Exercise Training in Elderly Cancer Patients: A Systematic Review.

Due to the aging of the population, in 70% of cases, a new cancer diagnosis equals a cancer diagnosis in a geriatric patient. In this population, beyond the concept of mortality and morbidity, functional capacity, disability, and quality of life remain crucial. In fact, when the functional status is preserved, the pathogenetic curve towards disability will stop or even regress. The present systematic review investigated the effectiveness of physical exercise, as part of a holistic assessment of the patient, for preventing disability and improving the patient's quality of life, and partially reducing all-cause mortality. This evidence must point towards decentralization of care by implementing the development of rehabilitation programs for elderly cancer patients either before or after anti-cancer therapy.

Potential Role of Global Longitudinal Strain in Cardiac and Oncological Patients Undergoing Cardio-Oncology Rehabilitation (CORE).

Although shown to be effective in improving survival and quality of life in patients with cancer, some treatments are well-known causes of cardiotoxicity, such as anthracyclines, monoclonal antibodies against human epidermal growth factor receptor 2 (HER2) and radiotherapy. To prevent cardiovascular disease (CVD) in patients living with cancer, cardiologists and oncologists promoted the development of cardio-oncology, an interdisciplinary field which aims to further improving life expectancy in these patients. Cardio-oncology rehabilitation (CORE), through correction of risk factors, prescription of drug therapies and structured exercise programs, tries to improve symptoms, quality of life, cardiorespiratory fitness (CRF) and survival in patients with cancer. Different imaging modalities can be used to evaluate the real effectiveness of exercise training on cardiac function. Among these, the global longitudinal strain (GLS) has recently aroused interest, thanks to its high sensitivity and specificity for cardiac dysfunction detection due to advanced ultrasound programs. This review summarizes the evidence on the usefulness of GLS in patients with cancer undergoing cardiac rehabilitation programs.

Short-term treatment of iron deficiency anemia after cardiac surgery.

Iron deficiency anemia (IDA) is frequent after cardiac surgery and is associated with increased morbidity and mortality. In a retrospective study, we analyzed 106 patients with IDA (hemoglobin [Hb] ≤ 12 g/dl in women and ≤ 13 g/dl in men, transferrin saturation [TSAT] ≤ 20%) on admission to a Cardiac Rehabilitation Unit after cardiac surgery. The patients were divided into two groups, one was treated with oral sucrosomial iron (SI) and the other with intravenous ferric carboxymaltose (FCM). Patients received a single 1000 mg dose of FCM from the day after admission to rehabilitation (T1), or a 120 mg/day dose of SI from T1 until discharge (T2); after discharge, SI was reduced to 30 mg/day until the end of follow-up (T3). Hb was evaluated at T1, T2 and T3; the other hematological parameters at T1 and T3; natriuretic peptides at T1, T2 and T3; 6-minute walk test (6MWT) at T1 and T2. Folate, vitamin B12 and reticulocytes were sampled on admission. Folate deficiency was documented in 60.4% of patients. Hb increased in both groups with no significant differences between the two treatments (p = 0.397). The other iron metabolism parameters (sideremia, transferrin, TSAT) displayed similar behavior, showing a significant increase at T3 (p < 0.001) with both therapies, although the increase was faster with FCM. Ferritin - high on admission - decreased at T3 in the SI group and rose significantly in the FCM group (SI 219.5 vs. FCM 689 ng/ml p < 0.0001). The 6MWT increased significantly at T2, with an overlap between SI and FCM. In conclusion, the results of this study show that SI and FCM exhibit the same effectiveness on IDA; the response time to therapy of both treatments is also equally fast. SI and FCM induce a similar increase in functional capacity. The study shows that SI can be a viable alternative to FCM after cardiac surgery in terms of effectiveness and tolerability.

Frailty in Acute and Chronic Coronary Syndrome Patients Entering Cardiac Rehabilitation.

