© 1996 American Heart Association, Inc.
Articles |
Characteristics of the Insulin Resistance Syndrome in a Japanese Population
The Jichi Medical School Cohort Study
From the Department of Internal Medicine, Awaji-Hokudan Public Clinic (K. Kario) and Hyogo Prefectural Awaji Hospital (K. Kario, T. Matsuo), Hyogo, Japan; Department of Community and Family Medicine (N.N., K. Kayaba) and Department of Cardiology (T.K., K.S.), Jichi Medical School, Tochigi, Japan; Department of Internal Medicine, Sakuma Hospital (T.S.), Shizuoka, Japan; Department of Internal Medicine, Takasu National Health Insurance Clinic (H.M.), Gifu, Japan; Department of Internal Medicine, Wara National Health Insurance Hospital (T.G.), Gifu, Japan; Department of Internal Medicine, Akaike Hospital (A.T., S.I.), Fukuoka, Japan; and Department of Internal Medicine, Reihoku Central Hospital (T. Miyamoto), Kohchi, Japan.
Correspondence to Dr Kazuomi Kario, 480 Ikuha, Hokudan, Tsuna, Hyogo, 656-16, Japan.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion Appendix References |
|---|
Abstract We investigated the relationships between hyperinsulinemia (a major indicator of the insulin resistance syndrome), blood pressure, dyslipidemia, and coagulation factors in 2606 community-dwelling Japanese individuals as part of the Jichi Medical School Cohort Study. An age-related decrease of the fasting insulin level was found in men but not in women. Body mass index, systolic and diastolic blood pressure, triglyceride and fasting glucose levels, and factor VII activity all increased in both sexes as the insulin level became higher, while the HDL cholesterol level decreased. In addition, total cholesterol and LDL cholesterol levels increased as the insulin level became higher and lipoprotein(a) levels decreased in the men. Fibrinogen levels were not related to the insulin level in either sex. Multiple logistic regression analysis revealed that fasting insulin levels were positively correlated with body mass index and fasting glucose and factor VII activity levels, whereas they were negatively correlated with HDL cholesterol in both sexes. In addition, fasting insulin levels were positively correlated with LDL cholesterol levels in men and with triglyceride levels in women. Our results indicate that hyperinsulinemia is associated with high factor VII activity in a general Japanese population as well as with high blood pressure and dyslipidemia. The accumulation of these cardiovascular risk factors in hyperinsulinemic subjects appears to contribute to cardiovascular events in the Japanese as well as in westerners.
Key Words: insulin resistance syndrome • Japanese • factor VII • dyslipidemia • blood pressure
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion Appendix References |
|---|
Recently, hyperinsulinemia has come to be considered an independent risk factor for cardiovascular disease,1 2 3 4 although it remains uncertain whether the cardiovascular disease is caused by confounding factors or by acceleration of atherosclerosis due to hyperinsulinemia itself. Hyperinsulinemia is often associated with hypertension, increased triglyceride levels, decreased HDL cholesterol levels, and increased levels of fibrinogen and tissue plasminogen activator inhibitor-1,5 6 7 8 9 10 11 and it precedes the development of these cardiovascular risk factors.12 The clustering of these cardiovascular risk factors on the basis of underlying insulin resistance has been proposed to constitute the "insulin resistance syndrome."5
Factor VII, a vitamin K–dependent glycoprotein, plays an important role in initiation of the tissue factor–induced coagulation pathway. An increase in factor VII activity has been proposed to be an independent risk factor for coronary artery disease.13 14 15 We recently found a close relationship between plasma factor VII levels and cardiovascular disease in elderly Japanese individuals.16 17 18 19 However, the relationship between the insulin level or insulin resistance and factor VII has not been investigated thoroughly.
