Plasma C-reactive protein concentrations in relation to 5-year body weight change among children: the Taipei Children Heart Study.

OBJECTIVE: C-reactive protein (CRP), a nonspecific inflammatory marker, may be associated with the development of cardiovascular disease (CVD) among adults. The purpose of this study is to evaluate the relation between plasma CRP levels and 5-y body weight and body mass index (BMI) change among school children in Taiwan. METHOD: In 1995, we conducted an epidemiological survey to evaluate the anthropometric characteristics and CVD risk factors among 1500, aged 12-15 y, school children in Taipei. We measured plasma high sensitivity CRP levels using nephelometric method. In 2000, we followed these children to evaluate their changes in body height, weight and BMI during 5 y. RESULTS: In general, boys were taller, heavier and had higher BMI than girls at the baseline (1995) and at the 5-y follow-up (2000). Baseline plasma CRP levels were positively correlated with body weight and BMI in both 1995 and 2000. However, plasma CRP levels were negatively correlated with 5-y BMI change in both genders. We further divided the children into three subgroups based on their baseline CRP levels (nondetected, 0.188-1.00 and >1.0 mg/dl). Children in the higher plasma CRP levels (>1.0 mg/dl) were heavier and had higher BMI (both in 1995 and 2000) than those children with nondetected CRP levels. However, children with higher CRP subgroup had a lower 5-y increasing of BMI and there was even a decrease of BMI levels among the higher CRP girls. CONCLUSION: From this prospective study, we found that baseline plasma CRP levels were positively correlated with the baseline and the 5-y follow-up body weight and BMI in both genders. However, plasma CRP levels may not be a good predictor of 5-y body weight and BMI changes among children in Taiwan.

Determinants and distributions of plasma total homocysteine concentrations among school children in Taiwan.

BACKGROUND: Plasma total homocysteine (tHcy) level is an independent risk factor for cardiovascular disease (CVD) even among children. The purpose of this study is to evaluate the determinants and distributions of plasma tHcy levels and the relationship between plasma tHcy, folate and vitamin B12 levels among school children in Taipei. METHODS: After multi-stage sampling, we randomly selected 1234 school children (609 boys and 625 girls) with the mean age of 13 years (from 12 to 15 years) in this study. Fasting plasma tHcy levels were measured using an ABBOTT IMx analyzer (Axis Biochemicals ASA, Oslo, Norway). Plasma folate and vitamin B12 levels were measured by ACS:180 automated chemiluminescence analyzer (Bayer, Tarrytown, NY, USA). RESULTS: The distribution of plasma tHcy levels were skewed to the right with the mean values of 10.50 and 8.95 micromol/l and medians of 9.67 and 8.474 micromol/l for boys and girls, respectively. Plasma tHcy concentrations were lower in younger children and progressively increased with increasing age. Boys had significantly higher plasma tHcy levels than girls (10.50 +/- 4.134 vs. 8.95 +/- 2.61 micromol/l, p < 0.01) and lower plasma folate levels (6.05 +/- 2.85 vs. 6.39 +/- 2.58 nmol/l, p < 0.01), and vitamin B12 levels (444.8 +/- 158.4 vs. 495.0 +/- 181.5 pmol/l, p < 0.001). Plasma tHcy levels were significantly positively associated with anthropometric measures in boys; but these characteristics attenuated and became insignificant after adjusting for other potential confounders in girls. Plasma tHcy levels were negatively associated with plasma folate and vitamin B12 levels even after adjusting for BMI and other potential confounders in both genders. CONCLUSIONS: From this study, the distributions of tHcy levels were skewed to the right and the boys had higher plasma tHcy levels than girls. Plasma tHcy levels were significantly positively associated with BMI among boys. Further studies are needed to evaluate the relationship between tHcy and CVD risk factors among children for the better prevention of heart disease in early life.

Obesity, leptin and blood pressure among children in Taiwan: the Taipei Children's Heart Study.

