1482

Does Obesit Influence Early Target Organ

Damage in Hypertensive Patients?
Roland E. Schmieder, MD, and Franz H. Messerli, MD

Background. Various prospective studies have found that lean hypertensive patients have greater
cardiovascular morbidity and mortality than obese hypertensive subjects. It was therefore hypothesized
that hypertension is more benign when associated with obesity. In the present study, we evaluated effects
of obesity on early target organ damage in patients with essential hypertension.
Methods and Results. In a total of 207 subjects, systemic and renal hemodynamics as well as left
ventricular structure and function were assessed by measuring cardiac output (indocyanine green dye
dilution), renal blood flow (clearance of 'l~I paraimmunohippuric acid), and mean arterial pressure
(invasively) and by two-dimensionally guided M-mode echocardiographic findings. Systemic and renal
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vascular resistance, compliance of the large arteries evaluated by the stroke volume/pulse pressure index,
and left ventricular mass served as parameters for early target organ damage. All individuals were
categorized into four groups: lean and obese normotensive as well as lean and obese hypertensive subjects.
In obese hypertensive patients, total peripheral resistance was significantly lower and stroke volume/pulse
pressure index was higher than in the lean hypertensive group, almost reaching values of normotensive
control subjects. No effect of obesity on the renal circulation was noted, whereas in hypertension, renal
vascular resistance was elevated. The degree of left ventricular hypertrophy was more pronounced in the
hypertensive groups than in their normotensive counterparts and progressively increased with obesity.
Nevertheless, in obese hypertensive patients, left ventricular function, as measured by fractional fiber
shortening and velocity of circumferential fiber shortening, was maintained despite the fact that the heart
had been exposed to the double burden of an increased preload (obesity) and afterload (hypertension).
Conclusions. Obesity had a disparate effect on target organs in hypertension. At rest, obesity seemed to
mitigate cardiovascular changes in the systemic vascular bed caused by hypertension. However, no such
mitigation was observed in the renal vasculature, and left ventricular hypertrophy was even exacerbated
by the presence of obesity. Our findings in part negate the concept that obesity is able to exert a protective
effect on early target organ damage in hypertensive patients and, in particular, on the heart. (Circulation
1993;87:1482-1488)
KEY WoRDs * obesity * hypertension

H ypertension and obesity are disorders that are
closely linked.1-3 For many years, it has been
well documented that obese patients are more
likely to be hypertensive than lean individuals and that
interim weight gain is predictive of later onset of hyper-
tension.1'4 Both obesity and arterial hypertension have
been identified as independent risk factors for cardiovas-
cular disease in the Framingham Heart Study.5-7 In the
Honolulu Heart Program, rates of coronary heart disease
and cardiovascular disorders were higher in obese than in
nonobese men for both normotensive and hypertensive
patients.8 In a prospective follow-up of 8 years, the relative
risk for fatal and nonfatal coronary heart disease in-
creased from the lowest to the highest quintile of obesity
in hypertensive women.9 The absence of a protective effect
From the Department of Medicine (R.E.S.), University of
Erlangen-Nurnberg, Nurnberg, Germany; and the Department of
Internal Medicine (F.H.M.), Section on Hypertensive Disease,
Ochsner Clinic and Alton Ochsner Medical Foundation, New
Orleans, La.
Address for reprints: Priv.-Doz. Dr. R. Schmieder, Department
of Medicine, University of Erlangen-Nurnberg, Kontumazgarten
14-18, 8500 Nurnberg 80, FRG.
Received October 3, 1992; accepted January 11, 1993.
in obesity hypertension is supported by a recent analysis of
the Framingham Heart Study, in which the risk ratio for
cardiovascular events was basically similar in lean and
obese subjects.510 These studies are in contrast to several
large-scale prospective studies that showed obese hyper-
tensives to be at a lower risk of cardiovascular disease than
lean hypertensivesl1-20 and therefore showed that obesity
might exert "protective" effects on the cardiovascular
system. In particular, in several studies in which the
question of whether obesity attenuates the impact of high
blood pressure on coronary arteries was addressed, pro-
spective analysis revealed a lower risk for coronary heart
disease in obese than in lean hypertensive subjects.16,17,19,20
It is difficult to explain the discordant results of the various
studies. A recent review of 11 prospective studies sug-
gested that the risk of major coronary artery disease-
related events in lean hypertensive men was not as high as
that in obese hypertensive men.21
Ever since Perera and Damon22 reported that acceler-
ated hypertension (defined by papilledema and biopsy-
verified arteriolar necrosis of kidney) is more prevalent in
lean than in obese women but not men, the concept of the
vascular protective effects of obesity in a subgroup of
hypertensive patients has been controversial. No study has
 Schmieder and Messerli Obesity and Organ Damage in Hypertension 1483

TABLE 1. Clinical Characteristics in Normotensive Subjects and Patients With Essential Hypertension Divided According to Body Mass
Index >27 kg/rM2 or s27 kg/M2
Lean Obese ANOVA*
Normo- Essential Normo- Essential Normotension/
tension hypertension tension hypertension essential Lean/ Inter-
(n=29) (n=61) (n=26) (n=85) hypertension obese action
Age (years) 39+ 11 44+12 33±11 44±9 0.001 ... ...

