Inverse association between pulmonary function and C-reactive protein in apparently healthy subjects

RATIONALE: Increased levels of systemic markers of inflammation have been reported in patients with impaired lung function due to obstructive or restrictive lung disease. OBJECTIVE: We tested the hypothesis that a decline in lung function within the normal range may be associated with a systemic subclinical inflammation. METHODS: Pulmonary function tests, cardiorespiratory fitness, components of the metabolic syndrome, and high-sensitivity C-reactive protein (CRP) were determined in 1,131 subjects without known pulmonary disease. MEASUREMENTS AND MAIN RESULTS: Ninety-six of the study participants (8.5%) had FEV(1) of less than 80% of predicted values. There was a strong inverse association between CRP levels and quartiles of FEV(1). The median CRP levels in nonsmoking participants were 2.5, 1.8, 1.7, and 1.3 mg/L in the first, second, third, and forth FEV(1) quartiles, respectively (p < 0.0001). A similar inverse association was present in smoking subjects (median CRP levels were 3.8, 2.3, 2.0, and 1.9 mg/L in the first, second, third, and fourth FEV(1) quartiles, respectively; p < 0.0001). These associations remained highly significant after adjustment for age, sex, components of the metabolic syndrome, and fitness level (p = 0.0005). CONCLUSIONS: An inverse linear relationship exists between CRP concentrations and measures of pulmonary function in subjects without pulmonary disease and in never-smokers. These results indicate that systemic inflammation may be linked to early perturbations of pulmonary function.     

Inverse association between circulating adiponectin levels and skeletal muscle strength in Japanese men and women

Background and aimsIncreased levels of circulating adiponectin in the elderly cause a negative impact on physical function and health status, which suggests that circulating adiponectin may be related to skeletal muscle function. However, data on the relationship between circulating adiponectin levels and skeletal muscle function is limited. Our objective was to investigate the association between serum adiponectin levels and muscle strength in adults.Methods and resultsThis cross-sectional study is a part of the Oroshisho Study of adult employees in Japan from 2008 to 2011. In our study, we used data gathered in 2008–2010 that had included serum adiponectin measurements (n = 1378; age, 19–83 years). From this population, 1259 subjects were evaluated for grip strength (949 men, 310 women), and 965 subjects were evaluated for leg extension power (716 men, 249 women). Multivariate linear regression analyses showed that adiponectin was associated significantly and negatively with both grip strength (β and standard error [SE]: men, −0.09 [0.01], p = 0.010; women, −0.20 [0.03], kg, p = 0.002) and leg extension power (men, −0.09 [0.02], p = 0.014; women, −0.14 [0.07], W, p = 0.032) after adjusting for age, physical activity, nutrient intake, depressive symptoms, metabolic syndrome, C-reactive protein, body mass index, and other lifestyle-related potential confounders.ConclusionThis population-based cross-sectional study indicates an inverse association between serum adiponectin levels and muscle strength in adults. Further studies are necessary to confirm this association and to clarify causality.     

The relationship between high-sensitive C-reactive protein and pulse wave velocity in healthy Japanese men

Although pulse wave velocity (PWV) and high-sensitive C-reactive protein (hsCRP) are known as predictors of future cardiovascular events, their association has not been examined. The present study was conducted to evaluate their association in the general population. In 2668 Japanese men (43 +/- 10 years old), PWV was obtained by volume rendering methods, and hsCRP was determined by the latex aggregation method. PWV showed a significant correlation with logarithm of hsCRP (r = 0.06, P < 0.01). The concentration of hsCRP in the highest quartile of PWV was higher than that in the other three groups (P < 0.01). However, multiple linear regression analyses demonstrated that logarithm of hsCRP was not significantly related to PWV, independent from conventional risk factors. Calculated Framingham risk score (FRS) was higher in the highest quartiles of both hsCRP and PWV than in the other groups (P < 0.05). Thus, while increased hsCRP related to increased PWV, they may be independent predictors of atherosclerotic cardiovascular risk. A prospective study to confirm the independency of their significance in predicting future cardiovascular events and to evaluate the usefulness of the combination of both parameters to screen subjects for cardiovascular risk is necessary.     

