New Insights in the Era of Clinical Biomarkers as Potential Predictors of Systemic Therapy-Induced Cardiotoxicity in Women with Breast Cancer: A Systematic Review.

Cardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) lacks clinical evidence and is based on limited clinical studies. AIM: To provide an overview of existing and potentially novel biomarkers that possess a promising predictive value for the early and late onset of CTRCD in the clinical setting. METHODS: A systematic review of published studies searching for promising biomarkers for the prediction of CTRCD in patients with breast cancer was undertaken according to PRISMA guidelines. A search strategy was performed using PubMed, Google Scholar, and Scopus for the period 2013-2023. All subjects were >18 years old, diagnosed with breast cancer, and received breast cancer therapies. RESULTS: The most promising biomarkers that can be used for the development of an alternative risk cardiac stratification plan for the prediction and/or early detection of CTRCD in patients with breast cancer were identified. CONCLUSIONS: We highlighted the new insights associated with the use of currently available biomarkers as a standard of care for the management of CTRCD and identified potentially novel clinical biomarkers that could be further investigated as promising predictors of CTRCD.

Eversion Carotid Endarterectomy: Cardiac Troponin Assessment.

Myocardial infarction (MI) is an eversion carotid endarterectomy (eCEA) complication, but most events are unknown, and true incidence and correlation remain controversial. Routine cardiac troponin measurement is a commonly used method for assessing early identification and treatment of MI and stratifying high-risk patients. The aim of the present study is to evaluate the effect of troponin elevation levels following eCEA and to investigate a possible correlation between adverse cardiovascular events and the incidence of postoperative myocardial infarction following emergent vascular surgery. The study included 54 patients who underwent eCEA. High-sensitive troponin I (hsTnI) levels were routinely monitored pre- and postoperatively, with an upper reference range of 34.5 pg/mL for men and 15.6 pg/mL for women. Increases were correlated with demographic and clinical risk factors, as well as clinical or subclinical cardiovascular events. hsTnI was increased in percentage (13%) postoperatively, and non-ST segment elevation MI was diagnosed in eight patients. No patient had clinical symptoms of MI and only two of them presented with simultaneous electrocardiographic changes. Increased levels did not correlate with comorbidities or other surgical risk factors. hsTnI elevation may occur in patients after eCEA and mostly correlates with silent non-ST segment elevation MI that occurred in the early postoperative phase, indicating a possible value as a tool for cardiovascular event diagnosis during the patient's hospitalization.

Does group-based high-intensity aerobic interval training improve the inflammatory status in patients with chronic heart failure?

BACKGROUND: Chronic heart failure (CHF) is a multifaceted syndrome associated with endothelial dysfunction and increased inflammation. Despite the existing controversies regarding the appropriate training modality, it is widely accepted that supervised cardiac rehabilitation (CR) interventions lead to proinflammatory biomarkers reduction and cellular adhesion molecules in patients with CHF. AIM: The aim of the study was to quantify the effects of 12-week group-based high-intensity aerobic interval training (HIAIT)/modified group-based HIAIT intervention (m-Ullevaal) vs. moderate continuous training (MICT) on serum levels of proinflammatory biomarkers. DESIGN: Single-blind, two-arm, prospective randomized controlled trial conducted on CHF outpatients performing group-based CR interventions throughout a 12-week period. SETTING: The setting of the study was the Medical Center of Outpatient Rehabilitation and Sports Medicine, Plovdiv, Bulgaria. POPULATION: The population included a total of 120 outpatients of both genders, mean age of 63.73±6.68 years, with stable CHF (NYHA classes II to IIIB, were randomly assigned to HIAIT/ m-Ullevaal (N.=60) or to MICT (N.=60) group. METHODS: Functional exercise capacity (FEC) of the eligible subjects was evaluated through 6-minute walk test (6MWT) and peak oxygen uptake. Blood samples were drawn at baseline, after 12 weeks follow-up for analyses of C-reactive protein (CRP), tumor necrosis factor-α (TNFα) and cellular adhesion molecules (CAM). RESULTS: Significant decreases in the serum levels of CRP (P=0.029), TNF-α (P=0.036), and vascular cell adhesion molecule-1 (VCAM-1) (P=0.040), were observed after 48 training sessions in the group-based HIAIT/m-Ullevaal intervention, except for intercellular adhesion molecule-1 (ICAM-1), which was higher in the MICT (P=0.034). FEC was significantly inversely related to CRP (r=-0.72, P<0.05), and the levels of VCAM-1 (r=-0.68, P<0.05). CONCLUSIONS: Both group-based CR interventions (HIAIT/m-Ullevaal and MICT) significantly reduced the serum levels of CRP, TNF- α, ICAM-1 and VCAM in patients with CHF. However, selected proinflammatory biomarkers changes and CAMs favorably decreased in the group-based HIAIT/m-Ullevaal intervention. The responses on serum levels of proinflammatory biomarkers and CAMs are dependent upon the type, intensity, and CR intervention duration. CLINICAL REHABILITATION IMPACT: The group-based high-intensity aerobic interval training reduces significantly the proinflammatory biomarkers and cellular adhesion molecules in patients with chronic heart failure.

