Oncology and Cardiac Rehabilitation: An Underrated Relationship.

Cancer and cardiovascular diseases are globally the leading causes of mortality and morbidity. These conditions are closely related, beyond that of sharing many risk factors. The term bidirectional relationship indicates that cardiovascular diseases increase the likelihood of getting cancer and vice versa. The biological and biochemical pathways underlying this close relationship will be analyzed. In this new overlapping scenario, physical activity and exercise are proven protective behaviors against both cardiovascular diseases and cancer. Many observational studies link an increase in physical activity to a reduction in either the development or progression of cancer, as well as to a reduction in risk in cardiovascular diseases, a non-negligible cause of death for long-term cancer survivors. Exercise is an effective tool for improving cardio-respiratory fitness, quality of life, psychological wellbeing, reducing fatigue, anxiety and depression. Finally, it can counteract the toxic effects of cancer therapy. The protection obtained from physical activity and exercise will be discussed in the various stages of the cancer continuum, from diagnosis, to adjuvant therapy, and from the metastatic phase to long-term effects. Particular attention will be paid to the shelter against chemotherapy, radiotherapy, cardiovascular risk factors or new onset cardiovascular diseases. Cardio-Oncology Rehabilitation is an exercise-based multi-component intervention, starting from the model of Cardiac Rehabilitation, with few modifications, to improve care and the prognosis of a patient's cancer. The network of professionals dedicated to Cardiac Rehabilitation is a ready-to-use resource, for implementing Cardio-Oncology Rehabilitation.

Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: results from the MAGGIC individual patient data meta-analysis.

BACKGROUND: Anaemia is common among patients with heart failure (HF) and is an important prognostic marker. AIM: We sought to determine the prognostic importance of anaemia in a large multinational pooled dataset of prospectively enrolled HF patients, with the specific aim to determine the prognostic role of anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF, respectively). DESIGN: Individual person data meta-analysis. METHODS: Patients with haemoglobin (Hb) data from the MAGGIC dataset were used. Anaemia was defined as Hb < 120 g/l in women and <130 g/l in men. HF-PEF was defined as EF ≥ 50%; HF-REF was EF < 50%. Cox proportional hazard modelling, with adjustment for clinically relevant variables, was undertaken to investigate factors associated with 3-year all-cause mortality. RESULTS: Thirteen thousand two hundred and ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF-PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF (42.8 and 41.6% respectively). Compared with patients with normal Hb values, those with anaemia were older, were more likely to have diabetes, ischaemic aetiology, New York Heart Association class IV symptoms, lower estimated glomerular filtration rate and were more likely to be taking diuretic and less likely to be taking a beta-blocker. Patients with anaemia had higher all-cause mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25-1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HF-PEF and aHR 2.49 (2.13-2.90) in HF-REF. CONCLUSIONS: Anaemia is an adverse prognostic factor in HF irrespective of EF. The prognostic importance of anaemia was greatest in patients with HF-REF.

The worrisome liaison between left ventricular systolic dysfunction and mitral annulus calcification in type 2 diabetes without coronary artery disease: data from the SHORTWAVE study.

BACKGROUND AND AIM: Mitral annulus calcification (MAC) is a marker for coronary artery disease (CAD) and predicts poor outcome in the general population. No data are available on MAC in patients with type 2 diabetes. In these patients we assessed prevalence of MAC and the relation between MAC and left ventricular (LV) systolic function. METHODS AND RESULTS: As many as 386 patients with type 2 diabetes without CAD were studied with Doppler echocardiography. LV systolic dysfunction was defined by analyzing 120 healthy subjects. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (peak S') were considered as indexes of LV circumferential and longitudinal shortening and classified low if <89% and <8.5 cm/s, respectively (10th percentiles of controls). Patients who had MAC (107 = 28%) were older with longer duration of DM and were receiving more anti-hypertension medications than those who had not. At echocardiographic evaluation patients with MAC showed higher LV mass, larger left atrial volume (LAV), reduced sc-MS (88.4 ± 14.9 vs 92.6 ± 14.3%; p = 0.01) and peak S' (8.9 ± 2.2 vs 10.0 ± 2.0 cm/s; p < 0.001) than patients without MAC. Multiple logistic regression demonstrated older age (OR 1.03 [IC 1.01-1.06], p = 0.009), larger LAV (OR 1.19 [IC 1.11-1.28], p < 0.001) and combined reduction in sc-MS and peak S' (OR 3.00 [IC 1.57-5.72], p = 0.001) as independent factors associated with MAC. CONCLUSIONS: MAC is detectable in one fourth of patients with type 2 diabetes without CAD and is mostly related to LV systolic dysfunction expressed as combined impairment of LV circumferential and longitudinal fibers, independent of age and LAV.

Adjuvant trastuzumab cardiotoxicity in patients over 60 years of age with early breast cancer: a multicenter cohort analysis.

BACKGROUND: Adjuvant Trastuzumab with chemotherapy is the gold standard for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (HER2+ EBC). Older patients have been largely under-represented in clinical trials, and few data on Trastuzumab cardiotoxicity have been reported in this subgroup. PATIENTS AND METHODS: Four hundred and ninety-nine consecutive HER2+ EBC patients were treated with adjuvant trastuzumab and chemotherapy (aTrastC) at 10 Italian institutions. We evaluated disease prevalence and patient characteristics in the patients older than 60 years of age (over-60), prevalence of aTrastC cardiotoxicity and risk factors. RESULTS: There were 160 'over-60' patients (32%), in whom a higher prevalence of hypertension, diabetes, renal dysfunction, dyslipidemia and treatment with ACEi (40 versus 8%) and beta blockers (20 versus 8%) was found than in the younger patients (339 = 68%). Clinical heart failure occurred in 6% of the 'over-60' and in 2% of the younger patients. A reduction in left ventricular ejection fraction of >10 points was detected in 33% of the 'over-60' and in 23% of the younger patients (all P < 0.05). aTrastC was discontinued in 10% of the 'over-60' and in 4% of the younger patients (P = 0.003), restarted in 44% of the 'over-60' and in 58% of the younger women (P = ns). CONCLUSION: In clinical practice, 32% of HER2+ EBC patients treated with aTrastC are 'over-60'. These patients have an increased cardiovascular risk profile and develop aTrastC cardiotoxicity commonly.

