<IMT papers in 2000>

1: Arterioscler Thromb Vasc Biol 2000 Mar;20(3):703-707

Antibodies Against Oxidized LDL and Carotid Artery Intima-Media Thickness in a
Healthy Population.

Fukumoto M, Shoji T, Emoto M, Kawagishi T, Okuno Y, Nishizawa Y

Second Department of Internal Medicine (M.F., T.S., M.E., T.K., Y.N.) and the
Department of Cardiovascular Medicine, Institute of Geriatrics and Medical
Science (Y.O.), Osaka City University Medical School, Osaka, Japan.

Oxidation of LDLs plays an important role in atherosclerosis, and immune
response to oxidized LDL (oxLDL) may modulate atherogenesis. Although
immunization with oxLDL is shown to suppress atherogenesis in animal models, the
role of the immune response to oxLDL is not well established in humans. We
investigated the relationship between the titer of anti-oxLDL antibody (oxLDL
Ab) and arterial wall thickness in a healthy population with no clinical signs
of atherosclerosis. Intima-media thickness of the carotid arteries (CA-IMT) was
measured by high-resolution B-mode ultrasonography in 446 healthy subjects. The
titer of IgG-class oxLDL Ab was measured by a solid-phase ELISA. In univariate
analysis, CA-IMT correlated positively with age, systolic blood pressure, total
cholesterol, triglyceride, LDL cholesterol, body mass index, and waist-to-hip
ratio, whereas it correlated negatively with HDL cholesterol and oxLDL Ab titer.
The inverse association between oxLDL Ab titer and CA-IMT remained significant
in multiple regression analysis, which took other confounding variables into
account. These results indicate an independent inverse relationship between
oxLDL Ab titer and CA-IMT in healthy subjects, supporting the hypothesis that
immune response to oxLDL may have a protective role at an early stage of human
atherosclerosis.

Antiplatelet drugs attenuate progression of carotid intima-media thickness in
subjects with type 2 diabetes.

Kodama M, Yamasaki Y, Sakamoto K, Yoshioka R, Matsuhisa M, Kajimoto Y, Kosugi K,
Ueda N, Hori M

Department of Internal Medicine and Therapeutics, Osaka University Graduate
School of Medicine, Suita City, Japan.

The intima-media thickness of the carotid artery has been established as a
surrogate of definite atherosclerosis in subjects with high risk of vascular
events. This study was done to evaluate the effectiveness of long-term
antiplatelet therapy in attenuating progression of the intima-media thickness of
the carotid artery of subjects with type 2 diabetes. Subjects who had an
intima-media thickness over the threshold of the normal subjects but showed no
symptoms of vascular events were randomly divided into groups given antiplatelet
drugs [ticlopidine (n = 34) or a small dose of aspirin (n = 40)] or no drugs (n
= 74). For the follow-up period (3.0+/-0.06 years), the subjects not given
antiplatelet drugs showed a significantly higher progression of intima-media
thickness (0.067+/-0.009 mm/year) than those given ticlopidine (0.034+/-0.013
mm/year) or aspirin (0.033+/-0.010 mm/year). Stepwise multivariant regression
analysis showed that long-term administration of ticlopidine or aspirin
significantly reduced the progression of intima-media thickness of diabetic
subjects by 0.041 mm/year or 0.032 mm/ year, respectively. These data indicated
that despite differences of their pharmacological mechanisms, antiplatelet drugs
could attenuate the progression of intima-media thickness of the carotid artery
wall of asymptomatic type 2 diabetics who had early-stage carotid
atherosclerosis.

[Brain computerized tomographic and ultrasonographic findings in patients with
asymptomatic carotid bruits].

Iwamoto T, Ami M, Kubo H, Shimizu T, Tanaka Y, Umahara T, Takasaki M

Department of Geriatric Medicine, Tokyo Medical University.