Inverse association between serum adiponectin level and transaminase activities in Japanese male workers

BACKGROUND/AIMS: Since a novel polypeptide named adiponectin was shown to prevent the development of steatosis and steatohepatitis in animal models, we studied whether it was also possible in a clinical situation. METHODS: Associations between serum adiponectin levels and serum transaminase activities were studied in 791 Japanese males who were not heavy drinkers, and had no autoimmune or HBV- or HCV-induced liver diseases. RESULTS: Various markers of metabolic diseases including levels of body mass index (BMI), serum triglyceride, total cholesterol, and insulin resistance assessed by the homeostasis model were significantly higher in subjects with increased transaminase activities when compared to those with normal activities. Single regression analyses demonstrated that the logarithmic serum adiponectin level was inversely correlated with the levels of logarithmic serum AST (r=-0.229, P<0.0001), ALT (r=-0.305, P<0.0001), and gammaGTP (r=-0.278, P<0.0001). Even in multiple regression analyses in which subjects' age and levels of BMI, serum triglyceride, total cholesterol, and insulin resistance were adjusted, the inverse correlations were significant (P=0.0426, 0.0332, and 0.0011, respectively). CONCLUSIONS: Hypoadiponectinemia may worsen liver diseases associated with metabolic diseases in clinical cases. In addition to aggravation of insulin resistance and hyperlipidemia, some hypoadiponectinemia specific mechanisms may stand behind the association.     

Association between C-reactive protein and hypertension in healthy middle-aged men and women

OBJECTIVE: To ascertain whether C-reactive protein (CRP), an inflammatory marker related to increased cardiovascular risk, is associated with blood pressure in a sample of healthy, middle-aged people. METHODS AND RESULTS: A case-control study among 904 participants, 39-50 years old, from a cardiovascular risk screening study. Participants with systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg (n=120) were considered as case participants and all others as control participants (n=784). Exposure was defined using quintiles of high-sensitivity CRP among control participants. A continuous increase in blood pressure was observed across CRP quintiles. Systolic blood pressure increased 1.17 mmHg [95% confidence interval (CI), 0.60-1.74] and diastolic blood pressure 1.04 mmHg (95% CI, 0.64-1.45) from one quintile to the next. The prevalence of hypertension was 13.3% and it increased with CRP exposure: Q1, 8.9%; Q2, 11.9%; Q3, 12.2%; Q4, 14.3%; and Q5, 18.6%. After adjustment for sex, obesity, race, serum insulin level and family history of coronary heart disease, odds ratios for hypertension increased progressively across CRP quintiles. Participants in the highest CRP quintile were 2.35 times more likely to have hypertension than those in the lowest quintile (P=0.03, trend test P=0.04). CONCLUSION: These results are consistent with a continuous, independent association between serum CRP and elevated blood pressure.     

Relationship between C-reactive protein and visceral adipose tissue in healthy Japanese subjects

AIM: Recent studies have suggested that the elevated C-reactive protein (CRP) levels are associated with body fat, especially visceral adipose tissue, but most of them were investigated in Westerners who had higher body mass index (BMI) than Asians. To investigate the association between CRP concentrations, parameters of visceral obesity, the insulin resistance syndrome and carotid atherosclerosis in healthy Japanese who had a lower BMI than Westerners. METHODS: We explored the relationships between fatness and visceral obesity parameters [by anthropometry, bioelectrical impedance analysis and abdominal computed tomography (CT)] and CRP (high sensitivity) and examined their associations with components of insulin resistance syndrome, interleukin-6 (IL-6), tissue necrosis factor-alpha (TNF-alpha) and intima-media thickness (IMT) of common carotid arteries (CCAs) by ultrasonograms in 116 healthy Japanese subjects. RESULTS: In crude regression analyses, CRP was significantly associated with measures of obesity. After adjustment for age, gender and smoking, the association with CRP was stronger for parameters of visceral obesity (waist circumference, waist-to-hip ratio and visceral adipose tissue accumulation) than for other parameters of obesity. IL-6 and TNF-alpha were not associated with CRP. Blood pressure (BP), metabolic variables and CCA-IMT were also significantly associated with CRP. But, after being adjusted for age, gender, smoking and BMI, BP and high-density lipoprotein cholesterol (HDLc) were significantly associated. CONCLUSION: CRP level is associated with visceral adipose tissue and is significantly associated with the components of insulin resistance syndrome in healthy Japanese subjects. These data support a possible role of visceral adipose tissue in inflammation component of atherosclerosis, and further studies are needed to study the mechanism of CRP elevation caused by visceral adipose tissue.     

