Rheumatoid arthritis: links with cardiovascular disease and the receptor for advanced glycation end products

Cardiovascular (CV) disease is increased in patients with chronic inflammatory disease, including rheumatoid arthritis (RA). Furthermore it has become clear at a pathophysiological level, that atherosclerosis has striking similarities with autoimmune disease. This realization has come at a time of paradigm shift in how rheumatologists manage RA, with the availability of biological agents targeting key inflammatory cytokines. This review will focus on the possible causes of increased vascular disease in RA, including the role of traditional CV risk factors. Mechanisms potentially at play, such as C-reactive protein (CRP), altered coagulation, and cyclooxygenase (COX) -2 inhibitors will be covered in brief. The Receptor for Advanced Glycation End Products (RAGE) has been identified as a candidate molecule influencing response to ongoing inflammation and autoimmunity. There will be a focus on the role of RAGE in CV disease and RA. As has been the case with many novel molecules, functional polymorphisms are thought to alter disease expression and assist us in coming to terms with the biological activities of the parent molecule. The review will conclude with a discussion of the potential role of the RAGE Glycine 82 Serine polymorphism

Walking performance, oxygen uptake kinetics and resting muscle pyruvate dehydrogenase complex activity in peripheral arterial disease

In the present study, we tested the hypothesis that walking intolerance in intermittent claudication (IC) is related to both slowed whole body oxygen uptake (Vo(2)) kinetics and altered activity of the active fraction of the pyruvate dehydrogenase complex (PDCa) in skeletal muscle. Ten patients with IC and peripheral arterial disease [ankle/brachial index (ABI) = 0.73 +/- 0.13] and eight healthy controls (ABI = 1. 17 +/- 0.13) completed three maximal walking tests. From these tests, averaged estimates of walking time, peak Vo(2) and the time constant of Vo(2) (tau) during submaximal walking were obtained. A muscle sample was taken from the gastrocnemius medialis muscle at rest and analysed for PDCa and several other biochemical variables. Walking time and peak Vo(2) were approx. 50 % lower in patients with IC than controls, and tau was 2-fold higher (P < 0.05). r was significantly correlated with walking time (r = -0.72) and peak Vo(2) (r = -0.66) in patients with IC, but not in controls. PDCa was not significantly lower in patients with IC than controls; however, PDCa tended to be correlated with tau (r = -0.56, P = 0.09) in patients with IC, but not in controls (r = -0.14). A similar correlation was observed between resting ABI and tau (r = -0.63, P = 0.05) in patients with IC. These data suggest that the impaired Vo(2) kinetics contributes to walking intolerance in IC and that, within a group of patients with IC, differences in Vo(2) kinetics might be partly linked to differences in muscle carbohydrate oxidation.

Strengthening cardiac rehabilitation and secondary prevention for Aboriginal and Torres Strait Islander peoples

This article summarises the findings of a project funded and supported by a principal committee of the National Health and Medical Research Council, the Health Advisory Committee, chaired by Professor Adele Green.

Influence of arterial compliance on presence and extent of ischaemia during stress echocardiography

Objective: To seek an association between total arterial compliance (TAC) and the extent of ischaemia at stress echocardiography. Design: Cohort study. Setting: Regional cardiac centre. Methods: 255 consecutive patients (147 men; mean (SD) age 58 (8)) presenting for stress echocardiography for clinical indications were studied. Wall motion score index (WMSI) was calculated and ischaemia was defined by an inducible or worsening wall motion abnormality. Peak WMSI was used to reflect the extent of dysfunction (ischaemia or scar), and Delta WMSI was indicative of extent of ischaemia. TAC was assessed at rest by simultaneous radial applanation tonometry and pulsed wave Doppler in all patients. Results: Ischaemia was identified by stress echocardiography in 65 patients (25%). TAC was similar in the groups with negative and positive echocardiograms (1.08 (0.41) v 1.17 (0.51) ml/ mm Hg, not significant). However, the extent of dysfunction was associated with TAC independently of age, blood pressure, risk factors, and use of a beta blocker. Moreover, the extent of ischaemia was determined by TAC, risk factors, and use of a b blocker. Conclusion: While traditional cardiovascular risk factors are strong predictors of ischaemia on stress echocardiography, TAC is an independent predictor of the extent of ischaemia.