Worldwide population ageing is partly due to advanced standard of care, leading to increased incidence and prevalence of geriatric syndromes such as frailty and disability. Hence, the age at the onset of acute coronary syndromes (ACS) keeps growing as well. Moreover, ageing is a risk factor for both frailty and cardiovascular disease (CVD). Frailty and CVD in the elderly share pathophysiological mechanisms and associated conditions, such as malnutrition, sarcopenia, anemia, polypharmacy and both increased bleeding/thrombotic risk, leading to a negative impact on outcomes. In geriatric populations ACS is associated with an increased frailty degree that has a negative effect on re-hospitalization and mortality outcomes. Frail elderly patients are increasingly referred to cardiac rehabilitation (CR) programs after ACS; however, plans of care must be tailored on individual's clinical complexity in terms of functional capacity, nutritional status and comorbidities, cognitive status, socio-economic support. Completing rehabilitative intervention with a reduced frailty degree, disability prevention, improvement in functional state and quality of life and reduction of re-hospitalization are the goals of CR program. Tools for detecting frailty and guidelines for management of frail elderly patients post-ACS are still debated. This review focused on the need of an early identification of frail patients in elderly with ACS and at elaborating personalized plans of care and secondary prevention in CR setting.

Exercise for slowing the progression of atherosclerotic process: effects on inflammatory markers.

Atherosclerosis is a dynamic process driven by all cardiovascular risk factors that can be briefly divided into an early and a late phase. Inflammation is one of the fundamental substrates that initiates the atherosclerotic process in the early stages and promotes and maintains it in the final stages. In the last decades, clinical and experimental data have shown that inflammation is supported by mediators that respond to physical activity. The present review aimed at investigating the effect of physical exercise on inflammatory mediators, both the positive ones that have a proinflammatory effect (interleukin 6, c-reactive protein and tumor necrosis factor α, interferon γ, high-mobility group box-1), and the negative ones which have an anti-inflammatory effect (interleukin 10). Pooled data support the evidence that physical exercise can directly modulate the activity of inflammatory cytokines slowing down or preventing the formation of the atherosclerotic stage.

The core components of cardio-oncology rehabilitation.

The increased efficacy of cancer therapy has resulted in greater cancer survival and increasing number of people with cancer and cardiovascular diseases. The sharing of risk factors, the bidirectional relationship between cancer and cardiovascular diseases and the cardiotoxic effect of chemotherapy and radiotherapy, are the cause of the rapid expansion of cardio-oncology. All strategies to preserve cardiovascular health and mitigate the negative effect of cancer therapy, by reducing the cardiovascular risk, must be pursued to enable the timely and complete delivery of anticancer therapy and to achieve the longest remission of the disease. Comprehensive cardiac rehabilitation is an easy-to-use model, even in cancer care, and is the basis of Cardio-Oncology REhabilitation (CORE), an exercise-based multi-component intervention. In addition, CORE, besides using the rationale and knowledge of cardiac rehabilitation, can leverage the network of cardiac rehabilitation services to offer to cancer patients exercise programs, control of risk factors, psychological support, and nutrition counseling. The core components of CORE will be discussed, describing the beneficial effect on cardiorespiratory fitness, quality of life, psychological and physical well-being, and weight management. Furthermore, particular attention will be paid to how CORE can counterbalance the negative effect of therapies in those at heightened cardiovascular risk after a cancer diagnosis. Barriers for implementation, including personal, family, social and of the health care system barriers for a widespread diffusion of the CORE will also be discussed. Finally, there will be a call-to-action, for randomized clinical trials that can test the impact of CORE, on morbidity and mortality.

Frailty is highly prevalent in specific cardiovascular diseases and females, but significantly worsens prognosis in all affected patients: A systematic review.