This study was conducted to clarify brain and carotid lesions in patients with
asymptomatic carotid bruits and their characteristics. We studied 37 patients
with carotid bruits, who had various diseases other than stroke and were all
neurologically normal, using by brain computerized tomography (CT) and
ultrasonography (US). On CT, localized low density areas (LDAs) and their
distribution were assessed, as well as the grade of periventricular lucency
(PVL). Carotid lesions on US were classified into 3 categories: plaque (locally
thickened intima-media complex of 2.1 mm or more in thickness), stenosis
(narrowed lumen between 50% and 90% of the linearly measured diameter), and
occlusion (severely narrowed lumen more than 90%). Ankle pressure index (API)
less than 0.9 was defined as low. Mean age was 73.2 years-old and 28 of them
were men. Bruits were heard bilaterally in 15 patients. CT findings showed LDA
in 13 patients (35%) and severe PVL in 12 patients (32%). Twenty-three LDAs (13
in the left hemisphere and 10 in the right hemisphere) were seen and all were
considered to be infarctions. Nineteen LDAs, 13 of them seen in the basal
ganglia, were lacunae. Another 3 LDAs were seen in the watershed zone between
the middle and posterior cerebral arteries, whereas the remaining one was a
small cortical infarction in the left premotor area in the middle cerebral
artery territory. Ultrasonography showed carotid lesions in 65 of 74 carotid
arteries (plaque in 28, stenosis in 26, and occlusion in 11) and low API in 18
of 37 patients. Compared with patients with normal CT finding, the frequency of
hypertension (92% vs 50%) and ischemic heart disease (69% vs 29%) was
significantly high in 13 patients with silent infarction, although there was no
difference in US findings. In the hemisphere ipsilateral to the carotid with
bruits, which was frequently stenotic, the frequency of infarction was similar
to that in the hemisphere ipsilateral to the carotid with no bruit. Regression
analysis revealed that hypertension significantly correlated with the presence
of cerebral infarction. These findings indicated that incidence of infarction in
the elderly patients with asymptomatic carotid bruits was high and was
associated with hypertension and advanced atherosclerosis in many organs,
including the carotid and peripheral arteries. The reason for the lack of
symptoms was considered to be that most of the infarctions were lacunae and
located in the basal ganglia, although infarction did not significantly
correlate with bruits or carotid lesions.

4: Eur J Clin Invest 2000 Jan;30(1):18-25

Cholesteryl ester transfer protein gene polymorphisms are associated with
carotid atherosclerosis in men.

Kakko S, Tamminen M, Paivansalo M, Kauma H, Rantala AO, Lilja M, Reunanen A,
Kesaniemi YA, Savolainen MJ

University of Oulu, Oulu, Finland. sakari.kakko@oulu.fi

BACKGROUND: The cholesteryl ester transfer protein (CETP) is involved in the
reverse cholesterol transport and is therefore a candidate gene for
atherosclerosis. DESIGN: The prevalences of the I405V and the R451Q
polymorphisms were studied in a population sample of 515 men and women.
Genotypes were determined by PCR and carotid atherosclerosis by ultrasonography
as the mean intima-media thickness (IMT) of the carotid arteries. RESULTS: The
Q451 allele was associated with significantly lower intima media thickness in
men (P = 0.001). The Q451 allele was, in our earlier study, associated with high
plasma CETP activity in men. The VV405 genotype was associated with lower plasma
CETP activity compared with the II405 genotype (P < 0.01 for the difference). In
the general linear model general factorial procedure the interaction between
alcohol consumption and the I405V genotype on IMT was significant (P = 0.013) in
men, and when the interaction term was taken into the model the I405V genotype
also significantly affected IMT (P = 0.008). The VV405 genotype seems to be most
harmful for men with the highest alcohol consumption. CONCLUSIONS: We describe
two polymorphisms of the CETP gene associated with intima media thickness in
men. A significant interaction was found between alcohol consumption and the
I405V genotype on IMT.

5: Braz J Med Biol Res 2000 Jan;33(1):55-64

Intima-media thickness evaluation by B-mode ultrasound: correlation with blood
pressure levels and cardiac structures.

Plavnik FL, Ajzen S, Kohlmann O Jr, Tavares A, Zanella MT, Ribeiro AB, Ramos OL

Nefrologia, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brasil.