Relationship between myocardial perfusion and dysfunction in diabetic cardiomyopathy: A study of quantitative contrast echocardiography and strain rate imaging

Objective: To use quantitative myocardial contrast echocardiography (MCE) and strain rate imaging (SRI) to assess the role of microvascular disease in subclinical diabetic cardiomyopathy. Methods: Stress MCE and SRI were performed in 48 patients (22 with type II diabetes mellitus (DM) and 26 controls), all with normal left ventricular systolic function and no obstructive coronary disease by quantitative coronary angiography. Real-time MCE was acquired in three apical views at rest and after combined dipyridamole-exercise stress. Myocardial blood flow (MBF) was quantified in the 10 mid- and apical cardiac segments at rest and after stress. Resting peak systolic strain rate (SR) and peak systolic strain (epsilon) were calculated in the same 10 myocardial segments. Results: The DM and control groups were matched for age, sex and other risk factors, including hypertension. The DM group had higher body mass index and left ventricular mass index. Quantitative SRI analysis was possible in all patients and quantitative MCE in 46 (96%). The mean e, SR and MBF reserve were all significantly lower in the DM group than in controls, with diabetes the only independent predictor of each parameter. No correlation was seen between MBF and SR (r = -0.01, p = 0.54) or between MBF and epsilon ( r = -0.20, p = 0.20). Conclusions: Quantitative MCE shows that patients with diabetes but no evidence of obstructive coronary artery disease have impaired MBF reserve, but abnormal transmural flow and subclinical longitudinal myocardial dysfunction are not related.

Are echo techniques comparable for measurement of left ventricular dysynchrony? Comparison of real time 3D and tissue Doppler echocardiography in patients with ischaemic cardiomyopathy

Tissue Doppler (TD) assessment of dysynchrony (DYS) is established in evaluation for bi-ventricular pacing. Time to regional minimal volume by real-time 3D echo (3D) has been applied to DYS. 3D offers simultaneous assessment of all segments and may limit errors in localization of maximum delay due to off-axis images.We compared TD and 3D for assessment of DYS. 27 patients with ischaemic cardiomyopathy (aged 60±11 years, 85% male) underwent TD with generation of regional velocity curves. The interval between QRS onset and maximal systolic velocity (TTV) was measured in 6 basal and 6 mid-cavity segments. Onthe same day,3Dwas performed and data analysed offline with Q-Lab software (Philips, Andover, MA). Using 12 analogous regional time-volume curves time to minimal volume (T3D)was calculated. The standard deviation (S.D.) between segments in TTV and T3D was calculated as a measure ofDYS. In 7 patients itwas not possible to measureT3D due to poor images. In the remaining 20, LV diastolic volume, systolic volume and EF were 128±35 ml, 68±23 ml and 46±13%, respectively. Mean TTV was less than mean T3D (150±33ms versus 348±54 ms; p < 0.01). The intrapatient range was 20–210ms for TTV and 0–410ms for T3D. Of 9 patients (45%) with significantDYS (S.D. TTV > 32 ms), S.D. T3D was 69±37ms compared to 48±34ms in those without DYS (p = ns). In DYS patients there was concordance of the most delayed segment in 4 (44%) cases.Therefore, different techniques for assessing DYS are not directly comparable. Specific cut-offs for DYS are needed for each technique.

Comparison between myocardial integrated backscatter and strain rate imaging in the quantitative assessment of subepicardial function post-myocardial infarction

Transmural extent of infarction (TME) may be an important determinant of functional recovery and remodeling. Recent animal data suggest that strain rate imaging (SRI) maybe able to identify subendocardial ischemia.We compared SRI and cyclic variation of integrated backscatter (CVIB) for predicting TME in the quantitative assessment of regional subepicardial function. Forty-nine (n = 49) postmyocardial infarct patients (61±10 years, EF 41±10%) underwent tissue Doppler echocardiography (TDE) and contrast enhanced magnetic resonance imaging (CMR). A15 mm×2mm sampling volume (tracked to wall motion) was placed over the long axis subepicardial region of each segment during TDE offline analysis to measure peak longitudinal systolic strain rate (SR), peak longitudinal systolic strain (PS), and CVIB. Findingswere compared with TME classified into two categories of scar thickness by CMR: Non-transmural (TME≤50%), and transmural (TME > 50%). Of 213 segments identified with resting wall motion abnormalities, 145 segments showed delayed hyperenhancement on CMR. SR, PS and CVIB were similar with no significant differences between transmural and non-transmural infarcts regardless of the echo modality.

Comparison between real-time three-dimensional echocardiography, T1-201 single photon emission computed tomography and cardiac magnetic resonance imaging in the quantitative assessment of left ventricular volumes

Left ventricular (LV) volumes have important prognostic implications in patients with chronic ischemic heart disease. We sought to examine the accuracy and reproducibility of real-time 3D echo (RT-3DE) compared to TI-201 single photon emission computed tomography (SPECT) and cardiac magnetic resonance imaging (MRI). Thirty (n = 30) patients (age 62±9 years, 23 men) with chronic ischemic heart disease underwent LV volume assessment with RT-3DE, SPECT, and MRI. Ano vel semi-automated border detection algorithmwas used by RT-3DE. End diastolic volumes (EDV) and end systolic volumes (ESV) measured by RT3DE and SPECT were compared to MRI as the standard of reference. RT-3DE and SPECT volumes showed excellent correlation with MRI (Table). Both RT- 3DE and SPECT underestimated LV volumes compared to MRI (ESV, SPECT 74±58 ml versus RT-3DE 95±48 ml versus MRI 96±54 ml); (EDV, SPECT 121±61 ml versus RT-3DE 169±61 ml versus MRI 179±56 ml). The degree of ESV underestimation with RT-3DE was not significant.