Regional differences in physicians' behavior and factors influencing the intensity of PCSK9 inhibitor therapy with alirocumab: a subanalysis of the ODYSSEY APPRISE study.

Background: Despite better accessibility of the effective lipid-lowering therapies, only about 20% of patients at very high cardiovascular risk achieve the low-density lipoprotein cholesterol (LDL-C) goals. There is a large disparity between European countries with worse results observed for the Central and Eastern Europe (CEE) patients. One of the main reasons for this ineffectiveness is therapeutic inertia related to the limited access to appropriate therapy and suitable dosage intensity. Thus, we aimed to compare the differences in physicians' therapeutic decisions on alirocumab dose selection, and factors affecting these in CEE countries vs. other countries included in the ODYSSEY APPRISE study. Methods: ODYSSEY APPRISE was a prospective, single-arm, phase 3b open-label (≥12 weeks to ≤30 months) study with alirocumab. Patients received 75 or 150 mg of alirocumab every 2 weeks, with dose adjustment during the study based on physician's judgment. The CEE group in the study included Czechia, Greece, Hungary, Poland, Romania, Slovakia, and Slovenia, which we compared with the other nine European countries (Austria, Belgium, Denmark, Finland, France, Germany, Italy, Spain, and Switzerland) plus Canada. Results: A total of 921 patients on alirocumab were involved [modified intention-to-treat (mITT) analysis], including 114 (12.4%) subjects from CEE countries. Therapy in CEE vs. other countries was numerically more frequently started with lower alirocumab dose (75 mg) at the first visit (74.6 vs. 68%, p = 0.16). Since week 36, the higher dose was predominantly used in CEE patients (150 mg dose in 51.6% patients), which was maintained by the end of the study. Altogether, alirocumab dose was significantly more often increased by CEE physicians (54.1 vs. 39.9%, p = 0.013). Therefore, more patients achieved LDL-C goal at the end of the study (<55 mg/dl/1.4 mmol/L and 50% reduction of LDL-C: 32.5% vs. 28.8%). The only factor significantly influencing the decision on dose of alirocumab was LDL-C level for both countries' groups (CEE: 199.2 vs. 175.3 mg/dl; p = 0.019; other: 205.9 vs. 171.6 mg/dl; p < 0.001, for 150 and 75 mg of alirocumab, respectively) which was also confirmed in multivariable analysis (OR = 1.10; 95% CI: 1.07-1.13). Conclusions: Despite larger unmet needs and regional disparities in LDL-C targets achievement in CEE countries, more physicians in this region tend to use the higher dose of alirocumab, they are more prone to increase the dose, which is associated with a higher proportion of patients reaching LDL-C goals. The only factor that significantly influences decision whether to increase or decrease the dose of alirocumab is LDL-C level.

Characteristics of shared decision making in Romania from the patient perspective: A cross-sectional multicentric study.

BACKGROUND: Shared decision making (SDM) is very important from patients' perspective. This process has not yet been evaluated in Romania. The study aims to evaluate SDM from the patients' perspective and to evaluate patients' characteristics that associate with SDM. MATERIAL AND METHODS: A cross-sectional multicentric study comprising eight recruitment centres was performed. Inpatients and outpatients who referred to Hospital Units treating autoimmune diseases or atrial fibrillation were included. Another sample consisted of members of the Autoimmune Disease Patient Society, who completed an online anonymous questionnaire. All participants completed the Romanian translated version of the 9-item Shared Decision Making Questionnaire (SDM-Q-9), as these samples were used for the validation of this questionnaire, too. Patients had to refer to the visit in which the decision concerning the antithrombotic treatment was taken (atrial fibrillation patients), or the immunosuppressive treatment was last time changed (autoimmune disease patients). Ordinal regression having the total SDM score as dependent variable was used. RESULTS: A total of 665 questionnaires were filled in within the hospital setting (n = 324; 48.7%) and online (n = 341; 51.3%). The median score for SDM was 34 of 45, but it differed between hospital completion -39/45 and online completion (anonymous) -20/45 (P < .001). Patients with higher education were influenced most by the setting, giving the best marks in hospital and low marks online, while those with lower education gave lower marks in both settings. In ordinal regression with SDM score as dependent variable, hospital completion of the questionnaire (OR = 9.5, 95% confidence interval, 5.69-16), collagen disease diagnosis (OR = 2.4, 95% confidence interval, 1.39-4.14), and immunosuppressive treatment (OR = 2.16, 95% confidence interval, 1.43-3.26) were independent predictors. CONCLUSION: In our study, full anonymity was associated with significantly lower scores for the SDM process. The patients with higher education were most influenced by this condition, while those with the lowest education were the most critical.

