Uric acid is an independent risk factor for carotid atherosclerosis in a Japanese elderly population without metabolic syndrome.

BACKGROUND: Carotid intima-media thickness (IMT) is an useful surrogate marker of cardiovascular disease. Associations between uric acid (UA), metabolic syndrome (MetS) and carotid IMT have been reported, but findings regarding the relationship have been inconsistent. METHODS: A total of 1,579 Japanese elderly subjects aged ≥65 years {663 men aged, 78 ± 8 (mean ± standard deviation) years and 916 women aged 79 ± 8 years} were divided into 4 groups according to UA quartiles. We first investigated the association between UA concentrations and confounding factors including MetS; then, we assessed whether there is an independent association of UA with carotid IMT and atherosclerosis in participants subdivided according to gender and MetS status. RESULTS: Carotid IMT was significantly increased according to the quartiles of UA in both genders without MetS and women with MetS. Multivariate logistic regression analysis showed that odds ratio (OR) {95% confidence interval (CI)} in men for carotid atherosclerosis was significantly increased in the third (OR, 1.75; 95% CI, 1.02-3.02), and fourth quartiles (OR, 2.01; 95% CI, 1.12-3.60) of UA compared with that in the first quartile of UA, and the OR in women was significantly increased in the fourth quartile (OR, 2.10; 95% CI, 1.30-3.39). Similarly, the ORs were significantly associated with increasing quartiles of UA in both genders without MetS, but not necessarily increased in those with MetS. CONCLUSIONS: UA was found to be an independent risk factor for incidence of carotid atherosclerosis in both genders without MetS.

A slightly low hemoglobin level is beneficially associated with arterial stiffness in Japanese community-dwelling women.

Pulse wave velocity (PWV) is a simple and noninvasive method of measuring arterial stiffness for the assessment of cardiovascular disease in high-risk populations. This association may be further confounded by hemoglobin status, which is involved in the development of atherosclerosis. We randomly recruited 120 men and 223 women aged 69 ± 9 and 68 ± 7 years, respectively, during their annual health examination in a single community. Arterial stiffness was evaluated by brachial-ankle PWV (baPWV). The value of baPWV was different from men and women. In men, baPWV was not related to hemoglobin levels (r = 0.013, P = .886), but in women baPWV increased significantly and progressively with increased hemoglobin levels (r = 0.276, P < .001). Stepwise multiple regression analysis using the baPWV as objective variables, adjusted for confounding factors as explanatory variables, showed that only in women, hemoglobin levels (ß = 0.165, P = .001) as well as age (ß = 0.268, P < .001), body mass index (BMI; ß = -0.165, P < .001), systolic blood pressure (SBP; ß = 0.429, P < .001), prevalence of antihypertensive (ß = 0.154, P = .002), heart rate (HR; ß = 0.108, P = .017), and antilipidemic medication (ß = 0.094, P = .036), and estimated glomerular filtration rate (eGFR; ß = -0.147, P = .003) were significantly and independently associated with baPWV. Multivariate-adjusted baPWV was significantly higher in hemoglobin groups of ≥12.7 g/dL (Group-2, Group-4) than in the lowest hemoglobin group (10.0-12.6 g/dL; P = .032). A slightly low hemoglobin level was beneficially associated with arterial stiffness in community-dwelling women but not men.

Association between fasting plasma glucose and high-sensitivity C-reactive protein: gender differences in a Japanese community-dwelling population.

BACKGROUND: High sensitivity C-reactive protein (hsCRP) is an acute phase reactant and a sensitive marker of inflammation. Hyperglycemia can potentially promote the production of CRP. The aim of this study was to determine whether increased fasting plasma glucose (FPG) levels are associated with elevated hsCRP concentrations by gender. METHODS: We recruited 822 men (mean age, 61 ± 14 years) and 1,097 women (63 ± 12 years) during their annual health examination from a single community. We cross-sectionally examined whether FPG levels are associated with hsCRP concentrations, and whether this association is independent of gender, body mass index (BMI) and other components of the metabolic syndrome. RESULTS: In women only, hsCRP increased significantly and progressively with increasing FPG (r = 0.169, P < 0.001). The stepwise multiple linear regression analysis using hsCRP as an objective variable, adjusted for confounding factors as explanatory variables, showed that FPG as well as age, BMI, systolic blood pressure, high-density lipoprotein cholesterol (HDL-C), uric acid, and high molecular weight adiponectin were significantly associated with hsCRP in women, but not in men. There was significant gender interaction, and an increase in hsCRP levels that was greater in women with BMI ≥ 25 kg/m2 and higher FPG than in men. CONCLUSIONS: These results suggested that hsCRP levels increase continuously across the FPG spectrum starting from the lowest FPG in both men and women. However, increase in hsCRP levels was greater in women than men.