Cardiologists are more often confronted with older (>60 years) cardiovascular disease (CVD) patients. These patients have particular needs in clinical care because, for example, of frailty. However, it remains to be established what is the prevalence of frailty in different CVD's and how it relates to mortality. In this systematic review studies were included if they: (i) examined subjects (men and women) aged ≥60 years who suffered from any CVD with or without cardiac surgery, (ii.) examined the presence of frailty with a well-defined frailty tool and (iii.) reported prevalence rates of frailty. From thirty studies comprising 96.841 participants, it is found that 1. Frailty is highly common in older patients with CVD (in particular in females (approximately 1.6 times more than in males), in heart failure (up to 80 % of patients) and aortic valve disease (up to 74 % of patients)), and 2. Frailty is related to a 2.5-3.5-fold elevated mortality risk, even in patients with less severe CVD (e.g. percutaneous coronary intervention). Moreover, there is a lack of consistency on how to assess frailty as up to 20 different tools/assessment batteries are currently used. It is concluded that frailty should be assessed in all older CVD patients in a uniform manner to enhance clinical care and outcomes.

Association between Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Carotid Intima-Media Thickness in Postmenopausal Women Without Overt Cardiovascular Disease and on LDL-C Target Levels.

BACKGROUND: atherosclerotic process inexorably advances in patients reaching low-density lipoprotein cholesterol (LDL-C) targets. An attractive hypothesis is that lipoprotein particles (very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL)), could contribute to residual risk. The present study aims to investigate the relationship between carotid intima-media thickness (IMT) and different lipoprotein subfractions in a cohort of healthy postmenopausal women. METHODS: 75 postmenopausal women, at LDL-C target levels without overt cardiovascular disease, underwent biochemical analyses (including subfraction assay of plasma lipoproteins) and carotid ultrasound examination. RESULTS: a statistically significant correlation between VLDL and carotid IMT (p < 0.001) was found. No significant correlation was found between carotid IMT and LDL-C (p = 0.179), IDL-C (p = 0.815), high-density lipoprotein (HDL) (p = 0.855), and LDL score (p = 0.240). Moreover, IMT is significantly correlated to LDL particle diameter (p = 0.044). After adjusting for age, systolic blood pressure, body mass index, smoking habits, glucose plasma concentration, and Lipoprotein(a) (Lpa) levels, multivariate analysis showed that women in the third tertile of VLDL-C, compared with those in the first tertile, were significantly associated to the highest IMT (p = 0.04). CONCLUSIONS: in this cohort of postmenopausal women, VLDL-C was significantly associated to carotid IMT, independent of main cardiovascular risk factors. These findings pave the way for targeting circulating concentrations of VLDL-C to reduce cardiovascular events in patients with target LDL-C levels.

Individual patient data meta-analysis of the effects of the CARILLON® mitral contour system.

AIMS: Functional mitral regurgitation (MR) (FMR) is common in heart failure with reduced ejection fraction and worsens morbidity and mortality, even when mild. The CARILLON® mitral contour system (Cardiac Dimensions, Kirkland, WA, USA), a mitral annuloplasty device delivered percutaneously to the coronary sinus, is designed to reduce the mitral annular dimension by virtue of the close anatomic relationship between the coronary sinus and the posterior mitral annulus. We performed a comprehensive individual patient data meta-analysis of all studies that used CARILLON® device vs. control that have measured mitral regurgitation severity, left ventricular (LV) remodelling, functional status, and heart failure-related outcomes in heart failure with reduced ejection fraction patients. METHODS AND RESULTS: The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in July 2020. Primary outcomes of interest were measures of MR severity, LV remodelling, New York Heart Association functional class and heart failure-related outcomes [mortality and heart failure hospitalization (HFH) during follow up]. All data were received as individual patient and individual time point data-points. Mean differences and 95% confidence intervals (CIs) were calculated for continuous data using a fixed-effects model. Three studies (REDUCE FMR, TITAN and TITAN II) enrolling 209 participants were identified and included. Pooled analysis showed that, compared with control, CARILLON® device significantly improved both MR volume (mean difference MD -9.20, 95% C.I. -16.11 to -2.29 mL, P = 0.009) and MR grade (MD -1.12, 95% CI -1.36 to -0.88, P < 0.00001) and this was associated with a significant reduction in LA volume, MD -7.54 mL, 95% CI -14.90 to - 0.18, P = 0.04. Significant LV reverse remodelling was also seen in terms of EDV (MD -16.53, 95% CI -28.61 to -44.4 mL, P = 0.007), and a trend in ESV (MD -8.68, 95% CI -18.69 to -1.34 mL, P = 0.09) but no significant effect on LVEF (MD 0.88, 95% CI -1.52% to 2.38%, P = 0.47), due presumably to the greater residual MR in the control patients falsely elevating the LVEF. In addition, the CARILLON® device significantly improved New York Heart Association functional Class (MD -0.22, 95% CI -0.24 to -0.16, P < 0.00001), associated with a lower rate of HFH compared with controls (45.3% vs. 64%, respectively, P = 0.04). As a sensitivity analysis we also restricted the analyses to those patients with Class 3+/4+ MR at baseline. In this cohort, the echocardiographic results were similar, and the reduction in HFH rates was even more marked (43.9% vs. 82.9%, respectively, P = 0.04). CONCLUSIONS: This comprehensive meta-analysis of individual patient data has shown that CARILLON® device provides statistically significant and clinically meaningful benefits on MR severity, LA and LV volumes, and remodelling and rates of subsequent heart failure hospitalization.

