Persistence of impaired vascular function despite an improved metabolic profile following three months of significant weight loss

JACC

March 19.2003

ABSTRACTS

POSTER SESSION

1202

Vascular

group,

and Endothelial

- Vascular Disease, Hypertension, CNP

quently

Physiology

levels increased

decreased

another endothelium-derived (either chronically or acutely).

Tuesday, April 01, 2003, 3:00 p.m.-!?00 p.m. McCormick Place, Hall A Presentation Hour: 4:00 p.m.-!500 p.m.

lation. Baseline

Toshihide

Hinoi,

Hrdeo Sasaki, Chikako

lto, Hiroshima

A-Bomb

Casualty,

disease

is the most common

subjects with type 2 diabetes mellitus is a non-invasive method to estimate

effect of diabetes

on arterial

study in single center. Methods- A total of 11,602 (OGTT),

blood chemistry age

We diagnosed,

impaired

glucose

stiffness,

we conducted

subjects

were

years,

14%

and death

75g-oral

glucose

and were enrolled

hypertension,

56%

641 impaired

tolerance

test

in the present study

dyslipidaemia,

37%

fasting

(IFG), 3,360

glucose

current

(IGT), and 2,236 Type 2 DM.

RESULTS-Compared with normal group, abnormal groups (IFG, IGT and type 2 DM) had signiftcantly increased PWV(6.4 versus 6.7, 6.9 and 9.lmIsec .p
showed

that age, gender

male, systolic

blood pressure,

serum

triglycerides,

hour plasma glucose. and sigma-IRI (sum of insulin yalue in OGTT) were positively related with PWV, and lower serum HDL-cholesterol was inversely correlated P
Linear

relationship

p=o.o14 ). CONCLUSION-These

results

associated

was appreciated suggest

between

that, in addition

sigma-IRI

and PWV(

to age, sex, systolic

Michigan,

Ann Arbor,

Background:

is markedly

reduced,

whereas

acute episodes

but significant

increase

in plasma

of sleep

CNP levels.

2 cor(all

r=0.966,

blood pres-

as assessed

in newly diagnosed

by OGTT

type 2 DM.

Obesity

Impairs endothelial

if weight

Lynn Glazewski,

function

loss significantly

and arterial compliance.

improves

vascular

to cardiovascular

events.

by brachral

(CRP), and asymmetric

We therefore

flow-mediated

dilatation

(FMD) and nitroglycerin-mediated

dimethyl

arginine

(ADMA)

were also assessed.

Results: Body weight was reduced by an average of 6.6 % after 3 months. BMI (34.9 * 4.6 to 32.7 f 4.6 kg/m*. p
decreased.

LDL-C (114 * 27 to 104 * 25 mg/dl, p=O.o05), LDL

particle concentration (1339 f 359 to 1222 f 325 mmolll, p=O.O09), insulin (8.8 * 4.1 to 7.4 * 2.7 UU/ml, p=O.O02), and glucose (68.3 * 6.8 to 65.5 * 9.2 mg/dl. p=O.O69) Vascular

function,

CRP, and ADMA were not altered

ance. These results are important

because

more prolonged time period, of weight overweight adults.

they demonstrate

loss may be required

that a greater amount, to restore vascular

or a

health in

FMD (%)

3.66 * 3.54

3.74 * 3.76

0.66

NMD (%)

17.16 * 5.69

18.67 * 7.11

0.13

10.2 * 3.6

10.5 * 5.7

0.74

SVC ((ml/mm

Hg) x 100)

LVC ((ml/mm

Methods:

oresentina

397 consecutive

subiects

to the cardiac catheterization

laboratow

homozygosity

for G649T

at both

loci (TT)

who

belong

to DD and

II ACE

genotype

(groups 1 and 2) and those who are negative for this polymorphism (GG) and belong to either DD or II genotype (groups 3 and 4) were identified. The four groups then underwent determination

of conduit

endothelial

function.

variant of the ACE were not studied. Results Median FMD value in the TT-DD 2.23% (-0.29.4.17)

Hg) x 100)

CRP (mg/dL)

loss

Heterozygosity

group

GIL?~* -Asp or the ID

was 0.20 (-3.17,

2 01) compared

in the GG-II group. Median values in the TT-II and the GG-DD

to

groups

lation

with the ACE homozygous

in individuals

P

1202-l

in determining

atherosclerosis

vasodi-

endothelial

dys-

Koen M. Maraues.

