Cardiovascular outcomes of cancer patients in rural Australia

BackgroundCancer and heart disease are the two most common health conditions in the world, associated with high morbidity and mortality, with even worse outcomes in regional areas. Cardiovascular disease is the leading cause of death in cancer survivors. We aimed to evaluate the cardiovascular outcomes of patients receiving cancer treatment (CT) in a regional hospital.MethodsThis was an observational retrospective cohort study in a single rural hospital over a ten-year period (17th February 2010 to 19th March 2019). Outcomes of all patients receiving CT during this period were compared to those who were admitted to the hospital without a cancer diagnosis.Results268 patients received CT during the study period. High rates of cardiovascular risk factors: hypertension (52.2%), smoking (54.9%), and dyslipidaemia (38.4%) were observed in the CT group. Patients who had CT were more likely to be readmitted with ACS (5.9% vs. 2.8% p = 0.005) and AF (8.2% vs. 4.5% p = 0.006) when compared to the general admission cohort. There was a statistically significant difference observed for all cause cardiac readmission, with a higher rate observed in the CT group (17.1% vs. 13.2% p = 0.042). Patients undergoing CT had a higher rate of mortality (49.5% vs. 10.2%, p ≤ 0.001) and shorter time (days) from first admission to death (401.06 vs. 994.91, p ≤ 0.001) when compared to the general admission cohort, acknowledging this reduction in survival may be driven at least in part by the cancer itself.ConclusionThere is an increased incidence of adverse cardiovascular outcomes, including higher readmission rate, higher mortality rate and shorter survival in people undergoing cancer treatment in rural environments. Rural cancer patients demonstrated a high burden of cardiovascular risk factors

The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis

Aging promotes a range of degenerative pathologies characterized by progressive losses of tissue and/or cellular function. Fibrosis is the hardening, overgrowth and scarring of various tissues characterized by the accumulation of extracellular matrix components. Aging is an important predisposing factor common for fibrotic heart and respiratory disease. Age-related processes such as senescence, inflammaging, autophagy and mitochondrial dysfunction are interconnected biological processes that diminish the regenerative capacity of the aged heart and lung and have been shown to play a crucial role in cardiac fibrosis and idiopathic pulmonary fibrosis. This review focuses on these four processes of aging in relation to their role in fibrosis. It has long been established that the heart and lung are linked both functionally and anatomically when it comes to health and disease, with an ever-expanding aging population, the incidence of fibrotic disease and therefore the number of fibrosis-related deaths will continue to rise. There are currently no feasible therapies to treat the effects of chronic fibrosis therefore highlighting the importance of exploring the processes of aging and its role in inducing and exacerbating fibrosis of each organ. The focus of this review may help to highlight potential avenues of therapeutic exploration</p

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Pathogenesis of aortic stenosis : implications regarding impairment of nitric oxide signalling.

Aortic valve stenosis (AS) is now the most common valve disease in Western world and its prevalence and incidence are rising. The earliest clinically detectable stage of this process, aortic valve sclerosis (ASc), reflects abnormal aortic valve morphology in the absence of haemodynamic obstruction, but may progress to AS. The prevalence of ASc is as high as 25% in populations over 65 years of age: - thus it carries important epidemiological, clinical and pathophysiological implications. Despite the increased interest into studies of ASc/AS, the pathogenesis of this condition remains largely elusive, except to say that rather than the notion of being just a “wear and tear” inevitable process, it is now accepted to be an active pathophysiological process. The relevant literature is reviewed in Chapter 1. Studies described in this thesis address the determinants of occurrence and progression of ASc in a cohort of aging subjects followed for 4 years. Novel methodology of aortic valve ultrasonic backscatter was utilized to quantitate ASc severity and progression. In the subsequent studies the effects of ASc on left ventricular hypertrophy (LVH) were evaluated in a separate cohort of healthy aging individuals, with no significant cardiovascular risk factors or hypertensive therapy. Finally, effects of aging on integrity of the nitric oxide (NO) signalling cascade were examined in the population cohort recruited for evaluation of progression of ASc. The key findings from this thesis are: (1) Platelet NO responsiveness is a determinant of both the occurrence and progression of ASc, while age and BMI are determinant of occurrence only. Calcium levels and arterial stiffness correlate only with progression. Categorical assessment of progression reveals that use of inhibitors of the renin-angiotensin system is associated with lack of ASc progression. (2) Whilst ASc is not correlated with the development of LVH in the absence of treated hypertension, markers of NO generation and of the NO/ cyclic GMP signalling cascade in the peripheral circulation predict both LV mass index and LV diastolic function in a normal, untreated, aging population, irrespective of ASc status. (3) Aging is associated with both increases in ADP-induced platelet aggregation and plasma asymmetric dimethyarginine (ADMA) concentrations, and with reductions in platelet NO responsiveness. Female gender is associated with more severely impaired platelet NO responsiveness, greater arterial stiffness and a more pronounced fall in platelet NO responsiveness with time, which in turn was also observed in subjects with lower plasma vitamin D concentrations. There is a significant relationship between deterioration in platelet NO responsiveness and increases in ADMA concentrations. Finally, use of angiotensin convertin enzyme inhibitors/angiotensin receptor blockers is associated with preserved platelet NO responsiveness and lower arterial stiffness. In summary, the aging process is associated with a remarkable degree of attenuation of NO generation and signalling, which constitutes both a correlate of ASc development/progression and of the development of LVH (although the latter is not closely associated with ASc in "normal" populations). Furthermore, the rate of deterioration of NO signalling is greatest in females, in the presence of low vitamin D levels and correlates with rises in ADMA concentrations.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201

Elevated parathyroid hormone predicts high asymmetric dimethylarginine (ADMA) concentrations in obese diabetic patients

Impaired vascular endothelial function has been suggested as a possible mechanism to explain the nexus between vitamin D deficiency and increased adverse cardiovascular outcomes. In addition, elevated PTH is also found associated with increased arterial stiffness and impaired endothelial function, improved after lowering of PTH with parathyroidectomy. Previously, we have shown that in an ageing population, low vitamin D levels are associated with elevated plasma concentrations of asymmetric dimethylarginine (ADMA). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), has been shown to be a critical circulating biomarker of endothelial function, and adverse cardiovascular outcomes. However, we did not assess the relationship between ADMA and PTH. Given, the high prevalence of low vitamin D and high parathyroid hormone (PTH) levels in obese diabetic patients, we sought to examine in this study, whether the relationship between ADMA and vitamin D is independent of PTH levels in obese diabetic