Atherosclerotic disease is increased in recent-onset rheumatoid arthritis: a critical role for inflammation

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

A new technique for assessing arterial pressure wave forms and central pressure with tissue Doppler

BACKGROUND: Non-invasive assessment of arterial pressure wave forms using applanation tonometry of the radial or carotid arteries can be technically challenging and has not found wide clinical application. 2D imaging of the common carotid arteries is routinely used and we sought to determine whether arterial waveform measurements could be derived from tissue Doppler imaging (TDI) of the carotid artery. METHODS: We studied 91 subjects (52 men, age 52 ± 14 years) with and without cardiovascular disease. Tonometry was performed on the carotid artery simultaneously with pulsed wave Doppler of the LVOT and acquired digitally. Longitudinal 2D images of the common carotid artery with and without TDI were also acquired digitally and both TDI and tonometry were calibrated using mean and diastolic cuff pressure and analysed off line. RESULTS: Correlation between central pressure by TDI and tonometry was excellent for maximum pressure (r = 0.97, p < 0.0001). The mean differences between central pressures derived by TDI and tonometry were minimal (systolic 5.36 ± 5.5 mmHg; diastolic 1.2 ± 1.2 mmHg). CONCLUSION: Imaging of the common carotid artery motion with tissue Doppler may permit acquisition of a waveform analogous to that from tonometry. This method may simplify estimation of central arterial pressure and calculation of total arterial compliance

Doing Good in HCI:Can We Broaden Our Agenda?

Heatmap depicting DNA damage gene expression across treatment cohorts. Color bar indicates log-fold expression change compared to control tumors. (PDF 92 kb

Cardiac and vascular structure and function parameters do not improve with alternate nightly home hemodialysis: An interventional cohort study

Background: Nightly extended hours hemodialysis may improve left ventricular hypertrophy and function and endothelial function but presents problems of sustainability and increased cost. The effect of alternate nightly home hemodialysis (NHD) on cardiovascular structure and function is not known

Correlates of preclinical cardiovascular disease in Indigenous and Non-Indigenous Australians: a case control study

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 (β = -0.34; p < 0.0001), age (β = 0.48; p < 0.0001), and smoking (β = 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

Non-Invasive Assessment of Arterial Elasticity: Clinical Manifestations and Treatment Implications

