Hisashi Adachi

Plasma Aldosterone Levels and Development of Insulin Resistance: Prospective Study in a General Population

Aldosterone plays a role in hypertension, and hypertension is prevalent in patients with insulin resistance. Cross-sectional studies have reported that plasma aldosterone levels are higher in patients with insulin resistance. However, it is not known whether plasma aldosterone levels predict the development of insulin resistance. Subjects of the present study were 1235 local residents (490 men and 745 women) who participated in health screenings in Japan in 1999. Plasma aldosterone levels were measured by radioimmunoassay. We investigated the cross-sectional relationship between plasma aldosterone levels and insulin resistance (homeostasis model assessment index ≥1.73 according to the diagnostic criteria used in Japan) in 1088 nondiabetic participants. At the 10-year follow-up, 141 subjects had died, and 260 subjects refused re-examination. We performed a prospective analysis of 564 subjects to predict incident insulin resistance. We found a significant (P<0.001) cross-sectional relationship between plasma aldosterone and homeostasis model assessment index at baseline. In the prospective analysis, a significantly higher (P<0.05) relative risk (1.71 [95% CI: 1.03–2.84]) was observed in the highest tertile versus lowest tertile of plasma aldosterone for the development of insulin resistance, after adjustment for confounding factors. This 10-year prospective study demonstrated that plasma aldosterone levels predicted the development of insulin resistance in a general population.

LDL-C/HDL-C Ratio Predicts Carotid Intima-Media Thickness Progression Better Than HDL-C or LDL-C Alone

High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are strong predictors of atherosclerosis. Statin-induced changes in the ratio of LDL-C to HDL-C (LDL-C/HDL-C) predicted atherosclerosis progression better than LDL-C or HDL-C alone. However, the best predictor of subclinical atherosclerosis remains unknown. Our objective was to investigate this issue by measuring changes in carotid intima-media thickness (IMT). A total of 1,920 subjects received health examinations in 1999, and were followed up in 2007. Changes in IMT (follow-up IMT/baseline IMT × 100) were measured by ultrasonography. Our results showed that changes in IMT after eight years were significantly related to HDL-C (inversely, P < 0.05) and to LDL-C/HDL-C ratio (P < 0.05). When the LDL-C/HDL-C ratios were divided into quartiles, analysis of covariance showed that increases in the ratio were related to IMT progression (P < 0.05). This prospective study demonstrated the LDL-C/HDL-C ratio is a better predictor of IMT progression than HDL-C or LDL-C alone.

Serum vaspin levels are positively associated with carotid atherosclerosis in a general population

OBJECTIVESnVaspin is a novel adipocytokine with potential insulin-sensitizing properties. Insulin resistance (IR) plays a role in the development and progression of atherosclerosis. However, the relationship between serum vaspin levels and atherosclerosis remains unknown. Therefore, we investigated whether vaspin was correlated with carotid intima-media thickness (c-IMT).nnnMETHODSnData for fasting vaspin levels of 201 subjects (78 men and 123 women aged over 40 years) were obtained from a general population in Japan. We obtained anthropometric parameters and blood chemistries, and calculated homeostasis model assessment-IR (HOMA-IR) index. C-IMT was measured by B-mode ultrasonography. The mean values of each parameter by tertiles of vaspin were compared with analysis of variance, and the associations of vaspin with IR and c-IMT were evaluated by multiple stepwise regression analysis.nnnRESULTSnUnivariate analysis revealed that vaspin levels were positively correlated with BMI, insulin, HOMA-IR index, estimated glomerular filtration rate (eGFR), c-IMT and hypertensive medication. Multiple stepwise regression analysis revealed that HOMA-IR index, c-IMT and eGFR were significantly and independently associated with vaspin. We performed multivariate analyses with c-IMT as the dependent variable. Age, hypertensive medication and vaspin were significant for c-IMT. Moreover, a mediation analysis demonstrated that vaspin was significantly related to c-IMT, independently of IR.nnnCONCLUSIONSnThe present study not only confirmed the previous finding of the positive association of vaspin with IR but also demonstrated that serum vaspin level was positively associated with c-IMT, independently of IR in a general population. Our results may suggest a role of vaspin in atherosclerosis in humans.

Independent association of elevated serum hepatocyte growth factor levels with development of insulin resistance in a 10‐year prospective study

Hepatocyte growth factor (HGF) receptors form a hybrid complex with insulin receptors in the liver of mice, which lead to robust signalling to regulate glucose metabolism. Serum HGF levels are high in subjects with metabolic syndrome and/or obesity. Accordingly, we prospectively investigated the relationship between HGF and the development of insulin resistance (IR) in a general population without IR at baseline.