Hugo J. Spruijt,

University

Center, Amsterdam,

Medical

Nice Westerhof,

Cees A. Visser. Frans C. Visser, VU

The Netherlands,

ICaR-VU,

Amsterdam,

The

Netherlands Background Classically, limitation of the maximal

epicardial stenoses are thought to exert their clinical effect by flow capacity. In animal studies, artificial coronary stenoses

have been shown to decrease

the microvascular

resistance

(MR) to compensate

for the

epicardial obstruction. In human studies, data on the effect of atherosclerotic epicardial stenoses on the MR are conflicting. A constrictor response of the microcirculation (MC), supplied

by a severely

narrowed

epicardial

coronary,

was found to pacing induced

tachy-

cardia. We simultaneously

pressure

measured

(Pd) distal to a coronary

mean

stenosis,

flow velocity

at baseline

(APV)

and maximal

and distal coronary hyperemia,

induced

by adenosine. The MR was defined as the hyperemic ratio of Pd by APV. Data were acquired in 23 normal coronaries (group A), in 54 arteries with an intermediate stenosis without

ischemia

(group

B), and rn 29 stenoses

with evidence

of ischemia.

detected

Conclusion

higher

(‘~‘0.05)

compared

The

and the

that the MC can aggravate

by severe coronary

stenoses

the effect of a severe coronary

post PCI the MR was significantly

lower compared

is ele-

stenosis.

to normal arteries.

group A

group B

group c

0.75

APV(cm/sec)

50*11

46tl4

33+15

56+17

0.47 * 0.41

0.40 * 0.45

0.23

Pd (mm Hg)

92*15

65*14

64+15

60+12

MR (mmHg.sec/cm)

2.0*0.5

2.1+0 7

2.6kl.4.

1.7+0.6’

Mikolaj

Winnicki.

Carolyn

Levels

(OSA)

MN

has been related

diswith

properties.

We hypothesized

that OSA

might be associated with reduced plasma CNP concentration. METHODS. Plasma CNP levels were measured during the night (at 9:30 p.m., 2 a.m., 6 a.m.) in 15 healthy male controls.

RESULTS.

Baseline

CNP levels before sleep

Mariolein

Hensens.

Groningen, Background:

Buikema,

Maarten

P. van den Berq, Azuwerus

Wiek H. van Gilst. Thoraxcenterof

Groningen, Depression

the Universrtv

is associated

with

a significantly

Because Selective

Serotonin

Re-uptake

Inhibitors

(SSRls)

are frequently

in the control

Methods:

p=O.OlZ).

However,

in the OSA

increased

risk of cardiac

events in patients who had coronary artery bypass graft (CABG) surgery. It is unknown whether antidepressive medication can improve cardiac prognosis in these patients. depressants, we studred the vasoactive response of human (IMA) preparations to sertraline, whtch is one of the SSRls.

pglml,

van B&en,

Hosoital

The Netherlands

were significantly lower in the OSA than in the control group (21.3i2.3 vs. 32.9*4.0 pg/ ml, respectively, p=O.O13). During the night, there was a gradual decrease rn CNP levels to 21.0*3.1

group D

Direct Vasodilatory Effects of the Antidepressant Sertraline in the Human Internal Mammary Artery

1202-151 Fieseler,

dence of hypertension, atherosclerosis, arterial thrombosis and other cardiovascular eases. C-type natriuretic peptide (CNP) is a novel endothelium-derived mediator and anti-thrombotic

by

(‘p
We found that the MR in areas perfused

vated, suggesting

to the other groups

0.51

Mayo Clinic, Rochester,

(from 32.9k4.0

flow mediated

and preexistent

17.7 * 6.6

rnci-

group

Atheroscle-

0.95 * 0.15

sleep apnea

and in 10 matched

(p=NS by ANOVA).