Romanian version of SDM-Q-9 validation in Internal Medicine and Cardiology setting: a multicentric cross-sectional study.

BACKGROUND: Shared decision making (SDM) is becoming more and more important for the patient-physician interaction. There has not been a study in Romania evaluating patients' point of view in the SDM process yet. Therefore, the present study aims to evaluate the psychometric parameters of the translated Romanian version of SDM-Q-9. MATERIAL AND METHODS: A multicentric cross-sectional study was performed comprising eight recruitment centers. The sample consisted of in- and outpatients who referred to Hospital Units for treatment for atrial fibrillation or collagen diseases. Furthermore, patients who were members of Autoimmune Disease Patient Society were able to participate via an online survey. All participants completed the Romanian translated SDM-Q-9. RESULTS: Altogether, 665 questionnaires were filled in within the hospital setting (n = 324; 48.7%) and online (n = 341; 51.3%). The Romanian version had good internal consistency (Cronbach α coefficient of 0.96.) Corrected item correlations were good ranging from 0.64 to 0.89 with low corrected item correlations for item 1 and item 7. PCA found a one-factorial solution (similar with previous reports) but the first item had the lowest loading. CONCLUSION: SDM-Q-9 is a useful tool for evaluation and improvement in health care that was validated in Romania and can be used in clinical setting in this country.

Significance of arterial stiffness and relationship with other noninvasive methods for the assessment of subclinical atherosclerosis inpatients with metabolic syndrome.

UNLABELLED: Measurement of arterial stiffness is an accurate method of assessment of endothelial dysfunction, together with other noninvasive methods, in the diagnosis of atherosclerotic burden in patients with MetS. MATERIAL AND METHODS: The study included 63 patients: MetS group (18 men, 20 women, mean age 58.86 +/- 8.86 years) and the control group (14 men, 11 women, mean age 59.68 +/- 10.0 years). They underwent the following examinations: assessment of arterial stiffness--pulse wave velocity (PWVao), augmentation index of brachial artery (Aixbr) and aorta (Aixao), central systolic blood pressure (SBPao); carotid ultrasound for detection of plaques and measurement of intima-media thickness (IMT); echocardiography--left ventricular hypertrophy (LVH); ankle-brachial index (ABI); biochemical parameters: C-reactive protein (CRP), fibrinogen (Fb), cholesterol (Col), HDLcol, LDLcol and triglycerides. RESULTS: MetS patients had higher PWVao (10.06 +/- 2.12 m/s vs 8.29 +/- 1.33 m/s, p = 0.0001) and SBPao (135.06 +/- 19.80 mmHg vs. 121.76 +/- 18.62 mmHg, p = 0.009). Carotid IMT was higher in MetS group (0.92 +/- 0.11 vs. 0.83 +/- 0.10 mm, p = 0.003). Almost all MetS patients were hypertensive (94.7% vs. 52%, p = 0.01); LVH was present in 57.9% of MetS patients and 20% of the controls (p = 0.05). The MetS group presented higher Col (208.76 +/- 38.41 vs. 176.20 +/- 30.08 mg/dl, p = 0.0003) and CRP levels (0.872 +/- 0.852 mg/dl vs. 0.476 +/- 0.392 mg/dl, p = 0.01). CONCLUSIONS: In MetS patients the most reliable marker of arterial stiffness was PWVao, followed by SBPao. Higher values of carotid IMT are also parameters of high atherosclerotic risk. CRP and Col can be considered biomarkers of high risk in MetS.

[Upper-extremity deep vein thrombosis: current concepts in diagnosis and treatment]. / Tromboza venoasa profunda a membrelor superioare: noutati în diagnostic si tratament.