BACKGROUND: Obesity is associated with the occurrence of hypertension; however, the mechanisms of obesity-induced high blood pressure (BP) remain unclear. Leptin, the obese (ob) gene product, is associated with the occurrence of obesity and related disorders in humans. The purpose of this study was to evaluate the association between plasma leptin and BP among children. METHODS: After multistage sampling, we randomly selected 1265 children (618 boys and 647 girls) with a mean age of 13.3 years (12 to 16 years old) in this cross-sectional survey. Obesity measurements included body mass index (BMI) and waist-to-hip circumference ratio (WHR). Plasma leptin levels were measured by radioimmunoassay. RESULTS: The mean and median plasma leptin levels were 4.1 and 2.4 ng/mL among boys and 10.1 and 8.8 ng/mL among girls. Children in the highest quintile of leptin level (mean, 11.1 and 19.7 ng/mL for boys and girls, respectively) had higher body weight, BMI, WHR, BP, and insulin levels than children in the lowest quintile (mean, 1.1 and 3.9 ng/mL for boys and girls, respectively). Boys had a higher BMI, WHR, and BP levels, yet had lower leptin levels than girls. In both genders, BMI and plasma leptin levels were significantly positively correlated with BP. In multivariate regression analyses, plasma leptin levels were positively associated with BP; however, this association became insignificant among girls and even inversely associated with systolic BP among boys after adjusting for BMI. CONCLUSIONS: Obesity is positively associated with BP among school children in Taiwan; however, the role of plasma leptin on the development of obesity-related hypertension is still controversial among school children.

Plasma leptin concentrations and obesity in relation to insulin resistance syndrome components among school children in Taiwan--The Taipei Children Heart Study.

OBJECTIVE: Leptin, an adipose tissue-derived product of the obesity (OB) gene, is an important regulator of energy metabolism and may be associated with the occurrence of insulin resistance and diabetes in humans. The purpose of this study was to evaluate the association of plasma leptin concentration with obesity and the components of insulin resistance syndrome (IRS) among school children in Taiwan. METHODS: After multistage sampling of 85 junior high schools in Taipei, we randomly selected 1,264 children (617 boys and 647 girls) aged 12-16y. Obesity measurements included body mass index (BMI) and waist-to-hip circumference ratio (WHR). We calculated an IRS summary score for each individual by adding the quartile ranks from the distribution of systolic blood pressure (BP), serum triglyceride (TG), HDL-cholesterol (inverse), and insulin levels. RESULTS: Boys had a higher BMI and WHR, BP and IRS score and lower leptin, insulin, TG and HDL-C levels than girls. BMI, WHR and plasma leptin levels were significantly associated with the IRS summary score and each of its components in both genders. Children with higher plasma leptin levels (> 75th percentiles) have significantly higher BP, TG, insulin levels and IRS score than children with low leptin levels. The associations between plasma leptin level and the IRS components and score were still significant after adjusting for BMI in boys, but less so in girls. In both genders, after adjusting for WHR, plasma leptin levels were still significantly associated with the IRS components and summary score (P< 0.001). The final model that included the standard covariates, BMI and leptin, but not WHR, was the most predictive of the IRS summary score among school children. CONCLUSIONS: Insulin resistance syndrome in childhood, characterized by high blood pressure, dyslipidemia, and hyperinsulinemia, may be an early marker of cardiovascular risk. From the present BMI and leptin in combination are the most predictive markers of insulin resistance syndrome among school children in Taiwan.

Lipoprotein profiles, not anthropometric measures, correlate with serum lipoprotein(a) values in children: the Taipei children heart study.

OBJECTIVE: Plasma lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease. The purpose of this study is to evaluate the correlation of anthropometric measures, lipids and lipoprotein profiles and serum Lp(a) values among children in Taiwan. We will attempt to find parameters that will be able to predict Lp(a) levels in children. DESIGN AND METHODS: After a probability-proportional-to size, multi-stages sampling procedure, we randomly sampled 1500 schoolchildren from 10 schools in Taipei city. Anthropometric measures including body weight, body height, waist and hip circumference and skinfolds were measured. We used standard methods to measure serum total cholesterol (CHOL), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 and B (ApoA1 and ApoB) and Lp(a) levels. We also calculated low density lipoprotein-cholesterol (LDL-C) and CHOL HDL-C ratio (TCHR) by formula. RESULTS: We sampled 1283 children (635 boys and 648 girls) with a mean age of 13.3 years (from 12 to 16 years) in this study. The mean and medium serum Lp(a) levels were 16.8 and 8.8 mg/dl among boys and 20.8 and 11.9 mg/dl among girls. Children in the highest quintile of Lp(a) (mean = 49.6 and 58.6 mg/dl for boys and girls, respectively) had higher CHOL, LDL-C, ApoB levels and TCHR than children in the lowest quintile (mean = 3.1 and 3.7 mg/dl for boys and girls, respectively). Lipids and lipoprotein profiles, such as CHOL, LDL-C, Apo-B and TCHR were positively correlated with Lp(a) levels in both genders. Furthermore, the children with Lp(a) levels greater than or equal to 30 mg/dl had higher CHOL, LDL-C and Apo-B levels when compared to children with Lp(a) levels less than 30 mg/dl. After adjusting for age, cigarette smoking, alcohol drinking, puberty development and heart rates, LDL-C and ApoB levels were significantly positively associated with Lp(a) levels while ApoA1 was negatively associated among boys. Among girls, only Apo-B was significantly positively associated with Lp(a) and TG was negatively associated with Lp(a) levels. Most importantly, none of the anthropometric measures were significantly correlated with Lp(a) levels. CONCLUSIONS: From this study, we found that lipids and lipoproteins profiles, rather than degree of adiposity as reflected by anthropometric measures, are significantly associated with serum Lp(a) levels among school children.

