C-reactive protein, cardiovascular risk, and renal disease in a remote Australian Aboriginal community

Rates of cardiovascular and renal disease in Australian Aboriginal communities are high, but we do not know the contribution of inflammation to these diseases in this setting. In the present study, we sought to examine the distribution of C-reactive protein (CRP) and other markers of inflammation and their relationships with cardiovascular risk markers and renal disease in a remote Australian Aboriginal community. The study included 237 adults (58% of the adult population) in a remote Aboriginal community in the Northern Territory of Australia. Main outcome measures were CRP, fibrinogen and lgG concentrations, blood pressure (BP), presence of diabetes, lipids, albuminuria, seropositivity to three common micro-organisms, as well as carotid intima-media thickness (IMT). Serum concentrations of CRP [7 (5-13) mg/l; median (inter-quartile range)] were markedly increased and were significantly correlated with fibrinogen and lgG concentrations and inversely correlated with serum albumin concentration. Higher CRP concentrations were associated with lgG seropositivity to Helicobacter pylori and Chlamydia pneumoniae and higher lgG titre for cytomegalovirus. Higher CRP concentrations were associated with the following: the 45-54-year age group, female subjects, the presence of skin sores, higher body mass index, waist circumference, BP, glycated haemoglobin and greater albuminuria. CRP concentrations increased with the number of cardiovascular risk factors, carotid IMT and albuminuria independently of other risk factors. These CRP concentrations were markedly higher than described in other community settings and are probably related, in a large part, to chronic and repeated infections. Their association with markers of cardiovascular risk and renal disease are compatible with the high rates of cardiovascular and renal disease in this community, and provide more evidence of strong links between these conditions, through a shared background of infection/inflammation. This suggests that a strong focus on prevention and management of infections will be important in reducing these conditions, in addition to interventions directed at more traditional risk factors.

Carotid intima-media thickness, cardiovascular risk factors and albuminuria in a remote Australian Aboriginal community

Background: Rates of cardiovascular disease and renal disease in Australian Aboriginal communities are high, as is the prevalence of some 'traditional' cardiovascular (CV) risk factors, such as diabetes and cigarette smoking. Recent work has highlighted the importance of markers of inflammation, such as C-reactive protein (CRP), homocysteine and albuminuria as predictors of cardiovascular risk in urban westernised settings. It is not clear how these factors relate to outcome in the setting of these remote communities, but very high CRP concentrations have been shown in this and other Aboriginal communities. Methods and results: In a cross-sectional survey including 237 adults in a remote Aboriginal community in the Northern Territory of Australia, we measured carotid intima-media thickness (IMT), together with blood pressure, diabetes, lipid levels, smoking and albuminuria, CRP and fibrinogen, serum homocysteine concentration, and IgG titres for Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus. Median carotid IMT was 0.63 [interquartile range 0.54-0.71] mm. As a categorical outcome, the prevalence of the highest IMT quartile ('increased IMT', greater than or equal to0.72 mm) was compared with the lower three quartiles. Increased IMT was associated in univariate analyses with greater waist circumference, systolic BP, fibrinogen and serum albumin concentrations, urine albumin/creatinine ratio and older age as continuous variables. Associations of increased IMT with some continuous variables were not linear; univariate associations were seen with the highest quartile (versus all other quartiles) of CRP and homocysteine concentration and CMV IgG titre. In a multivariate model age, smoking, waist circumference and the highest quartile of CRP concentrations (greater than or equal to14 mg/l) remained significant predictors of IMT greater than or equal to0.72 mm. Conclusions: Measurement of carotid IMT was possible in this remote setting. Increased IMT (greater than or equal to0.72 mm) was associated with increased CRP concentrations over a range that suggests infection/inflammation may be important determinants of cardiovascular risk in this setting. The associations of IMT with markers of renal disease seen in univariate analyses were explained in this analysis by confounding due to the associations of urine ACR with other risk factors. (C) 2004 Published by Elsevier Ireland Ltd.

Therapeutic effects and possible mechanisms of a snake venom preparation in the fibrotic rat liver

The effects of a Chinese snake venom preparation from Agkistrodon halys pallas, used for treatment of hepatic fibrosis/cirrhosis in China, was investigated in an {in vivo} rat model and using in situ hepatic perfusion. Four groups were used in the experiments: (i) healthy, (ii) healthy/venom-treated, (iii) carbon tetrachloride (CCl4)-treated, and (iv) CCl4/venom-treated. Treatment effects were assessed by determining hepatic histopathology, biochemistry and fibrosis index parameters, bile production, biliary taurocholate recovery, hepatic mRNA expression of four bile salt transporters (Ntcp, Bsep, Oatp-1, and Oatp-3), comparison of hepatic microcirculation, fibrinolytic activity, and antithrombotic effects. Liver histopathology, biochemistry, and fibrosis index showed a dramatic improvement in venom-treated animals. There were significant differences in bile production between healthy/venom-treated and all other experimental groups and between CCl4/venom-treated and CCl4-treated animals, but no significant differences were found between CCl4/venom-treated and healthy animals. Biliary taurocholate recovery was significantly increased in healthy/venom-treated and CCl4/venom-treated animals. The expression of mRNA levels of the four bile salt transporters showed an increase after venom treatment. The hepatic microcirculation studies showed normalized sinusoidal beds in CCl4/venom-treated animals compared to healthy animals, whereas CCl4-treated animals showed abnormal profiles to the healthy and the CCl4/AHPV-treated animals. The fibrinogen and plasma thromboxane B-2 levels of healthy rats decreased with increasing dose after venom treatment. It was concluded that snake venom treatment may be therapeutic in treatment of hepatic fibrosis/cirrhosis by possibly a combination of increased bile flow and improved hepatic microcirculation, changes in bile salt transporter expression, and fibrinolytic and antithrombotic effects of the snake venom preparation.