The aim of this study was to analyze the thickness of the intima-media complex
(IMC) using a noninvasive method. The carotid and femoral common arteries were
evaluated by noninvasive B-mode ultrasound in 63 normotensive and in 52
hypertensive subjects and the thickness of the IMC was tested for correlation
with blood pressure, cardiac structures and several clinical and biological
parameters. The IMC was thicker in hypertensive than in normotensive subjects
(0.67 +/- 0.13 and 0.62 +/- 0.16 vs 0.54 +/- 0.09 and 0.52 +/- 0.11 mm,
respectively, P<0.0001). In normotensive patients, the simple linear regression
showed significant correlations between IMC and age, body mass index and 24-h
systolic blood pressure for both the carotid and femoral arteries. In
hypertensives the carotid IMC was correlated with age and 24-h systolic blood
pressure while femoral IMC was correlated only with 24-h diastolic blood
pressure. Forward stepwise regression showed that age, body mass index and 24-h
systolic blood pressure influenced the carotid IMC relationship (r2 = 0.39) in
normotensives. On the other hand, the femoral IMC relationship was influenced by
24-h systolic blood pressure and age (r2 = 0.40). In hypertensives, age and 24-h
systolic blood pressure were the most important determinants of carotid IMC (r2
= 0.37), while femoral IMC was influenced only by 24-h diastolic blood pressure
(r2 = 0.10). There was an association between carotid IMC and echocardiographic
findings in normotensives, while in hypertensives only the left posterior wall
and interventricular septum were associated with femoral IMC. We conclude that
age and blood pressure influence the intima-media thickness, while
echocardiographic changes are associated with the IMC.

6: BMJ 2000 Jan 29;320(7230):273-8

Risk of cardiovascular disease measured by carotid intima-media thickness at age
49-51: lifecourse study.

Lamont D, Parker L, White M, Unwin N, Bennett SM, Cohen M, Richardson D,
Dickinson HO, Adamson A, Alberti KG, Craft AW

Department of Child Health, University of Newcastle, Sir James Spence Institute
of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP.

Objective: To quantify the direct and indirect effects of fetal life, childhood,
and adult life on risk of cardiovascular disease at age 49-51 years. Design:
Follow up study of the "Newcastle thousand families" birth cohort established in
1947. Participants: 154 men and 193 women who completed a health and lifestyle
questionnaire and attended for clinical examination between October 1996 and
December 1998. Main outcome measures: Correlations between mean intima-media
thickness of the carotid artery (carotid intima-media thickness) and family
history, birth weight, and socioeconomic position around birth; socioeconomic
position, growth, illness, and adverse life events in childhood; and adult
socioeconomic position, lifestyle, and biological risk markers. Proportions of
variance in carotid intima-media thickness that were accounted for by each stage
of the lifecourse. Results: Socioeconomic position at birth and birth weight
were negatively associated with carotid intima-media thickness, although only
social class at birth in women was a statistically significant covariate
independent of adult lifestyle. These early life variables accounted directly
for 2.2% of total variance in men and 2.0% in women. More variation in carotid
intima-media thickness was explained by adult socioeconomic position and
lifestyle, which accounted directly and indirectly for 3.4% of variance in men
(95% confidence interval 0.5% to 6.2%) and 7.6% in women (2.1% to 13.0%).
Biological risk markers measured in adulthood independently accounted for a
further 9.5% of variance in men (2.4% to 14.2%) and 4.9% in women (1.6% to
7.4%). Conclusions: Adult lifestyle and biological risk markers were the most
important determinants of the cardiovascular health of the study members of the
Newcastle thousand families cohort at age 49-51 years. The limited overall
effect of early life factors may reflect the postwar birth year of this cohort.

7: J Vasc Surg 2000 Jan;31(1 Pt 1):69-83

Vein interposition cuffs decrease the intimal hyperplastic response of
polytetrafluoroethylene bypass grafts.

Kissin M, Kansal N, Pappas PJ, DeFouw DO, Duran WN, Hobson RW 2nd

Division of Vascular Surgery and Program in Vascular Biology, Department of
Surgery, UMDNJ-New Jersey Medical School, Newark, NJ 07103-2714, USA.

