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In this study, we investigated possible relations between left ventricular (LV) concentric remodeling and plasma levels of high-sensitivity C-reactive protein (hs-CRP) and serum amyloid-A (SAA) in subjects who had essential hypertension; 65 consecutive subjects who had hypertension, did not have diabetes, and had normal LV mass were categorized as those whose LV relative wall thickness was <0.44 (n = 41) and those whose relative wall thickness was > or =0.44. Venous blood samples were collected for determination of metabolic profile and plasma levels of hs-CRP and SAA. Subjects whose relative LV wall thickness was > or =0.44 compared with those whose relative LV wall thickness was <0.44 had significantly increased systolic blood pressure by 4.5 mm Hg (p = 0.015) and higher levels of plasma hs-CRP (1.80 vs 1.39 mg/L, p = 0.001) and SAA (10.22 vs 4.86 mg/dl, p = 0.000), although the 2 groups did not differ with regard to age, gender, waist-to-hip ratio, and diastolic blood pressure (p = NS for all). In the entire study population, log hs-CRP and SAA exhibited positive relations with systolic blood pressure (r = 0.21 and r = 0.29, respectively; p <0.05 for the 2 markers) and relative wall thickness (r = 0.26 and r = 0.81, respectively; p <0.05 for the 2 markers). Multiple linear regression analysis showed that age, gender, and diastolic blood pressure were significantly associated with LV mass index (p <0.05), whereas gender, body mass index, log hs-CRP, and SAA were significantly associated with relative wall thickness (p <0.003). By analysis of covariance, log hs-CRP and SAA were significantly different between subjects whose relative LV wall thickness was > or =0.44 and those whose relative LV wall thickness was <0.44 after the adjustment for age, gender, body mass index, and systolic/diastolic blood pressure (p <0.005 for the 2 markers). In conclusion, alterations in LV geometry are associated with increased serum CRP and SAA levels in patients who are newly diagnosed with essential hypertension.
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PMID:Relation of left ventricular concentric remodeling to levels of C-reactive protein and serum amyloid A in patients with essential hypertension. 1601 52

Type 2 diabetes is associated with a systemic low-grade inflammation. First data provided by cross-sectional studies from as early as the 1960s demonstrated elevated systemic levels of glycoproteins and acute-phase reactants and increased leukocyte counts in type 2 diabetes patients. Subsequently, prospective studies showed that elevated concentrations of several acute-phase proteins and cytokines are predictive of later type 2 diabetes. Immune gene variants in man and in animal models were found to affect insulin resistance and diabetes incidence. Antidiabetic treatment by medication, diet or physical activity results in a significant decrease of systemic immune mediator concentrations. Immunological analyses of the KORA Survey S4 (1999/2001) allowed us to show that levels of circulating acute-phase proteins like CRP and of IL-6 are highly correlated and associated not only with overt type 2 diabetes, but already with impaired glucose tolerance (IGT) pointing out a role of these mediators in the pathogenesis of type 2 diabetes. On the contrary, TNFalpha was neither coregulated with CRP nor associated with diabetes status. Our study therefore shows that type 2 diabetes is accompanied by a non-random and differential upregulation of components of the innate immunity and suggests that this inflammatory condition is involved in the aetiology of the disease. Future work will extend the range of analysed immune mediators to chemokines and will also investigate the association of immune markers with indices of obesity to elucidate the relevance of this traditional risk factor for low-grade inflammation.
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PMID:Inflammation and type 2 diabetes: results from KORA Augsburg. 1603 28

Several diseases (atherosclerosis, diabetes mellitus, chronic renal failure) are associated with oxidative and carbonyl stress, microinflammation and eventually autoimmune reaction. Both oxidative and carbonyl stress cause damage to important biological structures-proteins, carbohydrates, lipids and nucleic acids and may enhance inflammatory response. New compounds and modified structures are formed, among them advanced oxidation protein products (AOPP), advanced glycation end products (AGEs-e.g. pentosidine, carboxymethyllysine) and advanced lipoperoxidation end products (ALEs). Accumulation of glycoxidation products, upregulation of protective mechanisms like glyoxalase I as well as enhanced transcription of genes coding for cytokines, growth factors and adhesive molecules via AGE-RAGE (receptor for AGEs) interaction and subsequent increase of classical acute phase reactants (e.g. CRP-C-reactive protein or orosomucoid) can be observed in a variety of chronic diseases. Additionally, several RAGE gene polymorphisms have shown association with some pathological states-diabetic complications, vascular damage, inflammatory response or antioxidant status. Recent advances in understanding the pathogenesis of chronic diseases provide new possibilities for diagnostics and monitoring of severely ill patients, however, further studies are still required to establish efficient therapeutical strategies.
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PMID:Advanced glycoxidation end products in chronic diseases-clinical chemistry and genetic background. 1608 33

