, and pulsed continuous wave
and color-flow Doppler capabilities. A standardized protocol was followed under which the parasternal acoustic
window was used to record ⱖ10 consecutive beats of
two-dimensional and M-mode recordings of the LV internal diameter and wall thicknesses just below the tips of the
mitral leaflets in long and short-axis views, long-axis
views of the mitral valve and color flow recordings to
detect mitral and aortic regurgitation, and M-mode and
two-dimensional short and long-axis views of the aortic
root and left atrium. The apical window was used to record
ⱖ10 cycles of two- and four-chamber images and color
Doppler recordings to assess LV wall motion and to detect
valvular regurgitation. All elements of the protocol were
recorded on videotape. Principal sonographers received
training including written material as well as didactic and
hands-on training at the Reading Center in New York. In
addition, test tapes were sent to each center as part of
sonographer training, and feedback on echocardiographic
studies was provided to monitor compliance with the
protocol.
Echocardiographic Measurements
Correct orientation of planes for imaging and Doppler
recordings was verified using standard procedures.27 Measurements were made using a computerized review station
equipped with digitizing tablet and monitor screen overlay
for calibration and performance of measurement. The LV
internal dimension and septal and posterior wall thicknesses were measured at end-diastole and end-systole by
American Society of Echocardiography recommendations28 on up to three cardiac cycles. When optimal orientation of LV M-mode beams could not be obtained,
correctly oriented linear two-dimensional measurements
were made by the American Society of Echocardiography
leading-edge convention.29 Wall motion was assessed in
parasternal long and short axis views and apical two-,
three-, and four- chamber views, dividing the LV into five
segments at the base, five at the papillary muscles, and
four at the apex.30 Echocardiograms were preliminarily
read by a first reader and subsequently over-read by highly
experienced readers, blinded to clinical data. In a separate
series of 183 hypertensive adults, we reported excellent
reliability of LV mass measurement (␳ ⫽ 0.93) and good
reliability of LV functional measurements (␳ ⫽ 0.61 to
0.71) on paired echocardiograms using methodology similar to that in the present study.31
AJH–December 2002–VOL. 15, NO. 12
Calculation of Derived Variables
End-diastolic LV dimensions were used to calculate LV
mass by a formula that yields values closely related (r ⫽
0.90) to necropsy LV weight32 and has proved to be
valuable for cardiovascular risk stratification.33 The LV
mass was indexed by height2.7 to identify LV hypertrophy
using previously reported sex-specific partition values,
46.7g/m2.7 in women and 49.2g/m2.7 in men.34 Relative
wall thickness (RWT), an estimate of LV geometric concentricity, was calculated as posterior wall thickness/internal radius. The LV hypertrophy with increased or normal
RWT defined concentric or eccentric LV hypertrophy.
End-diastolic and end-systolic LV volumes were calculated by the Teichholz method35 using linear measurements of LV internal diastolic and systolic diameters, as
has been validated by invasive and Doppler reference
standards.26 Linear measurement– derived ejection fraction (EF) was calculated as the percent reduction of LV
volume from diastole to end-systole. To estimate global
LV EF, accounting for the contribution of each LV segment to systolic reduction of LV volume, we assigned a
score of 4.5 to each segment with normal wall motion
(yielding global EF of 63%), scores of 3.5, 2.5, 1.5, 0, or
–1 if segments were mildly, moderately, or severely hypokinetic or if they were akinetic or dyskinetic.
Measures of Myocardial Function
Myocardial contractile efficiency was evaluated by assessing LV systolic shortening– end-systolic stress relations.
Primary reliance was placed on the relation of midwall
shortening (MWS) to midwall circumferential end-systolic
stress (cESS) at the level of the LV minor axis.35–37
Midwall shortening was calculated taking into account the
epicardial migration of the midwall during systole. Estimates of end-systolic stress by this method were closely
related to values calculated by substituting central-BP
estimated by applanation tonometry for cuff-BP (r ⫽
0.95).38 In another sample of 418 hypertensive adults with
or without diabetes, cuff systolic BP correlated closely to
central BP estimated by tonometry (r ⫽ 0.93).