Another interesting point is that the association between insulin levels and blood pressure apparently shows racial differences.20 The Japanese have a higher salt intake than western populations, and insulin promotes sodium retention,21 but the Japanese also have a lower fat intake. Thus, the relationships between insulin level, blood pressure, lipid levels, and coagulation factors may be different in Japanese and western populations. However, there have been few population-based studies on the linkage of hyperinsulinemia with cardiovascular disease risk factors in Japan, despite the many studies performed in western countries.1 2 3 4 5 6 7 8 9 10 11 12 Accordingly, we investigated the relationships between fasting insulin level, blood pressure, lipid levels, and coagulation factors in a Japanese population.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion Appendix References |
|---|
Subjects
We studied 2606 Japanese individuals (1124 men and 1482 women) aged 30 to 90 years who were participants in the Jichi Medical School (JMS) Cohort Study performed from April 1992 to November 1993. The JMS Cohort Study aims to investigate the risk factors for cardiovascular disease in Japan. Entry began in 1992, and ultimately nearly 10 000 Japanese from 12 rural communities located around Japan will have participated in the study.22 23 The subjects of the present study consisted of the residents in 5 rural communities (Wara, Takasu, Sakuma, Ohkawa, and Ainoshima) where fasting insulin levels were measured. This study was carried out with the cooperation of the local government in each community, and letters were sent to all potential subjects inviting them to participate on a voluntary basis. As a result, 1124 men and 1482 women
30 years old were enrolled in the
present study. The overall response rate for all eligible
individuals was about 61% (77% for Wara, 58% for Takasu, 46% for
Sakuma, 46% for Ohkawa, and 50% for Ainoshima). Of the 2606 subjects,
96 men and 83 women with fasting blood glucose level 115 mg/dL were
excluded from the present study. Blood pressure was measured in the sitting position with an automated sphygmomanometer (BP203RV-II, Nippon Colin Co, Ltd) after subjects had rested for 5 minutes. Body mass index (BMI) was calculated as weight (kg)/height2 (m2).
Blood Collection
Blood samples were obtained before noon
after an overnight fast.
Blood samples were drawn from the antecubital vein of the seated
subject with minimal tourniquet use. Specimens for the assay of
coagulation factors (factor VII activity and fibrinogen) were collected
into disposable siliconized vacuum glass tubes containing a 1/10 volume
of 3.8% trisodium citrate by the two-syringe method. The specimens
for glucose and lipid determinations were collected into tubes
containing sodium fluoride and plain tubes, respectively.
Samples were centrifuged at 3000g for 15 minutes at
room temperature. After separation, the serum samples for lipids were
stored at 4°C in refrigerated containers if analysis was to
be performed within a few days; otherwise, the samples for insulin were
frozen until analysis. Plasma samples were stored in
refrigerated containers with dry ice for a maximum of 6 hours, then
frozen as rapidly as possible to -80°C for storage until
laboratory determinations were performed.
Assay Procedures
Serum insulin levels were determined by use
of a
radioimmunoassay kit (Dainabot; interassay coefficient of variation
[CV], 4.5%). The lower detection limit was 2.5 µU/mL, and
insulin
levels below this limit were taken as 2.0 µU/mL. Factor VII activity
was measured by a chromogenic assay with human placental
calcified thromboplastin reagent (Chromoquick; Behringwerke), human
factor VII–deficient plasma (Behringwerke), and a
chromogenic assay autoanalyzer (Behring
Chromotimer; interassay CV, 3.8%).24 Fibrinogen levels
were determined with a one-stage clotting assay kit, Data-Fi (Dade;
interassay CV, 2.5%). Serum total cholesterol and
triglyceride levels were determined by use of enzyme assay
kits (Wako; interassay CV, 0.65% for total cholesterol and
0.76% for triglycerides). Serum HDL
cholesterol was determined by an enzymatic procedure after
precipitation with phosphotungstic acid (Wako; interassay CV, 1.3%).
Plasma glucose was determined with a commercial enzyme assay kit (Kanto
Chemistry; interassay CV, 0.45%). Lipoprotein(a) levels were measured
with an enzyme-linked immunosorbent assay kit (Biopool; interassay
CV, 3.5%). The minimum detectable lipoprotein(a) level was 1 mg/dL and
undetectable lipoprotein(a) values were recorded as 0.5 mg/dL.