PURPOSE: The modification of the distal anastomosis of polytetrafluoroethylene
(PTFE) bypass grafts with vein interposition cuffs (VCs) has been reported to
increase graft patency. However, the mechanisms that are responsible for this
improved patency are unclear. Because intimal hyperplasia (IH) is a primary
cause of prosthetic graft failure, we hypothesized that VCs affect the distal
anastomosis by decreasing the IH response of the outflow artery. METHODS:
Twenty-three female domestic Yorkshire pigs (mean weight, 35 kg) underwent 42
femoral PTFE bypass grafting procedures. The PTFE bypass grafts were separated
into the following three groups according to distal anastomotic configuration:
end-to-side anastomoses (ES), VCs, and cuffs constructed with PTFE (PCs). Four
femoral arteries from two pigs served as healthy controls. At sacrifice, the
grafts were perfusion fixed, and the distal anastomoses harvested at 1 and 4
weeks. The specimens were hemisected and serially sectioned to identify the
heel, toe, and mid-anastomotic regions. The sections were cut into 5-microm
segments and analyzed for intima and media thickness and area, intima/media area
ratio, and the distribution of IH in the vein cuff. The roles of transforming
growth factor-beta1 and platelet-derived growth factor-BB in IH development were
assessed with immunohistochemistry. RESULTS: IH development was significantly
lower at all areas of the anastomosis, with VCs compared with ES and PCs at 4
weeks (P </=.001). IH decreased in VCs from 1 to 4 weeks in all areas of the
anastomosis (P </=.001). PCs showed pronounced IH at the mid-anastomosis as
compared with VCs and ES (P </=.001). IH was most pronounced at the toe with ES
and PCs (P </=.001). Qualitatively, VCs altered the site of IH development,
sparing the recipient artery with preferential thickening of the vein cuff and
formation of a pseudointima at the vein-PTFE interface. Immunohistochemistry
results showed positive staining for transforming growth factor-beta1,
platelet-derived growth factor-BB, and smooth muscle alpha-actin in the
hyperplastic intima. CONCLUSION: PTFE bypass grafts with VCs had less IH develop
than did grafts with ES and PC anastomoses. IH regression in VCs at 4 weeks
suggests compensatory vessel wall remodeling mediated by the presence of the VC.
Furthermore, VCs caused a redistribution of hyperplasia to the vein-PTFE
interface, delaying IH-induced outflow obstruction in the recipient artery. The
marked increase in IH with PCs, despite a similar geometric configuration to
VCs, suggests that the biologic properties of autogenous tissue dissipate IH
development. Similarly, the flow patterns in PCs and VCs should be identical,
which suggests a less important role of hemodynamic forces in VC-mediated
protection.

8: Am J Epidemiol 2000 Mar 1;151(5):478-87

Carotid wall thickness is predictive of incident clinical stroke: the
Atherosclerosis Risk in Communities (ARIC) study.

Chambless LE, Folsom AR, Clegg LX, Sharrett AR, Shahar E, Nieto FJ, Rosamond WD,
Evans G

Department of Biostatistics, School of Public Health, University of North
Carolina, Chapel Hill 27514, USA.

Few studies have determined whether carotid artery intima-media thickness (IMT)
is associated prospectively with risk of first ischemic stroke. In the
Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized
atherosclerosis, was defined as the mean of IMT measured by B-mode
ultrasonography at six sites of the carotid arteries. The authors assessed the
relation of mean IMT to stroke incidence over 6-9 years' follow-up (1987-1995)
among 7,865 women and 6,349 men aged 45-64 years without prior stroke at
baseline in four US communities. There were 90 incident ischemic stroke events
for women and 109 for men. In sex-specific Cox proportional hazards models
adjusting only for age, race, and community, the hazard rate ratios comparing
extreme mean IMT values (> or =1 mm) to values less than 0.6 mm were 8.5 for
women (95% confidence interval: 3.5, 20.7) and 3.6 for men (95% confidence
interval: 1.5, 9.2). The relation was graded, and models with cubic splines
indicated significant nonlinearity, with hazards increasing more rapidly at
lower IMTs than at higher IMTs. Thus, models using linear IMT values
substantially underestimate the strength of the association at lower IMTs. The
strength of the association was reduced by the inclusion of putative stroke risk
factors, but it remained elevated at higher IMTs. Hence, mean carotid IMT is a
noninvasive predictor of future ischemic stroke incidence.

9. Stroke 2000 Mar;31(3):574-81

Sex differences in the relationship of risk factors to subclinical carotid
atherosclerosis measured 15 years later : the tromso study.

Stensland-Bugge E, Bonaa KH, Joakimsen O, Njolstad I

Institute of Community Medicine, University of Tromso (Norway).

