Search

HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and its inhibition exerts profound effects on cellular metabolism. Inhibitors of this enzyme are used in clinical practice to lower plasma cholesterol levels and are commonly collectively referred to as ‘statins’. A number of in vitro, in vivo animal, and clinical studies suggest that properties of statins other than cholesterol lowering may be of biological importance. These diverse properties are often referred to as ‘pleiotropic’ and suggest that statins may affect a number of diseases of ageing. In this article we review the biological plausibility and clinical evidence of a role for statins in modulating two diseases of ageing: osteoporosis and dementia (including Alzheimer's disease). In both diseases, there is a sound cellular and laboratory basis for a plausible therapeutic effect of statins. In the case of osteoporosis, there are conflicting data regarding clinical benefit, with both negative and positive results reported. In particular, secondary analyses of randomised, controlled studies have shown no reduction of fracture risk by statins. In the case of dementia there are fewer clinical studies but there is clear anticipated benefit in macrovascular dementias attributable to statin-mediated reduction of the risk of stroke. Overall, there are a lack of prospective, placebo-controlled, randomised data testing statins and modulation of the risk of osteoporosis-related fracture or of clinical dementia, where these are primary outcomes. Until such data are available, the use of statins appears promising but cannot be recommended as a primary therapeutic modality for either condition. [ABSTRACT FROM AUTHOR]

Colchicine inhibits coronary and cerebrovascular events in patients with coronary artery disease (CAD), and although known to have anti-inflammatory properties, its mechanisms of action are incompletely understood. In this study, we investigated the effects of colchicine on platelet activation with a particular focus on its effects on activation via the collagen glycoprotein (GP)VI receptor, P2Y12 receptor, and procoagulant platelet formation. Therapeutic concentrations of colchicine in vitro (equivalent to plasma levels) significantly decreased platelet aggregation in whole blood and in platelet rich plasma in response to collagen (multiplate aggregometry) and reduced reactive oxygen species (ROS) generation (H2DCF-DA, flow cytometry) in response to GPVI stimulation with collagen related peptide-XL (CRP-XL, GPVI specific agonist). Other platelet activation pathways including P-selectin expression, GPIIb/IIIa conformational change and procoagulant platelet formation (GSAO+/CD62P+) (flow cytometry) were inhibited with higher concentrations of colchicine known to inhibit microtubule depolymerization. Pathway specific mechanisms of action of colchicine on platelets, including modulation of the GPVI receptor pathway at low concentrations, may contribute to its protective role in CAD. [ABSTRACT FROM AUTHOR]

Myocardial bridging is a congenital anomaly wherein a segment of a coronary artery passes under a 'bridge' of heart muscle rather than resting upon the heart's surface. Although it is usually benign, myocardial bridging has been associated with adverse clinical events including ischaemia, arrhythmia and sudden death. Moreover, there is a tendency for atherosclerotic lesions to develop upstream of the bridge. These lesions may be the result of adverse fluid dynamic phenomena induced by the periodic compression of the artery by the overlying myocardial bridge. It is not possible to visualise these phenomena in vivo, and in this study we present an in vitro model capable of replicating the bridging conditions. This model is comprised of a pressure-measuring guide wire and catheter, a piston pump, a scaled artery model, and a 'myocardial bridging mechanism' which periodically compresses the artery model. A proportional-integral-derivative (PID) controller allowed the piston pump to recreate a patient-specific aortic pressure waveform upstream of the occluded artery model segment for each study. Stationary occlusions—achieved by placing 3D printed 'stenosis inserts' within the artery model—induced globally reduced pressures downstream of the stenosis when compared against the upstream pressure waveform. Conversely, the pressures downstream of the dynamic stenoses generated by the bridging mechanism closely matched the upstream pressures at all stages of the cardiac cycle except at the end of systole. This divergent pressure behaviour at the end of systole was similarly observed in vivo within a patient with a myocardial bridge. Flow visualisation using a laser sheet enabled dynamic flow structures to be observed, including recirculating flow regions, which may be precursors to arterial dysfunction. [ABSTRACT FROM AUTHOR]