Upper-extremity deep vein thrombosis is a rare manifestation of venous thromboembolic disease. In the past few decades, the clinical importance of upper-extremity deep vein thrombosis has increased because of the wider use of central venous catheters and the development of ultrasonography as a simple and accurate objective diagnostic method. Primary upper-extremity deep vein thrombosis is a rare disorder (2 per 100,000 persons per year), which comprises (1) Paget-Schroetter Syndrome, also known as effort thrombosis, and (2) idiopathic upper-extremity deep vein thrombosis. Secundary upper-extremity deep vein thrombosis develops in patients with upper extremity central venous catheters, pacemakers or cancer and accounts for most cases of upper-extremity deep vein thrombosis. The imaging modes used for diagnosis are: duplex ultrasound, magnetic resonance. Contrast venogram is the standard diagnostic test for characterization of the anatomy. A staged, multimodal approach to Paget-Schroetter Syndrome can effectively restore venous patency, reduce the risk of rethrombosis, and return the patient to normal function. Primary care physicians should be aware of this condition and its atypical presentations, because delayed recognition in a high-functioning persons can be potentially disabling.

[The importance of carotid ultrasound in the risk stratification of patients with ischaemic heart disease]. / Importanta practica a ultrasonografiei carotidiene in stratificarea riscului la pacienti cu cardiopatie ischemica.

UNLABELLED: The stratification of cardiovascular risk is important both in primary and secondary prevention. In the clinical evaluation, besides the well-known risk factors, the European Guide of Cardiovascular Prevention recommends the identification of additional markers of risk, one of them being the detection of atherosclerotic alterations by carotid ultrasound examination. The objectives of this study were: assessment of carotid ultrasound alterations in patients with known cardiovascular disease; their relation with the other risk factors, the clinical status and echocardiography. METHOD: The study included 144 patients, aged 41-80 (84 males, 60 women) with cardiovascular disease (stable angina, myocardial infarction, peripheral arterial disease, arterial hypertension). Risk factors as smoking, hypercholesterolemia, diabetes mellitus, obesity have been determined, followed by a clinical assessment and echocardiographic examination. Ultrasound of the extracranial carotid arteries included measurement of IMT of the common carotid arteries, the identification of atherosclerotic plaques and the presence of stenoses. The plaques were considered if the IMT was more than 1.3 mm. RESULTS: Patients with IMT > 0.8 are older (61.5 +/- 8.2 vs. 56.1 +/- 8.2 years, p = 0.001); the prevalence of arterial hypertension is greater (63.8% vs. 21.6%, p = 0.05), and at an IMT of more than 1.1 mm all were hypertensive; the association with peripheral arterial disease is significant at the IMT = 0.8 mm (23.6% vs. 4.8%, p = 0.01). The relationship with echocardiographic markers of left ventricular hypertrophy is present at an IMT of 0.8 mm and is evident at IMT = 1 mm (interventricular septum 13.2 +/- 3 vs. 12 +/- 2.3, p = 0.05; left ventricular wall 14 +/- 5.4 vs. 12 +/- 1.7, p = 0.01; left ventricular mass 323 +/- 94 vs. 282 +/- 68, p = 0.03), and also the relation with the degree of diastolic dysfunction expressed by E/A ratio (0.71 +/- 0.24 vs. 0.99 +/- 0.39, p = 0.001). The presence of atherosclerotic plaques correlates with gender (45.1% at male vs. 24.3%, p = 0.01) and older age (61.7 +/- 8.6 vs. 56.2 +/- 8.5 years, p = 0.001). IMT and carotid plaques are not significantly correlated either with such risk factors as smoking, hypercholesterolemia, diabetes mellitus or clinical conditions as myocardial infarction and angina. CONCLUSION: IMT greater than 0.8 mm is a marker of increased cardiovascular risk, associated with age, presence of peripheral arterial disease, arterial hypertension, left ventricular hypertrophy, and diastolic dysfunction. IMT seems to be a more reliable index of cardiovascular risk than carotid plaques. Measurement of IMT is easy to be done in clinical practice, and is recommended for more accurate risk stratification in patients with atherosclerotic cardiovascular disease.

[Adult onset Still's disease with normal level of serum ferritin]. / Boala Still a adultului cu manifestari aterosclerotice sistemice severe.

We present a case of an adult onset Still's disease: a 51 year old men presented with one month history of high spiking fever, asymmetric migratory polyarthritis and a previous history of pharyngitis. The diagnostic was based upon clinical criteria and laboratory findings, and necessitated the exclusion of infectious, neoplastic, and other "autoimmune" disease. The systemic involvement in our case induced us to comment therapy with corticosteroid. Patients with systemic disease have a favorable prognosis, with only rare serious complications from the disease (pericarditis, tamponade, diffuse intravascular coagulation, amyloidosis, hepatic disease, and respiratory failure) or the treatment (infections, gastrointestinal bleeding etc.).