Background and Purpose-Ultrasound measurement of carotid artery intima-media
thickness (IMT) is regarded as a valid index of atherosclerosis. Determinants of
IMT in cross-sectional studies have been established, but the long-term
relationship between cardiovascular risk factors and subclinical atherosclerosis
has not been investigated thoroughly. Methods-We included in the study 3128
middle-aged men and women in Tromso, Norway, who in 1980 attended the baseline
examination with measurements of cardiovascular risk factors and who underwent
carotid ultrasonography after 15 years of follow-up. Results-Age, blood
pressure, total cholesterol, HDL cholesterol, and body mass index were
independent long-term predictors of IMT in both men and women. Triglyceride
levels were associated with an increase in IMT in women only, while physical
activity and smoking were predictors of IMT in men only. However, smoking was
associated with increased risk of having atherosclerotic plaque in both men and
women. There were no differences in the strength of risk factor effects on IMT
in the common carotid artery and the carotid bifurcation. Conclusions-The
present study indicates that established cardiovascular risk factors are
independent predictors of subclinical atherosclerosis measured after 15 years of
follow-up. However, there may be significant sex differences in the relationship
between triglycerides, smoking, and physical activity and the risk of
atherosclerosis.

10: Stroke 2000 Mar;31(3):568-73

Effects of stress reduction on carotid atherosclerosis in hypertensive african
americans.

Castillo-Richmond A, Schneider RH, Alexander CN, Cook R, Myers H, Nidich S,
Haney C, Rainforth M, Salerno J

Center for Natural Medicine and Prevention (A.C.-R., R.H.S., C.N.A., S.N., M.R.,
J.S.), Maharishi University of Management, College of Maharishi Vedic Medicine,
Fairfield, Iowa.

Background and Purpose-African Americans suffer disproportionately higher
cardiovascular disease mortality rates than do whites. Psychosocial stress
influences the development and progression of atherosclerosis. Carotid
intima-media thickness (IMT) is a valid surrogate measure for coronary
atherosclerosis, is a predictor of coronary outcomes and stroke, and is
associated with psychosocial stress factors. Stress reduction with the
Transcendental Meditation (TM) program decreases coronary heart disease risk
factors and cardiovascular mortality in African Americans. B-mode ultrasound is
useful for the noninvasive evaluation of carotid atherosclerosis. Methods-This
randomized controlled clinical trial evaluated the effects of the TM program on
carotid IMT in hypertensive African American men and women, aged >20 years, over
a 6- to 9-month period. From the initially enrolled 138 volunteers, 60 subjects
completed pretest and posttest carotid IMT data. The assigned interventions were
either the TM program or a health education group. By use of B-mode ultrasound,
mean maximum IMT from 6 carotid segments was used to determine pretest and
posttest IMT values. Regression analysis and ANCOVA were performed. Results-Age
and pretest IMT were found to be predictors of posttest IMT values and were used
as covariates. The TM group showed a significant decrease of -0.098 mm (95% CI
-0. 198 to 0.003 mm) compared with an increase of 0.054 mm (95% CI -0.05 to
0.158 mm) in the control group (P=0.038, 2-tailed). Conclusions-Stress reduction
with the TM program is associated with reduced carotid atherosclerosis compared
with health education in hypertensive African Americans. Further research with
this stress-reduction technique is warranted to confirm these preliminary
findings.

11: Clin Chim Acta 2000 Mar 1;293(1-2):105-113

Cell adhesion molecules - can they be used to predict coronary artery disease in
patients with familial hypercholesterolaemia?

Paiker JE, Raal FJ, Veller M, von Arb M, Chetty N, Naran NH

Department of Chemical Pathology, South African Institute for Medical Research
and University of the Witwatersrand, Johannesburg, South Africa

Adhesion of leukocytes to endothelial cells via cell adhesion molecules (CAMS)
is thought to be pivotal in the initiation of atherosclerosis. As patients with
familial hypercholesterolaemia (FH) are known to develop severe, premature
coronary artery disease (CAD), we investigated the usefulness of soluble forms
of CAMS namely vascular cellular adhesion molecule-1 (VCAM), intercellular cell
adhesion molecule-1 (ICAM) and E-selectin as predictive markers of the presence
and severity of atherosclerosis in this patient group. Twenty heterozygous FH
patients without CAD; 24 heterozygous FH patients with CAD; 17 homozygous FH
patients without documented CAD; nine homozygous FH patients with overt CAD; and
50 healthy controls were studied. Carotid artery intima media thickness (IMT)
was also measured in the homozygous patients. Levels of the adhesion molecules
VCAM, ICAM and E-selectin were not significantly elevated in homozygous FH
patients and heterozygous FH patients, both with and without CAD, compared to
the normal control subjects. In addition the range of results was so wide and
the overlap of values with normal controls so great, that the use of an
individual level of either VCAM, ICAM or E-selectin was not predictive of either
the presence or degree of atherosclerosis in the FH subjects.