Relationship between hyperuricemia and other cardiovascular disease risk factors among adult males in Taiwan.

Hyperuricemia is associated with cardiovascular disease risk factors such as obesity, impaired glucose tolerance, hypertension, and hyperlipidemia. However, this relationship between serum uric acid (SUA) concentrations and cardiovascular disease (CVD) is a controversial one, especially among males. The purpose of this study is to evaluate the association between SUA concentrations and other CVD risk factors among adult males in Taiwan. After multi-stage sampling procedures, we randomly selected 1743 Taiwanese males with a mean age of 35 years (from 22 to 54) in this study. Anthropometric, blood pressure and biochemical variables, including serum uric acid, glucose, total cholesterol and triglyceride concentrations, were measured. Among the study population, the mean SUA concentration was 6.5 +/-1.5 mg/dl. There were 290 (16.6%) subjects with SUA concentrations > or = 8.0 mg/dl (defined as hyperuricemia). Compared to normouricemic subjects, hyperuricemic subjects had significantly greater age-adjusted body weight (75.3 vs. 69.2 kg, p < 0.001), body mass index (BMI, 25.5 vs. 23.6 kg/m2, p < 0.001), higher blood pressure (BP, 120.2 vs. 115.2 mmHg for systolic BP and 78.5 vs. 75.3 mmHg for diastolic BP, both p < 0.001) and blood lipid concentrations (193.8 vs. 182.1 mg/dl for total cholesterol and 123.7 vs. 94.4 mg/dl for triglycerides, both p < 0.001). SUA concentration was positively correlated with body weight, BMI, BP and serum lipid concentrations (all p < 0.001). In multivariate regression analyses, after adjusting for potential confounders, SUA concentration was significantly positively associated with diastolic BP, serum total cholesterol and triglyceride concentrations. An increase of 1 mg/dl of SUA was associated with a 2.1 mg/dl elevation in serum total cholesterol (p < 0.001) and a 5.4 mg/dl increase in triglyceride (p < 0.001). From this study, we found that hyperuricemia in subjects is associated with being overweight, and having high blood pressure and hyperlipidemia. There is a significantly positive association between SUA concentration and other CVD risk factors among adult males in Taiwan.

Cardiovascular effect and simultaneous pharmacokinetic and pharmacodynamic modeling of pimobendan in healthy normal subjects.

Pimobendan is a new inotropic agent with vasodilator properties. We have reported the pharmacokinetics of enantiomers of pimobendan in healthy humans. The present report focuses on the pharmacodynamic effect of pimobendan and a simultaneous pharmacokinetic-pharmacodynamic modeling. Eight normal healthy volunteers were studied with oral administration of 7.5 mg and i.v. administration of 5 mg of racemic pimobendan. Concentrations of enantiomers of pimobendan were determined by high performance liquid chromatography. Cardiovascular effects of pimobendan were evaluated by echocardiography. Oral pimobendan significantly reduced 29.0% and 16.5% of the left ventricle end-systolic dimension (LVESD) and end-diastolic dimension, respectively. The mean velocity of circumferential fiber shortening, ejection fraction, and fractional shortening significantly increased 105.9%, 29.8%, and 46% from their baseline values, respectively. The cardiovascular effects of i.v. pimobendan were similar but to a lesser extent. Plots of effect versus plasma concentration (Cp) showed counterclockwise hysteresis loops. A hypothetical effect compartment was established and incorporated into a sigmoid Emax model to describe the time courses of Cps of pimobendan and effects on LVESD. The maximal changes (Emax) in LVESD would be 2.60 +/- 0.51 cm and 2.30 +/- 0.13 cm as estimated from plasma data of (+)- and (-)-pimobendan, respectively. The estimated effect-site concentrations corresponding with 50% of the maximal effect (Ce50) were 6.54 +/- 1.35 and 6.64 +/- 1.35 ng/ml for (+)- and (-)-pimobendan, respectively. A simultaneous pharmacokinetic-pharmacodynamic model could be established to suppress the hysteresis loop and to predict the pharmacological effect based on Cp.