[Role of the exercise test in the assessment of left ventricular performance in ischemic heart disease]. / Rolul testarii de efort în evaluarea performantei ventriculare stângi în cardiopatia ischemica.

The exercise testing is indicated at patients with ischemic heart disease for multiple purposes: it reveals ischemic changes during the exercise and the severity of them; the ekg alterations correlate with the location and the extension of coronary stenoses. The exercise capacity is a strong predictor of survival. Exercise testing is indicated in the evaluation of patients with angina pectoris, after myocardial infarction and after revascularisation procedures and the results are useful in the risk stratification of the patients.

[Carotid atherosclerotic alterations revealed at ultrasonographic examination in patients with coronary heart disease]. / Modificari aterosclerotice carotidiene evidentiate la examinarea ultrasonografica la pacienti coronarieni.

UNLABELLED: Carotid ultrasound examination is a noninvasive method with large indications in the evaluation of atherosclerotic lesions at cardiac patients. The aims of the study were: the ultrasound assessment of extra cranial carotid system at patients with coronary heart disease; relationship with the cardiovascular risk factors, lipid profile and echocardiographic data. METHODS: There were studied 47 patients with coronary heart disease (angina, myocardial infarction, ischemic cardiomyopathy, CABG). The evaluation included cardiovascular risk factors, clinical examination, serum lipids and glucose, echocardiographic data. The ultrasound examination of the carotid arteries included the measurement of the diameter and intima-media thickness (IMT) of the common carotid arteries, the presence and location of atherosclerotic plaques and the presence and severity of carotid stenosis. RESULTS: There was a significant increase of the diameter and IMT with age (p=0.009 respectively p=0.05). Males had a greater medium diameter than women (7.8 +/- 0.9 mm vs. 7.3 +/- 0.8 mm, p=0.04). There was no significant relationship between the cardiovascular risk factors (smoking, arterial hypertension, diabetes mellitus, dyslipidemia) and IMT. The thickness of the interventricular septum (at the echocardiographic examination) correlated with the IMT (p=0.03). All the patients with myocardial infarction revealed carotid atherosclerotic plaques and most of the smokers had carotid plaques (88.9% vs. 44.8%, p=0.03). Patients with carotid plaques were older (60.9 +/- 10.1 vs. 54.8 +/- 6.1, p=0.02). CONCLUSIONS: The incidence of carotid atherosclerosis increases with age; the carotid diameter is greater at males and older patients; IMT is influenced mainly by age; carotid plaques are present mainly at older patients, at smokers and those with myocardial infarction and can be considered an additional risk factor for vascular

[Ischemic left ventricular diastolic dysfunction at females: clinical aspect]. / Disfunctia ventriculara stânga la sexul feminin: aspecte clinice.

UNLABELLED: The prevalence of the coronary heart disease at females becomes close to that of the male gender at older ages. However, studies of the assessment of ischemic cardiac disfunction include a few women. The objective of the paper is the analysis of the clinical profile of women with ischemic heart disfunction. METHODS: There have been studied 189 patients with coronary heart disease (chronic myocardial infarction, stable angina, ischemic cardiomyopathy): 63 females and 126 males. The prevalence of the coronary diseases, risk factors, symptoms, lipidic profile, radiologic and echocardiographic alterations were analysed. RESULTS: Mean age of the male group was 56.8 +/- 12.2, and of the female was 66.3 +/- 10.9 years, significantly older (p = 0.00001). Ischemic cardiomyopathy had a greater prevalence at women (33.3% vs 11.9%, p = 0.0004), while myocardial infarction dominated at the male gender (61.9% vs 28.6%, p = 0.0001); stable angina had similar rates (20.6%, respectively 19%). Episodes of cardiac decompensation were more often at women (20.6% vs 7.1%, p = 0.0003). Arterial hypertension prevailed at females (77.8% vs 60.3%, p = 0.01), and smoking at males (72.2% vs 7.5%, p = 0.00001). Women declared more often dyspnoea (p = 0.02) and the resting heart rate was higher (87 +/- 23/min vs 75 +/- 13/min, p = 0.0007). Mean values of cholesterol were higher at women, particularly LDL: 165 +/- 49 mg% vs 149 +/- 46 mg%, p = 0.04. At X-ray examination, cardiomegaly and pulmonary congestion were dominant at females. At echo examination, the ejection fraction had similar values (52.3 +/- 9.3% at women and 51.2 +/- 11.6% at men), but left ventricular hypertrophy and diastolic disfunction were prevalent at women (87.3% vs 69.1%, p = 0.01). CONCLUSIONS: Ischemic heart disfunction at females appears at older ages, with the dominance of ischemic cardiomyopathy and angina. At similar levels of sistolic disfunction, the diastolic disfunction, the left ventricular hypertrophy and the cardiac decompensations are more frequently at female gender.