Characteristics of structured physical training currently provided in cardiac patients: insights from the Exercise Training in Cardiac Rehabilitation (ETCR) Italian survey.

BACKGROUND: Uncertainty exists about current delivery levels of exercise training (ET) during Cardiac Rehabilitation (CR) programmes. AIM OF THE STUDY: To evaluate ET modalities in the real world of CR facilities in Italy. METHODS: This was an observational survey of aggregate data, collected from CR facilities on a voluntary basis. Snapshots of a single working day at a local site were made, in terms of characteristics of patients and ET programmes delivered. RESULTS. Overall, 612 patients from 26 CR units were included, with an in-patient vs. out-patient ratio of 3:1. Coronary artery disease (57.6%), heart failure (20.3%), and valve disease/surgery (22.1%) were the most represented target groups. The prevalence of endurance continuous training, interval training, and resistance/strength training was 66.7%, 11.1%, and 9.0%; other non-aerobic endurance and non-resistance training modalities such as respiratory muscle training and calisthenics were reported in 39.9% and 42.9% of cases respectively. Workloads for endurance exercise training were determined by cardiopulmonary test, conventional 12-leads ECG exercise testing, 6min-walking test, theoretical determination of heart rate, and rating of perceived exertion in 9%, 8%, 27%, 9%, and 40% of cases respectively. The average duration of the programmes (on an intention to treat basis) was 25 sessions of 42±11  minutes, with a frequency of >4 sessions/week in 67% of patients. CONCLUSIONS: Despite advances in CR interventions, there is a significant need for improvement of functional evaluation and exercise training prescription, and consideration of a wider range of training modalities in Italy. .

Frailty and cardiac rehabilitation: A call to action from the EAPC Cardiac Rehabilitation Section.

Frailty is a geriatric syndrome characterised by a vulnerability status associated with declining function of multiple physiological systems and loss of physiological reserves. Two main models of frailty have been advanced: the phenotypic model (primary frailty) or deficits accumulation model (secondary frailty), and different instruments have been proposed and validated to measure frailty. However measured, frailty correlates to medical outcomes in the elderly, and has been shown to have prognostic value for patients in different clinical settings, such as in patients with coronary artery disease, after cardiac surgery or transvalvular aortic valve replacement, in patients with chronic heart failure or after left ventricular assist device implantation. The prevalence, clinical and prognostic relevance of frailty in a cardiac rehabilitation setting has not yet been well characterised, despite the increasing frequency of elderly patients in cardiac rehabilitation, where frailty is likely to influence the onset, type and intensity of the exercise training programme and the design of tailored rehabilitative interventions for these patients. Therefore, we need to start looking for frailty in elderly patients entering cardiac rehabilitation programmes and become more familiar with some of the tools to recognise and evaluate the severity of this condition. Furthermore, we need to better understand whether exercise-based cardiac rehabilitation may change the course and the prognosis of frailty in cardiovascular patients.