Relationships between lipid profiles and metabolic syndrome, insulin resistance and serum high molecular adiponectin in Japanese community-dwelling adults.

BACKGROUND: There are few studies to demonstrate the associations between newly addressed lipid profiles and metabolic syndrome (MetS)-associated variables. METHODS: Study participants without medications for hypertension, diabetes, or dyslipidemia {614 men aged 58 ± 14 (mean ± standard deviation; range, 20-89) years and 779 women aged 60 ± 12 (range, 21-88) years} were randomly recruited from a single community at the time of their annual health examination. The association between lipid profiles (total cholesterol (T-C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, T-C/HDL-C, TG/HDL-C, LDL-C/HDL-C ratio and MetS, Insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR), and serum HMW adiponectin were analyzed. RESULTS: In multiple linear regression analysis, TG/HDL-C and T-C/HDL-C ratios as well as TG showed significantly strong associations with all three MetS-associated variables in both men and women. In men, the ROC curve analyses showed that the best marker for these variables was TG/HDL-C ratio, with the AUC for presence of MetS (AUC, 0.82; 95% CI, 0.77-0.87), HOMA-IR (AUC, 0.75; 95% CI, 0.70-0.80), and serum HMW adiponectin (AUC, 0.67; 95% CI, 0.63-0.71), respectively. The T-C/HDL-C ratio, TG, HDL-C, LDL-C/HDL-C ratio, and non-HDL-C also discriminated these markers; however all their AUC estimates were lower than TG/HDL-C ratio. These results were similar in women. CONCLUSION: In Japanese community-dwelling adults, lipid ratios of TG/HDL-C, T-C/HDL-C, LDL-C/HDL-C as well as TG and HDL-C were consistently associated with MetS, insulin resistance and serum HMW adiponectin. Lipid ratios may be used as reliable markers.

High-sensitivity C-reactive protein and gamma-glutamyl transferase levels are synergistically associated with metabolic syndrome in community-dwelling persons.

BACKGROUND: Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. Increased high-sensitivity C-reactive protein (hsCRP) levels are associated with MetS and its components. Changes in gamma-glutamyl transferase (GGT) levels in response to oxidative stress are also associated with MetS, and the levels could be modulated by hsCRP. METHODS: From a single community, we recruited 822 men (mean age, 61 ± 14 years) and 1,097 women (63 ± 12 years) during their annual health examination. We investigated whether increased hsCRP and GGT levels are synergistically associated with MetS and insulin resistance evaluated by Homeostasis of model assessment of insulin resistance (HOMA-IR). RESULTS: Of these subjects, 141 men (17.2%) and 170 women (15.5%) had MetS. Participants with MetS had a higher hsCRP and GGT level than those without MetS in both genders, and the HOMA-IR increased significantly in correlation with an increase in hsCRP and GGT. In men, the adjusted odds ratios (95% confidence interval) for MetS across tertiles of hsCRP and GGT were 1.00, 1.69 (1.01-2.80), and 2.13 (1.29-3.52), and 1.00, 3.26 (1.84-5.78) and 6.11 (3.30-11.3), respectively. In women, the respective corresponding values were 1.00, 1.54 (0.92-2.60), and 3.08 (1.88-5.06), and 1.00, 1.70 (1.04-2.79) and 2.67 (1.66-4.30). The interaction between increased hsCRP and GGT was a significant and independent determinant for MetS and insulin resistance in both genders. CONCLUSIONS: These results suggested that higher CRP and GGT levels were synergistically associated with MetS and insulin resistance, independently of other confounding factor in the general population.

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults.

BACKGROUND: The aim of the present study was to examine how lipid profiles are associated with insulin resistance in Japanese community-dwelling adults. METHODS: This cross-sectional study included 614 men aged 58 ± 14 (mean ± standard deviation; range, 20-89) years and 779 women aged 60 ± 12 (range, 21-88) years. The study sample were 1,042 (74.8%) non-obese (BMI < 25.0 kg/m²) and 351 (25.2%) overweight (BMI ≥ 25 kg/m²) subjects. Insulin resistance was defined by homeostasis model assessment of insulin resistance (HOMA-IR) of at least 2.5. The areas under the curve (AUC) of the receiver operating characteristic curves (ROC) were used to compare the power of these serum markers. RESULTS: In non-obese subjects, the best marker of insulin resistance was low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio of 0.74 (95% confidence interval (CI), 0.66-0.80). The HDL-C, triglyceride (TG)/HDL-C ratio, and non-HDL-C also discriminated insulin resistance, as the values for AUC were 0.31 (95% CI, 0.24-0.38), 0.69 (95% CI, 0.62-0.75) and 0.69 (95% CI, 0.62-0.75), respectively. In overweight subjects, the AUC for TG and TG/HDL-C ratio were 0.64 (0.58-0.71) and 0.64 (0.57-0.70), respectively. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: TG/HDL-C ratio of ≥ 1.50 and LDL-C/HDL-C ratio of ≥ 2.14 in non-obese subjects, and ≥ 2.20, ≥ 2.25 in overweight subjects. In non-obese subjects, the positive likelihood ratio was greatest for LDL-C/HDL-C ratio. CONCLUSION: In non-obese Japanese adults, LDL-C/HDL-C ratio may be the best reliable marker of insulin resistance.