Background: Chest pain is the second most common presenting symptom to emergency departments (ED) in Australia, although up to 85% of these patients do not have an acute coronary syndrome (ACS). Cardiologist-led rapid access chest pain clinics (RACPC) have been proposed overseas to assist in the management of such patients, with prompt outpatient assessment if patients are deemed low risk and discharged from the ED. The use of RACPCs in Australia has been only recently proposed; we therefore sought to examine one such RACPC in an Australian context.Methods and Results: 1133 consecutive patients were seen at a metropolitan RACPC, between August 2008 and February 2017. There was a high preponderance of cardiovascular risk factors. Exercise stress testing (EST) was the default investigation upon discharge from ED, with a total of 1038 ESTs performed in 1113 patients (93%), with low numbers of other functional tests, and a small, but increasing number of coronary computed tomography (CT) scans performed over this period. Eighteen patients subsequently underwent revascularisation (1.6% of the total cohort), and none of these patients were readmitted at any time with an ACS between the interval of their index ED presentation to these investigations or treatments. Five (0.4%) patients represented to ED within 48hours, none due to a cardiovascular cause. A total of 24 (2.1%) patients represented between 2 and 28 days, with none of these due to an ACS.Conclusions: Following ED assessment of acute chest pain as low risk-with direct ED referral for exercising testing followed by RACPC review-results in very low readmission rates at 48hours and at 28 days. Moreover, these readmissions were almost always not of cardiovascular aetiology, and occurred despite relatively longer waiting periods for both EST (8 days) and between EST and RACPC review (11 days), than the prespecified 72 to 96hours as defined by the clinic protocol. Further investigation into this model of care in Australia is suggested. [ABSTRACT FROM AUTHOR]

Background Long-term studies following acute pulmonary embolism (PE) remain limited in the current era. A recent study from our collaborative group, in a contemporary adult population, showed substantially increased cardiovascular mortality following PE. We sought to evaluate the contribution of cardiovascular mortality to long-term outcomes in a different demographic that comprised of a significantly younger PE cohort. Methods and results Demographic and clinical characteristics were retrospectively collected for this cohort, and similar methods and outcome measures were applied as detailed in the original study. We compared a population from a different metropolitan area (LH: Liverpool Hospital) to that from the original study (CRGH: Concord Hospital) over a similar time period. A total of 815 patients comprised this cohort with mean 5.3 ± 3.8 year follow-up. There were similar demographics between the two cohorts, though the mean age was significantly younger in LH group (60 vs 68 years, p < 0.001). Prior history of cardiovascular disease in the LH group was half of that present in the CRGH cohort. The overall mortality was 7.4% per patient-year. Patients with underlying cardiovascular disease when presenting with an acute PE had a 2.3-fold increased risk of death during follow-up compared to those without. Multivariate analysis showed that older age, male gender, malignancy, diabetes, cardiovascular disease and chronic pulmonary disease were independent predictors of post-discharge mortality. Conclusions Despite our cohort being significantly younger with a lower incidence of pre-existing cardiovascular disease, cardiovascular disease was still a significant contributor to long-term outcomes and an important predictor of mortality following acute PE. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy (MD) is a multisystem, autosomal dominant disorder best known for its skeletal muscle manifestations. Cardiac manifestations arise as a result of myocardial fatty infiltration, degeneration and fibrosis and present most commonly as arrhythmias or conduction disturbances. Guidelines regarding the optimal cardiac management of patients with MD are lacking. The present article provides a summary of the pathophysiology of cardiac problems in patients with MD and provides a practical approach to contemporary cardiac monitoring and management of these patients with a focus on the prevention of complications related to conduction disturbances and arrhythmias. Methods : A literature search was performed using PubMed and Medline. The keywords used in the search included "myotonic dystrophy", "cardiac manifestations", "heart", "arrhythmia", "pacemaker" and "defibrillator", all terms were used in combination. In addition, "myotonic dystrophy" was searched in conjunction with "electrophysiology", "electrocardiogram", "echocardiograph", "signal averaged electrocardiograph", "magnetic resonance imaging" and "exercise stress testing". The titles of all the articles revealed by the search were screened for relevance. The abstracts of relevant titles were read and those articles which concerned the cardiac manifestations of myotonic dystrophy or the investigation and management of cardiac manifestations underwent a full manuscript review. [ABSTRACT FROM AUTHOR]

Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147), which binds to the platelet-specific collagen receptor glycoprotein (GP) VI, is expressed in a range of cell types including platelets and leukocytes, and has been implicated in neoplastic disease and atherosclerotic coronary disease. Both CD147 and GPVI can be shed from cell membranes and detected in plasma. However, while the relationship between soluble CD147 (sCD147), soluble GPVI (sGPVI) and standard markers of platelet activation has received little attention, such analysis may help reveal pathways mediating release of sCD147. We investigated the relationship between sCD147 and platelet markers including sGPVI, soluble and platelet-bound CD62P (P-selectin), active αIIbβ3 (assessed by PAC-1 binding) and platelet CD147 in 25 patients with stable angina pectoris (SAP), 13 patients with no coronary artery disease (CAD) and 10 healthy donors. Plasma levels of sCD147 significantly correlated with sGPVI ( r = 0.46, p = .004), but did not correlate with any other platelet markers examined. Linear regression analysis identified that sCD147 levels could be predicted by sGPVI levels ( β = .445, p = 0.003) and age ( β = 0.304, p = 0.038), but were independent of potential clinical confounders such as CAD, diabetes and medication usage. As sCD147 strongly correlates with platelet-specific sGPVI, a common platelet source and/or mechanism of release may contribute to sCD147 levels in vivo. [ABSTRACT FROM AUTHOR]