12: J Hypertens 2000 Feb;18(2):197-201

Baseline reproducibility of B-mode ultrasonic measurement of carotid artery
intima-media thickness: the European Lacidipine Study on Atherosclerosis.

Tang R, Hennig M, Thomasson B, Scherz R, Ravinetto R, Catalini R, Rubba P,
Zanchetti A, Bond MG

Division of Vascular Ultrasound Research, Wake Forest University School of
Medicine, Winston-Salem, North Carolina 27104, USA. ytang@wfubmc.edu

BACKGROUND AND OBJECTIVE: The European Lacidipine Study of Atherosclerosis
(ELSA) is a prospective, randomized, double-blind, multi-national interventional
trial to determine the effect of four-year treatment using the calcium
antagonist lacidipine versus the beta-blocker atenolol on the progression of
carotid atherosclerosis in 2259 asymptomatic hypertensive patients. B-mode
ultrasound is used to measure the primary and secondary endpoints including the
mean maximum intima-media thickness (IMT) of the carotid bifurcations and the
common carotid arteries (CBM(max)), the mean maximum IMT of 12 standard carotid
sites (M(max)) and the overall maximum IMT (T(max)). This paper reports the
cross-sectional reproducibility of ultrasound measurements at baseline. METHOD:
To evaluate measurement reliability, each patient is scanned twice at baseline
and again at four annual visits, with 80% of the replicate scans performed by
the same sonographer and 20% by a different sonographer; 50% of the replicate
scans are read by the same reader and the other 50% by different readers.
RESULTS: The overall coefficient of reliability (R) was 0.859 for CBM(max),
0.872 for M(max) and 0.794 for T(max). The reliability for CBM(max) was stable
during the 1 3/4-year baseline period (R = 0.848 to 0.953) and was uniform among
the 23 field centres (R = 0.798 to 0.926). Intra- and inter-reader reliability
were 0.915 and 0.872 respectively, and intra-sonographer reliability was 0.866.
CONCLUSION: The results demonstrate that by implementing standardized protocols
and strict quality control procedures, highly reliable ultrasonic measurements
of carotid artery IMT can be achieved in large multi-national trials.

13: J Clin Endocrinol Metab 2000 Feb;85(2):574-84

Hypopituitary females have a high incidence of cardiovascular morbidity and an
increased prevalence of cardiovascular risk factors.

Bulow B, Hagmar L, Eskilsson J, Erfurth EM

Department of Diabetology and Endocrinology, University Hospital, Lund, Sweden.

We recently reported that female patients with hypopituitarism receiving
controlled thyroid and steroid hormone substitution, but without GH replacement,
had a more than 2-fold increase in cardiovascular mortality compared to the
general population. In the present study we investigated the incidence of
cardiovascular disease as well as the prevalence of cardiovascular risk factors
in 33 females with hypopituitarism for 6-46 yr (median, 18) compared to those in
33 control subjects recruited from the general population in the same
geographical area and matched for sex, age, smoking habits, educational level,
and residence location. The patients were with a very high probability GH
deficient, as 29 had subnormal serum insulin-like growth factor I levels, and
the other 4 were GH deficient, as assessed by an insulin tolerance test. The
incidence of cardiovascular disease was significantly higher among the
hypopituitary patients (incidence ratio, 3.7; 95% confidence interval,
1.2-11.3), and the consumption of cardioactive drugs was also significantly
higher (P = 0.002). Hypopituitary patients had a lower degree of physical
exercise during their spare time (P = 0.02), a higher waist/hip ratio (P =
0.01), lower high density lipoprotein cholesterol (P = 0.002), and higher low
density/high density lipoprotein ratio (P = 0.009). Furthermore, the patients
had a significantly increased left atrium size (P = 0.05), but no difference was
observed for other cardiac measures. In the patients, serum insulin-like growth
factor I levels significantly correlated with left ventricular mass index (r =
0.48; P = 0.006), suggesting that GH has a strong impact on cardiac size. More
episodes of bradycardia (P = 0.05), but no increased occurrence of
extrasystolies, were encountered in the patients during 24-h continuous
electrocardiogram monitoring. Carotid artery intima-media thickness and plaque
numbers did not differ between patients and controls. In conclusion,
hypopituitary females exhibit an increased incidence of cardiovascular disease,
higher cardioactive drug consumption, and an increased prevalence of
cardiovascular risk factors. The increased cardiovascular morbidity could not be
ascribed to inadequate estrogen or thyroid hormone treatment, and unsubstituted
GH deficiency is probably an important contributing factor.