Serum uric acid is associated with non-dipping circadian pattern in young patients (30-40 years old) with newly diagnosed essential hypertension.

BACKGROUND: We aimed at evaluating the relationship between the circadian blood pressure rhythm and UA level in young patients (30-40 years old) with newly diagnosed essential hypertension. METHODS: The study included 62 essential hypertensive patients and 29 healthy controls (20 men, 35 ± 3 years) divided into two groups according to 24-hour ABPM results: 30 dippers and 32 nondippers. RESULTS: Nondippers showed significantly higher both serum UA levels compared to dippers and controls (6.1 ± 0.7, 5.2 ± 0.9 and 4.1 ± 0.9 mg/dL, p < 0.001, respectively); and high sensitivity C-reactive protein (hsCRP) (4.1 ± 2.2 mg/L, 3.3 ± 1.9 mg/L, and 1.4 ± 0.9 mg/L, p < 0.001, respectively). After adjusting for age, sex, body mass index, smoking, creatinine levels, hsCRP and comorbidity, multivariate logistic regression analysis revealed an independent association between serum UA levels and nondipper pattern (OR 2.44, 95%CIs 1.4-4.1, p = 0.002). CONCLUSION: Serum UA is independently associated with nondipper circadian pattern in young patients with newly diagnosed essential hypertension.

Does comprehensive geriatric assessment improve the estimate of surgical risk in elderly patients? An Italian multicenter observational study.

BACKGROUND: The evaluation of surgical risk is crucial in elderly patients. At present, there is little evidence of the usefulness of comprehensive geriatric assessment (CGA) as a part of the overall assessment of surgical elderly patients. METHODS: We verified whether CGA associated with established surgical risk assessment tools is able to improve the prediction of postoperative morbidity and mortality in 377 elderly patients undergoing elective surgery. RESULTS: Overall mortality and morbidity were 2.4% and 19.9%, respectively. Multivariate analysis showed that impaired cognitive function (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.15 to 4.22; P < .02) and higher Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (OR, 1.11; 95% CI, 1.00 to 1.23; P < .04) are predictive of mortality. Higher comorbidity is predictive of morbidity (OR, 2.12; 95% CI, 1.06 to 4.22; P < .03) and higher American Society of Anesthesiologists (OR, 2.18; 95% CI, 1.31 to 3.63; P < .001) and National Confidential Enquiry into Patient Outcome of Death score (OR, 2.03; 95% CI, 1.03 to 4.00; P < .04). CONCLUSIONS: In elective surgical elderly patients, the morbidity and mortality are low. The use of CGA improves the identification of elderly patients at higher risk of adverse events, independent of the surgical prognostic indices.

Exercise training improves cardiopulmonary and endothelial function in women with breast cancer: findings from the Diana-5 dietary intervention study.

To investigate whether exercise training (ET) improves cardiopulmonary and endothelial function in women with breast cancer (BC). Fifty-one female patients (aged between 39 and 72 years) with a history of primary invasive BC within the previous 5 years and enrolled in the Mediterranean diet-based DIANA (diet and androgens)-5 Trial were subdivided into 2 groups: an ET group (n = 25) followed a formal ET program of moderate intensity (3 session/week on a bicycle at 60-70 % VO2peak for 3 months, followed by one session/week until 1-year follow-up), while a control group (n = 26) did not perform any formal ET. At baseline and at 1-year follow-up, all patients underwent cardiopulmonary exercise stress test (CPET) and measurements of vascular endothelial function by peripheral artery tonometry (Reactive Hyperemia Index, RHI). There were no significant differences between the groups in baseline anthropometrical, BC characteristics, and metabolic profile. No differences in baseline CPET and RHI parameters were found. Peak oxygen consumption (VO2peak) significantly increased in ET group (from 12.4 ± 2.9 to 14.3 ± 3.3 mL/kg/min, p < 0.001) compared to the control group (from 12.8 ± 2.5 to 12.6 ± 2.8 mL/kg/min, p = 0.55; p < 0.001 between groups). Compared to the control group (from 2.0 ± 0.4 to 1.9 ± 0.4, p = 0.62), the ET group showed a significant improvement of RHI after 1 year (from 2.1 ± 0.7 to 2.5 ± 0.8, p < 0.001). Changes in VO2peak were correlated with changes in RHI (ΔVO2peak vs. ΔRHI: r = 0.47, p = 0.017). In BC survivors, ET program improves cardiopulmonary functional capacity and vascular endothelial function after 12 months. Whether these changes may favorably modulate some of the pathophysiological mechanisms implied in cancer evolution should be investigated.