Anaemia is common in patients with diabetes and associated with an increased risk of diabetic complications. Although the role of anaemia in heart failure is established, we hypothesize that anaemia also contributes to an increased risk of cardiac dysfunction in patients with Type II diabetes. In the present study, 228 consecutive adults with diabetes were investigated using transthoracic echocardiography. Echocardiographic parameters were correlated with the Hb (haemoglobin) level and adjusted for other risk factors for cardiac dysfunction using multivariate analysis. More than one in five patients (23%) had anaemia, which was an independent risk factor for cardiac dysfunction on echocardiography. Over one-third of all patients with evidence of abnormal cardiac function (diastolic and/or systolic dysfunction) on echocardiography had anaemia compared with <5% of patients with normal echocardiographic findings. Most patients with anaemia had cardiac dysfunction (94%), with the major abnormality being diastolic dysfunction associated with an increased left ventricular mass and impaired relaxation indices. A continuous association between diastolic function and Hb was also observed in patients without anaemia. In patients with a history of cardiovascular disease, systolic dysfunction was twice as common in patients with anaemia. Anaemia was also correlated with plasma markers of cardiac risk, including BNP (brain natriuretic peptide), CRP (C-reactive protein) and AVP (arginine vasopressin). Notably, the predictive utility of these markers was eliminated after adjusting for Hb. Consequently, the inexpensive measurement of Hb may be a useful tool to identify diabetic patients at increased risk of cardiac dysfunction.
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PMID:Diastolic dysfunction is associated with anaemia in patients with Type II diabetes. 1618 Nov 49

We investigated prospectively the association between serum levels of interleukin (IL)-18 and the risk of type 2 diabetes in a case-cohort study conducted in middle-aged men and women who represented 7,936 participants of the three MONItoring of trends and determinants in CArdiovascular disease (MONICA)/Cooperative Research in the Region of Augsburg (KORA) surveys. Levels of IL-18 were measured in stored samples of 527 case subjects with incident type 2 diabetes and 1,698 noncase subjects. Elevated levels of IL-18 were associated with a significantly increased risk of type 2 diabetes after adjustment for age, sex, survey, BMI, systolic blood pressure, ratio of total cholesterol to HDL cholesterol, physical activity, alcohol intake, smoking status, and parental history of diabetes. Hazard ratios and 95% confidence intervals comparing quartile extremes were 1.73 (1.25-2.40). Further adjustment for C-reactive protein and IL-6 had no impact on the observed associations. However, the risk of developing type 2 diabetes was highest among subjects with elevated levels of both IL-18 and CRP or IL-18 and IL-6, respectively. In conclusion, elevated levels of IL-18 are associated with a considerably increased risk of type 2 diabetes. This association is independent of a generalized proinflammatory state, but subjects with elevated levels of several inflammatory markers seem to be particularly prone to develop type 2 diabetes.
Diabetes 2005 Oct
PMID:Elevated levels of interleukin-18 predict the development of type 2 diabetes: results from the MONICA/KORA Augsburg Study, 1984-2002. 1618 95

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.
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PMID:Relation of microalbuminuria to adiponectin and augmented C-reactive protein levels in men with essential hypertension. 1618 22

Abnormal glucose tolerance is associated with subclinical chronic inflammation in patients with type 2 diabetes. The aim of this study was to investigate whether plasma concentrations of inflammatory markers are associated with measures of obesity, insulin sensitivity, and hyperglycemia. IL-6, adiponectin, CRP, and IL-10 plasma concentrations were evaluated in 142 patients with a wide range of obesity, insulin sensitivity and glucose tolerance. In parallel with the impairment of glucose tolerance, there was a significant increase in IL-6, and CRP, and a significant decrease in adiponectin and IL-10 plasma concentrations. There were significant correlations between the plasma concentrations of all inflammatory markers and % body fat, insulin sensitivity, and fasting plasma glucose. However, multivariate linear regression analysis identified insulin sensitivity as determined by glucose infusion rate during the steady state of an euglycemic-hyperinsulinemic clamp as the strongest predictor of adiponectin, CRP, IL-6, and IL-10 plasma concentrations. In addition, fasting plasma glucose was a significant determinant of adiponectin, CRP, and IL-6 plasma concentrations, whereas body fat content was only a significant predictor of CRP plasma concentration. In conclusion, our data suggest that abnormal inflammatory markers in patients with type 2 diabetes are primarily related to decreased insulin sensitivity.
Exp Clin Endocrinol Diabetes 2005 Oct
PMID:Association of interleukin-6, C-reactive protein, interleukin-10 and adiponectin plasma concentrations with measures of obesity, insulin sensitivity and glucose metabolism. 1623 56

