著者

SATO Atsuhisa SARUTA Takao

出版者

日本高血圧学会

雑誌

Hypertension research : clinical and experimental : official journal of the Japanese Society of Hypertension (ISSN:09169636)

巻号頁・発行日

vol.27, no.5, pp.303-310, 2004-05-01

参考文献数

41

被引用文献数

21 71

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<B>In recent years, it has been clarified that aldosterone can directly damage various organs, such as the heart, blood vessel, and kidneys, <I>via</I> non-epithelial mineralocorticoid receptors, independent of changes in blood pressure. Anti-aldosterone drugs have been clinically reported to be useful for their organ-protecting effects. The fact that these effects have been considered important for almost 10 years seems to indicate that aldosterone-induced organ damage can develop as a consequence of plasma aldosterone levels being in disproportion to salt status. In a previous study, cardiac fibrosis could not be induced in an experimental model of hyperaldosteronism with a low-salt diet. It is, therefore, extremely important to understand the relationship between plasma aldosterone level and inappropriate salt balance when considering diseases or states for which an anti-aldosterone drug is called for. In this paper we review the fundamental and clinical studies reported to date, mainly to investigate the pathology of organ damage induced by aldosterone and excess salt. Aldosterone-induced direct organ damage mediated through vasculitis essentially requires salt, which is inappropriate for plasma aldosterone level, and studies performed from this standpoint may provide a clue to the clarification of the involvement of salt in the actions of aldosterone <I>via</I> non-epithelial mineralocorticoid receptors. In humans, it is also strongly suggested that organ damage may occur, even at a plasma aldosterone level within a normal range, if salt intake is imbalanced to the aldosterone level. This means that the new aldosterone blocker eplerenone may also have significance as a drug inhibiting inflammation, possibly serving as a trigger of organ damage. (<I>Hypertens Res</I> 2004; 27: 303-310)</B>

著者

Shuichi TAKAGI Naoharu IWAI Ryoko YAMAUCHI Sunao KOJIMA Shinji YASUNO Takeshi BABA Masahiro TERASHIMA Yoshiaki TSUTSUMI Shoji SUZUKI Isao MORII Sotaro HANAI Koh ONO Shunroku BABA Hitonobu TOMOIKE Atsushi KAWAMURA Shunichi MIYAZAKI Hiroshi NONOGI Yoichi GOTO

出版者

日本高血圧学会

雑誌

Hypertension Research (ISSN:09169636)

巻号頁・発行日

vol.25, no.5, pp.677-681, 2002 (Released:2003-04-26)

参考文献数

28

被引用文献数

49 113

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In epidemiological studies, moderate alcohol consumption has been consistently associated with a reduced risk of myocardial infarction (MI). About half of Japanese show an extremely high sensitivity to alcohol (ethanol), which is due to a missense mutation from glutamic acid (Glu) to lysine (Lys) at codon 487 in an isoenzyme of aldehyde dehydrogenase (ALDH2) with a low Km. We obtained a preliminary result that subjects homozygous for the Lys 487 allele had higher risk for myocardial infarction. The purpose of the present study was to assess this hypothesis by employing a larger cohort of subjects with MI. The experimental group consisted of 342 male subjects with demonstrated MI who were selected randomly from our outpatient clinic. As controls, we employed 1, 820 male subjects with no cardiovascular complications who were selected from the Suita Study. All subjects provided their written informed consent to participate in the genetic analyses. Subjects with MI were older and had higher body mass index, higher prevalence of diabetes mellitus, higher prevalence of smoking habit, higher prevalence of the Lys/Lys genotype (homozygous for Lys 487 allele), and lower high density lipoprotein (HDL) cholesterol level (HDL-C). The ALDH2 genotype affected the level of alcohol consumption, and HDL-C. Multiple logistic analyses indicated that the odds ratio of the Lys/Lys genotype to the Lys/Glu+Glu/Glu genotype was 1.56 (p =0.0359). Inclusion of HDL-C as one of the independent variables downplayed the importance of the ALDH2 genotype. This may indicate that the ALDH2 genotype affects MI via its effects on HDL-C. In conclusion, the ALDH2 Lys/Lys genotype is a risk factor for myocardial infarction in Japanese men due to its influence on HDL cholesterol level. (Hypertens Res 2002; 25: 677-681)

著者

Kunitoshi ISEKI Saori OSHIRO Masahiko TOZAWA Yoshiharu IKEMIYA Koshiro FUKIYAMA Shuichi TAKISHITA

出版者

日本高血圧学会

雑誌

Hypertension Research (ISSN:09169636)

巻号頁・発行日

vol.25, no.2, pp.185-190, 2002 (Released:2002-09-13)