Serum levels of insulin, total cholesterol, triglycerides, and HDL cholesterol and plasma levels of glucose and fibrinogen were determined at the central laboratory of Special Reference Laboratory (Tokyo, Japan). Plasma factor VII activity levels were assayed by a single laboratory specialist at the central laboratory of Hyogo Prefectural Awaji Hospital (Sumoto, Japan). Factor VII activity was not measured in the Sakuma population. LDL cholesterol was calculated according to the Friedewald equation.25
Statistical Analysis
Statistical analysis was performed by
use of SAS
statistical software (edition 6.08; SAS Institute). The distributions
of fasting insulin, triglycerides, and lipoprotein(a)
levels were highly skewed; these data were transformed into natural
logarithms for parametric analysis. Results are
expressed as the arithmetic (or geometric) mean (95% confidence
interval).
First, we analyzed the effects of advancing age, sex, and
BMI
on fasting insulin level (Tables 1 and
2). The unpaired Student's t test was used
for comparison of mean insulin values between men and women in each
subgroup with the same range of age. To assess age-dependent
changes of the fasting insulin level in each sex, the Scheffé's
F test was used after ANOVA, and each age subgroup was compared with
the group aged <40 years. To study the effect on the insulin level of
BMI in addition to age, Scheffé's F test was used after ANOVA
for comparison of the mean insulin values in each age subgroup, and
each quartile was compared with the lowest quartile (quartile 1) (Table
2
).
|
To study the univariate relations between insulin levels and other cardiovascular risk factors, we divided subjects into three subgroups by insulin tertiles (Tables 3 and 4). The tertile classification was used because the insulin levels of 33% (335 of 1028) of the men were <2.5 µU/mL; thus, we treated those with insulin levels below the detection limit as one group. After ANOVA, tertiles 2 and 3 were compared with the lowest tertile (tertile 1) by Scheffé's F test. For the multivariate analysis, an unconditional multiple logistic model was also used to assess the effect of each variable on the fasting insulin level (Tables 5 and 6). In this analysis, variables (LDL cholesterol and lipoprotein[a] level in women) that did not have a significant relation with insulin levels as assessed by univariate analysis were excluded.
A probability of less than.05 was taken to indicate statistical significance.
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion Appendix References |
|---|
The histograms of the fasting insulin levels in Japanese men and women are shown in the Figure
. Highly skewed
distributions to the left were obtained in both sexes.
|
The effect of sex and age on the fasting insulin level is shown in
Table 1. Fasting insulin levels tended to decrease slightly
with
advancing age in the men, and a significant difference was observed
between the insulin level in the group aged <40 years and that in the
group aged 60 to 69 years. However, this age-related pattern of
change was absent in the women. The fasting insulin level was
significantly higher in women aged 50 years than in men aged 50
years, whereas there was no significant sex-related difference
in those <50 years old.
|
Table 2
shows the effect of BMI on the fasting insulin level
in each
age group of men and women. In all age groups of both sexes, BMI was
positively related to the fasting insulin level.
Tables 3 and 4 show the cardiovascular risk
factors in
three equal subgroups (tertiles) of each sex defined according to the
fasting insulin level. In both sexes, BMI, systolic and
diastolic blood pressure, and the levels of
triglycerides, fasting glucose, and factor VII activity
increased along with insulin level, while HDL cholesterol
decreased. In men, the total cholesterol and LDL
cholesterol levels increased as the insulin level increased
(Table 3), but the differences between subgroups were not
significant
for women (Table 4). The lipoprotein(a) level decreased
significantly
in men as the insulin level increased. Fibrinogen levels did not change
significantly between subgroups in either sex.
|
|
Table 5 shows the results of multiple logistic regression
analysis of the relations between the fasting insulin level and
the risk factors with significant associations listed in Tables
3 and 4. The fasting insulin level was
positively correlated with BMI,
fasting glucose level, and factor VII activity, whereas it was
negatively correlated with HDL cholesterol in both sexes.