Sex (male: female) 20:9 31:30 18:8 61:24 ... 0.01 ...

Race (white: black) 27:2 45:16 22:4 53:32 0.01 0.01 ...

Height (cm) 170±20 170±8 171±9 173±9 ... ... ...

Weight (kg) 69±10 70±9 100±18 94±14 ... 0.001 ...

Body mass index (kg/M2) 23.8±2.4 24.0±2.2 34.0±6.2 31.5±4.3 ... 0.001 ...
Mean arterial pressure (mm Hg) 86±7 112±14 91±5 109±12 0.001 ... 0.03
*See text for further details.

looked at these protective effects of obesity at an early
stage of hypertensive disease, i.e., before cardiovascular
death or irreversible target organ damage (World Health
Organization stage III) has developed.
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All normotensive patients had casual pressure values
consistently below 140/90 mm Hg when measured in
the outpatient clinic. Therefore, individuals whose
casual blood pressure was more than or less than

Our current investigation extended our previous anal- 140/90 mm Hg were excluded from the study. Each
yses of the interaction between obesity and hyperten- participant had a complete clinical workup to exclude
sion.23-27 Using hemodynamic as well as echocardio- secondary causes of arterial hypertension, diabetes
graphic techniques, we report our experience in more mellitus, any form of renal disease, or cardiovascular
than 200 patients in an attempt to elucidate the ques- impairment (in particular, coronary heart disease).28
tion of whether obesity exerts any protective effects on Most patients had never been treated for high blood
the systemic circulation, renal vasculature, and cardiac pressure. In those who had received treatment, anti-
structure in early hypertensive disease. hypertensive therapy was discontinued at least 4 weeks
Methods before the invasive and echocardiographic study. The
Study Groups protocol of the study was approved by the institutional
clinical investigation committee, and informed consent
The study population was composed of 207 subjects was obtained from each patient.
(mean age, 42±10 years) consecutively enrolled in the Participants were classified as "lean" when their body
study protocol. All patients with high blood pressure mass index ranged between 19 and 27 kg/M2. Body mass
were referred to the outpatient clinic of the Ochsner
Clinic (single-center study) to specify the cause and index >27 kg/M2 was chosen as a cutoff point between
stage of arterial hypertension (tertiary referral cen- "obese" and "lean." Patients whose body mass index
was between 27 and 31 kg/M2 were graded as "mildly
ter). The normotensive control group that voluntarily
participated in the echocardiographic and hemody- obese," and those whose body mass index was >31
namic study had been referred to Ochsner Clinic kg/M2 were considered "severely obese." These bench-
because of obesity or unspecific gastrointestinal disor- marks of obesity, 27 and 31 kg/M2, respectively, were
ders. Arterial hypertension was said to be present if chosen according to the survey of NHANES II.29 The
casual blood pressure exceeded 140 mm Hg systolic cutoff points of 27 and 31 kg/m2 further correspond very
and 90 mm Hg diastolic on at least three successive closely to being 20-40%, respectively, over the desir-
measurements taken with a regular cuff for the lean able weight for persons of medium build as determined
subjects and with a large cuff for the obese subjects. by the Metropolitan Life Insurance Company in 1983.30
TABLE 2. Systemic Hemodynamics in Normotensive Subjects and Patients With Essential Hypertension Divided According to Body Mass
Index >27 kg/M2 or <27 kg/M2
Lean Obese ANCOVA*
Normo- Essential Normo- Essential Normotension/
tension hypertension tension hypertension essential Lean/ Inter-
(n=29) (n=61) (n=26) (n=85) hypertension obese action
Systolic pressure (mm Hg) 119+10 158+24 124+7 153+21 0.001 ... 0.06
Diastolic pressure (mm Hg) 69+6 89+11 75+5 88+10 0.001 ... 0.03
Heart rate (bpm) 67±9 68±9 71+ 11 67+10 ... ... ...

Cardiac output (Llmin) 5.41±+1.1 5.28+1.0 6.7± 1.6 6.27±2.3 ... 0.001 ...
Stroke volume (mL) 81+17 78±15 96+23 95+21 ... 0.001 ...

Total peripheral resistance (units) 16.6±4.2 21.8+4.7 14.3+3.7 18.2+4.0 0.001 0.001 ...
Stroke volume/pulse pressure (mUmm Hg) 1.64±0.48 1.27±0.41 1.94±0.40 1.50±0.47 0.02 0.001 ...
bpm, Beats per minute.
*See text for further details.
 1484 Circulation Vol 87, No 5 May 1993

TABLE 3. Renal Hemodynamics in Normotensive Subjects and Patients With Essential Hypertension Divided According to Body Mass
Index >27 kg/iM2 or '27 kg/m2
Lean Obese ANCOVA*
Normo- Essential Normo- Essential Normotension/
tension hypertension tension hypertension essential Lean/ Inter-
(n=29) (n=61) (n=26) (n=85) hypertension obese action
Renal plasma flow (mL/min) 670±127 599±125 754±181 602±191 0.06 ... ...

