Cardiovascular safety of oncologic agents: A double-edged sword even in the era of targeted therapies – part 1

Introduction: Patients with cancer are subject to the cardiotoxic effects of cancer therapy and as more patients survive cancer due to improved treatment they are exposed to various forms of cardiovascular (CV) disease as they age, and vice-versa. Such an interplay of age with both malignancy and CV disease may contribute to increased morbidity and mortality.

Areas covered: This two-part review considers the effects of cancer drug treatment on the CV system. In Part I, the various types of CV and cardiometabolic toxicity of anti-cancer drugs and the possible mechanisms involved are discussed. Also, among the specific oncologic agents, the CV effects of the classical agents and of the large molecule immunological agents (monoclonal antibodies, including immune checkpoint inhibitors) are detailed.

Expert opinion: Oncologic agents produce a variety of CV adverse effects, including cardiomyopathy and heart failure, peri-myocarditis, coronary artery disease, peripheral vascular disease, hypertension (HTN), cardiac arrhythmias, valvular heart disease, and pulmonary HTN. Both the oncologist and the cardiologist need to be aware of such adverse effects and of the specific agents that produce them. They need to join forces to prevent, anticipate, recognize, and manage such complications.     

Cardiovascular safety of oncologic agents: a double-edged sword even in the era of targeted therapies – Part 2

Introduction: Patients with cancer are subject to the cardiotoxic effects of cancer therapy. Improved cancer treatments lead to more cancer-survivors, who though are exposed to various forms of cardiovascular (CV) disease (CVD) as they age. Aging patients are at increased risk of developing both malignancy and CVD or they may have survived some form of CVD as a result of effective CV treatments. Furthermore, patients with CVD may develop cancer and require treatment (and vice versa), all contributing to increased morbidity and mortality. The prevalence of both malignancy and CVD will increase due to the trend toward a longer lifespan.

Areas covered: In part 2 of this review, the discussion of the CV effects of specific oncology drugs is completed with inclusion of additional immunological agents, current hormonal and other agents. Early detection and monitoring of cardiotoxicity, use of biomarkers and other imaging and diagnostic methods and prevention and treatment options are also discussed.

Expert opinion: As outlined in part 1 of this review, oncologists need to be aware of the CV adverse-effects of their treatments and make careful and expectant clinical decisions, especially in patients with preexisting CVD or CV risk factors. Similarly, cardiologists should consider a detailed previous history of treatment for malignant disease, including prior chemotherapy exposure, dose(s) received, and/or combined modality therapy with chest radiotherapy. Both specialists should collaborate in order to minimize the impact of these two ubiquitous diseases (cancer and CVD) and mitigate the adverse effects of treatment modalities.     

End-inspiratory occlusion maneuver during transesophageal echocardiography for patent foramen ovale detection in intensive care unit patients

Objective Mechanically ventilated patients in the intensive care unit cannot cooperate to perform the Valsalva maneuver during echocardiography for detection of patent foramen ovale. We evaluated the effectiveness of the end-inspiratory occlusion maneuver to enhance detection of patent foramen ovale in this patient population. Design Prospective interventional study. Setting The 40-bed intensive care unit of a university hospital. Patients and participants Twenty five sedated and mechanically ventilated intensive care unit patients referred by their attending physician for bedside transesophageal echocardiography and agitated saline contrast study for detection of patent foramen ovale. Intervention Agitated saline contrast study with end-inspiratory occlusion maneuver. Measurements and results All patients underwent a complete transesophageal echocardiographic study without any complications. Reduction in right atrial cross-sectional area (from 15.80 ± 6.08 cm² to 12.40 ± 4.63 cm²; p < 0.001) and interatrial septum deviation during the maneuver were recorded in all patients. Microbubbles imaged in the left atrium within three cardiac cycles after injection of agitated saline diagnosed patent foramen ovale in three patients. When end-inspiratory occlusion maneuver was added, patent foramen ovale was diagnosed in seven patients (McNemar χ² = 9.33, p = 0.0023). Conclusions The end-inspiratory occlusion maneuver enhances the sensitivity of transesophageal echocardiography with agitated saline contrast study for diagnosing intermittent patent foramen ovale in critically ill mechanically ventilated patients. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Sexual dysfunction: the 'prima ballerina' of hypertension-related quality-of-life complications