Clustering of cardiovascular disease risk factors among obese schoolchildren: the Taipei Children Heart Study.

BACKGROUND: Childhood obesity increases the risk of obesity in adulthood and is associated with cardiovascular disease (CVD) risk factors such as hypertension, diabetes mellitus, and dyslipidemia. OBJECTIVE: We evaluated the clustering of CVD risk factors among obese schoolchildren in Taiwan. DESIGN: After multistage sampling of 85 junior high schools in Taipei, we randomly selected 1366 children (681 boys and 685 girls) aged 13.3 y (range: 12-16 y). Anthropometric, blood pressure (BP), and biochemical CVD risk factors (including blood glucose, lipid, and lipoprotein concentrations) were measured. RESULTS: Boys had a higher body mass index, systolic BP, and glucose concentrations than girls and girls had higher lipid and lipoprotein concentrations than boys. After adjustment for age, obese boys had a significantly higher BP, ratio of total to HDL cholesterol, and glucose, cholesterol, triacylglycerol, HDL cholesterol, LDL cholesterol, apolipoprotein A-I, and apolipoprotein B concentrations than nonobese boys. BP, HDL cholesterol, LDL cholesterol, and ratio of total to HDL cholesterol were significantly different between nonobese and obese girls. Approximately 70% of obese boys had one and 25% had two or more CVD risk factors other than obesity. Obese girls had a significantly higher prevalence of high BP and a higher prevalence of CVD risk factor clustering than nonobese girls. CONCLUSIONS: Boys had higher glucose concentrations and BP and lower lipid concentrations than girls. We found an association between obesity and higher BP and between obesity and blood glucose and lipid concentrations for both sexes. Clustering of CVD risk factors was especially apparent among the obese children. A clustering of CVD risk factors may begin during early adolescence among the obese.

Plasminogen activator inhibitor-1 and angiotensin I converting enzyme gene polymorphism in patients with hypertension.

Deletion polymorphism of angiotensin I-converting enzyme (ACE) gene has been reported to be an independent risk factor for myocardial infarction. Plasminogen activator inhibitor-1 (PAI-1) was proposed to be a link between the renin-angiotensin system and thrombotic risk. This study was undertaken to investigate the possible association between the insertion/deletion (I/D) polymorphism of the ACE gene and plasma PAI-1 levels in 160 patients with mild-to-moderate hypertension. The I/D genotypes were determined by polymerase chain reaction with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene. Baseline levels of PAI-1 antigen and activity and tissue plasminogen activator (t-PA) antigen were determined in fasting morning plasma samples. It was found that patients with homozygote deletion (DD, n = 37) ACE genotype did not have significantly higher plasma levels of PAI-1 antigen (31.2 +/- 15.6 ng/mL v 28.4 +/- 15.1 ng/mL or 27.2 +/- 13.2 ng/mL, P = .42), PAI-1 activity (16.2 +/- 10.6 IU/mL v 14.1 +/- 9.4 IU/ mL or 15.0 +/- 9.9 IU/mL, P = .60), or t-PA antigen (14.6 +/- 6.0 ng/mL v 13.4 +/- 4.9 ng/mL or 14.6 +/- 5.7 ng/mL, P = .40) as compared to those with heterozygote (DI, n = 67) or homozygote insertion (II, n = 56) genotypes. On multiple regression analysis, the ACE genotypes did not appear to be significant predictors for plasma PAI-1 levels and t-PA antigen after adjustment with age, sex, body mass index, plasma triglyceride, cholesterol, and glucose. In conclusion, the results indicated that the I/D polymorphism of the ACE gene was not related to plasma PAI-1 levels in a Chinese population with hypertension. The ACE genotypes may not have a role in influencing the fibrinolysis in hypertension.

Relationship between anthropometric variables and lipid levels among school children: The Taipei Children Heart Study.