We studied the efficacy of four different treatment regimens (sulphonylurea and metformin+/-acarbose versus glimepiride and rosiglitazone versus glimepiride and bedtime NPH insulin versus multiple actrapid and NPH insulin injections) in poorly controlled type 2 diabetes subjects on hs-CRP, VCAM-1 and AGE at 4, 8 and 12 weeks of treatment. Multiple insulin injections rapidly improved HbA(1c) by 0.6+/-0.9% (p<0.005), 1.2+/-1.3% (p<0.0005) and 1.3+/-1.4% (p<0.0005) at week 4, at week 8 and week 12, respectively. Subjects who continued their existing combination treatment of sulphonylurea, metformin+/-acarbose also showed a significant reduction in HbA(1c) (p<0.05). Although effective in reducing glycemic parameters, there was no reduction in CRP levels in either treatment group. The treatment regimen consisting of rosiglitazone and glimepiride significantly lowered hs-CRP by -2.6 (3.9) mg/L (p<0.05) at week 12 in spite of no improvement in blood glucose. AGE improved in all groups irrespective of type of treatment, glycaemic control and CRP levels. Our data indicate rapid glycaemic control alone does not necessarily result in improvement in markers of inflammation in type 2 diabetes patients.
Diabetes Res Clin Pract 2006 Apr
PMID:Improvement in C-reactive protein and advanced glycosylation end-products in poorly controlled diabetics is independent of glucose control. 1625 80

Impaired oxygenation sometimes occurs in patients with acute aortic dissection, however, the mechanism has not been fully investigated. We hypothesized that impaired oxygenation is related to inflammation secondary due to aortic dissection. Patients with acute aortic dissection who had received 14 days of conservative treatment were retrospectively examined. Patients who had undergone surgery or died within 14 days were excluded. Patients who had evidence of having pneumonia or pulmonary congestion during this period were also excluded. Twenty-six patients were divided into a preserved oxygenation group (minimum oxygenation index > or = 200, n = 13) and an impaired oxygenation group (minimum oxygenation index < 200, n = 13). Maximum serum C-reactive protein (max CRP) and other factors (age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, Stanford type, thrombosed false lumen, pleural effusion, atelectasis, use of intravenous vasodilators) for the two groups were compared. Max CRP was the only predictor for impaired oxygenation as calculated by single/multiple logistic regression analysis. Max CRP was significantly higher in the impaired oxygenation group (20.1 +/- 2.1 mg/dL) than in the preserved oxygenation group (10.5 +/- 1.4 mg/dL, P < 0.05). These results suggest that impaired oxygenation is related to inflammation, which is secondary due to acute aortic dissection.
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PMID:C-reactive protein is related to impaired oxygenation in patients with acute aortic dissection. 1627 70

End stage renal disease (ESRD) is a situation with a cardiovascular risk profile of almost unique severity. While traditional risk factors dominate the scene in the general population, non traditional risk factors like inflammation (high C Reactive Protein, CRP), high brain natriuretic peptide, as an expression of left ventricular hypertrophy and left ventricular dysfunction, and accumulation of the endogenous inhibitor of the NO synthase, asymmetric dimethyl arginine are all markers of high CV risk of ESRD patients. To obtain a quantitative insight on the predictive power of traditional and emerging risk factors in ESRD, we performed a detailed multivariate survival analysis in the cardiovascular risk extended evaluation (CREED) cohort database. As expected, traditional risk factors (ie, age, sex, smoking, diabetes, and risk factors peculiar to the uremic state such as low serum albumin level) and treatment modality contributed to explain the all-cause mortality (37%) and cardiovascular variation mortality (24%) variation as well. When cardiovascular comorbidities were considered in this analysis, the explained variation in mortality increased to 45.4% and 36.4%, respectively. Furthermore, a combined score based on 2 biomarkers (brain natriuretic peptide and C-reactive protein levels) increased the explanatory power of these models by about 10%. In conclusion, traditional risk factors explain about half of all-cause and cardiovascular mortality variation in the ESRD population. The combined use of 2 biomarkers reflecting inflammation and left ventricular mass and function increases by about one fifth the explained mortality variation in this population. Biomarkers give information beyond that provided by traditional risk factors and therefore represent an useful adjunct for the definition of the risk profile of ESRD patients.
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PMID:Predictors of cardiovascular death in ESRD. 1629 55


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