Statistical Analysis
Continuous variables are expressed as mean ⫾ SD. Because of the skewed distribution of fasting insulin concentrations, values were log transformed. Simple correlations
between insulin and clinical and LV variables were performed by Pearson’s or, when appropriate, Spearman’s
method. Regression analyses were performed taking into
account potential confounders (age, sex, ethnicity, BP,
body mass index, height and use of major classes of
antihypertensive medications [angiotensin converting enzyme inhibitors, angiotensin receptor blockers, ␤ blockers,
calcium channel blockers, and diuretics]), and partial correlations were calculated with the same covariates for
comparison with the bivariate coefficients. Participants
were also classified into groups with insulin levels within
INSULIN AND THE HEART IN HYPERTENSION
1031
Table 1. Characteristics of study population
Variable
Mean ⴞ SD
Age (y)
Systolic blood pressure
(mm Hg)
Diastolic blood pressure
(mm Hg)
Body mass index
(kg/m2)
Total cholesterol
(mg/dL)
High-density lipoprotein
cholesterol (mg/dL)
Triglycerides (mg/dL)
Creatinine (mg/dL)
Glucose (mg/dL)
Creatinine (mg/dL)
Insulin (␮U/mL)
HOMA
54 ⫾ 11
Range
23–87
132 ⫾ 21
76–231
75 ⫾ 12
39–118
31.5 ⫾ 7.0
16.2–73.7
201 ⫾ 39
102–390
52
135
1.00
98
1.00
9.7
2.5
⫾
⫾
⫾
⫾
⫾
⫾
⫾
16
22–138
85
24–808
.27 0.50–4.30
15
52–125
0.27 0.50–4.30
8.6
0.5–143.6
4.2
0.1–130.0
HOMA ⫽ homeostasis model assessment.
or above the reference range for the assay, and differences
between groups were assessed using the general linear
procedure with entry of relevant covariates. Supplemental
analyses examined relations in participants above or below
the median age (years) and after exclusion of participants
with impaired fasting glucose. Alternative analyses that
substituted a single indicator variable for the presence or
absence of antihypertensive treatment for the codes for
separate classes had almost no effect on results. Fisher’s
exact test and odds ratios with 95% confidence intervals
were used to test differences for categoric variables in 2 ⫻
2 tables. Two-tailed values of P ⬍ .05 were considered to
be statistically significant.
Results
Characteristics of Study Population
Of the 2170 hypertensive participants in the HyperGEN
Study, 70 (3.2%) were excluded because LV mass could
not be measured, 158 because of lack of fasting insulin
levels, and 401 because of diabetes. Of the 1542 participants in the present study, 916 (59%) were women. In all,
620 (40%) were non-Hispanic white, and 60% were African American. Additional characteristics are given in Table 1. On average, the participants were middle-aged, their
BP was in the upper normal range (because of current
antihypertensive treatment in 86%), and they were obese
as shown by body mass index and by a mean adipose mass
of 34.7 ⫾ 14.0 kg with a fat-free body mass of 53.3 ⫾ 11.7
kg. Metabolic parameters ranged widely in the study population; insulin levels spanned a nearly 300-fold range as
did values for the homeostasis model assessment (HOMA)
index (Table 1).
1032
INSULIN AND THE HEART IN HYPERTENSION
AJH–December 2002–VOL. 15, NO. 12
Table 2. Left ventricular findings
Variable
Mean ⴞ SD
Septal thickness (cm)
Left ventricular internal diameter (cm)
Posterior wall thickness (cm)
Left ventricular mass (g)
Left ventricular mass/height2.7 (g/m2.7)
Relative wall thickness
Fractional shortening (%)
Midwall shortening (%)
End-systolic stress (kdyne/cm2)
Stress-corrected midwall shortening (%)
End-systolic stress/volume index
(kdyne/cm2/mL/m2)
0.95
5.17
0.89
176
43.54
0.35
33
17.0
165
104
⫾
⫾
⫾
⫾
⫾
⫾
⫾
⫾
⫾
⫾
Range
0.13
0.54
0.11
47
10.8
0.05
6
2.5
45
13
0.60–1.70
3.80–7.50
0.60–1.50
73–399
18.1–114.0
0.21–0.60
7–51
4.9–23.9
62–445
41–150
6.7 ⫾ 1.6
Cardiac Findings
On average, LV wall thicknesses and chamber size was
within the normal range (Table 2). However, when these
values were combined with calculated LV mass and relative wall thickness, LV hypertrophy was present in 432
(28.2%) of the study population, including 391 (25.5%)
with eccentric hypertrophy and 41 (2.7%) with concentric
hypertrophy, whereas 45 (2.9%) had concentric LV remodeling. Systolic LV function was subnormal in 14.6%
for endocardial fractional shortening and 10.5% for midwall shortening.