The reciprocal association of adipocytokines with insulin resistance and C-reactive protein in clinically healthy men

In experimental models, adiponectin improves and tumor necrosis factor alpha (TNF- alpha ) impairs insulin action, and the expression of these adipocytokines seems to have a reciprocal regulation. The aim was to examine whether in a cross-sectional study, associations supporting this concept may be found in 58-year-old clinically healthy men, and also the relation to C-reactive protein (CRP). In 102 men, euglycemic hyperinsulinemic clamp was used to assess glucose infusion rate (GIR). Total body fat (dual-energy x-ray absorptiometry), plasma adiponectin (radioimmunoassay), TNF-alpha , and CRP (enzyme-linked immunosorbent assay) were measured. Adiponectin correlated positively to GIR (r=0.33, P<.001) and negatively to total fat mass (r=-0.29, P=.004), whereas TNF- alpha showed reverse associations (r=-0.31, P<.01, and r=0.31, P<.01). Adiponectin and TNF- alpha were negatively correlated (-0.28, P=.006). An interaction term (TNF- alpha /adiponectin ratio) and body fat together explained 31.3% (P<.001) in GIR variability. The odds ratio for having insulin resistance was 9.3 (95% CI, 2.2-38.9) in subjects with TNF-alpha values above and adiponectin levels below the median, as compared to subjects with TNF- alpha values below and adiponectin levels above the median. Total fat and TNF-alpha , but not adiponectin, were significantly associated with log CRP (R2=20%, P<.001). In conclusion, this study in man showed that plasma adiponectin and TNF-alpha were independently and reversely associated with insulin resistance. C-reactive protein levels were related to TNF-alpha and obesity.     

Body fat and C-reactive protein levels in healthy non-obese men

BACKGROUND AND AIM: The relationships between C-reactive protein (CRP) levels, adipose tissue and metabolic alterations have not been clearly established in healthy non-obese subjects. We investigated the relationships between body fat, CRP levels and metabolic variables in healthy, non-obese sons of patients affected by metabolic syndrome (MS). METHODS AND RESULTS: Age, CRP and interleukin 6 (IL-6) levels, anthropometric measures (body mass index, BMI; waist circumference and waist-to-hip ratio, WHR), total and regional fat content (as determined by means of dual X-ray absorptiometry, DXA), total and LDL cholesterol, and the metabolic variables related to MS (HDL-cholesterol, triglyceride, glucose and insulin levels; the fasting insulin resistance index, FIRI; blood pressure) were evaluated in 85 healthy non-obese sons of MS patients. Linear and multiple regression analyses were used to evaluate the relationships between body fat, metabolic variables and CRP levels, and to investigate whether the association between body fat content and metabolic variables persists after adjustment for CRP levels. Body fat was associated with all of the investigated variables. CRP levels were associated with total and regional body fat, the anthropometric index of weight, age, and with some metabolic alterations (HDL-cholesterol and triglyceride levels, systolic blood pressure, and fasting insulin and LDL-cholesterol levels). The associations between total body fat and the metabolic variables did not change after adjustment for CRP levels. Total body fat was the best predictor of CRP levels (p<0.0001). CONCLUSIONS: In healthy, non-obese sons of MS patients, total body fat is the best predictor of CRP levels, and remains closely associated with metabolic abnormalities after adjustment for CRP levels. These findings strongly support the hypothesis that body fat is the main determinant of metabolic abnormalities and a low inflammatory state, at least in healthy subjects.     

Correlation between apoptotic endothelial microparticles and serum interleukin-6 and C-reactive protein in healthy men

Inflammation has been associated with increased cardiovascular risk, and endothelial cell (EC) apoptosis has been implicated in atherogenesis. The correlation between circulating concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and endothelial microparticles (EMPs) expressing an apoptotic (EMP31) or activation (EMP62E) phenotype in 20 middle-aged healthy men was investigated. IL-6 was significantly correlated with EMP31 (r = 0.6, p = 0.004), which persisted after adjusting for body mass index and CRP. CRP was significantly correlated with body mass index (r = 0.49, p = 0.02) but not with EMP31 or EMP62E. EC apoptosis is associated with IL-6 levels in men and might be partially responsible for the increased cardiovascular risk associated with subclinical inflammation.     

Survey of C-reactive protein and cardiovascular risk factors in apparently healthy men

Several prospective studies have demonstrated a direct association between C-reactive protein (CRP) levels and the risks of developing cardiovascular disease. Few studies, however, have explored the interrelations between CRP levels and other risk factors for cardiovascular disease. We evaluated the relation of CRP with several cardiovascular risk factors in a cross-sectional survey of 1,172 apparently healthy men. There were significant positive associations between CRP levels and age, number of cigarettes smoked per day, body mass index, systolic and diastolic blood pressure, total cholesterol, triglycerides, lipoprotein(a), apolipoprotein B, tissue-type plasminogen activator antigen, D-dimers, total homocysteine, and fibrinogen (all p values <0.05). Significant inverse associations were observed for exercise frequency, high-density lipoprotein cholesterol, and apolipoprotein A-I and A-II (all p values <0.02). In multivariate analysis, age, smoking status, and serum levels of tissue-type plasminogen activator antigen, fibrinogen, lipoprotein(a), and total homocysteine were independent correlates of CRP levels. Finally, in an analysis controlled either for all the independent correlates or for several usual risk factors, we observed progressive increases in levels of CRP with increasing prevalence of risk factors (p for trend <0.001 for independent correlates and <0.01 for usual risk factors). In conclusion, in a large cohort of apparently healthy men, CRP levels were associated with several cardiovascular risk factors. These data are compatible with the hypothesis that CRP levels may be a marker for preclinical cardiovascular disease.     