OBJECTIVES: To evaluate the association between anthropometric parameters and lipid levels among Taiwanese school children. DESIGN AND METHODS: Using a probability-proportional-to size sampling and multi-stages sampling procedure, we sampled 1500 school children from 10 schools in Taipei city. Anthropometric parameters including body weight, body height, waist circumference, hip circumference and skinfolds were measured. Serum total cholesterol (CHOL), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 and B (ApoA1 and ApoB) were measured by standard methods, low density lipoprotein-cholesterol (LDL-C) and CHOL/HDL-C ratio were calculated by formula. RESULTS: We included in our analyses 1366 children (681 boys and 685 girls) with a mean age of 13.3 y (from 12 to 16 y) and with valid anthropometric and biochemical parameters. The boys had higher body height (P < 0.001) and larger body weight (P < 0.05), waist circumference (P < 0.01) and waist/hip ratio (WHR, P < 0.001) than the girls. However, the girls had larger skinfolds than the boys. After adjusting for age, girls had higher total CHOL, TG, HDL-C, LDL-C, ApoA1 and ApoB concentrations than boys. In general, TG was positively associated with most anthropometric parameters (except body height); a similar negative association between HDL-C and anthropometric variables was noted. After controlling, for age, cigarette smoking, alcohol drinking and puberty development, shorter body height was the strongest predictor of total CHOL, LDL-C and ApoB concentrations among boys. Although body mass index (BMI) was a significant positive predictor (P < 0.01) of the CHOL/HDL-C ratio; skinfold measurements were the strongest anthropometric predictors of most lipid concentrations among boys. Among girls, we found WHR and BMI to be the strongest positive predictors of TG and ApoB level respectively (both P < 0.001), but skinfold measurements were best for predicting HDL-C, LDL-C, ApoA1 and the CHOL/HDL-C ratio. CONCLUSIONS: From this large study of school-age children from Taiwan, we found anthropometric parameters, such as body height, BMI or WHR, are adequate predictors of blood lipid levels; however, skinfold measurements are generally more strongly associated with lipid levels in both genders.

Gemfibrozil treatment of hypertriglyceridemia: improvement on fibrinolysis without change of insulin resistance.

The fibrinolytic and metabolic changes associated with gemfibrozil treatment of hypertriglyceridemia were evaluated in 16 patients with type IV hyperlipidemia by criteria of triglyceride levels > 250 mg/dl and total cholesterol levels < 220 mg/dl. The plasma triglyceride level was significantly lower (323 +/- 71 vs 189 +/- 57 mg/dl; p = 0.000) and high-density lipoprotein cholesterol level significantly higher (33.5 +/- 4.6 vs 38.0 +/- 6.7 mg/dl; p = 0.005) after 3 to 4 months of gemfibrozil treatment. However, the glucose and insulin metabolism measured by oral glucose challenge and insulin suppression tests showed no significant changes after gemfibrozil therapy. In contrast, plasma plasminogen activator inhibitor-1 antigen (36.9 +/- 12.4 vs 27.3 +/- 11.4 ng/ml; p = 0.008) and activity (15.5 +/- 5.5 vs 11.8 +/- 3.0 IU/ml; p = 0.009) and tissue plasminogen activator antigen (13.2 +/- 4.0 vs 10.4 +/- 3.7 ng/ml; p = 0.007) were significantly depressed, and tissue plasimogen activator activity (0.57 +/- 0.31 vs 0.69 +/- 0.38 IU/ml; p = 0.015) was significantly elevated by gemfibrozil. The data indicate that lowering plasma triglyceride and raising high-density lipoprotein cholesterol levels by gemfibrozil treatment also improved the fibrinolytic system without changes of insulin resistance and glucose intolerance in patients with isolated hypertriglyceridemia.

Angiotensin I converting enzyme gene polymorphism and insulin resistance in patients with hypertension.

BACKGROUND: The homozygote deletion (DD) genotype of the angiotensin I converting enzyme (ACE) gene has been shown to be associated with an increased risk of coronary heart disease independent of other risk factors. OBJECTIVE: To investigate the possible association of the insertion/deletion (I/D) polymorphism of the ACE gene with insulin resistance in a Chinese population with and without hypertension. SUBJECTS AND METHODS: The I/D polymorphism of the ACE gene was determined for 361 Chinese including 148 women and 96 men with normal blood pressures and 64 male and 53 female patients with mild-to-moderate hypertension. Insulin resistance was estimated by the insulin suppression test and glucose intolerance evaluated with an oral glucose-tolerance test for all of the subjects. RESULTS: Three hypertensive subgroups with DD, DI and II genotypes having similar ages and body mass indexes presented insignificantly different degrees of glucose intolerance and insulin resistance both among men and among women. Similar results were found for normotensive subjects. In addition, ACE genotypes were not significant predictors of insulin resistance and glucose intolerance either among men or among women after adjustment for age, body mass index, and hypertension. CONCLUSION: The present data indicated that the I/D polymorphism of the ACE gene was not related to insulin resistance for Chinese hypertensive and normotensive subjects. The increased risk of coronary heart disease associated with the DD genotype need not be mediated through the mechanism of insulin resistance and glucose intolerance for Chinese patients with hypertension.

