Melbourne Medical School Collected Works - Research Publications
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ItemReceptor for advanced glycation end products Glycine 82 Serine polymorphism and risk of cardiovascular events in rheumatoid arthritis(BIOMED CENTRAL LTD, 2007-01-01)Patients with rheumatoid arthritis (RA) are at risk of excess mortality, predominantly owing to cardiovascular (CV) events. The receptor for advanced glycation end products (RAGE) has been implicated in the perpetuation of the chronic inflammatory response in vascular disease. A Gly82-->Ser polymorphism in the RAGE gene, which is associated with enhanced RAGE signaling, is present more frequently in patients with RA than the general population. To investigate whether RAGE Gly82-->Ser polymorphism is associated with CV events in RA, we examined CV events, CV risk factors, features of RA and RAGE Gly82-->Ser polymorphism in 232 patients with RA attending a tertiary referral hospital. CV events, the duration and severity of RA, and risk factors for CV disease were determined using patient questionnaires, chart review, laboratory analysis and radiographs. DNA was typed for HLA-DRB1 genes and RAGE Gly82-->Ser polymorphism. The RAGE Ser82 allele, which is in linkage disequilibrium with the RA susceptibility allele HLA-DRB1*0401, was carried by 20% of patients. More than 20% of the cohort had suffered a vascular event; a shorter duration of RA, but not the RAGE genotype, was significantly associated with CV events. However, a history of statin use was protective. Thus, the RAGE Ser82 allele, associated with enhanced RAGE signaling, does not predispose to CV events in RA. However, treatment of hyperlipidemia with statins reduces the probability of a CV event.
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ItemTissue Doppler in critical illness: a retrospective cohort study(BIOMED CENTRAL LTD, 2007-01-01)BACKGROUND: There is a paucity of published data on tissue Doppler imaging (TDI) in the critically ill. In a critically ill cohort, we studied the distribution of TDI and its correlation with other echocardiographic indices of preload. To aid hypothesis generation and sample size calculation, associations between echocardiographic variables, including the ratio of peak early diastolic transmitral velocity (E) to peak early diastolic mitral annular velocity (E'), and mortality were also explored. METHODS: This retrospective study was performed in a combined medical/surgical, tertiary referral intensive care unit. Over a 2-year period, 94 consecutive patients who underwent transthoracic echocardiography with E/E' measurement were studied. RESULTS: Mean Acute Physiology and Chronic Health Evaluation III score was 72 +/- 25. Echocardiography was performed 5 +/- 6 days after intensive care unit admission. TDI variables exhibited a wide range (E' 4.7-18.2 cm/s and E/E' 3.3 to 27.2). E' below 9.6 cm/s was observed in 63 patients (rate of myocardial relaxation below lower 95% confidence limit of normal individuals). Fourteen patients had E/E' above 15 (evidence of raised left ventricular filling pressure). E/E' correlated with left atrial area (r = 0.27, P = 0.01) but not inferior vena cava diameter (r = 0.16, P = 0.21) or left ventricular end-diastolic volume (r = 0.16, P = 0.14). In this cohort, increased left ventricular end-systolic volume, but not E/E', appeared to be an independent predictor (odds ratio 2.1, P = 0.007) of 28-day mortality (31%; n = 29). CONCLUSION: There was a wide range of TDI values. TDI evidence of diastolic dysfunction was common. E/E' did not correlate strongly with other echocardiographic indices of preload. Further evaluation of echocardiographic variables, particularly left ventricular end-systolic volume, for risk stratification in the critically ill appears warranted.
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ItemCorrelates of preclinical cardiovascular disease in Indigenous and Non-Indigenous Australians: a case control study(BMC, 2008-07-16)BACKGROUND: The high frequency of premature death from cardiovascular disease in indigenous Australians is often attributed to the high prevalence of risk factors, especially type II diabetes mellitus (DM). We evaluated the relationship of ethnicity to atherosclerotic burden, as evidenced by carotid intima-media thickness (IMT), independent of risk factor status. METHODS: We studied 227 subjects (147 men; 50 +/- 13 y): 119 indigenous subjects with (IDM, n = 54), and without DM (InDM, n = 65), 108 Caucasian subjects with (CDM, n = 52), and without DM (CnDM, n = 56). IMT was measured according to standard methods and compared with clinical data and cardiovascular risk factors. RESULTS: In subjects both with and without DM, IMT was significantly greater in indigenous subjects. There were no significant differences in gender, body mass index (BMI), systolic blood pressure (SBP), or diastolic blood pressure (DBP) between any of the groups, and subjects with DM showed no difference in plasma HbA1c. Cardiovascular risk factors were significantly more prevalent in indigenous subjects. Nonetheless, ethnicity (beta = -0.34; p < 0.0001), age (beta = 0.48; p < 0.0001), and smoking (beta = 0.13; p < 0.007) were independent predictors of IMT in multiple linear regression models. CONCLUSION: Ethnicity appears to be an independent correlate of preclinical cardiovascular disease, even after correction for the high prevalence of cardiovascular risk factors in indigenous Australians. Standard approaches to control currently known risk factors are vital to reduce the burden of cardiovascular disease, but in themselves may be insufficient to fully address the high prevalence in this population.
