Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease: the updated SMART2 algorithm.

AIMS: The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations. METHODS AND RESULTS: Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options. CONCLUSION: The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk.

Chemoradiotherapy for locally advanced pancreatic cancer patients: is it still an open question?

Operable pancreatic cancer is characterized by a high risk of recurrence. Efforts are made to incorporate new therapies. Throughout the world there is a lack of uniform recommendations concerning the adjuvant treatment of pancreatic cancer patients, due to confusing evidence-based data. The patients recruited to clinical trials differ from the population of patients treated in everyday practice. These differences have an influence on tolerance of treatment, toxicity and results of therapy. The decision on administration of adjuvant treatment is made individually and differs from center to center. A review of the literature concerning both results and tolerance of postoperative chemoradiotherapy of pancreatic cancer patients is presented.

Memantine - neuroprotective drug in aging brain.

Aging is the process of progressive accumulation of changes over time, which is additionally connected with increasing susceptibility to some diseases and ultimately leads to death. Aging is associated mainly with loss of permanent cells, e.g. in heart, skeletal muscle and brain. During aging neurons die mainly in the apoptotic way. Apoptosis can be divided into three phases: initiation, execution and degradation. During the execution phase activation of specific enzymes, caspases, is observed. These enzymes are responsible for initiation of the death machinery. Caspase-9 is connected with the internal pathway of apoptosis, which begins at the mitochondrium in response to apoptotic stimulants, such as free radicals, UV radiation or chemotherapeutics. Before the executive phase starts, cytochrome c leaks from the mitochondrium to the cytoplasm, where it joins to the protein Apaf-1 and procaspase-9 and forms a complex called the apoptosome. Then procaspase-9 is converted by autolysis to caspase-9, which subsequently activates procaspase-3 to the active form which ultimately leads to apoptosis. Immunohistochemical analysis demonstrated a small decrease in caspase-9 and caspase-3 activation during normal aging and an increase in this process after application of stress factors. Also increased apoptosis in the cerebrum after administration of a drug for Alzheimer disease, memantine, to aging rats was observed. Taken together, the results obtained in this study seem to confirm the neuroprotective effect of memantine on increasing levels of cells with active caspase-3 and active caspase-9. It probably improves caspase-dependent apoptosis in the aging brain.

Secondary prevention of coronary heart disease in Poland: does sex matter? Results from the POLASPIRE survey.

INTRODUCTION: Adherence to health­promoting behaviors intended to mitigate modifiable risk factors plays an important role in secondary cardiovascular prevention. OBJECTIVES: We aimed to evaluate sex differences in the prevalence and control of risk factors in patients with coronary heart disease (CHD). PATIENTS AND METHODS: The study included 1236 patients who experienced acute coronary syndrome or coronary revascularization within the last 6 to 24 months. Definitions of risk factors and treatment goals were based on the 2016 European Society of Cardiology guidelines on cardiovascular prevention. RESULTS: The prevalence of modifiable risk factors in both sexes was high, and their control inadequate. Women were older (P <0.001) and had a higher accumulation of multiple cardiovascular risk factors than men (P = 0.036). They more frequently had central obesity (P <0.001) and reduced values of glomerular filtration rate (P <0.001). Women more often experienced anxiety (P <0.001), reported lower levels of education (P <0.001) and lower income (P = 0.001), and those in the youngest age group were more likely to be exposed to second­hand smoking (P = 0.01). A large fraction of the study patients, men and women alike, did not meet the recommended therapeutic goals. For both sexes, participation in cardiac rehabilitation programs was associated with more frequent attainment of the recommended level of physical activity (P = 0.046) and smoking cessation (P = 0.01). CONCLUSIONS: The prevalence of cardiovascular risk factors in patients with CHD is high, especially in women. Therapeutic goals are met infrequently in both sexes. This situation calls for widening the access to educational programs and paying greater attention to their proper implementation.

Effectiveness and safety of a simple home-based rehabilitation program in pulmonary arterial hypertension: an interventional pilot study.