Angiotensin I converting enzyme gene polymorphism in Chinese patients with hypertension.

Reports from different ethnic populations failed to show consistent findings on the association of hypertension with insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene. In this population association study in Chinese, we compared the distribution of the ACE genotypes and allele frequency in 150 healthy controls with normal blood pressure and 148 hypertensive patients categorized by age. Although the frequencies of homozygote deletion (DD) genotype and deletion allele were greater in Chinese with hypertension than in normotensive controls (0.23 vs 0.13 and 0.44 v 0.37, respectively), the differences were not significant by chi2 analysis (P = .07 and .09, respectively). Furthermore, we did not find the trend of decreasing number of DD genotype in older hypertensive Chinese patients. The results indicated a much lower prevalence of ACE/DD genotype in Chinese than in Caucasians and a modest association between I/D polymorphism of the ACE gene and hypertension in Chinese.

Effect of doxazosin on fibrinolysis in hypertensive patients with and without insulin resistance.

The fibrinolytic and metabolic changes associated with doxazosin treatment were evaluated in 20 patients with mild to moderate hypertension. Steady-state plasma glucose (SSPG) concentration was used to subdivide hypertensive patients into two groups of 10 each: Insulin-resistant (SSPG > 190 mg/dl) and nonresistant (SSPG < 190 mg/dl). The blood pressure was normalized after 4 to 6 months of doxazosin treatment in both groups, but it was associated with significantly lower fasting plasma triglyceride level, lower integrated insulin response to a 75 gm oral glucose load, lower SSPG concentration, significant decreases in plasma plasminogen activator inhibitor type one antigen and activity and tissue plasminogen activator antigen, and a significant increase in tissue plasminogen activator activity only in the insulin-resistant group but not in the nonresistant group. It was also noted that the improvement of the fibrinolytic and metabolic abnormalities in the insulin-resistant group tended to return to the less abnormal levels seen in the non-resistant group. The data suggested that doxazosin treatment of hypertension attenuated much of the abnormalities of insulin resistance but had little effect on insulin-sensitive patients. It may support a link between impaired fibrinolysis and insulin resistance in patients with hypertension.

Gemfibrozil treatment of endogenous hypertriglyceridemia: effect on insulin-mediated glucose disposal and plasma insulin concentrations.

Gemfibrozil or placebo was administered for 3 months to 24 individuals with endogenous hypertriglyceridemia and normal glucose tolerance. Mean ( +/- SEM) fasting plasma triglyceride (TG) concentrations decreased (4.01 +/- 0.55 to 1.34 +/- 0.12 mmol/L; P < 0.001) and high density lipoprotein cholesterol concentrations increased (0.54 +/- 0.03 to 0.67 +/- 0.04 mmol/L; P < 0.001) in gemfibrozil-treated patients, associated with lower (P < 0.01-0.001) plasma free fatty acid and TG concentrations when measured at hourly intervals in response to breakfast (0800 h) and lunch (1200 h). However, day-long plasma glucose and insulin responses to meals in the 2 groups were similar before and after treatment, as were the steady state plasma glucose and insulin concentrations at the end of a 180-min infusion of somatostatin, insulin, and glucose. Thus, marked decreases in both plasma TG and free fatty acid concentrations seen in association with gemfibrozil neither enhanced insulin-mediated glucose disposal nor lowered ambient plasma insulin concentrations in patients with endogenous hypertriglyceridemia.

Impaired fibrinolysis and insulin resistance in patients with hypertension.