The fasting insulin level was positively correlated with the LDL
cholesterol level in men and with the
triglyceride level in women. We also performed the same
analysis in subgroups (819 men and 1017 women) after excluding
subjects who were taking antihypertensive medication, and we obtained
similar results (Table 6).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion Appendix References |
|---|
The present study was performed on a large Japanese community-dwelling population with a high response rate of eligible residents. Thus, it allows us to assess the characteristics of insulin resistance syndrome in a general Japanese population. There are conflicting lines of evidence as to the relative importance of fasting insulin level and of the 2-hour post–glucose load insulin level as a risk factor for coronary artery disease. In both the Helsinki Policemen Study1 and the Paris Prospective Study,4 both fasting and 2-hour post–glucose load insulin levels were demonstrated to be related to coronary artery disease. However, under multivariate analysis, only 2-hour post–glucose load insulin level remained of predictive value in the former study, whereas in the latter study, fasting insulin level remained an independent risk factor. In the present study, fasting insulin level was used as an indicator of insulin resistance syndrome.
The new and most interesting finding of the present study is that
hyperinsulinemia is associated with an increase of
factor VII activity in both sexes in a Japanese population (Tables
2 and 3). Factor VII activity is known to be
positively correlated with
advancing age and BMI in the Japanese as well as in
whites.15 16 17 18 Factor VII
is also well known to have a
positive correlation with serum lipids (total cholesterol
and triglyceride levels) in various
races.15 16 17 18 Thus, we
analyzed the relation of the
fasting insulin level with various parameters by use of
multiple logistic regression analysis and found that the
association between fasting insulin and factor VII activity was
independent of age, BMI, serum lipids, and sex (Tables 5 and
6). These
findings suggest that an increase of factor VII activity may be another
important characteristic of the insulin resistance syndrome. As an
increased factor VII activity level is considered to predispose to
coronary artery disease, this association may contribute to an
increase of cardiovascular disease in insulin
resistance syndrome.
The direct effect of insulin on factor VII activation and metabolism has not been determined. However, free fatty acids are thought to be a source of factor XII activation in vivo, and factor VII can be subsequently activated by activated factor XII.26 27 28 Free fatty acid levels and hepatic lipase activity are elevated in subjects with insulin resistance.29 30 Thus, factor VII activation mediated via the activation of factor XII by free fatty acids may explain the relationship between factor VII activity, the fasting insulin level, and insulin resistance. Another possibility is that hyperinsulinemia might increase hepatic factor VII synthesis. Previous reports have shown that fibrinogen levels are positively correlated with fasting insulin levels,7 10 although other studies did not confirm this in whites.11 31 The present study showed that fibrinogen levels were not related to hyperinsulinemia in a Japanese population.
The present study also showed that
hyperinsulinemia was associated with higher
systolic and diastolic blood pressures without any
sex-related difference in a Japanese population (Tables 3 and
4).
However, this relationship was not independent of other risk factors in
multiple logistic regression analysis (Table 5), and the result
was the same when the subjects on antihypertensive therapy were
excluded (Table 6). A meta-analysis of recent studies has
shown a positive relationship between fasting insulin levels and both
systolic and diastolic blood pressure in western
populations,6 but racial differences in this relationship
have been pointed out.20 A recent study32
also showed that hyperinsulinemia is related to
hypertension in a general Japanese population. In a Chinese population,
there was a positive correlation between the fasting insulin level and
the systolic and diastolic blood pressure in both
sexes,33 whereas multivariate
analysis disclosed that the fasting insulin level was
correlated with systolic pressure independently of age and BMI
only in men. Thus, hyperinsulinemia is related to
hypertension in Asian populations (Japanese and Chinese) as well as
white populations, but some confounding factors might be involved in
this association.
A large population-based analysis of the relationship
between hyperinsulinemia and
dyslipidemia has not previously been reported for the
Japanese. The relationship of fasting insulin levels with
dyslipidemia showed sex-based differences in our
Japanese population (Tables 3 through
6). In both sexes,
triglyceride levels increased and HDL
cholesterol levels decreased as the insulin level became
higher (Tables 3 and 4). However, total
cholesterol and LDL
cholesterol levels were increased only in men with higher
insulin levels compared with those with lower insulin levels (Tables
3 and 4). Multiple logistic regression analysis
revealed that the
fasting insulin level had a positive correlation with LDL
cholesterol in men and with triglycerides in
women independent of other risk factors and a negative correlation with
the HDL cholesterol level in both sexes (Tables 5 and
6).