Renal blood flow (mL/min) 1,092±272 970±292 1,244±329 985±331 0.05 ... ...

Renal vascular resistance (units) 84±22 127±48 79±24 124±47 0.01 ... ...

Renal blood supply (RBF/CO; %) 20.5±4.4 18.5±5.6 19.0±5.1 15.9±5.1 0.04 0.001 ...
*See text for further details.

Hemodynamics velocity of circumferential fiber shortening were taken

Systemic and renal hemodynamics were assessed as
previously described.28 In brief, polyethylene tubing was
introduced into an antecubital vein and into the brachial
artery and advanced to the level of the superior vena
cava and the ascending aorta, respectively. Continuous
intra-arterial pressure was recorded, and mean arterial
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as indexes of global left ventricular function.
Statistical Analysis
Comparisons of lean and obese patients as well as of
normotensive and hypertensive subjects were made by
using two-way ANOVA with subsequent Scheffe's tests.

pressure was obtained by electrical integration. Cardiac
output in the supine position was measured in triplicate
using indocyanine green dye. Heart rate was measured
by continuous ECG. Renal plasma flow was determined
from the disappearance of a single injection of 131I
para-aminohippuric acid, using the two-compartment
model for calculations.28'3132 Stroke volume, total pe-
ripheral resistance, renal blood flow, renal blood supply
(renal blood flow divided by cardiac output), and renal
vascular resistance were calculated by standard formu-
las. The vascular compliance of large arteries was
estimated by the stroke volume/pulse pressure index.33
Echocardiography
Left ventricular structure and function were evalu-
ated by two-dimensionally guided M-mode echocardi-
ography during or immediately after the invasive study.
Echocardiographic tracings were recorded in the half
left-sided position in the third or fourth interspace and
analyzed by two independent observers according to the
recommendations of the American Society of Echocar-
diography (ASE).34 Because left ventricular mass by
ASE conventions systematically overestimates the true
anatomic left ventricular weight, the values for left
ventricular mass were corrected by using an equation
derived from a comparison of echocardiographic mass
with necropsy findings.35 Fractional fiber shortening and
Because the clinical characteristics such as age, sex, and
race differed among the four groups (Table 1), covari-
ance analyses were applied to exclude any concomitant
impact of age, sex, and race on our results. Because we
did not find significant interactions between obesity and
hypertension and sex, race, or age, covariance adjust-
ments were made in Tables 2-7. To allow ease of
comparison of the groups, age-adjusted values were
calculated for determinants of target organ damage
(total peripheral resistance, arterial compliance, renal
vascular resistance, and left ventricular mass). x2 anal-
yses were done when indicated. Our results in the text
and tables are expressed as mean+±1 SD and in the
figures as mean±1 SEM.
Results
According to the study design, mean arterial pressure
in the two hypertensive groups was different from mean
arterial pressure in the two normotensive groups. Mean
arterial pressure, however, did not differ within the
normotensive and hypertensive groups despite a signif-
icant difference in body mass index (Table 1). Height
was not different among the four groups, whereas age,
sex, and race differed significantly (Table 1). Therefore,
only results of the two-way ANCOVA were reported in
the following, thereby eliminating any impact of age,
sex, and race.

TABLE 4. Cardiac Structure and Function in Normotensive Subjects and Patients With Essential Hypertension Divided According to Body
Mass Index >27 kg/m2 or '27 kg/m2
Lean Obese ANCOVA*
Normo- Essential Normo- Essential Normotension/
tension hypertension tension hypertension essential Lean/ Inter-
(n=29) (n=61) (n=26) (n=85) hypertension obese action
Left ventricular wall thickness (mm) 16.8±2.7 20.7+3.0 18.3+2.7 21.6+3.0 0.001 0.05 ...
Diastolic diameter (mm) 47.9+8.6 47.6+6.6 49.6+6.8 48.8+5.8 ... 0.08 ...
Left ventricular mass (g) 173±66 223±64 204±67 246±69 0.01 0.05 ...
Fractional fiber shortening (%) 36±7 35±9 34±6 35±8 ... ... ...

Velocity of circumferential fiber shortening

(cir/sec) 1.20±0.30 1.12±0.31 1.11+0.19 1.15±0.28 ... ... ...

Left ventricular stroke work (mm HgxmL) 127±30 161±32 157±40 189±46 0.001 0.01 ...

*See text for further details.

 Schmieder and Messerli Obesity and Organ Damage in Hypertension 1485

When compared with lean subjects, cardiac output was

increased in the obese patients (p<0.001); this increase
was observed in the normotensive and hypertensive
groups (Table 2). Elevated cardiac output was predomi-
nantly produced by increased stroke volume, noted in the
obese patient groups (p<0.001), whereas heart rate was
similar among lean and obese groups; again, these
changes were independent of the level of arterial pres-
sure, whether normotensive or hypertensive.
Conversely, total peripheral resistance was decreased
in the obese groups (p<0.001) in comparison with their
lean counterparts, regardless of whether they were NORMOTENSION HYPERTENSION
normotensive or hypertensive (Table 2). Compliance of M LEAN M OBESE Z SEVERELY OBESE
the large arteries, as judged by the stroke volume/pulse
pressure index, was higher in the obese groups FIGURE 2. Bar graph of age-adjusted values for compliance
(p<O.OOl) than in the lean groups regardless of their (COMP adj) in lean, mildly obese, and severely obese patients.
level of arterial pressure. At a similar body mass index, A significant impact of obesity (p<0.01) and hypertension
hypertensive patients had a higher total peripheral (p<0.02) was evaluated.
resistance (p<0.001) and lower arterial compliance
(p<0.02) than normotensive patients. their normotensive counterparts, and obesity appeared
Renal plasma flow (p<0.06) and renal blood flow
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not to impair fractional fiber shortening or velocity of