Exercise training improves heart rate recovery in women with breast cancer.

PURPOSE: To determine whether exercise training improves autonomic function in women with breast cancer (BC). METHODS: Fifty-one patients (aged between 39 and 72 years) with a history of primary invasive BC within the previous 5 years and enrolled in the Mediterranean diet-based DIANA (Diet and Androgens)-5 Trial were subdivided in two groups: a ET group (n = 25) followed a formal ET program of moderate intensity (3 session/week on a bicycle at 60-70% VO2peak for 3 months, followed by one session/week until 1-year follow-up), while a control group (n = 26) did not perform any formal ET. At baseline and after 1-year, all patients underwent cardiopulmonary exercise stress test (CPET). Heart rate recovery (HRR) was calculated as the difference between heart rate at peak exercise and heart rate at first minute of the cool-down period. RESULTS: There were no significant differences between groups in baseline anthropometrical, BC characteristics, metabolic profile, CPET parameters and HRR. Compared to controls, at 1-year follow-up ET group showed a significant improvement in VO2peak (from 12.6 ± 3.0 to 14.5 ± 3.3 ml/kg/min, p < 0.001; p < 0.001 between groups); and in HRR (from 17.6 ± 6.4 to 23.0 ± 8.3 beats/min, p < 0.001; p < 0.001 between groups). In ET group the changes in HRR directly correlated with changes in VO2peak (r = 0.58, p = 0.002). CONCLUSIONS: Moderate intensity exercise training in BC survivors is associated with improvement of autonomic function. Whether the improvement of sympatho-vagal balance may favorably modulate some of the pathophysiological mechanisms implied in cancer evolution need further investigation.

Exercise training reduces high mobility group box-1 protein levels in women with breast cancer: findings from the DIANA-5 study.

PURPOSE: To determine whether exercise training might exert anti-inflammatory effect by reducing HMGB1 levels in women with breast cancer (BC). METHODS: We analyzed monocentric data from the DIANA (DIET AND ANDROGENS)-5 PROJECT. Study population consisted of 94 patients randomized into two groups: 61 patients (53 +/- 8 yrs, training group) were assigned to a structured exercise training intervention (3 times/week for the first 3 months, and once /week for the following 9 months); whereas 33 patients (52 +/- 7 yrs, control group) followed only the general indications to adhere to the life-style intervention suggestions of the DIANA protocol. At study entry and after 12 months, all patients underwent cardiopulmonary exercise testing, biochemical as- sessment [HMGB1, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6)]; and lipid and glycemic profile. RESULTS: There were no significant differences between groups in baseline clinical and inflammatory profile. Among the training group, only 19/61 patients had high adherence to the exercise intervention. After stratifying the study population according to the level of adhesion to the exer- cise intervention, 1-year HMGB1 levels were lower among patients more adherent to exercise (p for trend = 0.001). Further adjusting for age, body mass index and baseline values, 1-year HMGB1 levels remained significantly and inversely associated to the level of adhesion to the exercise intervention (B = -0.97, SE = 0.43, p = 0.01). CONCLUSIONS: Moderate intensity exercise training in BC survivors is associated with reduced HMGB1 levels that are proportional to the level of adhesion to the exercise intervention, independently from other classical inflammatory molecules, suggesting an exercise-induced anti-inflammatory effect mediated by HMGB1.

[Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure: Part I]. / Terapie antiremodeling: nuove strategie e prospettive future nell'insufficienza cardiaca cronica post ischemica: Parte I.