Inverse association between excessive alcohol drinking and cardiometabolically healthy status in middle-aged men with and without overweight and obesity

Aims

The aim of this study was to clarify the relationship between drinking and metabolically healthy status in men with normal weight, overweight and obesity.

Reciprocal association between visceral obesity and adiponectin: in healthy premenopausal women

BACKGROUND: Obesity is one of the well-known risk factors of vascular disorders; however, the molecular mechanisms underlying the association between the two remain undetermined. Previous studies have demonstrated that the plasma levels of adiponectin, an adipose-derived hormone, are reduced in obese subjects, and that this hypoadiponectinemia is associated with ischemic heart disease. In this study, we sought to identify the primary determinants of plasma adiponectin levels in healthy premenopausal women. METHODS AND RESULTS: We analyzed the plasma adiponectin concentrations in age-matched healthy obese premenopausal women [n=37, body mass index (BMI)> or= 25 kg/m(2)] and in healthy nonobese premenopausal women (n = 23, BMI < 25 kg/m(2)). Visceral and subcutaneous fat (VCF and SCF) areas were determined by abdominal computed tomography (CT) scan. Plasma levels of adiponectin in obese subjects were lower than in nonobese subjects (3.24 +/- 1.08 vs. 4.90 +/- 2.06 ug/ml, P < 0.01). Significant, univariate inverse correlations were observed between adiponectin levels and visceral fat areas (r = -0.643, p < 0.001), subcutaneous fat areas (r = -0.407, p < 0.01), and hsCRP (r = -0.36, p = 0.007). Plasma levels of adiponectin correlated positively with insulin sensitivity [quantitative insulin sensitivity check index (QUICKI): r = 0.38, p = 0.005] and high-density lipoprotein (HDL) cholesterol (r = 0.44, p = 0.001), and negatively with low-density lipoprotein (LDL) cholesterol (r = -0.29, p = 0.028), triglyceride (r = -0.33, p = 0.013), and BMI (r = -0.48, p < 0.001). By multivariate analysis, only visceral fat areas affected adiponectin plasma levels (beta = -0.016, p < 0.05, R(2) = 0.504). Plasma levels of HDL cholesterol remained significantly correlated to plasma adiponectin concentrations in multivariate analysis (beta = 0.067, p < 0.05). CONCLUSIONS: These results collectively indicate that plasma HDL cholesterol levels and visceral fat masses are independently associated with plasma adiponectin concentrations.     

Relation of microalbuminuria to adiponectin and augmented C-reactive protein levels in men with essential hypertension

Microalbuminuria, and recently, hypoadiponectinemia, have been associated with progression of atherosclerotic disease and increased cardiovascular risk. We examined the possible associations of urinary albumin excretion, expressed as the ratio of albumin to creatinine (ACR), with plasma adiponectin and high-sensitivity C-reactive protein (hs-CRP) levels in men who had essential hypertension. The study population consisted of 108 men who did not have diabetes and were newly diagnosed with stage I to II essential hypertension (age 44.6 years, office blood pressure 148/95 mm Hg) and 110 men matched according to age and body mass index as controls. According to ACR values, which were determined as the average of 2 nonconsecutive overnight spot urine samples, subjects who had hypertension were categorized into 2 groups: those who had microalbuminuria (n = 28; mean ACR 30 to 300 mg/g) and those who had normal albuminuria (n = 80; mean ACR <30 mg/g). Subjects who had hypertension compared with controls exhibited higher ACR and log hs-CRP levels and a trend toward lower log adiponectin values (p = 0.062), whereas those who had normal albuminuria compared with controls had similar log adiponectin levels but significantly higher levels of ACR and log hs-CRP. Moreover, subjects who had hypertension and microalbuminuria compared with those who had hypertension and normal albuminuria had higher log hs-CRP and lower log adiponectin concentrations independently of confounding factors. Among those who had hypertension, ACR exhibited an independent positive correlation with log hs-CRP and a negative correlation with log adiponectin. Multiple linear regression analysis showed that age, body mass index, systolic blood pressure, log hs-CRP, and log adiponectin were significant independent predictors of the ACR. In conclusion, microalbuminuria is accompanied by decreased adiponectin and increased hs-CRP levels in the setting of essential hypertension, reflecting a rather diffuse atherosclerotic process.