(p<0.05) were lower in hypertensive patients than in
normotensive patients; conversely, renal vascular resis-
tance was clearly elevated in established hypertension
(p<0.01) (Table 3). Obesity did not affect renal plasma
flow, renal blood flow, or renal vascular resistance.
Renal blood supply (renal blood flow divided by cardiac
output) was found to be low in the hypertensive groups
compared with the normotensive groups (p<0.01) pre-
dominantly because of the reduction in renal blood flow
(p<0.05). Renal blood supply decreased even more in
the presence of obesity (p<0.001) because cardiac
output was elevated in both obese groups (Table 3).
Left ventricular mass increased progressively with
obesity and evidence of sustained hypertension (Table
4). The ANCOVA (excluding any bias of age, sex, or
race) revealed significant influences of obesity (p<0.05)
and hypertension (p<0.01) on left ventricular mass.
Left ventricular wall thickness was increased with hy-
pertension (p<0.001) and with obesity (p<0.05). Dia-
stolic diameter tended to be increased in the obese
groups (p=0.08) regardless of whether they were nor-
motensive or hypertensive. In this stage of hypertensive
disease (WHO stage I or II), left ventricular function
was preserved in hypertensive patients compared with
circumferential fiber shortening (Table 4). Left ventric-
ular stroke work, the product of stroke volume and
systolic pressure, was most elevated in obese hyperten-
sive patients (p<0.01) because of increased stroke
volume related to obesity and because of increased
systolic pressure in hypertension (Table 4).
To illustrate these results, total peripheral resistance
and compliance of the large arteries, both of which are
considered to reflect the severity of target organ dam-
age in the systemic circulation, and renal vascular
resistance and left ventricular mass were expressed as
age-adjusted values in Figures 1-4. Furthermore, obese
subjects were subdivided into mildly obese (defined by
body mass index >27 kg/m2 but <31 kg/m2) and severely
obese patients (defined by body mass index exceeding
31 kg/m2). Total peripheral resistance (p<0.01) was
higher and compliance of large arteries (p<0.05) was
lower in the lean than in the mildly obese as well as the
severely obese groups. This pattern was similar in the
normotensive and hypertensive groups, although, of
course, total peripheral resistance was elevated in sus-
tained hypertension (p<0.01). Age-adjusted values for
renal vascular resistance indicated that obesity did not
affect renal hemodynamics in either the mildly obese or

An
TPR adi (U)
1

26 -

20 -

15 -

10 -

6-

0- EI
SO
1810N HYPERTENSION

M LEAN M OBESE = SEVERELY OBESE M LEAN M OBESE = SEVERELY OBESE

FIGURE 1. Bargraph of age-adjusted values for totalperiph- FIGURE 3. Bar graph of age-adjusted values for renal
eral resistance (TPR adj) in lean, mildly obese, and severely vascular resistance (RVR adj) in lean, mildly obese, and
obese patients. A significant impact of obesity (p<0.01) and severely obese patients. No significant impact of obesity was
hypertension was observed (p<0.01). observed, in contrast to the impact of hypertension (p<O.01).
 1486 Circulation Vol 87, No S May 1993

