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Effects of Hormone Replacement Therapy on Plaque
Stability, Inﬂammation, and Fibrinolysis in
Hypertensive or Overweight Postmenopausal Women
Kwang Kon Koh,
, Jeong Yeal Ahn,
, Moon Ho Kang,
Dae Sung Kim,
, Dong Kyu Jin,
, Min Soo Sohn,
, Gi Soo Park,
In Suck Choi,
, and Eak Kyun Shin,
bservational studies of the long-term effects of
hormone replacement therapy (HRT) have gen-
erally demonstrated favorable cardiovascular effects.
The beneﬁcial effects of HRT may involve nonlipid
mechanisms that affect endothelial function: plaque
stability, inﬂammatory responses, and ﬁbrinolysis.
Hypertension and obesity are associated with “insulin
resistance syndrome” and a prothrombic state.
cordingly, HRT may not have comparable beneﬁtin
hypertensive or overweight postmenopausal women.
Although inﬂammation of the arterial wall in the
vicinity of atherosclerotic plaques (especially those
with rupture and thrombi) is often found at necropsy,
this manner of identiﬁcation is hardly useful in pa-
tients at risk for myocardial infarction and stroke.
Thus, we investigated serologic markers after HRT in
hypertensive or overweight postmenopausal women.
Twenty postmenopausal women (mean age Ϯ SD
60 Ϯ 7 years) participated in this study, all with
-estradiol levels Ͻ50 pg/ml and cessation
of menses for at least 1 year. Baseline lipoprotein
levels are listed in Table 1. We used the National
Heart, Lung, and Blood Institute’sdeﬁnitions
overweight and obesity as cutoff points (body mass
index Ն25.0 and Ն30.0 kg/m
, respectively). We
deﬁned systolic or diastolic blood pressure Ն140 or
Ն90 mm Hg, respectively, according to World Heath
Organization-International Society of Hypertension
We excluded severe hypertension. Five,
5, and 10 women were overweight, hypertensive, and
both, respectively. Four of 15 were obese. Mean body
mass index was 28.5 Ϯ 3.3. None were diabetic or
smokers. This study was a randomized, double-blind,
crossover design. Study participants received micron-
ized progesterone (MP) 100 mg or medroxyprogester-
one acetate (MPA) 2.5 mg with conjugated equine
estrogen (CEE) 0.625 mg/day during 2 months, with
the second treatment period initiated on completion of
the ﬁrst treatment period. The study was approved by
the Gil Hospital Institute Review Board and all par-
ticipants gave written, informed consent.
Blood samples for laboratory assays were obtained
at approximately 8:00
. after overnight fasting and
immediately coded so that investigators performing
laboratory assays were blinded to subject identity or
study sequence. Assays for lipids and plasminogen
activator inhibitor type-1 antigen were performed as
Plasma monocyte chemoat
tractant protein (MCP-1), tumor necrosis factor
, and matrix metalloproteinase–9 (MMP-9)
levels were measured in duplicates by enzyme-linked
immunosorbent assay (R & D Systems, Minneapolis,
Minnesota) and prothrombin fragment 1 ϩ 2byen-
zyme-linked immunosorbent assay from Behring Di-
agnostics Inc. (San Jose, California). The inter- and
intraassay coefﬁcients of variation were Ͻ8%.
Data are expressed as mean Ϯ SD. After testing
data for normality, we used Student’s paired t test or
the Wilcoxon signed-rank test to compare values at
baseline and after each therapy (Table 1). We pre-
sumed that the second baseline after washout was not
different from the ﬁrst baseline, because we deter-
mined no carryover effect of CEE and progestagen for
6 weeks from our previous studies
; thus, we used 2
months as the treatment period without washout and
the second baseline. We found no carryover effect in
this study. The effects of the 2 therapies on markers of
plaque stability, inﬂammation, and ﬁbrinolysis rela-
tive to baseline values were analyzed by 1-way repeat-
ed-measures analysis of variance (ANOVA) or Fried-
man’s repeated ANOVA on ranks. After demonstra-
From the Departments of Cardiology, Clinical Pathology, Endocrinol-
ogy and Metabolism, and Preventive Medicine (Biostatistics), Gachon
Medical School, Inchon, South Korea. This study was supported in
part by Grant 2000-8 from the Korean Society of Circulation, Seoul,
Korea. Dr. Koh’s address is: Cardiology, Gil Medical Center, Gachon
Medical School, 1198 Kuwol-dong, Namdong-gu, Inchon, South
Korea 405-760. E-mail: firstname.lastname@example.org. Manuscript received June
1, 2001; revised manuscript received and accepted August 9, 2001.
©2001 by Excerpta Medica, Inc. All rights reserved. 0002-9149/01/$–see front matter
The American Journal of Cardiology Vol. 88 December 15, 2001 PII S0002-9149(01)02126-9