Correlates of Plasma Insulin Level
In univariate analyses, log10 insulin showed weak but
statistically significant positive correlations with interventricular septal and posterior wall thickness (Table 3). Positive relations also existed between insulin and absolute
LV mass (Fig. 1A) or indexed LV mass as well as relative
wall thickness (Fig. 1B). Negative relations between log
insulin and measures of LV systolic function did not attain
statistical significance. Log10 insulin was also negatively
2.3–13.4
related to age and was positively related very strongly to
body mass index; it was higher in men than in women
(mean, 2.08 ⫾ 0.64 v 1.98 ⫾ 0.69, P ⫽ .005) and was
higher in white than in African American individuals
(mean, 2.09 ⫾ 0.70 v 1.98 ⫾ 0.58, P ⫽ .001). LV mass
was also positively related to body mass index (r ⫽ 0.22,
P ⬍ .001); it was higher in men than women (198 ⫾ 45 v
161 ⫾ 42 g) and was higher in African American than in
white individuals (178 ⫾ 50 v 173 ⫾ 41 g, P ⫽ .026).
Relations of log insulin to LV and demographic variables
were variably slightly stronger or weaker, with lower
statistical significance, in subgroups aged ⬍55 years versus ⱖ55 years and in subgroups with impaired fasting
glucose (n ⫽ 233) or fasting glucose ⬍110 mg/dL (data
not shown). The HOMA index was consistently slightly
more weakly related than insulin to the above variables as
was the fasting glucose level, with the exception of a weak
negative relation (r ⫽ ⫺0.052, P ⫽ .04) between fasting
glucose and LV midwall shortening.
When the relations of log10 insulin to LV variables
were examined in multivariate analyses that took into
Table 3. Univariate and multivariate correlates of plasma insulin concentration
Variable
Univariate
Correlation
P
Partial
Correlation*
P (Linear
Regression)
Septal thickness (cm)
Left ventricular internal diameter (cm)
Posterior wall thickness (cm)
Left ventricular mass (g)
Left ventricular mass/height2.7 (g/m2.7)
Relative wall thickness
Fractional shortening (%)
Midwall shortening (%)
Stroke volume (mL)
Age (y)
Body mass index
Systolic blood pressure (mm Hg)
Height
0.081
0.036
0.083
0.078
0.064
0.050
⫺0.004
⫺0.026
0.027
⫺0.105
0.497
⫺0.014
0.022
0.001
NS
0.001
0.002
0.012
0.052
NS
NS
NS
⬍0.001
⬍0.001
NS
NS
⫺0.021
⫺0.127
⫺0.029
⫺0.115
⫺0.110
0.059
0.040
⫺0.001
⫺0.119
—
—
—
—
0.396
0.002
0.945
0.019
⬍0.001
0.021
0.284
0.722
0.001
—
—
—
—
NS ⫽ not significant.
* Adjusted for age, sex, ethnicity, systolic pressure, body mass index, and antihypertensive medications.
AJH–December 2002–VOL. 15, NO. 12
INSULIN AND THE HEART IN HYPERTENSION
1033
(ⱕ23 ␮U/mL) or above it were compared to each other.
Elevated plasma insulin levels were present in 4.9% of
women and 4.8% of men (P ⫽ not significant [NS]) and in
6.3% of white and 2.8% of African American subjects (P
⫽ .001). Individuals with elevated insulin levels were
slightly younger (51 ⫾ 12 v 54 ⫾ 11 years, P ⫽ .01) and
much heavier (body mass index, 38.9 ⫾ 7.7 v 31.1 ⫾ 6.8
kg/m2, P ⬍ .001) but did not differ with regard to mean
arterial pressure (133/76 v 132/75 mm Hg, P ⫽ NS). In
analyses that adjusted for ethnicity, age, and body mass
index, individuals with elevated insulin levels were statistically similar (all P ⬎ .20) to those with insulin values
within the reference range with regard to septal and posterior wall thickness, LV relative wall thickness, LV mass
and LV mass/height2.7, and endocardial and midwall LV
fractional shortening.
Discussion
FIG. 1. Panel A) A weak but statistically significant positive relation existed between log10 insulin (horizontal axis) and left ventricular mass (vertical axis) in nondiabetic hypertensive adults.
Panel B) A weak but statistically significant positive relationship
was found between log10 insulin (horizontal axis) and left ventricular relative wall thickness.
account the potentially confounding effects of body mass
index, age, sex, ethnicity, and antihypertensive medication
classes, LV wall thicknesses and, especially, LV chamber
diameter had negative relations to the fasting plasma insulin concentration. As a result, LV mass and indexed
mass were negatively related to plasma insulin level when
covariates were taken into account. In contrast, a weak but
positive independent relation existed between plasma insulin level and LV relative wall thickness. Neither endocardial nor midwall fractional shortening were related to
log10 insulin level in multivariate analyses.