Effect of a Severe Coronary Stenosis and Percutaneous Cornary Intervention on the Coronary Microcirculation

50

MR after PCI was significantly

to an increased

anti-atherogenic

DD genotype,

with established

Joost P. van Melle, Hendrik Obstructive

the four groups

16.6 zt 6.3

Abu Shamsuzzaman,

Virend K. Somers,

did not differ between

0.95 *0.13

C-Type Natriuretic Peptide and Adrenomedullin in Patients With Obstructive Sleep Apnea

Robert Walk, Anna Svatikova,

additively

Immediately

(MM)

OSA patients

of the homozygous

of the University of Michigan over a period of 16 months were recruited. DNA was extracted and PCR analvsis for ACE and NOS oolvmorohisms oerformed. Patients with

MR in group C was statistically

Post weight

vasodilatory,

the influence

non-invasive tests (group C), and in 14 arteries (group D) immediately after PCI. Results A significant difference was found between the MR of the different groups.

Baseline

BACKGROUND.

to determine

in NOS Ill on peripheral conduit artery endothelial role. if any, of a common ACE polymorphism.

Methods

(Table).

Conclusion: Despite reduced adiposity and a significant improvement in the metabolic profile, 3 months of weight reduction did not alter endothelial function or vascular compli-

Bruce Johnson,

We wished

G649T(Gl@s + Asp) polymorphism function and to elucidate the modifier

health.

dilatation (NMD). Large (LVC) and small (SVC) vessel compliance was determined by computerized arterial pulse waveform analysis. Metabolic parameters, C-reactive protein

1202-148

Converting

function

Sanjay Rajagopalan,

Methods: 43 adults (BMI 2 27 ks/ms) without other risk factors underwent a 3 month trial of diet + orlistat (120 mg PO QAC). Endothelial-dependent and independent vasomotion

improved.

and Angiotensin

rosis burden as assessed by angiography were not different across the groups. Conclusions: The homozygous NOS III variant (GG) status does not seem to interact

to determine

were determined

(NOS)

Persistence of Impaired Vascular Function Despite an Improved Metabolic Profile Following Three Months of Significant Weight Loss

response

Robert D. Brook, Robert L. Bard, Louis D’Alecy. University of Michigan, Ann Arbor, Ml Background:

of Nitric Oxide Synthase

were 3.04(-1.16. 6.61) and 2.46% (-1.63. 6.52) respectively. These values were not statistically significant (p>O.O5 by one way ANOVA). Median nitroglycerin mediated dilation

hyper-insulin

with early atherosclerosis

47

MI

The products

in the four groups

ADMA

levels of

is independently

sure and triglycerides,

sought

and subse-

plasma

Enzyme (ACE) play a critical role rn determining ve~~sl wall structure and function. Polymorphisms in both genes have been independently demonstrated to influence propensity

a large scale and cross-sectional

performed

5,593 were normal,

tolerance

cause of disability

(DM). Measurement of pulse wave velocity arterial stiffness. In order to determine the

and PWV measurement,

64.5+/-8.9

smoker).

1202-l

apnea,

to CNP,

Michael A. Schmidt Anjan Chakrabarti, Dana Pfeninnger, Nice Kacirotti, Claire Duvernoy, Anthony Killeen, Robert D. Brook, Sanjay Rajagopalan. University of

Background-Cardiovascular

(mean

sleep

In contrast

Interactive Effects of the ACE DD Polymorphism With the NOS Ill Homozygous G649T (Glu298-Asp) Variant in Determining Endothelial Function in Coronary Artery Disease

Hiroshrma,

Japan

among (PWV)

of untreated

therapy.

309A

vasodilator, adrenomedullin, were not affected by OSA CONCLUSION. OSA exerts a twofold effect on CNP regu-

CNP production

impact of Insulin Resistance and Hyperinsulin Response on Arterial Stiffness

46

the period

to CPAP

apnea during the night cause a modest,

1202-149 1202-l

during

in response

and Prevention

IMAs

(n=22)

were

harvested

during

CABG

Internal

surgery

and

prescribed Mammary

antiArtery

cut into rings.

In