Drug-induced hepatitis with autoimmune features during minocycline therapy.

A 25-year-old woman with no history of liver disease developed liver dysfunction associated with severe jaundice and general malaise following a prolonged therapy with minocycline for acne vulgaris. Serum anti-nuclear antibody was detected and immunoglobulin G level was elevated. Symptoms resolved and liver function normalized following minocycline discontinuation and corticosteroid administration. Our diagnosis was drug-induced hepatitis with autoimmune features, as liver histology revealed acute hepatitis. Drug-induced hepatitis should be considered when liver dysfunction or systemic symptoms develops during long-term minocycline therapy.

Usefulness of combining serum uric acid and high-sensitivity C-reactive protein for risk stratification of patients with metabolic syndrome in community-dwelling women.

Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. In women, increased uric acid (UA) levels are associated with MetS and its components. High-sensitivity C-reactive protein (hsCRP) levels are also associated with MetS, and hsCRP levels could be modulated by UA. We investigated whether combining UA and hsCRP levels are independently associated with MetS and insulin resistance in Japanese community-dwelling women. From a single community, we recruited 1,097 women (63 ± 12 years) during their annual health examination, and examined the cross-sectional relationship between UA, hsCRP, and MetS and insulin resistance, which was evaluated by homeostasis of minimal assessment of insulin resistance. Of these subjects, 218 women (19.9 %) had MetS. Multiple linear regression analysis was performed to evaluate the contribution of each confounding factor for MetS and insulin resistance, both UA and hsCRP as well as age and alcohol consumption, were independently and significantly associated with MetS and insulin resistance. The adjusted-odds ratios (95 % confidence interval) for MetS across tertiles of UA and hsCRP were 1.00, 1.45 (0.95-2.22), and 2.61 (1.74-3.93), and 1.00, 1.80 (1.18-2.74), and 3.23 (2.15-4.85), respectively. In addition, the combination increased UA, and hsCRP was also a significant and independent determinant for MetS and insulin resistance. In direction associations, we also observed a synergistic effect between these two molecules (F = 2.76, P = 0.027). These results suggested that combined assessment of UA and hsCRP levels provides incremental information for risk stratification of patients with MetS, independent of other confounding factors in community-dwelling women.

Hemoglobin is associated with serum high molecular weight adiponectin in Japanese community-dwelling persons.

AIM: Serum high molecular weight (HMW) adiponectin improves insulin sensitivity, and a decreased level of serum HMW adiponectin has been reported as a risk factor for the development of diabetes and coronary heart disease. This association may be further confounded by the hemoglobin status, which is involved in the development of atherosclerosis. METHODS: A cross-sectional study was carried out in 2002. Study participants, consisting of 897 men aged 61±14 (mean±standard deviation) years and 1,148 women aged 63±12 years, were randomly recruited from a single community at the time of their annual health examination. RESULTS: Serum HMW adiponectin levels were lowered dose-dependently with an increased hemoglobin level. Stepwise multiple linear regression analyses for serum HMW adiponectin revealed that the hemoglobin status was independently and significantly associated with serum HMW adiponectin levels as well as sex, age, body mass index (BMI), alcohol consumption, total cholesterol, triglycerides, high density lipoprotein cholesterol, antilipidemic medication, uric acid, serum gamma glutamyltransferase, and insulin resistance. Inclusion of hemoglobin levels in the model further increased the coefficient of determination. In stratified analysis, mean serum HMW adiponectin levels were significantly and similarly decreased as hemoglobin levels increased in men, ages ≥ 65 years, BMI < 23.0 kg/m(2), alcohol drinkers, and lower insulin resistance, and there were significant interactions between the two groups for BMI, alcohol consumption and insulin resistance. CONCLUSION: Hemoglobin status is inversely associated with serum HMW adiponectin levels in community-dwelling persons, especially those aged ≥ 65 years, BMI < 23.0 kg/m(2), alcohol drinkers, and lower insulin resistance groups.