Women's cardiovascular health - the cardio-oncologic jigsaw.

Improvements in cancer care have led to an exponential increase in cancer survival. This is particularly the case for breast cancer, where 5-year survival in Australia exceeds 90%. Cardiovascular disease (CVD) has emerged as one of the competing causes of morbidity and mortality among cancer survivors, both as a complication of cancer therapies and because the risk factors for cancer are shared with those for CVD. In this review we cover the key aspects of cardiovascular care for women throughout their cancer journey: the need for baseline cardiovascular risk assessment and management, a crucial component of the cardiovascular care; the importance of long-term surveillance for ongoing maintenance of cardiovascular health; and strong evidence for the beneficial effects of physical exercise to improve both cancer and cardiovascular outcomes. There is general disparity in cardiovascular outcomes for women, which is further exacerbated when both CVD and cancer co-exist. Collaboration between oncology and cardiac services, with an emergence of the whole field of cardio-oncology, allows for expedited investigation and treatment for these patients. This collaboration as well as a holistic approach to patient care and key role of patients' general practitioners are essential to ensure long-term health of people living with, during and beyond cancer.

Implications of tropical cyclones on damage and potential recovery and restoration of logged forests in Vietnam.

Many natural forests in Southeast Asia are degraded following decades of logging. Restoration of these forests is delayed by ongoing logging and tropical cyclones, but the implications for recovery are largely uncertain. We analysed meteorological, satellite and forest inventory plot data to assess the effect of Typhoon Doksuri, a major tropical cyclone, on the forest landscapes of central Vietnam consisting of natural forests and plantations. We estimated the return period for a cyclone of this intensity to be 40 years. Plantations were almost twice as likely to suffer cyclone damage compared to natural forests. Logged natural forests (9-12 years after cessation of government-licensed logging) were surveyed before and after the storm with 2 years between measurements and remained a small biomass carbon sink (0.1 ± 0.3 Mg C ha-1 yr-1) over this period. The cyclone reduced the carbon sink of recovering natural forests by an average of 0.85 Mg C ha-1 yr-1, less than the carbon loss due to ongoing unlicensed logging. Restoration of forest landscapes in Southeast Asia requires a reduction in unlicensed logging and prevention of further conversion of degraded natural forests to plantations, particularly in landscapes prone to tropical cyclones where natural forests provide a resilient carbon sink. This article is part of the theme issue 'Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration'.

Cardiotoxicity of Radiation Therapy: Mechanisms, Management, and Mitigation.

OPINION STATEMENT: Radiation therapy is a key component of modern-day cancer therapy and can reduce the rates of recurrence and death from cancer. However, it can increase risk of cardiovascular (CV) events, and our understanding of the timeline associated with that risk is shorter than previously thought. Risk mitigation strategies, such as different positioning techniques, and breath hold acquisitions as well as baseline cardiovascular risk stratification that can be undertaken at the time of radiotherapy planning should be implemented, particularly for patients receiving chest radiation therapy. Primary and secondary prevention of cardiovascular disease (CVD), as appropriate, should be used before, during, and after radiation treatment in order to minimize the risks. Opportunistic screening for subclinical coronary disease provides an attractive possibility for primary/secondary CVD prevention and thus mitigation of long-term CV risk. More data on long-term clinical usefulness of this strategy and development of appropriate management pathways would further strengthen the evidence for the implementation of such screening. Clear guidelines in initial cardiovascular screening and cardiac aftercare following radiotherapy need to be formulated in order to integrate these measures into everyday clinical practice and policy and subsequently improve post-treatment morbidity and mortality for these patients.

Simple top-down preparation of magnetic Bi0.9Gd0.1Fe1-xTixO3 nanoparticles by ultrasonication of multiferroic bulk material.

We present a simple technique to synthesize ultrafine nanoparticles directly from bulk multiferroic perovskite powder. The starting materials, which were ceramic pellets of the nominal compositions Bi0.9Gd0.1Fe1-xTixO3 (x = 0.00-0.20), were prepared initially by a solid state reaction technique, then ground into micrometer-sized powders and mixed with isopropanol or water in an ultrasonic bath. The particle size was studied as a function of sonication time with transmission electron microscopic imaging and electron diffraction that confirmed the formation of a large fraction of single-crystalline nanoparticles with a mean size of 11-13 nm. A significant improvement in the magnetic behavior of Bi0.9Gd0.1Fe1-xTixO3 nanoparticles compared to their bulk counterparts was observed at room temperature. This sonication technique may be considered as a simple and promising route to prepare ultrafine nanoparticles for functional applications.

The nitric oxide redox sibling nitroxyl partially circumvents impairment of platelet nitric oxide responsiveness.

Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic heart disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and the NO donor sodium nitroprusside (SNP) were compared. While SNP (10µM) induced 29±3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10µM) caused 75±4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response ratio was markedly increased (p<0.01), consistent with partial circumvention of NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001) with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO, 200µM) inhibited SNP and IPA/NO responses by 92±7% and 17±4% respectively (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only partially NO-mediated. ODQ (10µM) inhibited IPA/NO responses by 36±8% (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of aggregation. There was no significant relationship between whole blood ROS content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents platelet NO resistance while acting, at least partially, as a haem-mediated sGC activator.

Prevention of aortic valve stenosis: a realistic therapeutic target?

Aortic valve stenosis (AS) is the most common form of valvular heart disease in the Western world, affecting ~40% of the population over the age of 80; to date the only established treatment is valve replacement. However, AS progression occurs over many years, and is associated from its earliest stages with increased risk of coronary events. Recent insight into the pathophysiology of AS has included central roles for angiotensin II, for diminished nitric oxide effect at the level of valve endothelium and matrix, and for inflammatory activation/redox stress culminating in activation of pro-calcific stimuli. Despite the presence of atheroma within the stenotic valve, hyperlipidemia per se does not play a critic role in the development of obstructive disease. We review emerging options for pharmacotherapy of AS, including in particular retardation of disease progression. The various clinical evaluations of lipid-reducing therapy have been uniformly unsuccessful in slowing AS progression. However, recent studies in animal models and retrospective evaluations in humans suggest that ACE inhibitors and/or angiotensin receptor blockers may be effective in this regard. Furthermore, agents normally utilized to treat osteoporosis also offer promise in retarding AS. Given the considerable morbidity, mortality and health care costs associated with AS, such therapeutic developments should be expedited.

Determinants of insulin responsiveness in young women: Impact of polycystic ovarian syndrome, nitric oxide, and vitamin D.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with incremental risk of atherosclerosis and possibly of cardiovascular events. Insulin resistance (IR) occurs frequently in PCOS subjects, which might be one of the mechanisms involved in engendering such risk. We sought to evaluate whether the impact of other factors potentially associated both with PCOS and with IR might differentially modulate degree of IR in women with and without PCOS. METHODS AND RESULTS: We measured body mass index (BMI), hs-CRP, plasma concentrations of asymmetric dimethylarginine (ADMA), vitamin D (25(OH)D3) levels and platelet responsiveness to nitric oxide donor sodium nitroprusside (NO responsiveness) in 47 young women (n=27 with PCOS and n=20 weight-matched controls) without metabolic syndrome, hypertension or overt cardiovascular disease. We performed univariate and multivariate regression analyses to establish correlates of the quantitative insulin-sensitivity check index (QUICKI), as a marker of IR. On univariate analysis, plasma 25(OH)D3 levels and low NO responsiveness tended to be direct correlates with QUICKI in the entire subject group. BMI, hs-CRP, and ADMA levels were significant inverse correlates of QUICKI in PCOS subjects, but not in subjects without PCOS. On multivariate analysis, NO responsiveness, and 25(OH)D3 levels, but not PCOS per se were significant correlates of QUICKI. CONCLUSIONS: In the entire cohort of young women, low NO responsiveness and vitamin D deficiency are associated with low QUICKI, while elevated ADMA, inflammatory activation and obesity are selectively associated with low QUICKI in PCOS subjects; this may contribute to the increased cardiovascular risk associated with this syndrome.

The endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) predicts LV mass independent of afterload.

BACKGROUND: Nitric oxide (NO) is a modulator of left ventricular hypertrophy (LVH) and myocardial relaxation. The impact of NO availability on development of LVH has never been demonstrated in humans. We tested the hypotheses that elevation of asymmetric dimethylarginine (ADMA) concentrations (biochemical marker of decreased NO generation), and impairment of vascular responsiveness to NO donor GTN, would each predict the presence of LVH and associated LV diastolic dysfunction in a normal aging population. METHODS AND RESULTS: In 74 subjects aged 68±6 years, LV volumes and mass indexed to height(2.7) (LVMI) were calculated from cardiac MRI. Despite the absence of clinically-defined LVH, there was a relationship (r=0.29; p=0.01) between systolic BP and LVMI. Both elevation of ADMA levels to the highest quartile or impairment of GTN responsiveness (determined by applanation tonometry) to the lowest quartile were determinants of LVMI independent of systolic BP (p=0.01 and p=0.03, respectively). Filling pressure (E/E' ratio from echocardiography) was increased in patients with impaired vascular NO responsiveness (p<0.05) irrespective of LVMI. ADMA remained a significant determinant of LVMI on multivariate analysis. CONCLUSIONS: These data imply that NO bioavailability within the myocardium modulates earliest stages of LVH development and facilitates development of diastolic dysfunction at a given LV mass.