Cardiovascular disease in women: Executive summary of the expert panel statement of women in cardiology of the hellenic cardiological society.

The perception that women represent a low-risk population for cardiovascular (CV) disease (CVD) needs to be reconsidered. Starting from risk factors, women are more likely to be susceptible to unhealthy behaviors and risk factors that have different impact on CV morbidity and mortality as compared to men. Despite the large body of evidence as regards the effect of lifestyle factors on the CVD onset, the gender-specific effect of traditional and non-traditional risk factors on the prognosis of patients with already established CVD has not been well investigated and understood. Furthermore, CVD in women is often misdiagnosed, underestimated, and undertreated. Women also experience hormonal changes from adolescence till elder life that affect CV physiology. Unfortunately, in most of the clinical trials women are underrepresented, leading to the limited knowledge of CV and systemic impact effects of several treatment modalities on women's health. Thus, in this consensus, a group of female cardiologists from the Hellenic Society of Cardiology presents the special features of CVD in women: the different needs in primary and secondary prevention, as well as therapeutic strategies that may be implemented in daily clinical practice to eliminate underestimation and undertreatment of CVD in the female population.

Group-based cardiac rehabilitation interventions. A challenge for physical and rehabilitation medicine physicians: a randomized controlled trial.

BACKGROUND: In recent decades, many studies are focused on different training modalities comparison in patients with cardiac diseases. High intensity aerobic interval training (HIAIT) has been considered as an alternative approach to moderate-intensity continuous training (MICT) in rehabilitation of patients with chronic heart failure (CHF). AIM: To highlight the superiority of the modified group-based HIAIT intervention (m-Ullevaal) compared to the moderate-intensity continuous training (MICT), also to encourage physical and rehabilitation medicine (PRM) physicians to apply the m-Ullevaal intervention in routine cardiac rehabilitation (CR) practice. DESIGN: А single-blind, prospective randomized controlled trial. SETTING: Medical Center of Rehabilitation and Sports Medicine, Plovdiv, Bulgaria outpatients were enrolled. POPULATION: One hundred and twenty subjects of both genders, mean age of 63.73±6.68 years, with stable CHF, NYHA classes II to IIIB, were randomly assigned to m-Ullevaal group (N.=60) or to MICT (N.=60) group. Both CR protocols were conducted throughout a 12-week period. METHODS: Functional exercise capacity (FEC), assessed with six-minute walk test, and peak oxygen uptake (VO2peak), left ventricular ejection fraction (LVEF), m-Borg's perceived exertion scale (mBPES), and quality of life (QoL) were outcome measures evaluated. RESULTS: Significant improvement in FEC (P<0.001), LVEF (P<0.001), mBPES and QoL (P<0.001), was observed 12 weeks after both CR interventions (T2). However, the participants performed m-Ullevaal protocol achieved a greater improvement compared to those performed MICT (P<0.001). CONCLUSIONS: The m-Ullevaal protocol seems to be more beneficial and more effective compared to MICT. PRM physicians can efficiently apply the m-Ullevaal protocol in CHF patients rehabilitation. CLINICAL REHABILITATION IMPACT: Group-based HIAIT interventions can be widely applied by PRM physicians in CHF patients rehabilitation.

Development of a multivariate model of the six-minute walked distance to predict functional exercise capacity in hypertension.