Plasma plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) antigens and activities were measured in 28 patients with hypertension and 12 normal controls. Steady state plasma glucose (SSPG) concentrations were also determined after an infusion of somatostatin, insulin and glucose. Patients with hypertension were further subdivided into two groups: insulin resistance (SSPG > 190 mg/dL, n = 14) and no insulin resistance (SSPG < 190 mg/dL, n = 14). As compared to normal controls, hypertensive patients, either with or without insulin resistance, had a significant (P < .005) increases in PAI-1 activity (18.6 +/- 1.3 upsilon 8.1 +/- 0.8 IU/mL), PAI-1 antigen (31.1 +/- 2.0 upsilon 12.7 +/- 0.9 ng/mL) and tPA antigen (15.5 +/- 0.9 upsilon 8.8 +/- 0.9 ng/mL), and significant decrease in tPA activity (0.43 +/- 0.05 upsilon 1.02 +/- 0.16 IU/mL) than normotensive controls. Furthermore, hypertensive patients with insulin resistance had significantly higher PAI-1 activity (22.0 +/- 2.2 upsilon 15.3 +/- 0.8 IU/mL, P = .006) and tPA antigen (17.4 +/- 1.2 upsilon 13.6 +/- 1.3 ng/mL, P = .02) than did hypertensive patients without insulin resistance. However, PAI-1 antigen was insignificantly higher (34.1 +/- 2.9 upsilon 28.1 +/- 2.4 ng/mL, P = .06) and tPA activity insignificantly lower (0.42 +/- 0.08 upsilon 0.43 +/- 0.08 IU/mL, P = .47) in hypertensive patients with insulin resistance than in those without insulin resistance. In addition, PAI-1 activity and tPA antigen were significantly correlated with blood pressure, SSPG, triglyceride, HDL-cholesterol and integrated glucose response to an oral load of 75 g glucose. Thus, patients with hypertension have impaired fibrinolytic activity due to increased PAI-1 when compared to normotensive controls, and the magnitude of this fibrinolytic defect is greater in hypertensive patients who have insulin resistance. Insulin resistance with associated metabolic abnormalities may be one of the causes for impaired fibrinolysis in hypertension.

Relationship between smoking status and cardiovascular disease risk factors in young adult males in Taiwan.

BACKGROUND: To evaluate smoking status and cardiovascular risk factors in young male adults in Taiwan. METHODS: After cluster sampling, we performed a cross-sectional survey to assess smoking status, duration, and number of cigarettes smoked in 781 young adult males (mean age 20 years, range 18-24). Cardiovascular disease risk factors, including anthropometric factors, blood pressure, lipoproteins and apolipoprotein levels were also measured. RESULTS: In total 211 subjects (27.0%) had never smoked, 38 subjects (4.9%) were ex-smokers, and 532 (68.1%) still smoked cigarettes. The prevalence of smoking was higher than in 1989 and 1990 (54.8 and 59.4%, respectively). Current smokers had significantly higher serum triglyceride and lower high-density lipoprotein-cholesterol levels than subjects who had never smoked (56.2 versus 46.9 and 55.6 versus 59.0 mg/dl, respectively; P < 0.05 for both). No difference was found in other cardiovascular risk actors among subjects in the different smoking groups or among current smokers who had smoked for different periods of time or who smoked different numbers of cigarettes. CONCLUSION: These data suggest that the prevalence of smoking in young adult males in Taiwan has increased progressively. No differences were found in anthropometric factors or blood pressure among subjects of different smoking status. Abnormal lipoprotein levels (higher triglyceride and lower high-density lipoprotein cholesterol) were found in current smokers compared with non-smokers. A longer follow-up study will be needed to confirm whether the smoking status of these young adults can be correlated with the risk of cardiovascular disease.

Suppression of non-esterified fatty acid concentrations by insulin in patients with hypertension.

BACKGROUND: Recent studies have suggested that insulin resistance may be involved in the development of hypertension. Although skeletal muscle accounts for the majority of peripheral insulin resistance, the effect of insulin on adipose tissue, (i.e., antilipolysis) has rarely been defined in hypertensive patients. To understand the effect of high blood pressure on adipose tissue lipolytic activity in vivo, plasma non-esterified fatty acid (NEFA) concentrations at basal insulin, and during physiological hyperinsulinemic state was compared in patients with essential hypertension and a group of normotensive subjects. METHODS: Twenty patients with untreated essential hypertension and 20 age, sex, body mass index (BMI)-matched normotensive subjects were studied. Oral glucose tolerance test (OGTT) in response to a 75-g oral glucose load was carried out for three hours after an overnight fasting. On separate morning, modified insulin suppression test was performed for three hours, which involved a constant infusion of insulin (25 mU/m2/min) glucose (240 mg/m2/min) and somatostatin (350 micrograms/h). The four values obtained every 10 min at last half hour were read as steady state plasma glucose (SSPG), insulin (SSPI) and final NEFA concentrations. RESULTS: Patients with hypertension had significantly higher fasting plasma insulin (101 +/- 9 vs 69 +/- 8 pmol/L, p < 0.02) and NEFA (543 +/- 38 vs 453 +/- 25 mumol/L, p < 0.05) concentrations compared to normotensive subjects. In response to OGTT, the plasma glucose and insulin concentrations increased significantly in the hypertensive group when compared with normotensive group (p < 0.05 and p < 0.01, respectively), whereas plasma NEFA concentrations were suppressed to a similar extent in these two groups. During modified insulin suppression test, the mean SSPG concentrations were significantly higher (10.1 +/- 0.7 vs 7.8 +/- 0.8 mmol/L, p < 0.01) in patients with hypertension compared with normal subjects despite that the mean SSPI concentrations were similar. Plasma NEFA concentrations fell markedly during the period of physiological hyperinsulinemia and achieved similar levels during the last 30 min of infusion in both hypertensive and normal individuals (92.3 +/- 4.9 vs 86.5 +/- 7.3 mumol/L, p = NS). CONCLUSIONS: Patients with hypertension are glucose intolerant, hyperinsulinemic and insulin resistant compared to a group of normotensive subjects. Hypertensive patients have higher than normal fasting plasma NEFA and insulin concentrations indicating that they might lose the ability to regulate adipocyte metabolism in fasting state.