BACKGROUND: Rehabilitation plays an important role in the management of patients with pulmonary arterial hypertension (PAH) and current guidelines recommend implementation of a monitored individualized exercise training program as adjuvant therapy for stable PAH patients on optimal medical treatment. An optimal rehabilitation model for this group of patients has not yet been established. This randomized prospective study assessed the effectiveness and safety of a 6-month home-based caregiver-supervised rehabilitation program among patients with pulmonary arterial hypertension. METHODS: A total of 39 patients with PAH were divided into two groups: intervention group (16 patients), subjected to a 6-month home-based physical training and respiratory rehabilitation program adapted to the clinical status of participants, and control group (23 patients) who did not perform physical training. The 6-min walk test (6MWT), measurement of respiratory muscle strength, quality of life assessment (SF-36, Fatigue Severity Scale - FSS) were performed before study commencement, and after 6 and 12 months. Adherence to exercise protocol and occurrence of adverse events were also assessed. RESULTS: Physical training significantly improved 6MWT distance (by 71.38 ± 83.4 m after 6 months (p = 0.004), which remained increased after 12 months (p = 0.043), and respiratory muscle strength after 6 and 12 months (p < 0.01). Significant improvement in quality of life was observed after the training period with the use of the SF-36 questionnaire (Physical Functioning, p < 0.001; Role Physical, p = 0.015; Vitality, p = 0.022; Role Emotional, p = 0.029; Physical Component Summary, p = 0.005), but it did not persist after study completion. Adherence to exercise protocol was on average 91.88 ± 14.1%. No serious adverse events were noted. CONCLUSION: According to study results, the home-based rehabilitation program dedicated to PAH patients is safe and effective. It improves functional parameters and quality of life. Strength of respiratory muscles and 6MWD remain increased 6 months after training cessation. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03780803 . Registered 12 December 2018.

Management of Dyslipidemia in Women and Men with Coronary Heart Disease: Results from POLASPIRE Study.

Cardiovascular diseases (CVDs) are the leading cause of death in Poland. Starting from 1992, a gradual decrease in mortality due to CVDs has been observed, which is less noticeable in women. Following this notion, we assessed sex differences in the implementation of ESC recommendations regarding lipid control and the use of statins as part of secondary CVDs prevention in 1236 patients with acute coronary syndrome or elective coronary revascularization within the last 6-24 months. During hospitalization women had more frequently abnormal TC levels than men (p = 0.035), with overall higher TC levels (p = 0.009) and lower HDL-C levels (p = 0.035). In the oldest group, they also had more frequently elevated LDL-C levels (p = 0.033). Similar relationships were found during the follow-up visit. In addition, women less often achieved the secondary lipid therapeutic goal for non-HDL-C (p = 0.009). At discharge from hospital women were less frequently prescribed statins (p = 0.001), which included high-intensity statins (p = 0.002). At the follow-up visit the use of high-intensity statins was still less frequent in women (p = 0.02). We conclude that women generally have less optimal lipid profiles than men and are less likely to receive high-intensity statins. There is a need for more organized care focused on the management of risk factors.

Serum Chemerin Concentration Is Associated with Proinflammatory Status in Chronic Coronary Syndrome.

BACKGROUND: Chemerin is an adipokine and a chemoattractant for leukocytes. Increased chemerin levels were observed in patients with coronary artery disease (CAD). We investigated associations between chemerin and biochemical measurements or body composition in CAD patients. METHODS: In the study, we included patients with stable CAD who had undergone percutaneous coronary intervention (PCI) in the past. All patients had routine blood tests, and their insulin and chemerin serum levels were routinely measured. Body composition was assessed with the DEXA method. RESULTS: The study group comprised 163 patients (mean age 59.8 ± years, 26% of females, n = 43). There was no significant difference in serum chemerin concentrations between patients with diabetes and the remaining ones: 306.8 ± 121 vs. 274.15 ± 109 pg/mL, p = 0.1. Chemerin correlated positively with the white blood cell (WBC) count, the neutrophil to lymphocyte ratio, hsCRP, all fractions of cholesterol, triglycerides, platelet count, fasting insulin, and c-peptide. Chemerin levels were also correlated with total fat mass but only in a subgroup with normal glucose metabolism. CONCLUSION: In patients with CAD, serum chemerin levels are correlated with inflammation markers, insulin resistance, and an unfavorable lipid profile. Correlation with fat mass is dependent on glucose metabolism status. Depending on the presence of diabetes/prediabetes, the mechanisms regulating chemerin secretion may be different.

Smoking cessation in patients with established coronary artery disease: data from the POLASPIRE survey.

BACKGROUND: Smoking cessation in patients with coronary artery disease (CAD) is related to decreased risk of cardiovascular events. AIMS: To evaluate factors related to persistent smoking in patients with established coronary artery disease. METHODS: Patients aged 80 years or younger and hospitalized for acute coronary syndrome or a myocardial revascularization procedure were interviewed 6 to 18 months after the recruiting event. Medical history, smoking behavior, and exposure to environmental smoke were assessed during the interview. Self--reported smoking status was validated by carbon monoxide in exhaled air measurement. Persistent smoking was defined as smoking at the time of interview among those who smoked during the month prior to the recruiting event. RESULTS: We analyzed the data of 1034 patients, including 764 (73.9%) who reported smoking at any time in the past and 296 (28.6%) who smoked within 1 month before the recruiting hospitalization. At the time of the interview, the overall smoking rate was 17.2%, whereas 54.7% of patients were persistent smokers. Secondhand smoke exposure and duration of smoking were associated with lower likelihood whereas older age, high socioeconomic status, cardiac rehabilitation following a cardiovascular event, and consultation with a cardiologist were associated with higher likelihood of smoking cessation. CONCLUSIONS: Over half of all smokers hospitalized for CAD are still smoking 6 to 18 months after discharge. Older age, secondhand smoking, low socioeconomic status, lack of consultation with a cardiologist, and cardiac rehabilitation following hospitalization were related to persistent smoking. Our findings may help develop strategies aimed at assisting smoking cessation in patients with CAD.