Until recently, tests of vascular structure, function and compliance have been used predominantly for assessing the efficacy of treatment – for example, aggressive medical therapy may yield improvements in vascular structure and function with a concomitant decrease in cardiac events. However, the role of abnormal vessel function in the development of atherosclerosis, and the relationship of structural changes in peripheral vessels with coronary disease might suggest that these tests could be used as a screening test for patients with subclinical coronary disease. At present, there is insufficient evidence to support the theory that normal vascular structure and function can rule out significant coronary disease, and indeed, such an association may be confounded by the presence of risk factors that alter these test results in the absence of significant coronary artery disease (CAD). The overall hypothesis of the studies undertaken in this thesis was that utilizing contemporary technology during ultrasonic and tonometric assessment of arterial structure, function and compliance, it is possible to non-invasively characterise both early and advanced arterial dysfunction and identify patients both at risk and with cardiovascular disease. The aim of these studies was to determine whether these tests can be used to guide intervention when arterial dysfunction is diagnosed and whether they are robust enough as a follow-up tool. The thesis initially reviews arterial structure, function and compliance and their relationship to cardiovascular risk and in particular, CAD. This review provides a rationale for the studies undertaken here to resolve clinical and technical issues as well as provide an insight into the tests chosen to assess arterial function. The second chapter discusses the methodology used in these studies to assess arterial structure, function and compliance, diagnose coronary artery disease and determine cardiovascular risk. They range from stress echocardiography for the diagnosis of CAD to tests for arterial structure (carotid intima-media thickness [IMT]), endothelial function (brachial artery reactivity [BAR]), local arterial distensibility (distensibility coefficient [DC]) and systemic or total arterial compliance (TAC). In addition, several methods will be discussed for assessing local arterial elasticity with a novel imaging technique. The rationale for using tests for arterial structure, function and compliance in patients with CAD as well as cardiovascular risk is examined in chapter 3. Chapter 3 examines the use of TAC, IMT and BAR in patients undergoing dobutamine stress echocardiography (DSE) in a group of patients with and without disease. TAC was neither an independent predictor of CAD risk or patients having CAD in this study. BAR was a predictor of risk status but not of patients having CAD. Only IMT was an independent predictor of both patients at risk for CAD and those with CAD. In chapter 3 both pulse pressure and total arterial compliance were only univariate predictors of risk for CAD. Chapter 4 examines three different methods of estimating TAC, all based on the two-element Windkessel model in 320 patients with and without cardiovascular risk. The pulse-pressure method (PPM) is based on a combination of pressure, obtained using applanation tonometry of the radial artery, and an estimate of stroke volume obtained by Doppler echocardiography of the left ventricular outflow and by 2D echocardiographic dimension of the left ventricular outflow tract. The area method (AM) is an integral variation of the Windkessel equations and is based on the derived central pressure waveform. The stroke volume-pulse pressure method (SVPP) is a simple ratio of stoke volume and pulse pressure. We conclude that they correlate well and show similar differences between groups with and without risk. The PPM had the smallest difference from the mean and standard deviation in Bland Altman analysis and we therefore used the PPM for most future studies. Chapter 5 discusses the use of tissue Doppler for the derivation of central pressure and determination of distensibility coefficient, a marker of local arterial elasticity. Tissue Doppler can be used to evaluate the low frequency, high amplitude signals which come from tissue by changing filtering settings on an ultrasound machine. Using off-line software, the tissue velocities can be extracted and with a processing algorithm, vessel wall displacement values over time can be generated. These vessel wall displacement values which are in microns (µm) can then be used to calculated distensibility coefficient which is calculated as 2*((net displacement/minD)/PP). We studied a large group of patients with and without cardiovascular risk and conclude that DC using tissue Doppler correlates highly with DC by B-mode and M-mode imaging and is also very reproducible. In a subgroup, the vessel displacement values were “calibrated” using mean and diastolic pressure and with specialised software and a transfer function, central pressure wave forms were reconstructed. In this study we conclude that the central pressure obtained using tissue Doppler displacement of the carotid artery correlates highly with that obtained using applanation tonometry although there are technical challenges involved. With the known prognostic value of pulse pressure, chapter 6 explores whether there is added benefit to measuring total arterial compliance over pulse pressure alone. Once again patients with and without disease were studied and we conclude that brachial pulse pressure correlates well with TAC in men with normal cardiac function. However, in women and in patients at the low and high extremes of function, and in patients with preclinical and overt cardiovascular disease, there appears to be incremental value in measuring TAC. The role of cardiovascular risk factors in association with TAC is examined in chapter 7. Several studies have shown that TAC is lower in certain groups due to age, height, hypertension, hyperlipidaemia or other factors. We studied 720 patients with and without cardiovascular risk factors and did several multiple linear regression models based on anthropomorphic variables. Age was an independent correlate of TAC in most of the regression models and we conclude that TAC is associated with multiple risk factors, but age is a major determinant. The influence of age and other correlates may dwarf the contribution of individual risk factors and therefore their alteration with therapy. Chapter 8 examines the correlates of preclinical cardiovascular disease in both indigenous and non-indigenous Australians with and without diabetes mellitus (DM). DM is a major health problem in the Indigenous population in Australia and CVD occurs earlier in this group than in caucasians and is responsible for 1/3 of all deaths. We studied a large group of indigenous Australians with and without DM and matched them to a caucasian population. There were no differences in BAR between the groups probably due to large standard deviations in the measurements. In assessing DC, both DM groups had significantly lower DC than the non-DM groups. However, in the IMT analysis both of the indigenous groups had significantly higher IMT than their caucasian counterparts and even after IMT was corrected for age, Indigenous patients even at an early age had significantly higher IMT. We conclude that despite a high incidence of risk factors in indigenous Australians both with and without DM, ethnicity (and various other risk factors for which it is a marker) appears to be an independent predictor of preclinical cardiovascular disease. In chapter 3 we determined that TAC was not an independent correlate of patients either at risk of CAD or with CAD. Chapter 9 discusses the results of a study of patients presenting for stress echocardiography for either detection of CAD or risk stratification. Ischaemia was detected in 25% of cases and TAC was similar in those with and without ischaemia. In multiple linear regression models however, in addition to cardiovascular risk factors TAC was independently associated with both the presence of CAD and the extent of ischaemia at stress echocardiography. Several studies have used vascular function as an outcome measure in intervention trials, either lifestyle or pharmacologic. In chapter 10 we undertook a lifestyle and diet intervention study in a large group of healthy patients with type-II DM. The tests for IMT, BAR and TAC were used in addition to biochemical markers and fitness assessment. At follow-up the intervention group had significant changes in weight and BMI and significantly increased fitness but failed to show any changes in any of the vascular parameters. We conclude that while metabolic and fitness parameters respond to treatment in patients with type-II DM, the early changes seen in vascular structure, function and compliance may not change in the long term. Although TAC has been correlated with hypertension, LVH, myocardial ischaemia and heart failure there are few data existing regarding the relationship of TAC to outcome. In the final chapter of this thesis we sought whether TAC was predictive of outcome in a large, primary prevention group of patients with varying degrees of cardiovascular risk. We followed up 719 patients who were studied between 2001 and 2008 in Brisbane, Australia and examined TAC in relation to mortality and a composite endpoint of death or hospital admission. There were significant differences in groups having low and normal TAC for both death and the composite endpoint and in patients with intermediate and high Framingham 10-year risk TAC was an independent predictor of both death and the composite endpoint. We conclude that TAC correlates with outcome in patients with varying degrees of cardiovascular risk and also adds incremental benefit to Framingham risk alone in patients with intermediate risk

Clinical application and laboratory protocols for performing contrast echocardiography

Technically difficult echocardiographic studies with suboptimal images remain a significant challenge in clinical practice despite advances in imaging technologies over the past decades. Use of microbubble ultrasound contrast for left ventricular opacification and enhancement of endocardial border detection during rest or stress echocardiography has become an essential component of the operation of the modern echocardiography laboratory. Contrast echocardiography has been demonstrated to improve diagnostic accuracy and confidence across a range of indications including quantitative assessment of left ventricular systolic function, wall motion analysis, and left ventricular structural abnormalities. Enhancement of Doppler signals and myocardial contrast echocardiography for perfusion remain off-label uses. Implementation of a contrast protocol is feasible for most laboratories and both physicians and sonographers will require training in contrast specific imaging techniques for optimal use. Previous concerns regarding the safety of contrast agents have since been addressed by more recent data supporting its excellent safety profile and overall cost-effectiveness