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ItemAtherosclerotic disease is increased in recent-onset rheumatoid arthritis: a critical role for inflammation(BIOMED CENTRAL LTD, 2007-01-01)Rheumatoid arthritis (RA) patients have increased mortality and morbidity as a result of cardiovascular and cerebrovascular disease. What is not clear, however, is either how early accelerated atherosclerosis begins in RA or how soon risk factors must be rigorously controlled. Furthermore, given the strong relationship of vascular disease to RA mortality and of inflammation to the accelerated atherosclerosis associated with RA, it is important to evaluate indices that could serially and noninvasively quantify atherosclerotic disease in RA patients. The carotid intima-media thickness (cIMT) and plaque, measured by ultrasound, correlate closely with direct measurement of the local and systemic atherosclerotic burden. To investigate the presence of subclinical atherosclerosis in the early stages of RA, the cIMT and plaque were measured using carotid duplex scanning in 40 RA patients with disease duration < 12 months and in 40 control subjects matched for age, sex and established cardiovascular risk factors. Patients with RA had significantly higher average cIMT values and more plaque than the control group (cIMT 0.64 +/- 0.13 mm versus 0.58 +/- 0.09 mm, respectively; P = 0.03). In RA patients, the cIMT was predicted by age and C-reactive protein level at first presentation to the clinic (R2 = 0.64). C-reactive protein was associated with age of disease onset and history of smoking. Since inflammation has been shown to predate onset of clinical RA, the accelerated atherogenic process related to inflammation may precede RA symptom onset.
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ItemCombination of contrast with stress echocardiography: a practical guide to methods and interpretation.(Springer Science and Business Media LLC, 2004-08-26)Contrast echocardiography has an established role for enhancement of the right heart Doppler signals, the detection of intra-cardiac shunts, and most recently for left ventricular cavity opacification (LVO). The use of intravenously administered micro-bubbles to traverse the myocardial microcirculation in order to outline myocardial viability and perfusion has been the source of research studies for a number of years. Despite the enthusiasm of investigators, myocardial contrast echocardiography (MCE) has not attained routine clinical use and LV opacification during stress has been less widely adopted than the data would support. The purpose of this review is to facilitate an understanding of the involved imaging technologies that have made this technique more feasible for clinical practice, and to guide its introduction into the practice of the non-expert user.
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ItemBaseline and follow-up assessment of regional left ventricular volume using 3-dimensional echocardiography: comparison with cardiac magnetic resonance(BIOMED CENTRAL LTD, 2009-11-19)The assessment of regional volumes is an option for analysis of the response of LV segments to interventions such as revascularization or cell therapy. We sought to compare regional volumes from 3D-echocardiography (3DE) with cardiac magnetic resonance (CMR) over follow-up. CMR regional volumes were assessed at baseline and after one year follow-up in 30 unselected patients (28 men, 65 +/- 11 years) presenting for evaluation of cardiac function with previous infarction. 3DE images were also gathered over 4 cardiac cycles and measurements were performed off-line. CMR images were obtained using a 1.5 Tesla scanner and measured offline by method of landmarks and by centre of mass. Regional volumes were measured at end-diastole (rEDV) and end-systole (rESV) and the change in volume was compared for each over follow-up. There was good correlation between 3DE and both CMR methods at baseline and follow-up. Changes in rEDV with 3DE vs CMR(L) were comparable (0.11 +/- 3 ml vs 0.12 +/- 3 ml, p = 0.94), as was change in CMR(M) (0.26 +/- 2 ml, p = 0.69). However the change in regional volume by 3DE and CMR(L) correlated poorly (r = 0.03, p = 0.68), as did change in 3DE vs CMR(M) (r = 0.04, p = 0.65). Similarly, changes in rESV with 3DE and CMR(L) were similar (0.27 +/- 2 ml vs 0.36 +/- 2 ml, p = 0.70), as was change in CMR(M) (0.05 +/- 1 ml, p = 0.31). Again, correlations between rESV by 3DE vs CMR(L) were poor (r = 0.03, p = 0.72), as well as 3DE vs CMR(M) (r = 0.07, p = 0.40). Although global 3DE volumes compare well with CMR volumes, new developments in image quality and automated software will be needed before changes in regional volumes can be reliably followed with 3DE.
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ItemInflammation predicts accelerated brachial arterial wall changes in patients with recent-onset rheumatoid arthritis(BMC, 2009-01-01)INTRODUCTION: Patients with recent-onset rheumatoid arthritis (RA) have impaired brachial artery endothelial function compared with controls matched for age, sex and cardiovascular risk factors. The present study examined endothelium-dependent (flow-mediated dilatation (FMD)) and independent (glyceryl trinitrate (GTN)-mediated dilatation (GMD)) structural responses in early RA patients, and determined progress over one year. METHODS: Brachial artery FMD and GMD and carotid intima media thickness (cIMT) were studied using ultrasound in 20 patients diagnosed with early RA in whom symptoms had been present for less than 12 months, and in 20 control subjects matched for age, sex and established cardiovascular risk factors. FMD and GMD were re-assessed after 12 months in RA patients and the change in each parameter was calculated. Data were analysed by univariate regression. RESULTS: Mean FMD and GMD were significantly lower in early RA patients at baseline than in controls, but each parameter significantly improved in one year. FMD and GMD responses were positively associated with each other. Patients' age, C-reactive protein (CRP) level and cIMT at baseline and CRP level at one year, were negatively associated with change in brachial responses in one year. CONCLUSIONS: Patients with recent-onset RA have altered brachial artery responses signifying both functional and structural abnormalities. However, early control of inflammation may reduce arterial dysfunction and thus the tendency for atherosclerotic progression.