BACKGROUND: Hypertension is associated with deterioration of musculoskeletal function and functional capacity. Existing prediction models for assessment of the 6-min walk test (6MWT) do not capture the disease-related functional capacity. This study developed a multivariate prediction model of the measured 6-min walked distance (6MWDM) in hypertension and proposed target-values based on optimal therapeutic aims. METHODS: Seventy-six patients (38 men, 56.1 ±â€¯14.3 years, systolic pressure 156.7 ±â€¯17.5 mmHg, diastolic pressure 92.9 ±â€¯6.9 mmHg) underwent anamnesis, physical examination, and laboratory analysis. Functional capacity was assessed using the 6MWT, being the 6MWDM considered as the dependent variable. Independent variables included sex (S, coded 'male' = 1, 'female' = 0), age (A), body height (H), body mass, mean blood pressure (MBP), and physical activity (IPAQ, coded 1-5). Target-values were derived from theoretical scenarios of optimal blood pressure and physical activity, separately and combined. RESULTS: Patients walked 324.5 ±â€¯10.1 m in the average of two trials 30-min apart. Pearson's correlation coefficient showed moderate-to-weak significant associations between 6MWDM and all independent variables. The final multivariate model was 6MWDP = 611.347-4.446 × MBP + 267.630 × H - 1.511 × A + IPAQcode + Scode (adjusted R2 = 0.680, SE of bias = 6.3 m), suggesting that clinical, anthropometric, and hemodynamic information determines functional capacity. Predicted values yielded a group-average of 325 ±â€¯87 m. Target-values under the optimal scenario resulted in 420 ±â€¯60 m. CONCLUSIONS: Sex (men), higher body height, higher physical activity, lower mean blood pressure, and lower age are independently correlated with higher 6MWDM in patients with hypertension. Target-values can be estimated for therapeutic aims related to hemodynamics and lifestyle.

Therapeutic effects of the combination of inhaled beta2-agonists and beta-blockers in COPD patients with cardiovascular disease.

Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide, with co-morbidities contributing to the overall severity and mortality of the disease. The incidence and prevalence of cardiovascular disease among COPD patients are high. Both disorders often co-exist, mainly due to smoking, but they also share common underlying risk factors, such as aging and low-grade systemic inflammation. The therapeutic approach is based on agents, whose pharmacological properties are completely opposed. Beta2-agonists remain the cornerstone of COPD treatment due to their limited cardiac adverse effects. On the other hand, beta-blockers are administered in COPD patients with cardiovascular disease, but despite their proven cardiac benefits, they remain underused. There is still a trend among physicians over underprescription of these drugs in patients with heart failure and COPD due to bronchoconstriction. Therefore, cardioselective beta-blockers are preferred, and recent meta-analyses have shown reduced rates in mortality and exacerbations in COPD patients treated with beta-blockers.

Bilateral symmetry of local inflammatory activation in human carotid atherosclerotic plaques.

INTRODUCTION: Only a few studies have investigated the structural and functional characteristics of carotid arteries bilaterally. Furthermore, there is controversy as to whether inflammation in paired vascular beds is a local or systemic phenomenon. We aimed to examine, in patients with coronary artery disease, whether intra-subject left and right carotid arteries have similar inflammatory status, as determined non-invasively by microwave radiometry (MWR). METHODS: Consecutive patients (n=200) with significant coronary artery disease were evaluated via an ultrasound echo-colour Doppler (US-ECD) study of both carotid arteries and temperature measurements with MWR. During thermography, thermal heterogeneity (ΔT) was defined as the maximum temperature along the carotid artery minus the minimum temperature. RESULTS: Mean T was similar between the left and right carotid arteries (0.78 ± 0.48 vs. 0.84 ± 0.52°C, p=0.12). Mean right intima-media thickness (IMT) was greater compared to mean left IMT (2.16 ± 1.20 vs. 1.93 ± 0.94 mm, p<0.01). In all carotids, there was a correlation between left and right carotid plaque ΔT (R=0.38, p<0.001) and between left and right IMT (R=0.48, p<0.001). Independent predictors for the presence of bilateral carotid plaques were found to be the extent of coronary artery disease, high ΔT, and therapy with angiotensin II receptor blockers; predictors for the presence of high ΔT bilaterally were bilateral carotid plaques, male sex, diabetes mellitus, and hypertension. CONCLUSIONS: There is bilateral inflammatory activation in the carotid atherosclerotic lesions of patients with coronary artery disease. At this stage of carotid disease, arterial hypertension and diabetes mellitus are more strongly correlated with bilateral functional abnormalities in carotid plaques than with structural changes.