In a study of western nondiabetic individuals, the fasting insulin
level was positively correlated with triglyceride values
and negatively correlated with HDL cholesterol in both
sexes, but it was positively correlated with total
cholesterol only in men.8 Thus, the
sex-based differences in the relationship between
hyperinsulinemia and dyslipidemia
appear to be similar in westerners and Japanese, and a low HDL
cholesterol level is the most important characteristic of
this syndrome common to both sexes.
The Helsinki Policemen Study1 indicated that only the
highest quintile of fasting insulin level is predictive of increased
coronary artery disease incidence, whereas another study (the
Paris Prospective Study4 ) observed a broader association
of fasting insulin level with subsequent coronary artery
disease across quintiles. In contrast, no threshold of insulin level
was demonstrated in the relationships between insulin levels and other
cardiovascular risk factors in Japanese of either sex
in the present study (Tables 3 and 4).
Finally, an unexpected negative correlation was found between insulin
levels and lipoprotein(a) levels in men (Table 3). Sex hormones
may
lead to sex-based differences in the association between fasting
insulin and lipid levels, but the precise mechanism involved remains
unknown. Women with hyperinsulinemia who do not
have a high total cholesterol level may account for the
clinical evidence from a prospective study2 that
hyperinsulinemia was not associated with an
increase of cardiovascular events or death from
cardiovascular disease in females.
In conclusion, hyperinsulinemia is associated with high factor VII activity in a general Japanese population, as well as with high blood pressure and dyslipidemia. The accumulation of these cardiovascular risk factors in hyperinsulinemic subjects appears to contribute to cardiovascular events in the Japanese as well as in westerners.
|
Acknowledgments |
|---|
This study was supported by a grant-in-aid from the Foundation for the Development of the Community, Tochigi, Japan.
|
Appendix |
|---|
|
TopAbstractIntroductionMethods Results Discussion Appendix References |
|---|
The JMS Cohort Study Group included the following individuals: Kazunori Kayaba, Masahiro Igarashi, Hiroshi Yanagawa, Atsuhiko Tsukuda, Kazuyuki Shimada, Tadashi Kawai, Takashi Natsume, Ketsumi Iijima, Masaki Nagai, Yoshihisa Itoh, Naoki Nago, Yuri Shiraishi, Ryuichi Kawamoto, Yasuyuki Fujita, Kiyomi Sakata, Kouichi Nakamura, Toshio Kuroda, Yoshihiro Shibano, Hitoshi Matsuo, Tadao Goto, Takashi Yamada, Takeshi Miyamoto, Tatsujiro Gondaira, Tomohiro Saegusa, Jun Hiraoka, Akizumi Tsutsumi, Kazuomi Kario, Mitsukazu Terada, and Sizukiyo Ishikawa.
Received June 12, 1995; accepted November 30, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion Appendix References |
|---|
- Pyörälä K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland. Diabetes Care. 1979;2:131-141. [Abstract]
- Welborn TA, Wearne K. Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations. Diabetes Care. 1979;2:154-160. [Abstract]
- Ducimetiere P, Eschwege E, Papoz L, Richard JL, Claude JR, Rosselin G. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia. 1980;19:205-210. [Medline] [Order article via Infotrieve]
- Fontbonne A, Charles MA, Thibult N, Richard JL, Claude JR, Warnet JM, Rosselin GE, Eschwege E. Hyperinsulinaemia as a predictor of coronary heart disease mortality in healthy population: the Paris Prospective Study—15-year follow-up. Diabetologia. 1991;34:356-361. [Medline] [Order article via Infotrieve]
- Reaven GM. Role of insulin resistance in human disease. Diabetes. 1988;37:1595-1607. [Abstract]
- Denker PS, Pollock VE. Fasting serum insulin levels in essential hypertension: a meta-analysis. Arch Intern Med. 1992;152:1649-1651. [Abstract]
-
Winocour PH, Kaluvya S, Brown L, Farrer M, Millar JP,
Neil HAW, Alberti KGMM. The association of different measures of
insulinaemia with vascular risk factors in healthy normoglycaemic
normotensive non-obese men and women. Q J Med. 1991;79:539-560.