Ran LVM adi (9) vascular morbidity and mortality along with age and left
ventricular mass.40 In our current study in more than 200
300 -T participants, systemic vascular resistance was found to be
260 lower in the obese groups than in their lean counterparts
at similar levels of mean arterial pressure. The lower
200 level of total peripheral resistance suggested that obese
160 hypertensive patients were hemodynamically younger
than their lean counterparts with regard to the systemic
100-
circulation. Conversely, we found that obesity hyperten-
60 sion (as opposed to hypertension in the nonobese) is
0-
hemodynamically characterized by an increased cardiac
output, mainly due to a rise in stroke volume (which is
produced via the Frank-Starling mechanism by an in-
M LEAN M OBESE SEVERELY OBESE creased preload).41,42 Confirming our previous reports,23-
FIGURE 4. Bargraph ofage-adjusted values for left ventric- 27,41 these results indicate that the hemodynamic changes
ular mass (LVM adj) in lean, mildly obese, and severely obese in obesity were already evident in subjects whose body
patients. A significant impact of both obesity (p<O.OS) and mass index exceeded 27 kg/M2.
hypertension (p<O.Ol) was noted. In hypertension, the vascular compliance of the large
arteries was reduced, as indicated by a decreased stroke
volume/pulse pressure index.33 The presence of obesity
in the severely obese patients, whereas sustained hyper- appeared to counteract this process because this index
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tension did (p<0.01) (Figure 3). The degree of left
ventricular hypertrophy was most pronounced if obesity
and hypertension coexisted (Figure 4). Age-adjusted
values for left ventricular mass indicated that the degree
of left ventricular hypertrophy increased progressively
with obesity (p<0.05) and sustained hypertension
(p<O.Ol).
Finally, to analyze the impact of obesity in various
age, sex, and race groups, we calculated the ANCOVA
in the specific subgroups (Tables 5-7). The presence of
obesity resulted in a decrease in total peripheral resis-
tance that was more pronounced in women than in men
(for men, p<0.11; for women, p<0.001; Table 5), more
in black than in white individuals, and more in old than
in young subjects (allp<0.05). Renal vascular resistance
was not influenced by obesity in various sex, race, and
age groups (all not significant) in contrast to hyperten-
sion. As outlined above, the degree of left ventricular
mass was increased in hypertension if obesity coexisted;
however, this exaggeration held true only in the white
(p<0.01) and male (p<0.01) subjects and in the young
and old subjects, although only slightly (p<0.10), but
not in the female or black subjects.
Discussion
Systemic vascular resistance is the hallmark of systemic
vascular disease36-40 and was documented in a prospec-
tive study to be predictive for the development of cardio-
was higher in obese than in lean normotensive subjects.
This pattern was found in all subanalyses categorizing
our patients -young versus old, black versus white, and
male versus female patients. However, all hemodynamic
profile measurements were determined at rest only and
therefore do not represent the hemodynamic situation
during daily life activities.43-45
In two sets of experiments, we recently subjected lean
and obese patients to stress and found that obese
patients responded with an exaggerated blood pressure
response mediated by an increase in total peripheral
resistance.46 Thus, the seemingly protective hemody-
namic effects of obesity observed at rest appeared to be
blunted during exposure to stress.46 This new observa-
tion in two different study groups clearly limits the
interpretation of data determined at rest and questions
their applicability for daily life situations.
In the current study, we did not observe any signifi-
cant difference in renal blood flow and renal vascular
resistance among the lean and obese groups regardless
of whether the normotensive or hypertensive groups
were compared, which is in contrast to a preliminary
report that used analysis by matched pairs.47 Our cur-
rent analysis, however, was based on a larger sample of
patients and excluded any bias of age, sex, race, height,
or mean arterial pressure by ANCOVA and specific
subgroup analysis. In addition, a stepwise multiple
regression analysis yielded no significant association

TABLE 5. Determinants of Target Organ Damage in Lean Versus Obese Patients, Men and Women
Men Women
Parameters Lean Obese Impact Lean Obese Impact
for target Normo- Hyper- Normo- Hyper- of hyper- Normo- Hyper- Normo- Hyper- of hyper-
organ tensive tensive tensive tension/
tensive tensivetensive tensive tensive tension/
damage (n=20) (n=31) (n = 18) (n=61)
obesity* (n=9) (n=30) (n=8) (n=24) obesity*
TPR (units) 20.2±4.6 17.7±3.9 16.3±4.0 0.10/0.11 17.6±4.4 24.0±4.0 15.1±2.2 19.4±4.5 0.03/0.001
13.8±4.6
SV/PP
(mLjmm Hg) 1.64±0.49 1.32±0.42 2.05±0.42 1.76±0.53 NS/0.03 1.33±0.42 1.11±0.27 1.76±0.31 1.27±0.41 0.09/0.01
RVR (units) 79±22 123±51 69±15 116±44 0.05/NS 90±24 130±44 98±27 147±48 0.02/NS
LVM (g) 170±61 219±74 226±62 253±64 0.04/0.01 163±86 217±70 178±49 231±80 0.05/NS
TPR, total peripheral resistance; SV/PP, stroke volume over pulse pressure; RVR, renal vascular resistance; LVM, left ventricular mass.
*ANCOVA.
 Schmieder and Messerli Obesity and Organ Damage in Hypertension 1487

TABLE 6. Determinants of Target Organ Damage in Lean Versus Obese Patients, White and Black Patients
White subjects Black subjects
Lean Obese Lean Obese Impact
Parameters Impact of of
for target Normo- Hyper- Normo- Hyper- hyper- Normo- Hyper- Normo- Hyper- hyper-
organ tensive tensive tensive tensive tension/ tensive tensive tensive tensive tension/
damage (n=27) (n=45) (n=22) (n=53) obesity* (n=2) (n = 16) (n=4) (n =32) obesity*
TPR (units) 16.8±4.2 21.2+4.6 14.5+3.7 17.5+4.0 0.05/0.02 15.6±3.3 23.3±4.4 13.3+3.8 19.0+4.2 t/0.008
SV/PP
(mL/mm Hg) 1.61+±0.52 1.29±0.42 1.93±0.39 1.56±0.52 NS/0.03 1.79±0.22 1.18+0.40 1.99+0.49 1.31±0.43 t/0.003
RVR (units) 83±23 125±51 74+19 118+39 0.008/NS 89+32 129+38 104±38 135±55 t/NS
LVM (g) 173±69 213±68 213+74 241±54 0.04/0.01 123+35 260+37 171+13 253±88 t/NS
TPR, total peripheral resistance; SV/PP, stroke volume over pulse pressure; RVR, renal vascular resistance; LVM, left ventricular mass.
*ANCOVA.
tBecause only six black men were normotensive, no p values on normotension vs. hypertension are given.