14: J Hypertens 2000 Jan;18(1):75-81

Relative influence of insulin resistance versus blood pressure on vascular
changes in longstanding hypertension. ICARUS, a LIFE sub study. Insulin Carotids
US Scandinavia.

Olsen MH, Fossum E, Hjerkinn E, Wachtell K, Hoieggen A, Nesbitt SD, Andersen UB,
Phillips RA, Gaboury CL, Ibsen H, Kjeldsen SE, Julius S

Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital,
University of Copenhagen, Denmark.

BACKGROUND: Insulin resistance is associated with hypertension. The relative
influences of hyperinsulinaemia and high blood pressure on vascular hypertrophy
and carotid distensibility is unclear in patients with longstanding
hypertension. METHODS: In 88 unmedicated patients with stage II-III hypertension
and left ventricular hypertrophy on electrocardiogram we measured blood
pressure, minimal forearm vascular resistance (MFVR) using plethysmography,
intima-media thickness (IMT) and the wall distensibility of the common carotid
arteries using ultrasound, and insulin sensitivity using a 2-h isoglycaemic
hyperinsulinaemic clamp. RESULTS: IMT was positively correlated to systolic
blood pressure (r= 0.26, P < 0.05), whole body glucose uptake index (M/IG; r=
0.22, P< 0.05), age (r= 0.24, P< 0.05) and negatively correlated to body mass
index (r= -0.24, P < 0.05); IMT did not correlate to fasting serum insulin (r=
-0.14, NS). In men (n = 64) MFVR was positively correlated to systolic blood
pressure (r = 0.30, P < 0.05), but was unrelated to M/G and serum insulin. The
distensibility of the common carotid arteries was negatively correlated to
systolic blood pressure (r = -0.40, P< 0.001) and in untreated patients (n = 22)
positively correlated to M/IG (r = 0.47, P < 0.05). CONCLUSIONS: High systolic
blood pressure was related to vascular hypertrophy, whereas hyperinsulinaemia
and insulin resistance were not, suggesting that longstanding high blood
pressure is a far more important determinant for structural vascular changes
than insulin resistance at this stage of the hypertensive disease. However,
hyperinsulinaemia and insulin resistance were associated with low distensibility
of the common carotid arteries in the subgroup of never treated hypertensive
patients.

15: Am J Hypertens 2000 Jan;13(1 Pt 1):111-9

Carotid thickening, cardiac hypertrophy, and angiotensin converting enzyme gene
polymorphism in patients with hypertension.

Jeng JR

Department of Internal Medicine, Tri-Service General Hospital, National Defense
Medical Center, Taipei, Taiwan, Republic of China. jrjeng@ms5.hinet.net

An insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme
(ACE) gene has been associated with increased risk for myocardial infarction,
cardiomyopathy, carotid thickening, and cardiac hypertrophy. However, a
conclusive agreement about the role of ACE genotype in the genetics of
cardiovascular disease has not yet been reached. This study was undertaken to
investigate the relationship of the I/D polymorphism of the ACE gene with
carotid intima-media thickness (IMT) and left ventricular mass (LVM) in 175
Chinese patients with mild-to-moderate hypertension. The I/D genotypes were
detected by the polymerase chain reaction using primers flanking the polymorphic
region in intron 16 of the ACE gene. The IMT was measured in the common carotid
and carotid bifurcation by B-mode ultrasound. The LVM was calculated with M-mode
echocardiographic measures of the left ventricle. Patients with the DD genotype
(n = 41) showed significant greater carotid IMT (1.593 +/- 0.879 v 1.309 +/-
0.703 and 1.171 +/- 0.583 mm, P = .01) but insignificant higher LVM index (123.8
+/- 36.6 v 123.7 +/- 37.4 and 118.2 +/- 33.0 g/m2, P = .61) than did those with
the DI (n = 69) and II (n = 65) genotypes. The deletion polymorphism of the ACE
gene (P = .04) was a significant predictor for carotid IMT on multiple
regression analysis, controlling all the potential confounding factors including
age (P = .001), systolic blood pressure (P = .09), smoking (P = .08), and plasma
tissue plasminogen activator antigen (P = .03), but the LVM correlated only with
age (P = .02), sex (P < .001), and body mass index (P < .001). These results
indicated that the DD genotype of the ACE gene could be considered a risk factor
for the development of early atherosclerosis in carotid arteries but not for
left ventricular hypertrophy in the hypertensive population.