[Epigenetic effects as mediators of procoagulant action of thin dust with high metal content. Study on occupational epidemiology]. / Effetti epigenetici come mediatori dell'azione pro-coagulante delle polveri sottili ad alto contenuto metallico. Uno studio di epidemiologia occupazionale.

Blood hypo-methylation mediates the effects of metal-rich airborne particles on blood coagulation: An occupational epidemiological study. Particulate matter (PM) exposure is associated with increased coagulation and thrombosis, but the biological mechanism has not yet been clarified. DNA methylation represents a potential mechanism because it can be modified by environmental factors. Foundry workers are exposed to PM components and showed increased cardiovascular risk. In a group of 63 steel workers we found that PM and zinc airborne levels were negatively associated with leukocyte DNA methylation in genes NOS3 and ET-1 (b = -1.1; p = 0.002 and b = -1.5; p = 0.003, for zinc exposure respectively in multivariate regression models; b = -0.9 with p = 0.01 for PM10 exposure and NOS3) and in turn, DNA hypo-methylation resulted associated with increased Endogenous Thrombin Potential (for NOS3 b = -45.0, p = 0.001; and for ET-1 b = -16.4, p = 0.03). Our study based on healthy subject exposed in occupational setting, suggests that gene specific hypomethylation contributes to environmentally-induced hypercoagulability.

Blood leukocyte Alu and LINE-1 methylation and gastric cancer risk in the Shanghai Women's Health Study.

BACKGROUND: Recent data suggest a link between blood leukocyte DNA methylation, and cancer risk. However, reports on DNA methylation from a prospective study are unavailable for gastric cancer. METHODS: We explored the association between methylation in pre-diagnostic blood leukocyte DNA and gastric cancer risk in a case-control study nested in the prospective Shanghai Women's Health Study cohort. Incident gastric cancer cases (n=192) and matched controls (n=384) were included in the study. Methylation of Alu and long interspersed nucleotide elements (LINE)-1 were evaluated using bisulphite pyrosequencing. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated from logistic regression adjusting for potential confounders. RESULTS: Alu methylation was inversely associated with gastric cancer risk, mainly among cases diagnosed one or more years after blood collection. After excluding cases diagnosed during the first year of follow-up, the ORs for the third, second, and first quartiles of Alu methylation compared with the highest quartile were 2.43 (1.43-4.13), 1.47(0.85-2.57), and 2.22 (1.28-3.84), respectively. This association appeared to be modified by dietary intake, particularly isoflavone. In contrast, LINE-1 methylation levels were not associated with gastric cancer risk. CONCLUSION: Evidence from this prospective study is consistent with the hypothesis that DNA hypomethylation in blood leukocytes may be related to cancer risk, including risk of gastric cancer.

Effects of inhalable particulate matter on blood coagulation.

BACKGROUND: Particulate matter (PM) exposure has been linked to increased risk of cardiovascular disease, possibly resulting from hypercoagulability and thrombosis. Lung and systemic inflammation resulting from PM inhalation may activate blood coagulation, but mechanisms for PM-related hypercoagulability are still largely unknown. OBJECTIVES: To identify coagulation mechanisms activated by PM in a population with well-characterized exposure. METHODS: We measured prothrombin time (PT), activated partial thromboplastin time, endogenous thrombin potentials (ETPs) with/without exogenous triggers and with/without soluble thrombomodulin, tissue-type plasminogen activator (t-PA) antigen, D-dimer and C-reactive protein (CRP) in 37 workers in a steel production plant with well-characterized exposure to PM with aerodynamic diameter of < 1 mum (PM(1)) and coarse PM (PM(10) - PM(1)). Blood samples were collected from each subject on the first (baseline) and last (postexposure) day of a 4-day work week. We analyzed differences between baseline and postexposure levels using a paired Student's t-test. We fitted multivariate mixed-regression models to estimate the associations of interquartile range PM(1) and coarse PM exposure with parameter levels. RESULTS: None of the parameters showed any significant changes from baseline in postexposure samples. However, exposure levels were associated with shorter PT (beta[PM(1)] = -0.33 s, P = 0.08; beta[PM(coarse)] = - 0.33 s, P = 0.01), and higher ETP without exogenous triggers and with thrombomodulin (beta[PM(1)] = + 99 nm min, P = 0.02; beta[PM(coarse)] = + 66 nm min, P = 0.05), t-PA (beta[PM(1)] = + 0.72 ng mL(-1), P = 0.01; beta[PM(coarse)] = + 0.88 ng mL(-1), P = 0.04), and CRP (beta[PM(1)] = + 0.59 mg L(-1), P = 0.03; beta[PM(coarse)] = + 0.48 mg L(-1), P = 0.01). CONCLUSIONS: PM exposure did not show any short-term effect within the week of the study. The association of PM exposure with PT, ETP and CRP provides some evidence of long-term effects on inflammation and coagulation.