Testosterone deficiency: a determinant of aortic stiffness in men.

OBJECTIVE: Low testosterone levels and increased aortic stiffness are predictors of cardiovascular events. The influence of androgen level on the age- and blood pressure-related increase in aortic stiffness is unknown. METHODS: From January 2007 to June 2011 we enrolled 455 consecutive men with no evidence of cardiovascular disease from a large cohort followed in our Department for arterial function studies. Their total testosterone (TT) levels were measured and carotid-femoral pulse wave velocity (PWVc-f) was measured as an index of aortic stiffness. RESULTS: In multivariable analysis, PWVc-f values were inversely correlated to TT after adjustment for confounders (ß = -0.365, P < 0.001). In younger age categories (<50 yrs and 50-59 yrs), patients with testosterone deficiency (TD) had higher blood pressure-adjusted PWVc-f (P < 0.001 and P = 0.005, respectively) compared to subjects with normal TT, indicating an "aging effect" of 10 years, whereas in older age categories such a difference was not observed. Furthermore, in men with a higher mean pressure (102-108 mmHg and >108 mmHg), patients with TD had higher age-adjusted PWVc-f (P < 0.001) compared to subjects with normal TT, indicating a synergistic unfavorable effect of testosterone deficiency and blood pressure on aortic stiffness. CONCLUSIONS: TT levels are independently associated with aortic stiffening. The effect of low testosterone concentration on aortic stiffness is more prominent in young men and in subjects with higher blood pressure levels. These findings identify testosterone as a marker of arterial damage with special emphasis on young and hypertensive individuals and support its role as predictor of events.

Arterial function and intima-media thickness in hypertensive patients with erectile dysfunction.

OBJECTIVE: Erectile dysfunction is a predictor of cardiovascular risk with high prevalence in hypertensive men. We investigated whether erectile dysfunction is related to arterial structure and function in hypertensive patients. METHODS: We evaluated arterial structural and functional characteristics and measured systemic endothelial/inflammatory markers in 52 hypertensive men with vasculogenic erectile dysfunction and in 34 hypertensive men with normal erectile function, matched for age, blood pressure, risk factors and treatment. RESULTS: Hypertensive patients with erectile dysfunction had higher common carotid intima-media thickness (0.95 +/- 0.19 vs. 0.83 +/- 0.18 mm, P = 0.003) and carotid-femoral pulse-wave velocity (8.89 +/- 1.38 vs. 8.11 +/- 1.10 m/s, P = 0.007), lower flow-mediated dilation of the brachial artery (absolute values of 2.96 +/- 1.64 vs. 4.07 +/- 1.68%, P = 0.003) and a higher level of the systemic endothelial dysfunction marker asymmetric dimethylarginine (0.67 +/- 0.13 vs. 0.57 +/- 0.16 mumol/l, P = 0.003), and the inflammatory markers high-sensitivity C-reactive protein [2.03 (1.16-2.89) vs. 1.23 (0.67-1.90) mg/l, P = 0.029] and interleukin-6 (4.13 +/- 2.38 vs. 2.77 +/- 1.92 pg/ml, P = 0.011). Multivariable analysis adjusting for age, mean pressure, other risk factors and treatment showed independent associations between erectile dysfunction and parameters of arterial structure and function. In the erectile dysfunction group, there were no significant relationships between the severity of erectile dysfunction (as expressed by the Sexual Health Inventory for Men score) and the above arterial indices and level of circulating markers (all P = NS). CONCLUSION: In hypertensive men, the presence but not the severity of vasculogenic erectile dysfunction is associated with subclinical atherosclerosis, impairment of arterial function and systemic endothelial and inflammatory activation.

Functional electrical stimulation improves endothelial function and reduces peripheral immune responses in patients with chronic heart failure.