Sexual dysfunction is currently considered a serious quality-of-life-related health problem, exerting a major impact on patients' and their sexual partners' life. Available data indicate that essential hypertension is a risk factor for sexual dysfunction, as male and female sexual dysfunction is more prevalent in hypertensive patients than normotensive individuals. Several mechanisms have been implicated in the pathogenesis of sexual dysfunction in hypertensive patients, and major determinants include severity and duration of hypertension, age, and antihypertensive therapy. Female sexual dysfunction, although more frequent than its male counterpart, remains largely under-recognized. Older antihypertensive drugs (diuretics, beta-blockers, centrally acting) exert negative results, whereas newer drugs have either neutral (calcium antagonists, angiotensin-converting enzyme inhibitors) or beneficial effects (angiotensin receptor blockers). Erectile dysfunction is related to ischemic heart disease and might be an 'early therapeutic window' of asymptomatic coronary artery disease. It seems of utmost importance for every physician treating hypertensive patients to become familiar with sexual dysfunction (through better education and specific seminars) for the proper management of these patients.     

Pre-Dilatation Versus No Pre-Dilatation for Implantation of a Self-Expanding Valve in All Comers Undergoing TAVR: The DIRECT Trial

Objectives

The aim of this study was to compare the implantation of a self-expanding valve with or without balloon aortic valvuloplasty (BAV) in an open-label, noninferiority, randomized trial.

Exposure to Brominated Trihalomethanes in Water During Pregnancy and Micronuclei Frequency in Maternal and Cord Blood Lymphocytes

Background: Water disinfection by-products have been associated with an increased cancer risk. Micronuclei (MN) frequency in lymphocytes is a marker of genomic damage and can predict adult cancer risk.Objective: We evaluated maternal exposure to drinking water brominated trihalomethanes (BTHM) in relation to MN frequency in maternal and cord blood lymphocytes.Methods: MN frequency was examined in 214 mothers and 223 newborns from the Rhea mother–child cohort in Crete, Greece, in 2007–2008. Residential BTHM water concentrations were estimated during pregnancy using tap water analyses and modeling. Questionnaires on water related habits were used to estimate BTHM exposure from all routes. Associations between BTHM and MN frequency were estimated using negative binomial regression.Results: BTHM concentrations in residential tap water during pregnancy ranged from 0.06 to 7.1 μg/L. MN frequency in maternal binucleated lymphocytes was found to increase with BTHM concentrations in residential water for exposure during the first [rate ratio (RR) for 1 μg/L = 1.05; 95% CI: 1.00, 1.11] and second trimesters (RR for 1 μg/L = 1.03; 95% CI: 1.00, 1.06), and through all routes of BTHM exposure during the first trimester (RR for 1 μg/week = 3.14; 95% CI: 1.16, 8.50).Conclusions: These findings suggest that exposure to BTHM may increase the frequency of MN in maternal binucleated lymphocytes.Citation: Stayner LT, Pedersen M, Patelarou E, Decordier I, Vande Loock K, Chatzi L, Espinosa A, Fthenou E, Nieuwenhuijsen MJ, Gracia-Lavedan E, Stephanou EG, Kirsch-Volders M, Kogevinas M. 2014. Exposure to brominated trihalomethanes in water during pregnancy and micronuclei frequency in maternal and cord blood lymphocytes. Environ Health Perspect 122:100–106; http://dx.doi.org/10.1289/ehp.1206434     

Risks and Benefits of Green Spaces for Children: A Cross-Sectional Study of Associations with Sedentary Behavior,Obesity, Asthma,and Allergy