Serum Hepatocyte Growth Factor and Cancer Mortality in an Apparently Healthy Japanese Population

Background In patients with cancer, hepatocyte growth factor (HGF) is elevated and is a predictor of prognosis. We investigated whether serum HGF was a predictive marker for cancer death in a population of community-dwelling Japanese. Methods We studied 1492 apparently healthy Japanese adults who underwent health examinations in 1999. Those who reported a history of liver disease or malignancy on a baseline questionnaire were excluded, and plasma HGF was measured in the remaining 1470 participants, who were followed periodically for 10 years. Multivariate proportional hazards regression was used to estimate cancer mortality. Results A total of 169 participants died during follow-up (61 from cancer, 32 from cerebrocardiovascular disease, and 76 from other diseases). Mean HGF at baseline was significantly higher among decedents than among survivors (0.26 ± 0.11 vs 0.23 ± 0.09 ng/ml, respectively; P < 0.01). The Cox proportional hazards model showed that age, systolic blood pressure, HGF (hazard ratio, 1.27; 95% CI, 1.06–1.52; P = 0.009), albumin level, smoking status, and creatinine were independent predictors of all-cause death. Age, HGF (hazard ratio, 1.31; 95% CI, 1.04–1.65; P = 0.02), and total cholesterol were independent predictive markers for cancer death. Conclusions Serum HGF was a predictor of cancer death in an apparently healthy population of community-dwelling Japanese.

New computer model for prediction of individual 10-year mortality on the basis of conventional atherosclerotic risk factors

BACKGROUNDnLarge cohort studies have revealed that subjects with atherosclerotic risk factors have high mortality. However, there has been no method to predict individual mortality based on these risk factors. Accordingly, we developed a computer model predicting the 10-year mortality of an individual with atherosclerotic risk factors.nnnMETHODSnWe enrolled two different cohorts in Japan. One was from Tanushimaru-town and the other was from Uku-town. Residents over the age of 40 underwent baseline examinations and were followed-up for ten years. 1851 Subjects in Tanushimaru-town were randomly divided into 1486 training samples and 365 test samples. We applied supervised statistical pattern recognition (SSPR) techniques to develop, using the training samples, a computer model to predict the 10-year mortality of an individual based on 6 conventional risk factors. The test samples were then used to evaluate the predictive accuracy.nnnRESULTSnThere were 49 deaths and 316 survivors in the test samples in Tanushimaru-town. The correctly simulated number of deaths and survival was 36 and 250, respectively. The predictive accuracy of death was 73.5% (36/49) and that of survival was 79.1% (250/316) with c-statistics of 0.827. In order to verify our model, we predicted death and survival for the other test samples (Uku-town, nxa0=xa0170). The predictive accuracy of death was 72.9% (35/48) and that of survival was 76.2% (93/122) with c-statistics of 0.848.nnnCONCLUSIONSnThis is the first computer model to use SSPR methods to estimate individual 10-year mortality based on conventional risk factors with high accuracy.

High Serum N-Acetyl-ß-D-Glucosaminidase Activity Is a Predictor of 28-Year Mortality in a Population of Community-Dwelling Japanese—The Tanushimaru Study

on blood pressure: 11-year longitudinal population study. Br J Psychiatry 2008;193:108–113. 7. Paterniti S, Verdier-Taillefer MH, Geneste C et al. Low blood pressure and risk of depression in the elderly. A prospective community-based study. Br J Psychiatry 2000;176:464–467. 8. Godin O, Elbejjani M, Kaufman JS. Body mass index, blood pressure, and risk of depression in the elderly: A marginal structural model. Am J Epidemiol 2012;176:204–213. 9. Zimmerman JA, Mast BT, Miles T et al. Vascular risk and depression in the Hispanic Established Population for the Epidemiologic Study of the Elderly (EPESE). Int J Geriatr Psychiatry 2009;24:409–416. 10. Licht CM, de Geus EJ, Seldenrijk A et al. Depression is associated with decreased blood pressure, but antidepressant use increases the risk for hypertension. Hypertension 2009;53:631–638.

High Level of Plasma Remnant-like Particle Cholesterol May Predispose to Development of Hypertension in Normotensive Subjects

BACKGROUNDnRemnant-like lipoprotein particle cholesterol (RLP-C) is a highly atherogenic factor. RLP-C induces endothelial dysfunction and is associated with hyperinsulinemia. This study was designed to determine whether high plasma RLP-C levels predispose to the development of hypertension in subjects with normal blood pressure (BP).nnnMETHODSnA total of 1,485 subjects aged >40 years in a Japanese Cohort of the Seven Countries Study received health examinations. We examined BP, anthropometric parameters, and blood chemistries, including fasting RLP-C levels. RLP-C levels were measured by an immune-separation method. We excluded from the analysis 676 subjects who had hypertension (BP ≥ 140/90mm Hg), or were on antihypertensive medication, and/or were on antihyperlipidemic medication at baseline. Ten years later, 681 subjects were re-examined.nnnRESULTSnOf 681 normotensive subjects at baseline, 303 subjects had developed hypertension 10 years later. Baseline RLP-C level was significantly higher (P < 0.01) in the subjects who developed hypertension than in those who remained normotensive (3.7±1.9 vs. 3.3±1.6mg/dl). Multivariable logistic regression analysis demonstrated that baseline RLP-C was a significant factor for incident hypertension after adjustments for homeostasis model assessment index and other hypertension-related factors (odds ratio = 1.05, 95% CI = 1.00-1.10; P = 0.04).nnnCONCLUSIONSnA high level of plasma RLP-C in normotensive subjects may predispose to the development of hypertension in a population of community-dwelling Japanese.