Defining right ventricular dysfunction by echocardiography in normotensive patients with pulmonary embolism.

INTRODUCTION: Although the prognostic value of various echocardiographic parameters of right ventricular dysfunction (RVD) was reported in normotensive patients with acute pulmonary embolism (PE), there is no generally accepted definition of RVD. OBJECTIVES: The aim of the study was to compare echocardiographic parameters for the prediction of an adverse 30­day outcome and create an optimal definition of RVD.                                     Patients and methods: Echocardiographic parameters including the right ventricular to left ventricular diameter ratio (RV to LV ratio) and tricuspid annular plane systolic excursion (TAPSE) to predict PE­related mortality, hemodynamic collapse, or rescue thrombolysis within the first 30 days were directly compared in 490 normotensive patients with PE. RESULTS: An adverse outcome (AO) was present in 31 patients (6.3%); 8 of them (1.6%) died due to PE. Systolic blood pressure, RV to LV ratio, and TAPSE were independent predictors of AO. The receiver operator characteristic yielded an area under the curve of 0.737 (0.654-0.819; P <0.001) for the RV to LV ratio and 0.75 (0.672-0.828; P <0.001) for TAPSE with regard to an AO. The hazard ratio for AO was 2.5 for the RV to LV ratio of more than 1 (95% CI, 1.2-5.7; P <0.03) and 3.8 for TAPSE of less than 16 mm (95% CI, 1.74-8.11; P = 0.001). A combined RVD criterion (TAPSE <16 mm and RV to LV ratio >1) was present in 60 patients (12%), and showed a positive predictive value of 23.3% with a high negative predictive value of 95.6% regarding an AO (HR, 6.5; 95% CI, 3.2-13.3; P <0.001). CONCLUSIONS: Defining RVD on echocardiography by the RV to LV ratio of more than 1 combined with TAPSE of less than 16 mm identified patients with an increased risk of 30­day PE­related mortality, hemodynamic collapse, or rescue thrombolysis, while patients without this sign had a very good 30­day prognosis.

Chemokines profile in patients with chronic heart failure treated with cardiac resynchronization therapy.

PURPOSE: Inflammatory mechanisms have been suggested to play a role in the heart failure with reduced ejection fraction (HF-REF) development, but the role of chemokines is largely unknown. Cardiac resynchronization therapy (CRT) may reverse the HF-REF course. We aimed to evaluate selected chemokines concentrations in HF-REF patients and their relationship with disease severity and clinical response to CRT. MATERIALS AND METHODS: The study included 37 patients (64.1 ± 11.04 years, 6 females) with HF-REF subjected to CRT, controlled prior to implantation and after 6 months. The control population included 26 healthy volunteers (63.9 ± 8.1 years, 8 females). Serum chemokines concentrations were determined using multiplex method. RESULTS: HF-REF patients were characterized by the higher baseline MIF, NAP-2 and PF4 concentrations and lower Axl, BTC, IL-9, and IL-18 BPa concentrations comparing to controls. After 6 months of CRT only NAP-2 concentration decreased significantly in comparison to the baseline values. CONCLUSIONS: HF-REF patients present altered chemokines profile compared to the control group. The CRT-related alleviation of HF-REF causes only slight changes in the chemokines concentrations especially in the platelet-associated ones. The precise chemokines role in the HF-REF pathogenesis and their prognostic value remains to be established.

Secondary prevention of coronary artery disease in Poland. Results from the POLASPIRE survey.