Background: Green spaces have been associated with both health benefits and risks in children; however, available evidence simultaneously investigating these conflicting influences, especially in association with different types of greenness, is scarce.Objectives: We aimed to simultaneously evaluate health benefits and risks associated with different types of greenness in children, in terms of sedentary behavior (represented by excessive screen time), obesity, current asthma, and allergic rhinoconjunctivitis.Methods: We conducted a cross-sectional study of a population-based sample of 3,178 schoolchildren (9–12 years old) in Sabadell, Spain, in 2006. Information on outcomes and covariates was obtained by questionnaire. We measured residential surrounding greenness as the average of satellite-derived Normalized Difference Vegetation Index (NDVI) in buffers of 100 m, 250 m, 500 m, and 1,000 m around each home address. Residential proximity to green spaces was defined as living within 300 m of a forest or a park, as separate variables. We used logistic regression models to estimate associations separately for each exposure–outcome pair, adjusted for relevant covariates.Results: An interquartile range increase in residential surrounding greenness was associated with 11–19% lower relative prevalence of overweight/obesity and excessive screen time, but was not associated with current asthma and allergic rhinoconjunctivitis. Similarly, residential proximity to forests was associated with 39% and 25% lower relative prevalence of excessive screen time and overweight/obesity, respectively, but was not associated with current asthma. In contrast, living close to parks was associated with a 60% higher relative prevalence of current asthma, but had only weak negative associations with obesity/overweight or excessive screen time.Conclusion: We observed two separable patterns of estimated health benefits and risks associated with different types of greenness.Citation: Dadvand P, Villanueva CM, Font-Ribera L, Martinez D, Basagaña X, Belmonte J, Vrijheid M, Gražulevičienė R, Kogevinas M, Nieuwenhuijsen MJ. 2014. Risks and benefits of green spaces for children: a cross-sectional study of associations with sedentary behavior, obesity, asthma, and allergy. Environ Health Perspect 122:1329–1335; http://dx.doi.org/10.1289/ehp.1308038     

Multiple behavioral risk factors for chronic diseases in adults aged 50+: regional differences across eleven European countries

Aim

The aim of this study was to estimate the differences in prevalence of multiple behavioral risk factors (MBRFs) for chronic diseases in European adults, from eleven North, Central and South European countries.

Subjects and methods

We used data from 26,656 adults, aged 50+ years, participating in the Survey of Health, Ageing and Retirement in Europe (2004/05). Physical inactivity, high body weight, smoking and risky alcohol consumption were assessed and estimated based on sampling weights, controlling for socioeconomic characteristics.

Results

53.4 % of adults had 2+ MBRFs. Prevalence in the total sample was highest for physical inactivity (71.2 %) and lowest for smoking (18.1 %). The cluster of high body weight and physical inactivity had the highest prevalence of MBRFs (35.4 %), with higher prevalence in Southern Europe (p?<?0.05). Smoking and alcohol consumption presented the greatest degree of clustering (observed to expected ratio?=?2.44). Spain and Greece had the highest prevalence of clustering 2+ MBRFs, whereas Southern European countries had a higher mean number of MBRFs, compared to North and Central European regions (p?<?0.05).

Conclusion

Prevalence of MBRFs varied between countries, with Southern European countries engaging in more risky behaviors. Primary prevention programmes should be developed to reduce MBRFs in this population.     

Acute effects of second-hand smoke on complete blood count

We assessed the acute effects of a 1-h exposure to second-hand smoke (SHS) on complete blood count (CBC) markers in a controlled simulated bar/restaurant environment. Nineteen adult never-smokers completed a 1-h .exposure to SHS at bar/restaurant levels, and a 1-h exposure to normal room air. Blood samples were collected at the baseline at 30?min during each exposure, and at 0, 0.5, 1, 2, 3, and 4?h after each exposure. The values of white blood cells (WBC) at 1?h (p?=?0.010), 3?h (p?=?0.040), and 4?h (p?=?0.008) following SHS were significantly increased compared with the baseline values. Also, there was a positive association between the WBC and cotinine levels (r?=?0.28, p?=?0.007). A 1-h exposure to SHS at bar/restaurant levels significantly increased the WBC for at least 4?h following the exposure time. This effect of SHS on WBC has dose–response characteristics and should be considered to prescribing CBC.