16: J Hum Hypertens 2000 Jan;14(1):23-30

Relationships between cardiovascular remodelling and the pulse pressure in never
treated hypertension.

Baguet JP, Mallion JM, Moreau-Gaudry A, Noirclerc M, Peoc'h M, Siche JP

Department of Cardiology and Internal Medicine, Grenoble University Hospital,
France.

The role of pulse pressure (PP) in cardiovascular remodelling was studied in 61
never treated hypertensive subjects who were selected on the criteria of
ambulatory blood pressure (BP) monitoring (mean BP over 24 h: 147 +/- 14/96 +/-
10 mm Hg). Echocardiography and carotid ultrasonography were performed and the
vascular images analysed using a specific automatic measuring program. Thirty
percent of subjects had left ventricular hypertrophy (LVH). Left ventricular
mass index (LVMI) was related to the clinic (r = 0.35) and ambulatory (r = 0.41
over 24 h, r = 0.38 daytime and r = 0.42 night-time) PP and to the systolic BP.
PP was higher when there was LVH. Vascular thickening was found in 6.6% of
subjects (carotid intima-media thickness (IMT) >/=1.0 mm). Among the BP
parameters, IMT and cross-sectional area (CSA) were related only to the clinic
PP (r = 0.27, r = 0.29 respectively) and to the ambulatory PP (over 24 h: r=
0.29, r = 0.28; daytime: r = 0.22, r = 0.23; night-time: r = 0.32, r = 0.30). In
men, the relationship between CSA and PP (clinic and over 24 h) was independent
of age. A total of 16.7% of subjects with LVH had intima-media thickening in
contrast to 2.3% in the group without LVH. LVMI was related to the CSA (r =
0.37) and to the IMT (r = 0.31). However, after multivariate analysis taking
into account the PP, relationships between IMT or CSA and LVMI disappeared. Our
data showed that the PP was the most important BP parameter in the development
of cardiac and arterial remodelling in hypertension.Journal of Human
Hypertension (2000) 14, 23-30.

17: Diabetes Res Clin Pract 2000 Jan;47(1):25-35

Haemostasis and carotid artery wall thickness in non-insulin dependent diabetes
mellitus.

Metcalf PA, Folsom AR, Davis CE, Wu KK, Heiss G

Collaborative Studies Coordinating Center, University of North Carolina, Chapel
Hill, NC 27514-4145, USA.

The purpose of this study was to examine the associations of carotid artery
intima-media wall thickness (IMT) with hemostatic proteins and cardiovascular
risk factors (CVRFs) in participants with and without non-insulin dependent
diabetes mellitus (NIDDM). IMT measurements were determined by high resolution
B-mode ultrasound imaging of the carotid arteries in 921 participants with NIDDM
and 11,964 non-diabetic participants aged 45-64 years. Fasting glucose, serum
lipids and activated partial thromboplastin time, factor VIII fibrinogen, factor
VII, antithrombin III, protein C, and von Willebrand factor measurements were
made. Compared to non-diabetic participants, participants with NIDDM had a more
adverse pattern of CVRFs and a more procoagulatory profile. Participants with
NIDDM had 0.06 mm (8.1%) higher mean IMT compared to non-diabetic participants
after adjusting for age and gender (P < 0.001). However, only plasma fibrinogen
concentrations showed statistically significant positive associations with IMT
in both groups. After adjusting for CVRFs and fibrinogen, mean IMT remained 0.04
mm (5.4%) higher in diabetic compared to non-diabetic participants. Despite the
more procoagulatory profile in participants with NIDDM, only plasma fibrinogen
concentrations were independently associated with mean IMT. The association of
NIDDM with mean IMT was only partly explained by CVRFs.