Pharmacokinetics and pharmacodynamics of enantiomers of pimobendan in patients with dilated cardiomyopathy and congestive heart failure after single and repeated oral dosing.

Pharmacokinetics and pharmacodynamics of pimobendan were studied in eight patients with dilated cardiomyopathy and chronic congestive heart failure after single dosing and after 2-week repeated dosing of 5 mg racemic pimobendan. Enantiomers of pimobendan and its demethylated metabolite in plasma and in red blood cells were measured. In the single-dose study, the peak plasma levels of 16.3 +/- 4.0 and 17.0 +/- 3.1 ng/ml of (+)- and (-)-pimobendan were observed at 0.9 hour after dosing. The concentration-time curves followed a two-compartment model, with terminal half-lives of 2.56 +/- 0.35 and 2.93 +/- 0.33 hours for (+)- and (-)-pimobendan (p > 0.05), respectively. The oral volumes of distribution after equilibrium were 3.26 +/- 0.74 and 3.13 +/- 0.75 L/kg, and oral clearances were 28.6 +/- 7.0 and 21.9 +/- 4.1 ml/min/kg for (+)- and (-)-pimobendan (p > 0.05), respectively. In red blood cells, the respective (+)- and (-)-pimobendan concentrations were 5.8 and 8.4 times higher than those in plasma, indicating a stereoselective partitioning of drugs between plasma and red blood cells. The pharmacodynamic effect of pimobendan was evaluated by echocardiography. The ejection fraction, mean velocity of circumferential fiber shortening, aortic flow peak velocity, cardiac index, and stroke volume index significantly increased 50% to 60%. The left ventricular end-systolic dimension, systolic blood pressure, and diastolic blood pressure significantly decreased 8% to 11%. These effects lasted for more than 8 hours. In a 2-week repeated-dose study, there was no significant dose accumulation in plasma and red blood cells. The pharmacokinetic parameters were similar to those in the single-dose study, except for significantly shorter absorption half-lives. The baseline levels of cardiac index and stroke volume index were significantly higher than the baseline levels in the single-dose study. This suggests an accumulation of pharmacodynamic effects despite a relatively short elimination half-life.

Plasma and red blood cell pharmacokinetics of pimobendan enantiomers in healthy Chinese.

The pharmacokinetics of enantiomers of pimobendan and their demethylated metabolites in plasma and red cells were studied in 8 normal healthy volunteers. After racemic pimobendan 5 mg IV, the plasma concentration-time curve followed a two-compartment open-model with elimination half-lives of 1.81 h and 1.86 h for (+)- and (-)-pimobendan, respectively. The clearances and volumes of distribution postequilibrium were 13.5 ml.min-1.kg-1, 14.4 ml.min-1.kg-1; 1.74 l.kg-1 and 2.34 l.kg-1 for (+)- and (-)-pimobendan, respectively. Plasma protein binding (n = 3) of (+)-, (-)-pimobendan, (+)- and (-)-demethylated metabolites was 97.6, 97.6, 92.2 and 92.5%, respectively. The plasma concentration-time curve also followed a two-compartment open model after oral administration of 7.5 mg racemic pimobendan. The absolute bioavailabilities of (+)- and (-)-pimobendan were 0.51 and 0.55. Peak levels of (+)- and (-)-pimobendan, both at 1.2 h, were 15.8 and 16.8 ng.ml-1, respectively. The (+)- and (-)-pimobendan concentrations in red cells were determined and their pharmacokinetics were estimated using red blood cell data. Interesting phenomena were observed: the peak concentrations of (+)- and (-)-pimobendan in red blood cells were about 5.5- and 9.2-times higher than in plasma, and the AUCs were correspondingly elevated. The volume of distribution of the central compartment of (-)-pimobendan in red cell was significantly smaller than that of (+)-pimobendan. (0.24 vs. 0.42 l.kg-1.) Similar phenomena were found after IV administration.