[Abstract/Free Full Text] -
Winocour PH, Kaluvya S, Ramaiya K, Brown L, Millar JP,
Farrer M, Neil HAW, Laker MF, Alberti KGMM. Relation between
insulinemia, body mass index, and lipoprotein composition in healthy,
nondiabetic men and women. Arterioscler
Thromb. 1992;12:393-402.
[Abstract/Free Full Text] - Juhan-Vague I, Alessi MC, Vague P. Increased plasma plasminogen activator inhibitor 1 levels: a positive link between insulin-resistance and atherosclerosis. Diabetologia. 1991;34:457-462. [Medline] [Order article via Infotrieve]
- Juhan-Vague I, Vague P. Hyperinsulinemia and its effects of coagulation and fibrinolysis in cardiovascular disease. In: Francis RB, ed. Atherosclerotic Cardiovascular Disease, Hemostasis, and Endothelial Function. New York, NY: Marcel Dekker Inc; 1992:141-182.
- Negri M, Sheiban I, Arigliano PL, Tonni S, Montresor G, Carlini S, Manzato F. Interregulation between angiographic severity of coronary artery disease and plasma levels of insulin, C-peptide and plasminogen activator inhibitor-1. Am J Cardiol. 1993;72:397-401. [Medline] [Order article via Infotrieve]
- Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes. 1992;41:715-722. [Abstract]
- Meade TW. The epidemiology of atheroma, thrombosis and ischaemic heart disease. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD, eds. Haemostasis and Thrombosis. London, England: Churchill Livingstone Inc; 1994:1199-1227.
- Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WRS, Haines AP, Stirling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet. 1986;2:533-537. [Medline] [Order article via Infotrieve]
- Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet. 1993;342:1076-1079. [Medline] [Order article via Infotrieve]
- Kario K, Matsuo T, Nakao K. Factor VII hyperactivity in the elderly. Thromb Haemost. 1991;65:25-27. [Medline] [Order article via Infotrieve]
- Kario K, Matsuo T. Coronary artery disease and factor VII hyperactivity in elderly Japanese. Am J Cardiol. 1992;69:807-809. [Medline] [Order article via Infotrieve]
-
Kario K, Miyata T, Sakata T, Matsuo T, Kato H.
Fluorogenic assay of activated factor VII: plasma factor VIIa
levels in relation to arterial
cardiovascular diseases in Japanese.
Arterioscler Thromb. 1994;14:265-274.
[Abstract/Free Full Text] - Kario K, Matsuo T, Sakata T, Miyata T. Factor VII hyperactivity and ischaemic heart disease. Lancet. 1994;343:233.
- Saad MF, Lillioja S, Nyomba BL, Castillo C, Ferraro R, De Gregorio M, Ravussin E, Knowler WC, Bennett PH, Howard BV, Bogardus C. Racial differences in the relation between blood pressure and insulin resistance. N Engl J Med. 1991;324:733-739. [Abstract]
- DeFronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ. The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in men. J Clin Invest. 1975;55:845-855.
- Kario K, Matsuo T, Imiya M, Kayaba K, Kuroda T, Nago N, Matsuo H, Shimada K. Close relation between lipoprotein (a) levels and atherothrombotic disease in Japanese subjects >75 years of age. Am J Cardiol. 1994;73:1187-1190. [Medline] [Order article via Infotrieve]
-
Nago N, Kayaba K, Hiraoka J, Matsuo H, Goto T, Kario K,
Tsutsumi A, Nakamura Y, Igarashi M. Lipoprotein (a) levels in
the Japanese population: influence of age and sex, and relation to
atherosclerotic risk factors—the Jichi Medical School Cohort
Study. Am J Epidemiol. 1995;141:815-821.