between body mass index and renal hemodynamics,
thereby confirming the current results.48 The presence
of hypertension, in contrast, clearly reduced renal blood
flow and increased renal vascular resistance.49 Castle-
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favored the view that obesity in hypertensive patients is
deleterious to the cardiovascular system. It appears that
prospective studies might have been biased by the fact
that lean subjects tended to have more rapid progres-

man and Smithwick50-51 reported that the more renal sion of hypertensive disease and earlier manifestations
blood flow was reduced and vascular resistance ele- of cardiovascular complications than obese subjects.
vated, the more severe was nephrosclerosis in renal Consequently, when all patients with signs of cardiovas-
biopsies of patients with essential hypertension. Thus, cular disease at baseline were excluded (thereby also
hypertension but not obesity impaired renal perfusion. excluding lean hypertensive patients, who were more
In our study, left ventricular mass was greatest in the likely to die of cardiovascular complications), the so-
obese hypertensive groups. This was particularly signifi- called protective effects of obesity hypertension were no
cant in white subjects and in men, but it was not found in longer evident. Lean and obese hypertensive subjects
black subjects and women. The latter appeared to be had similar prognoses of the development of subsequent
related to the relatively high left ventricular mass in the fatal cardiovascular events.8,10 However, the four pro-
lean groups. Concomitantly, end-diastolic diameter was spective studies did not report statistical analysis of
slightly enlarged, reflecting increased preload. Although cardiovascular complications from cerebrovascular dis-
we observed no impairment of cardiac performance, pre- ease and end-stage renal disease.8,10-12 When looking at
vious analysis noted a depressed myocardial contractility individual data, it appears that the risk for renal failure
in patients with eccentric left ventricular hypertrophy of and cerebrovascular events was increased if obesity
obesity.52 Recently, we reported peak filling rate, duration coexisted with hypertension.8'10-12
of peak filling rate, and left atrial emptying index (indica- In conclusion, obesity and arterial hypertension dis-
tors of ventricular filling) to be reduced in obese nor- parately affected structural and functional cardiovascu-
motensive and obese hypertensive patients in comparison lar findings. Perfusion of the kidneys in hypertension
with their lean counterparts.53 Depressed myocardial con- was impaired to a similar extent in lean and obese
tractility and diastolic dysfunction, when sustained, will hypertensive patients. Patients with obesity were hemo-
eventually lead to premature congestive heart failure, dynamically younger than comparable lean subjects, at
particularly in patients with obesity hypertension.54-56 least during resting conditions. Left ventricular mass
Unloading from the heart the double burden of was found to be more markedly increased in obesity
obesity and hypertension by losing weight and control- hypertension, a fact that indicates an additional risk for
ling blood pressure should become a major goal of cardiovascular events. Thus, our analysis of early target
preventive cardiology. Although results from the four organ damage in obesity hypertension does not support
prospective studies examining the risks of obesity hy- the concept that obesity exerts renoprotective or car-
pertension were controversial,8 0-12 a closer analysis dioprotective effects on the cardiovascular system.
TABLE 7. Determinants of Target Organ Damage in Lean Versus Obese Patients in Young (<42-year-old) and
Old (>42-year-old) Patients
Parameters Young subjects Impact Old subjects Impact
for target Normo- Hyper- Normo- Hyper- of hyper- Normo- Hyper- Normo- Hyper- of hyper-
organ tensive tensive tensive tensive tension/ tensive tensive tensive tensive tension/
damage (n=20) (n=30) (n = 17) (n =30) obesity* (n = 10) (n=32) (n=8) (n=53) obesity*
TPR (units) 16.3+4.5 21.0+4.5 14.9+3.9 17.5+3.9 0.03/0.05 17.7±3.4 22.7±4.7 12.8±2.5 18.6±4.2 0.003/0.004
SV/PP
(mL/mm Hg) 1.70±0.59 1.36±0.41 1.96±0.39 1.76±0.45 NS/0.001 1.58±0.42 1.12±0.45 1.98±0.37 1.36±0.43 0.005/0.06
RVR (units) 78±20 112±39 73±14 108±33 0.001/NS 92±27 140±51 93±35 134±51 0.03/NS
LVM (g) 169±69 224±64 205±72 244±65 0.01/0.10 165±72 220±65 199±39 248±73 0.08/0.10