In recent years, the remarkable progress achieved in terms of survival after myocardial infarction have led to an increased incidence of chronic heart failure in survivors. This phenomenon is due to the still incomplete knowledge we possess about the complex pathophysiological mechanisms that regulate the response of cardiac tissue to ischemic injury. These involve various cell types such as fibroblasts, cells of the immune system, endothelial cells, cardiomyocytes and stem cells, as well as a myriad of mediators belonging to the system of cytokines and not only. In parallel with the latest findings on post-infarct remodeling, new potential therapeutic targets are arising to halt the progression of disease. In this review, we evaluate the results obtained from four new therapeutic strategies: in this part we evaluate gene therapy and novel aspect of stem cells therapy in remodeling; in the second part we will investigate, micro-RNA, posttranslational modification and microspheres based therapy.

[Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure. Part II]. / Terapie antiremodeling: nuove strategie e prospettive future nell'insufficienza cardiaca cronica post ischemica: Parte II.

In recent years, the remarkable progress achieved in terms of survival after myocardial infarction have led to an increased incidence of chronic heart failure in survivors. This phenomenon is due to the still incomplete knowledge we possess about the complex pathophysiological mechanisms that regulate the response of cardiac tissue to ischemic injury. These involve various cell types such as fibroblasts, cells of the immune system, endothelial cells, cardiomyocytes and stem cells, as well as a myriad of mediators belonging to the system of cytokines and not only. In parallel with the latest findings on post-infarct remodeling, new potential therapeutic targets are arising to halt the progression of disease. After the evaluation of the results obtained from gene therapy and stem cells, in this part we evaluate micro-RNA, post-translational modification and microspheres based therapy.

Cardiovascular disease and high-mobility group box 1--is a new inflammatory killer in town?

High-mobility group box 1 (HMGB-1) is a nuclear protein physiologically involved in the maintaining of DNA structure in the nucleus. When tissue damage occurs, necrotic cells as well as inflammatory cells, once activated, release this protein in circulating blood, where it seems to exert a direct proinflammatory action. Thus, HMGB-1 might be involved in the pathophysiology of several diseases, including cardiovascular disease. However, the experimental evidence has not yet clarified its cardiovascular role which is still debated. Specifically, it is still not completely resolved whether HMGB-1 plays a protective or detrimental role on cardiovascular function. In this review, we consider the role of HMGB-1 in pathological conditions and comment on the role of this protein in the cardiovascular disease.

Arterial stiffness and vitamin D levels: the Baltimore longitudinal study of aging.

CONTEXT: The importance of vitamin D for bone health has long been acknowledged. Recent evidence suggests that vitamin D can also play a role in reducing the risk of several other diseases, including cardiovascular disease. OBJECTIVE: The aim of this study is to test the hypothesis that 25-hydroxyvitamin D (25-OH D) is an independent cross-sectional correlate of central arterial stiffness in a normative aging study population. DESIGN AND SETTINGS: We conducted a cross-sectional analysis. SUBJECTS: We studied 1228 healthy volunteers (50% males; age, 70±12 yr) of the Baltimore Longitudinal Study of Aging. MAIN OUTCOME MEASURES: We measured carotid-femoral pulse wave velocity (PWV) and 25-OH D levels. RESULTS: We found a significant inverse association between PWV and 25-OH D levels (adjusted r2=0.27; ß=-0.43; P=0.001). After adjusting for age, gender, ethnicity, season of blood draw, estimated glomerular filtration rate, physical activity level, cardiovascular risk factors score (smoking, visceral obesity, hypercholesterolemia, hypertension, and diabetes), calcium/vitamin D supplementation, serum calcium, and PTH levels, the association between PWV and 25-OH D levels was only slightly reduced and remained statistically significant (adjusted r2=0.34; ß=-0.34; P=0.04). CONCLUSIONS: Vitamin D levels are inversely associated with increased arterial stiffness in a normative aging population, irrespective of traditional risk factor burden. Further research is needed to understand the mechanism of this association and to test the hypothesis that vitamin D supplementation can reduce arterial stiffness.