Correlates of Elevated
Plasma Insulin Level
Additional analyses were performed in which the participants whose insulin levels fell within the reference range
In recent years, the hypothesis that insulin resistance plays
a major role in stimulating high levels of several cardiovascular risk factors as well as promoting the likelihood of
experiencing morbid and mortal cardiovascular events38
has received considerable attention. Diminished insulin
sensitivity with regard to glucose utilization causes a substantial increase of insulin production in an attempt to
maintain normal glucose utilization, making it possible
that cardiovascular trophic effects and other actions of
insulin that were not blunted could, in fact, be exaggerated
in the setting of high insulin levels. A number of previous
studies have evaluated relations between fasting or postchallenge plasma insulin levels and LV geometry, with
variably positive or negative results.6 –22 The present
study, performed in a biethnic population of nondiabetic
hypertensive adults, documents associations (albeit weak)
between insulin levels and several measures of LV structure, thereby confirming previous positive reports. Of
equal importance, however, the present data also demonstrate that these univariate relations are markedly weakened or, more commonly, reversed, in multivariate analysis controlling for the confounding effects of body habitus,
age, and arterial pressure.
The positive association between the fasting insulin
level and body mass index or other measures of adiposity
observed in the present study has been previously reported.39 One mechanism of this association is the relative
insulin resistance of adipose tissue, causing overweight or
obese individuals to require greater insulin levels to maintain glucose levels within the normal range. In addition,
increased intra-abdominal fat augments free fatty acid
release into the portal circulation, contributing to the characteristic glucose and lipid abnormalities of the “insulin
resistance syndrome.” The present study differs from most,
but not all, previous reports of insulin-LV relations by
taking into account in multivariate analyses the variable
body mass, as well as other confounders with strong
associations with either the insulin level or LV measure-
1034
INSULIN AND THE HEART IN HYPERTENSION
ments. A notable result of these analyses is the elimination
and common reversal of positive univariate associations of
insulin level with LV measurements. It is presently unclear
whether insulin resistance, with secondary elevation of
insulin levels, or obesity is the originator of the syndrome.
If primary insulin resistance and the secondary elevation
of insulin causes individuals to deposit more weight, then
adjustment for body mass index may attenuate pathophysiologically important associations. If, however, primary
obesity increases insulin resistance, then the diminution or
elimination of associations of target organ damage with
insulin level is pathophysiologically appropriate. Although
the present cross-sectional data cannot determine which is
the correct model, the lack of additional positive associations of insulin measurements with LV abnormalities after
the simple clinical variable of body mass index is considered suggests that this additional and potentially expensive
laboratory determination provides limited independent information about the pathogenesis of LV abnormalities in
hypertension.
A potential limitation of the present study is assessment
of insulin levels in the fasting state but not in response to
glucose loading. Several studies have found positive associations between postload insulin levels or areas under
the postload insulin curve and LV structural variables,8,12–14,17,18,21 whereas several others have not.11,15,20
The lack of postload insulin measurements in HyperGEN
makes it impossible to determine whether there might
have been stronger relations between LV variables and
insulin responses to glucose loading than those observed
with fasting insulin. A second potential limitation of this
study is its cross-sectional nature, making it desirable in
the future to perform cardiovascular evaluation of individuals with previous serial data with regard to both insulin
levels and body mass index. In addition, the performance
of the present study in a predominately African American
population with a high prevalence of obesity and concurrent antihypertensive therapy may limit generalizability of
results to populations with other ethnic compositions or
with lower prevalences of obesity or antihypertensive
treatment.
One strength of the present study is the relatively large
number of nondiabetic individuals from a populationbased sample who were evaluated. Most previous studies
have assessed relatively small groups of individuals
(n ⫽ 26 to 120) from selected clinical samples.6,8,10,11,13–15,17,18,21,22,40 All previous populationbased studies of insulin-LV relations except one20 have
also involved smaller populations (n ⫽ 62 to 351, except
for 1388 in one report22) than in the present study. An
additional strength of the present study is the ability to
measure adipose body mass and percent body fat by bioelectric impedance.25 However, substitution of the latter
variables for body mass index did not alter the results of
the study, and findings using the more easily measured
body mass index are therefore presented.
In conclusion, after adjustment for body mass index
AJH–December 2002–VOL. 15, NO. 12
and other covariates, log10 insulin in nondiabetic hypertensive individuals is found to be weakly related to lower
LV chamber size and mass and to lower stroke volume but
not to measures of LV systolic function. Thus, insulin may
not play a major independent role in the pathogenesis of
hypertensive LV hypertrophy or dysfunction.
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