TPR, total peripheral resistance; SV/PP, stroke volume over pulse pressure; RVR, renal vascular resistance; LVM, left ventricular mass.
*ANCOVA.
 1488 Circulation Vol 87, No S May 1993
References
1. Stamler R, Stamler J, Riedlinger WE, Algera G, Roberts RH:
Weight and blood pressure: Findings in hypertension screening in
one million Americans. JAMA 1982;240:1607-1611
2. Chiang BN, Perlmal LV, Epstein FH: Overweight and hyperten-
sion: A review. Circulation 1969;39:403-421
3. Kannell WB, Brand N, Skinner JJ, Dawber T, McNamara P: Rela-
tion of adiposity to blood pressure and development of hyperten-
sion: The Framingham Study. Ann Intern Med 1967;77:48-56
4. Pfaffenberger RS, Thorne MC, Wing AL: Chronic diseases in
former college students: VIII. Characteristics in youth predispos-
ing to hypertension in later years. Am J Epidemiol 1968;88:25
5. Hubert HB, Feinleib M, McNamara PM, Castelli WP: Obesity as
an independent risk factor for cardiovascular disease: A 26-year
follow-up of participants in the Framingham Heart Study. Circu-
lation 1983;67:968-977
6. Gordon T, Kannel WB: Obesity and cardiovascular disease: The
Framingham Study. Clin Endocrinol Metab 1976;5:367-374
7. Kannel WB, Sorlie P: Hypertension in Framingham, in Paul 0
(ed): Epidemiology and Control of Hypertension. New York, Grune
& Stratton, 1975, pp 553-592
8. Bloom E, Dwayne Reed, Yano K, MacLean C: Does obesity
protect hypertensives against cardiovascular disease? JAMA 1986;
256:2972-2975
9. Manson JE, Colditz GA, Stampfer MJ, Willett WC, Rosner B, et
Downloaded from http://circ.ahajournals.org/ by guest on March 26, 2018
al: A prospective study of obesity and risk of coronary heart
disease in women. N Engl J Med 1990;322:882-889
10. Kannel WB, Zhang T, Garrison RJ: Is obesity related hypertension
less of a cardiovascular risk? The Framingham Study. Am Heart J
1990;120:1195-1201
11. Barrett-Connor E, Khaw KT: Is hypertension more benign when
associated with obesity? Circulation 1985;72:53-60
12. Cambien F, Chretien JM, Ducimetiere P, Guize L, Richard JL: Is
the relationship between blood pressure and cardiovascular risk
dependent on body mass index? Am JEpidemiol 1985;122:434-442
13. Frant R, Groen J: Prognosis of vascular hypertension. Arch Intern
Med 1950;87:727
14. Bechgaard P: Arterial hypertension: A follow-up study of one
thousand hypertonics. Acta Med Scand 1946;172(suppl):13
15. Breslin DJ, Gifford RW, Fairbairn JF: Essential hypertension-A
20-year follow-up study. Circulation 1966;33:87
16. Dimond GE: Hypertension, body weight and coronary heart dis-
ease. Arch Intern Med 1963;112:550
17. Sokolow M, Perloff D: The prognosis of essential hypertension
treated conservatively. Circulation 1961;23:697
18. Dyer AR, Stamler J, Berkson DM, Ludberg HA: Relationship of
relative weight and body mass index to 14 year mortality in the
Chicago Peoples Gas Company Study. J Chron Dis 1975;28:108
19. Rosenman RH, Friedman M, Straus R, Jenkins CD, Zyzanski SJ,
Wurm M: Coronary heart disease in the Western Collaborative
Group Study. J Chron Dis 1970;23:123
20. Goldbourt U, Holtzman E, Cohen-Mandelzweig, Neufeld HN:
Enhanced risk of coronary heart disease mortality in lean hyper-
tensive men. Hypertension 1987;10:22-28
21. Phillips A, Shaper AG: Relative weight and major ischaemic heart
disease events in hypertensive men. Lancet 1989;1:1005-1008
22. Perera GA, Damon A: Height, weight, and their ratio in the
accelerated form of hypertension. Arch Intern Med 1956;100:
263-265
23. Messerli FH, Sundgaard-Riise K, Reisin ED, Dreslinski G, Dunn
FG, Frohlich ED: Disparate cardiovascular effects of obesity and
arterial hypertension. Am J Med 1983;74:808-812
24. Messerli FH, Sundgaard-Riise K, Reisin ED, Dreslinski GR, Ven-
tura HO, Oigman W, Frohlich ED, Dunn FG: Dimorphic cardiac
adaptation to obesity and arterial hypertension. Ann Intern Med
1983;99:757-761
25. Messerli FH, Devereux RB: Left ventricular hypertrophy: Good or
evil? Am J Med 1983;75:1-31
26. Messerli FH, Sundgaard-Riise K, Ventura HO, Dunn FG,
Oigmann W, Frohlich ED: Clinical and hemodynamic determi-
nants of left ventricular dimensions. Arch Intern Med 1984;144:
477-481
27. Messerli FH: Cardiopathy of obesity-A not-so-Victorian disease.
N Engl J Med 1986;314:378-380
28. Messerli FH, DeCarvalho JGR, Christie B, Frohlich ED: Systemic
and regional hemodynamics in low, normal, and high cardiac out-
put borderline hypertension. Circulation 1978;58:441
29. National Center for Health Statistics: Plan and Operation of the
National Health and Nutrition Examination Survey, 1976-1980.
Washington, DC, US Public Health Service, DHHS publication