参考文献数

29

被引用文献数

13 22

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The incidence of end-stage renal disease due to diabetes mellitus (DM) is increasing. There have been too few epidemiological studies of the predictors of DM nephropathy, particularly type 2 DM, among a statistically significant population. We studied the prevalence and correlates of DM in a screened cohort in Okinawa, Japan. A total of 9, 914 screenees (6, 163 men and 3, 751 women) over 18 years of age underwent a 1-day health check at the Okinawa General Health Maintenance Association between April 1997 and March 1998. Subjects were considered to have DM if they showed a fasting plasma glucose ≥126 mg⁄dl and hemoglobin A1c ≥7.0%, or if they were receiving treatment for DM. Non-DM subjects were followed-up until March 2000 to see whether or not they developed DM. Relative risk for developing DM was evaluated by Cox proportional hazard analysis after adjusting for confounding variables. A total of 673 screenees (520 men and 153 women) were diagnosed with DM. The prevalence of DM was 67.9 per 1, 000 screenees (84.4 for men and 40.8 for women). A total of 7, 125 non-DM screenees were examined a second time. Among them, 164 screenees (130 men and 34 women) had developed DM during the follow-up period. Over 2 years, the cumulative incidence of DM was 2.3% (2.9% in men and 1.3% in women). The adjusted relative risk (95% confidence interval) for developing DM was highest for proteinuria, or 1.90 (1.14-3.17). The results indicated that the prevalence and incidence of DM were high among this screened cohort in Okinawa, Japan. Subjects with proteinuria may thus be at high risk for developing DM. (Hypertens Res 2002; 25: 185-190)

著者

Yoshiki YUI Tetsuya SUMIYOSHI Kazuhisa KODAMA Atsushi HIRAYAMA Hiroshi NONOGI Katsuo KANMATSUSE Hideki ORIGASA Osamu IIMURA Masao ISHII Takao SARUTA Kikuo ARAKAWA Saichi HOSODA Chuichi KAWAI JMIC-B Study Group

出版者

日本高血圧学会

雑誌

Hypertension Research (ISSN:09169636)

巻号頁・発行日

vol.27, no.7, pp.449-456, 2004 (Released:2004-08-07)

参考文献数

19

被引用文献数

21 27

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We stratified findings from the Japan Multicenter Investigation for Cardiovascular Diseases-B according to whether or not the patients had diabetes and compared the incidence of cardiac events occurring over a 3-year period between treatment with nifedipine retard and angiotensin converting enzyme (ACE) inhibitor. The primary endpoint was the overall incidence of cardiac events (cardiac death or sudden death, myocardial infarction, hospitalization for angina pectoris or heart failure, serious arrhythmia, and coronary interventions), and the secondary endpoints were a composite of other events (cerebrovascular accidents, worsening of renal dysfunction, non-cardiovascular events, and total mortality). The results showed no significant difference in the incidence of the primary endpoint between the nifedipine group (n =199) and the ACE inhibitor group (n =173) in diabetic patients: 15.08% vs. 15.03%, relative risk 1.06, p =0.838. Also in nondiabetic patients, no significant difference was observed between the former (n =629) and the latter (n =649): 13.67% vs. 12.33%, relative risk 1.04, p =0.792. Similar results were obtained for the incidence of the secondary endpoints: in diabetic patients, 5.03% vs. 5.20%, relative risk 0.89, p =0.799; in nondiabetic patients, 2.70% vs. 2.47%, relative risk 1.07, p =0.842. Achieved blood pressure levels were 138/76 and 136/77 mmHg in the nifedipine group and 140/78 and 138/79 mmHg in the ACE inhibitor group in diabetic and nondiabetic patients, respectively. This study showed that nifedipine retard was as effective as ACE inhibitors in reducing the incidence of cardiac events in extremely high-risk hypertensive patients with complications of diabetes and coronary artery disease. (Hypertens Res 2004; 27: 449-456)

著者

Yoshiki YUI Tetsuya SUMIYOSHI Kazuhisa KODAMA Atsushi HIRAYAMA Hiroshi NONOGI Katsuo KANMATSUSE Hideki ORIGASA Osamu IIMURA Masao ISHII Takao SARUTA Kikuo ARAKAWA Saichi HOSODA Chuichi KAWAI JMIC-B Study Group

出版者

日本高血圧学会

雑誌

Hypertension Research (ISSN:09169636)

巻号頁・発行日

vol.27, no.3, pp.181-191, 2004 (Released:2004-10-19)

参考文献数

29

被引用文献数

70 103

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The Japan Multicenter Investigation for Cardiovascular Diseases-B was performed to investigate whether nifedipine retard treatment was associated with a significantly higher incidence of cardiac events than angiotensin converting enzyme inhibitor treatment in Japanese patients. The study used a prospective, randomized, open, blinded endpoint (PROBE) design. Patients were enrolled at 354 Japanese hospitals specializing in cardiovascular disease. The subjects were 1,650 outpatients aged under 75 years who had diagnoses of both hypertension and coronary artery disease. There were 828 patients subjected to intention-to-treat analysis in the nifedipine retard group and 822 patients in the angiotensin converting enzyme inhibitor group. The patients were randomized to 3 years of treatment with either nifedipine retard or angiotensin converting enzyme inhibitor. The primary endpoint was the overall incidence of cardiac events (cardiac death or sudden death, myocardial infarction, hospitalization for angina pectoris or heart failure, serious arrhythmia, and coronary interventions). The primary endpoint occurred in 116 patients (14.0%) from the nifedipine retard group and 106 patients (12.9%) from the angiotensin converting enzyme inhibitor group (relative risk, 1.05; 95% confidence interval, 0.81-1.37; p =0.75). In the Kaplan-Meier estimates, there were no significant differences between the two groups (log-rank test: p =0.86). The incidence of cardiac events and mortality did not differ between the nifedipine retard and angiotensin converting enzyme inhibitor therapies. Nifedipine retard seems to be as effective as angiotensin converting enzyme inhibitors in reducing the incidence of cardiac events and mortality. (Hypertens Res 2004; 27: 181-191)