BACKGROUND: Previous studies have shown beneficial effects of functional electrical stimulation (FES) on muscle performance and exercise capacity of patients with chronic heart failure. This study evaluates the impact of FES on endothelial function and peripheral markers of immune activation in patients with moderate to severe heart failure. METHODS: Twenty-four patients with a left ventricular ejection fraction of less than 40% and New York Heart Association class II-III symptoms, undergoing optimized drug therapy, were randomly assigned (2 : 1) to a 6-week training programme of FES (n=16) or served as controls (n=8). Endothelial function was assessed by Doppler flow-mediated dilatation (FMD) of the brachial artery before and after the training programme. Peripheral pro-inflammatory/anti-inflammatory markers such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1 and IL-10 were also measured before and after training. RESULTS: A significant improvement on the 6-min walk test (7.5+/-3.3%), Minnesota Living Score (18.2+/-8.6%) and FMD (38.5+/-15.1%) was observed only in the FES-treated group. FES also causes a significant reduction of TNF-alpha (-11.5+/-8.9%), sICAM-1 (-13.1+/-9.8%), and sVCAM-1 (-10.6+/-6.6%), as well as a respective increase in the ratio IL-10/TNF-alpha (37.1+/-29.4%). In the FES group, the percentage improvement in the Minnesota Living Score was significantly correlated with respective changes in circulating TNF-alpha (r=0.624, P<0.01), sVCAM-1 (r=0.665, P<0.001) and the ratio IL-10/TNF-alpha (r=-0.641, P<0.01). CONCLUSION: FES is an exercise training programme that improves endothelial function in patients with chronic heart failure, and also has anti-inflammatory effects.

Type 5 phosphodiesterase inhibition by sildenafil abrogates acute smoking-induced endothelial dysfunction.

BACKGROUND: Endothelial dysfunction is a key early event in the process of atherosclerosis and a risk factor for cardiovascular events. Sildenafil, an effective oral treatment for patients with erectile dysfunction, inhibits cGMP degradation by specific type 5 phosphodiesterase (PDE) inhibition. Sildenafil has been shown to improve vascular function, however, the effect of type 5 PDE inhibition on acute smoking-induced endothelial dysfunction is unknown. METHODS: We studied the effect of 50 mg of sildenafil on acute smoking-induced endothelial dysfunction in 14 male smokers according to a randomized, placebo-controlled, cross-over design. Endothelial function was evaluated with flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasonography. RESULTS: Sildenafil abolishes the decrease in FMD of the brachial artery that is induced acutely by smoking (placebo/smoking session: from 4.56% +/- 0.60% to 2.80% +/- 0.43%, sildenafil/smoking session: from 3.83% +/- 0.64% to 4.33% +/- 0.47%, ie, improvement of 51%, P < .05). This was associated with no reversal effect of sildenafil on smoking-induced decrease in resting brachial artery diameter and with a partial reversal of the smoking-induced decrease in hyperemic brachial artery diameter (placebo/smoking session: from 4.68 +/- 0.13 mm to 4.53 +/- 0.15 mm, sildenafil/smoking session: from 4.72 +/- 0.12 mm to 4.64 +/- 0.13 mm, ie, improvement of 1.5%, P < .005). CONCLUSIONS: The present study shows, for the first time, that type 5 PDE inhibition with sildenafil abrogates the smoking-induced acute decrease in FMD of the brachial artery. These findings may have clinical implications given the detrimental consequences of smoking and the strategic role of normal endothelial function.

Effect of alcohol on endothelial function in healthy subjects.

While studies have shown that red wine improves endothelial function, the effect of pure alcohol, the common denominator of all alcoholic beverages, on endothelial function has not been defined. The effect of oral intake of alcohol (one ounce--a dose corresponding to two drink equivalents) on flow-mediated dilatation of the brachial artery was studied in 12 healthy subjects using high-resolution ultrasonography according to a randomized, sham procedure-controlled, single-blind protocol. Alcohol produced a significant vasodilatation of the brachial artery at resting conditions. Furthermore, it led to a significant increase of the brachial artery diameter at reactive hyperemia; however, the percentage flow-mediated dilatation did not change. This study shows, for the first time, that acute moderate intake of alcohol has a potent dilating effect on large arteries both at resting and at reactive hyperemic conditions, without affecting flow-mediated dilatation as a percentage. This may be useful for explaining the divergent effect of different alcoholic beverages on endothelial function and provides valuable insight into the mechanisms involved in the vascular effects of alcohol.