Shunichi Kumagae

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.

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.

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.

Low-density lipoprotein levels are one of the independent determinants of circulating levels of advanced glycation end products in nondiabetic subjects.

Nonenzymatic modification of proteins by reducing sugars leads to the formation of advanced glycation end products (AGEs), whose process has been reported to progress under diabetes. Recently, diet has been found to be a major environmental source of proinflammatory AGEs in humans. Further, fats or meat‐derived products processed by high heat such as broiling have been shown to contain more AGEs than carbohydrates boiled for longer periods. Since circulating levels of low‐density lipoprotein cholesterol (LDL‐C) are also regulated by dietary cholesterol, it is conceivable that intake of cholesterol‐rich foods could regulate serum levels of AGEs in humans. In this study, we investigated whether LDL‐C levels are one of the independent determinants of circulating AGEs levels in a nondiabetic general population.

P-240 Strong Association Between Plasma Aldosterone and Metabolic Syndrome. An Epidemiologic Study in Japanese General Population

ratio, 1.9 (95%CI: 1.09 3.33), 2.04 (956%CI:1.01 4.15) and 2.98 (95%CI: 1.36 6.55) respectively. This association of the ECG abnormalities with coronary death was independent of age, body mass index, systolic blood pressure, serum cholesterol level, blood sugar level, smoking and drinking. Conclusion: ST-segment depression, T-wave abnormality and ST-T abnormality in ECG are associated with significantly higher risk for CVD and CHD mortality in women.

P-206 Serum MCP-1 Levels Are Strongly Associated with Higher Ratio of LDL- to HDL-Cholestrol Levels and Lower Estimated GFR

cholesterol, triglyceride (TG), and high density lipoprotein (HDL) cholesterol at baseline and four weeks after treatment with the statin. Results: The total cholesterol and LDL levels in both groups were significantly decreased four weeks later, and HDL level was significantly increased in both groups, but not TG level in vytorin group. In addition, the change of LDL cholesterol in vytorin group was significantly higher than it in lipitor (52.4% vs 44.1% respectively p < 0.05). The central PWV (cfPWV) and peripheral PWV (cfPWV) in lipitor group was significantly decreased compared with those in vytorin group (p < 0.05). Conclusions: Although co-administration of simvastatin and ezetimibe might show much more lipid lowering effect compared with atorvastatin, only atorvastatin might show pleiotrophic effect for short-term treatment in hypercholesterolemia.

P-227 LDL-C/HDL-C Ratio Predicts IMT Progression More than HDL-C or LDL-C alone: 8-Year Follow-Up Study in a General Population

Purpose: Cyanotic congenital heart disease (CCHD) induces secondary erythrocytosis and CCHD is thought to be one of the risk factors for cholelithiasis, but the frequency of cholelithiasis and/or gallstones in patients with CCHD is unknown. Materials and Methods: A hundred and two patients with CHD were divided into 4 groups: group A 22 CCHD without reparative surgery or with palliative surgery; group B 35 CCHD after repair who were eliminated cyanosis; group C 17 acyanotic CHD without repair; and group D 28 acyanotic CHD after repair. Gallstones were studied by abdominal ultrasonography or CT in each patient. For analysis of risk factors, patient records regarding cyanotic period, family history and past abdominal surgery were reviewed and blood pressures, lipid profiles, blood sugar and liver enzyme were evaluated. Results: Cholecystectomy due to cholelithiasis was underwent in 7 of 279 CCHD patients (2.5%). In group A, 7 patients (31%) underwent cholecystectomy, and 3 patients (18%) have gallstones. In group B, 11 patients (37%) had gallstones. In group C, nobody had gallstones, and in group D 2 patients (7%) had gallstones. SPO2 was significantly lower and red blood cell, hemoglobin, hematocrit, HbA1C and total bilirubin levels were significantly higher in group A (p 19.8, 95%CI 1.30 300.1). Conclusions: The incidence of cholelithiasis and gallstones is significantly high in CCHD regardless of repair. The most important factor related to gallstones was having CCHD even after desaturation was improved by surgical repair.