Yasuki Nanjo

Higher heart rate may predispose to obesity and diabetes mellitus: 20-year prospective study in a general population.

BACKGROUND Emerging evidence indicates an association between sympathetic activation and metabolic syndrome. However, sympathetic activation in metabolic syndrome may be a cause, consequence, or just epiphenomenon. To elucidate this issue, the predictive power of resting heart rate for the development of abnormal glucose and lipid metabolisms after 20 years was evaluated in a general population. METHODS A total of 637 participants (>20 years old) underwent a health examination in 1979 including measurements of blood chemistries. Resting heart rate (bpm) was measured by an electrocardiogram. In 1999, all of the study participants again underwent a health examination, including electrocardiogram and blood chemistries. Because four of them had atrial fibrillation, and 19 subjects were taking antihypertensive medication in 1979, they were excluded from analysis. Therefore, a complete dataset of 614 subjects was available. RESULTS As was reported in our previous article, in 1999 we found a linear and significant (P < 0.05) cross-sectional relationship between resting heart rate and a cluster of cardiometabolic risk factors (blood pressure (BP), free fatty acid (FFA), plasma glucose, and homeostasis model assessment (HOMA) index). Baseline higher heart rate (heart rate >or=80 bpm in 1979) predicted the development of obesity, diabetes mellitus (DM), and insulin resistance in 1999 after adjustments for age, sex, and other confounders. CONCLUSION This is one of the first prospective reports demonstrating that higher heart rate may predispose to the development of obesity and DM, suggesting that the sympathetic nerve system may play a role in the development of obesity and DM.

Plasma Level of Asymmetric Dimethylarginine (ADMA) as a Predictor of Carotid Intima-Media Thickness Progression: Six-Year Prospective Study Using Carotid Ultrasonography

This study was designed to determine the relationship between plasma asymmetric dimethylarginine (ADMA) and the development of carotid atherosclerosis. Cross-sectional studies have revealed that plasma ADMA concentration is correlated with the intima-media thickness (IMT) of the carotid artery, but no prospective studies have appeared. Therefore we prospectively investigated whether or not plasma ADMA level can predict IMT progression. In a community-based cohort, we enrolled 712 subjects who were over 40 years old and who had no apparent cardiovascular diseases according to high-resolution carotid ultrasonography. Blood chemistries including ADMA were measured at baseline. In 575 subjects, IMT was re-measured 6 years later. The value of baseline ADMA for predicting IMT changes was investigated by multivariable analysis. At baseline, there was a significant (β=0.321; p<0.001) relationship between IMT and ADMA levels. Multiple linear regression analysis revealed that baseline ADMA (β=0.241; p<0.01) was the only predictor of IMT progression after adjustments for age, sex, baseline IMT, and four major risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) plus hyperuricacidemia. Plasma ADMA was a predictor of carotid IMT progression.

Serum Dehydroepiandrosterone Sulfate Levels Predict Longevity in Men: 27‐Year Follow‐Up Study in a Community‐Based Cohort (Tanushimaru Study)

OBJECTIVES: To determine whether serum dehydroepiandrosterone sulfate (DHEAS) levels could predict longevity in residents.

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.

Factors associated with serum high mobility group box 1 (HMGB1) levels in a general population

High mobility group box 1 (HMGB1), a nonhistone chromatin-associated protein, is implicated as a mediator of both infectious and non-infectious inflammatory conditions. Clinical research on this protein in humans just has begun; serum HMGB1 was reported to be elevated in a small number of critically ill patients suffering from sepsis. However, the kinetics, distribution and factors associated with circulating HMGB1 are unknown in a general population. In this study, we examined these issues in a large population of healthy subjects. Fasting blood samples were obtained from 626 subjects (237 males and 389 females). HMGB1 levels showed a skewed distribution with a mean of 1.65 +/- 0.04 ng/ml. Multiple stepwise regression analyses found that white blood cell (WBC) counts (P = .016) and the soluble form of receptor for advanced glycation end products (sRAGE; P < .001, inversely), which is also known to be a receptor for HMGB1, were independently associated with HMGB1 levels. We demonstrated for the first time that circulating HMGB1 levels were inversely associated with sRAGE levels in a general population. Because RAGE is involved in HMGB1 signaling, our present study suggests that sRAGE may capture and eliminate circulating HMGB1 in humans.

Factors associated with plasma ghrelin level in Japanese general population

Objective  Ghrelin is a novel gastric peptide identified in 1999 as a ‘hunger hormone’. Plasma ghrelin level is decreased in human obesity. Factors associated with ghrelin have been mainly investigated in western countries where the prevalence of obesity is high. The aim of this study is to examine factors associated with plasma ghrelin in a Japanese general population where obesity is not so common.

Decreased High‐Density Lipoprotein Cholesterol Level is an Independent Correlate of Circulating Tumor Necrosis Factor‐α in a General Population

Recent studies implicate a pathophysiological role of tumor necrosis factor‐α (TNF‐α) in atherosclerosis, thus suggesting that serum TNF‐α levels may be one of the biomarkers for future cardiovascular events. However, which anthropometric, metabolic, and inflammatory variables could regulate circulating TNF‐α levels in humans is not fully understood. In this study, we examined the independent determinants of serum TNF‐α levels in a Japanese general population.

High Level of Plasma Endothelin-1 Predicts Development of Hypertension in Normotensive Subjects

BACKGROUND Endothelin-1 (ET-1) is a potent vasoconstrictor derived from the endothelium. However, most large scale cross-sectional studies in humans have indicated no relationship between plasma ET-1 levels and hypertension. The present study was designed to determine whether high plasma ET-1 levels predict the development of hypertension. METHODS A total of 1,492 subjects received a health examination in the Japanese cohort of Seven Countries Study in 1999, when, we examined blood pressure (BP), body mass index (BMI), and blood chemistries. Data on fasting ET-1 were obtained from 1,451 individuals. Seven years later, 1,261 subjects (494 males and 767 females) were re-examined (follow-up rate = 87%). RESULTS Of 814 normotensives (BP <140/90 mm Hg without antihypertensive medications) at baseline, 222 subjects developed hypertension. We divided the baseline plasma ET-1 levels into quartiles. The odds ratio for the development of hypertension after 7 years was 1.79 (95% confidence interval (CI): 1.08-2.96) in the highest quartile vs. the lowest quartile of ET-1 level after adjustment for confounding factors. CONCLUSION A high level of plasma ET-1 predicted the development of hypertension in normotensive subjects.

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.