[Abstract/Free Full Text] - Kario K, Matsuo T, Asada R, Sakata T, Kato H, Miyata T. The strongest correlation between factor VII clotting activity using bovine thromboplastin and the activated factor VII. Thromb Haemost. 1995;73:429-434. [Medline] [Order article via Infotrieve]
- Friedewald WT, Levy R, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502. [Abstract]
- Mitropoulos KA, Miller GJ, Watts GF, Durrington PN. Lipolysis of triglyceride-rich lipoproteins activates coagulant factor XII: a study in familial lipoprotein-lipase deficiency. Atherosclerosis. 1992;95:119-125. [Medline] [Order article via Infotrieve]
- Mitropoulos KA, Esnouf MP. The autoactivation of factor XII in the presence of long-chain saturated fatty acids: a comparison with the potency of sulphatides and dextran sulphate. Thromb Haemost. 1991;66:446-452. [Medline] [Order article via Infotrieve]
- Mitropoulos KA, Martin JC, Burgess AI, Esnouf MP, Stirling Y, Howarth DJ, Reeves BEA. The increased rate of activation of factor XII in late pregnancy can contribute to the increased reactivity of factor VII. Thromb Haemost. 1990;63:349-355. [Medline] [Order article via Infotrieve]
- Reaven GM, Hollenbeck C, Jeng C-Y, Wu MS, Chen Y-DI. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM. Diabetes. 1988;37:1020-1024. [Abstract]
- Kasim S, Tseng K, Jen K-LC, Khilnani S. Significance of hepatic triglyceride lipase activity in the regulation of serum high density lipoproteins in type II diabetes mellitus. J Clin Endocrinol Metab. 1987;65:183-187. [Abstract]
- Landin K, Stigendal L, Eriksson E, Krotkiewski M, Risberg B, Tengborn L, Smith U. Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator-1. Metabolism. 1990;39:1044-1048. [Medline] [Order article via Infotrieve]
- Ohmori S, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, Nomiyama K, Yoshitake T, Ueda K, Fujishima M. Hyperinsulinemia and blood pressure in a general Japanese population: the Hisayama Study. J Hypertens. 1994;12:1191-1197. [Medline] [Order article via Infotrieve]
- Woo J, Cockram CS, Lau E, Chan A, Swaminathan R. Association between insulin and blood pressure in a community population with normal glucose tolerance. J Hum Hypertens. 1992;6:343-347.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  S. Yamada, T. Gotoh, Y. Nakashima, K. Kayaba, S. Ishikawa, N. Nago, Y. Nakamura, Y. Itoh, and E. Kajii Distribution of Serum C-Reactive Protein and Its Association with Atherosclerotic Risk Factors in a Japanese Population : Jichi Medical School Cohort Study Am. J. Epidemiol., June 15, 2001; 153(12): 1183 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Tsutsumi, K Kayaba, K Tsutsumi, and M Igarashi Association between job strain and prevalence of hypertension: a cross sectional analysis in a Japanese working population with a wide range of occupations: the Jichi Medical School cohort study Occup. Environ. Med., June 1, 2001; 58(6): 367 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Sakkinen, P. Wahl, M. Cushman, M. R. Lewis, and R. P. Tracy Clustering of Procoagulation, Inflammation, and Fibrinolysis Variables with Metabolic Factors in Insulin Resistance Syndrome Am. J. Epidemiol., November 15, 2000; 152(10): 897 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pyorala, H. Miettinen, P. Halonen, M. Laakso, and K. Pyorala Insulin Resistance Syndrome Predicts the Risk of Coronary Heart Disease and Stroke in Healthy Middle-Aged Men : The 22-Year Follow-Up Results of the Helsinki Policemen Study Arterioscler. Thromb. Vasc. Biol., February 1, 2000; 20(2): 538 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kario, T. Matsuo, H. Kobayashi, R. Asada, and M. Matsuo `Silent' Cerebral Infarction Is Associated With Hypercoagulability, Endothelial Cell Damage, and High Lp(a) Levels in Elderly Japanese Arterioscler. Thromb. Vasc. Biol., June 1, 1996; 16(6): 734 - 741. [Abstract] [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||