No. (PHS) 221:81-1317 (Vital and Health Statistics Series I, No.
15, 1981), 1981
30. Metropolitan Life Insurance Company: Metropolitan height and
weight tables. Stat Bull Metrop Life Insur Co 1984;64:2-9
31. Tauxe WN, Maher FT, Taylor WF: Effective renal plasma flow:
Estimation from the theoretical volumes of distribution of intrave-
nously injected 1311 orthioodo hippurate. Mayo Clinic Proc 1971;46:
524-531
32. Silikas GI, Jack D, Edelman CM Jr, Chervu LR, Blaufox MD,
Spitzer A: Simultaneous measurement of glomerular filtration rate
and renal plasma flow using plasma disappearance curves. JPediatr
1973;83:749-757
33. Ventura HO, Messerli FH, Oigman W, Suarez DH, Dreslinski GR,
Dunn FG, Reisin E, Frohlich ED: Impaired systemic arterial com-
pliance in borderline hypertension. Am Heart J 1984;108:132-136
34. Sahn DJ, de Maria A, Kisslo J, Weyman A: Recommendations
regarding quantitation in M-mode echocardiography: Results of a
survey of echocardiographic measurements. Circulation 1978;58:
1072-1080
35. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E,
Sachs I, Reichek N: Echocardiographic assessment of left ventric-
ular hypertrophy: Comparison to necropsy findings. Am J Cardiol
1986;57:450-458
36. Freis ED: Hemodynamics of hypertension. Physiol Rev 1960;40:27-54
37. Tarazi RC: Hemodynamics of hypertension, in Genest J, Kuchel
0, Hamet B, Cantin M (eds): Hypertension: Physiopathology and
Treatment, ed 2. New York, McGraw-Hill, 1983, pp 15-42
38. Lund-Johanson P: The hemodynamics of the aging cardiovascular
system. J Cardiovasc Pharmacol 1988;12(suppl 8):S-20-S-32
39. Folkow B: Physiological aspects of primary hypertension. Physiol
Rev 1982;62:347-504
40. Koren MJ, Savage DD, Laragh JH, Devereux RB: Relation of
hemodynamic parameters to prognosis in essential hypertension.
(abstract) Am J Hypertens 1990;3:13a
41. Messerli FH, Christi B, DeCarvalho JGR, Aristimuno EE, Suarez
DH, Dreslinski GR, Frohich ED: Obesity and essential hyperten-
sion: Hemodynamics, intravascular volume, sodium excretion, and
plasma renin activity. Arch Intern Med 1981;141:81-85
42. Alexander JK, Amad KH, Cole VW: Observations on some clin-
ical features of extreme obesity, with particular reference to car-
diorespiratory effects. Am J Med 1962;32:512-524
43. Schmieder RE, Grube E, Ruddel H, Schachinger H, Schulte W:
Relation of hemodynamic reaction during stress to left ventricular
hypertrophy in essential hypertension. Am J Hypertens 1990;3:
281-287
44. Asmar RG, Brunel PC, Panier BM, Cacolley PJ, Safar ME: Arte-
rial distensibility and ambulatory blood pressure monitoring in
essential hypertension. Am J Cardiol 1988;61:1066-1078
45. Eliot RS, Buell JC, Dembroski TM: The role of CNS in cardiovas-
cular disorders. Hosp Pract 1983;18:189-199
46. Rockstroh JK, Schmieder RE, Schachinger H, Messerli FH:
Impact of obesity on the hemodynamic response to stress in essen-
tial hypertension. Am J Cardiol 1992;70:1035-1039
47. Reisin E, Messerli FH, Ventura HO, Frohlich ED: Renal hemo-
dynamic studies in obesity hypertension. J Hypertens 1987;5:
397-400
48. Schmieder RE, Messerli FH, Garavaglia G, Schachinger H: Deter-
minants of renal blood flow in essential hypertension. J Hypertens
1990;8(suppl):S93
49. Hollenberg NK, Borucki UJ, Adams DF: The renal vasculature in
essential hypertension: Evidence for a pathogenetic role. Medicine
1978;57:167-178
50. Castleman B, Smithwick RH: The relation of vascular disease to
the hypertensive state. JAMA 1943;121:1256-1261
51. Castleman B, Smithwick RH: The relationship of vascular disease
to the hypertensive state. N Engl J Med 1948;239:729-732
52. Garavaglia GE, Messerli FH, Nunez BD, Schmieder RE, Gross-
mann E: Myocardial contractility and left ventricular function in
obese patients with essential hypertension. Am J Cardiol 1988;62:
594-597
53. Grossman E, Oren S, Messerli FH: Left ventricular filling in the
systemic hypertension of obesity. Am J Cardiol 1991;60:57-60
54. DeDivitis 0, Fazio S, Petitto M, Maddalena G, Contaldo F, Man-
cini M: Obesity and cardiac function. Circulation 1981;64:477-482
55. Alexander J, Pettigrove JR: Obesity and congestive heart failure.
Geriatrics 1967;22:101-106
56. Kannel WB, Castelli WP, McNamara PM, McKee PH, Feinleib M:
Role of blood pressure in the development of congestive heart
failure: The Framingham Study. N Engl J Med 1972;287:781-787
 Does obesity influence early target organ damage in hypertensive patients?
R E Schmieder and F H Messerli

Circulation. 1993;87:1482-1488
doi: 10.1161/01.CIR.87.5.1482
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