BACKGROUND: The highest priority in preventive cardiology is given to patients with established coronary artery disease (CAD). The aim of the study was to assess the current implementation of the guidelines for secondary prevention in everyday clinical practice by evaluating control of the main risk factors and the cardioprotective medication prescription rates in patients following hospitalization for CAD. METHODS: Fourteen departments of cardiology participated in the study. Patients (aged ≤ 80 years) hospitalized due an acute coronary syndrome or for a myocardial revascularization procedure were recruited and interviewed 6-18 months after the hospitalization. RESULTS: Overall, 947 patients were examined 6-18 months after hospitalization. The proportion of patients with high blood pressure (≥ 140/90 mmHg) was 42%, with high low-density lipoprotein cholesterol (LDL-C ≥ 1.8 mmol/L) 62%, and with high fasting glucose (≥ 7.0 mmol/L) 22%, 17% of participants were smokers and 42% were obese. The proportion of patients taking an antiplatelet agent 6-18 months after hospitalization was 93%, beta-blocker 89%, angiotensin converting enzyme inhibitor or sartan 86%, and a lipid-lowering drug 90%. Only 2.3% patients had controlled all the five main risk factors well (non-smoking, blood pressure < 140/90 mmHg, LDL-C < 1.8 mmol/L and glucose < 7.0 mmol/L, body mass index < 25 kg/m2), while 17.9% had 1 out of 5, 40.9% had 2 out of 5, and 29% had 3 out of 5 risk factors uncontrolled. CONCLUSIONS: The documented multicenter survey provides evidence that there is considerable potential for further reductions of cardiovascular risk in CAD patients in Poland. A revision of the state funded cardiac prevention programs seems rational.

Independent Impact of Gynoid Fat Distribution and Free Testosterone on Circulating Levels of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) in Humans.

BACKGROUND: Natriuretic peptides (NPs), including brain natriuretic peptide (BNP), are neurohormones involved in the regulation of water-sodium balance and the maintenance of cardiovascular homeostasis. A higher concentration of NPs is observed in females, but the mechanism behind this difference has not been fully elucidated. METHODS: Randomly chosen 255 volunteers from the general population were examined. Overall, 196 people without severe cardiovascular disease were included (mean age 48 years, 35.7% male). A comprehensive assessment was performed, including anthropometric measurements, N-terminal pro-brain natriuretic peptide (NT-proBNP), total testosterone (TT) and sex hormone-binding globulin (SHBG) concentration, transthoracic echocardiography (ECHO), and body composition analysis by direct dual-energy X-ray absorptiometry (DEXA). The univariate analysis adjusted by the known affecting factors determined which measurements were independently associated with NT-proBNP concentration. RESULTS: NT-proBNP concentration was positively associated with gynoid fat mass, gynoid/total fat (G/TF) mass index, SHBG and negatively with android/gynoid (A/G) fat mass index, TT and calculated free testosterone (CFT) concentrations. Furthermore, body composition parameters remained independently associated with NT-proBNP levels even after adjusting for CFT and SHBG. CONCLUSION: In the population without severe cardiovascular disease, the NT-proBNP concentration is independently associated with lower availability of testosterone and higher gynoid fat distribution, which may explain higher NPs levels in females.

The strengths and weaknesses of non-invasive parameters obtained by echocardiography and cardiopulmonary exercise testing in comparison with the hemodynamic assessment by the right heart catheterization in patients with pulmonary hypertension.

PURPOSE: Pulmonary hypertension (PH) diagnosis requires invasive assessment by right heart catheterization (RHC), but screening and monitoring are performed using non-invasive methods: echocardiography and cardiopulmonary exercise testing (CPET). The aim of the study was to assess correlations between the parameters obtained in non-invasive testing and RHC in patients with PH of different etiologies. MATERIAL/METHODS: The study included 53 medical records of PH patients (32 women) aged 29-81 years. We analyzed correlations between RHC (systolic pulmonary artery pressure (sPAP), diastolic pulmonary artery pressure (dPAP), pulmonary vascular resistance (PVR), cardiac output (CO)) and echocardiographic (tricuspid annular plane systolic excursion (TAPSE), sPAP) and CPET parameters (end-tidal oxygen and carbon dioxide pressures (PetO2, PetCO2), ventilation efficiency (VE/VCO2) slope). RESULTS: Echocardiographic estimation correlated well with RHC measurement of sPAP (r=0.65, P<0.001). TAPSE correlated with PVR assessed with thermodilution method (r=-0.5, P=0.005), dPAP (r=-0.53, P=0.002) and CO (r=0.53, P=0.002). PVR assessed with thermodilution and Fick methods showed positive correlation with PetO2 (r=0.74, P<0.001 and r=0.72, P<0.001) and negative correlation with PetCO2 (r=-0.59, P=0.004 and r=-0.64, P=0.002) at the anaerobic threshold. VE/VCO2 slope correlated with dPAP (r=0.43, P=0.04) and PVR calculated with both methods (r=0.52, P=0.01 and r=0.52, P=0.02). CONCLUSIONS: Simple cardiac function indicators obtained by commonly used non-invasive methods allow only approximate estimation of the main hemodynamic RHC-derived parameters: sPAP, CO and PVR. Obtained results suggest the relationship between RV dysfunction and ventilation abnormalities in PH patients.