[Physical exercise and vascular endothelium]. / Exercitiul fizic si endoteliul vascular.

Physical exercise has positive effects at patients with atherosclerotic cardiovascular diseases. These benefits are explained not only by the action upon the cardiovascular risk factors, but also by the improvement of the endothelial dysfunction. Physical exercise has vasodilator, antiplatelet, antioxidative, antiadhesive, antiproliferative and antiapoptotic effects upon the vascular endothelium. It improves the endothelium-mediated vasodilation in coronarian and peripheral beds in coronary heart disease, arterial hypertension, heart failure, diabetes mellitus, and also at sedentary and smokers, thus exerting a vasculoprotective action against atherosclerotic disease.

[Clinico-functional particularities of cardiac dysfunction in the elderly]. / Particularitati clinico-functionale ale disfunctiei cardiace la vârstnici.

UNLABELLED: Ischaemic left ventricular dysfunction is more frequent at the elderly and has a series of clinical and functional peculiarities. The aim of the paper is to define the clinical, biochemical, and echocardiograph features of the older patients with ischaemic heart disease. METHODS: 189 patients with ischaemic heart disease (old myocardial infarction, angina, ischaemic cardiomiopathy) have been parted, according to age, in Group A (n = 101) over 60 years old and Group B (n = 88) < 60 years old. Symptoms, cardiovascular risk factors, lipid profile, echocardiograph findings, and the exercise testing (at the bicycle) were analyzed. RESULTS: Ischaemic heart dysfunction appears earlier at the male gender, who is dominant at Group B (83%) in comparison with Group A (48%, p = 0.009). Myocardial infarction is more frequent at Group B (61 vs 42%, p = 0.006), and ischaemic cardiomiopathy at Group A (34% vs. 2%, p = 0.004). At Group A, symptomatic heart failure (dyspnoea of III or IV NYHA class) is prevalent (20% vs. 1%, p = 0.002). Arterial hypertension was dominant at Group A (73% vs. 58%, p = 0.02). At the echocardiograph examination, regional and diffuse contractility abnormalities were dominant at Group A, and the ejection fraction was lower (49 +/- 10%) in comparison to Group B (53 +/- 9%, p = 0.005). Diastolic dysfunction was found in 63% at Group A and 36% at Group B (p = 0.001). At the exercise testing there were not reported significant differences concerning the mechanical load according to age (87% of maximum heart rate at Group A and 83% at Group B). CONCLUSIONS: At the old patients with ischaemic left ventricular dysfunction the presence of a myocardial infarction is not so frequent. Systolic and diastolic dysfunction of the left ventricle is more severe, the ejection fraction is lower, but the exercise capacity did not differ significant.

[Chronic myocardial infarction. Clinical symptoms in elderly patients]. / Particularitati clinice ale pacientilor vârstnici cu infarct miocardic cronic.

UNLABELLED: Although there is an increasing prevalence of coronary heart disease at the old age, the frequency of chronic myocardial infarction seems to be less in favour of other forms of manifestation. The objective of the study was the assessment of the clinical features of patients with chronic myocardial infarction at a population of coronary patients over 65, admitted in the Department of Cardiac Rehabilitation. METHODS: There have been selected patients over 65 years with ischaemic heart disease: 29 with chronic myocardial infarction (Group A), and 31 with other forms of coronary heart disease (Group B). There were analysed cardiovascular risk factors, symptoms, lipidic profile, echocardiographic findings. RESULTS: Mean age of the groups A and B are 69.9 +/- 4.7 and respectively 71.6 +/- 4.9. Arterial hypertension is more frequent at group B (28/31 vs 22/29, p=0.05); at group A there is a higher rate of smoking (13/29 vs 8/31, p=0.007) and diabetes mellitus (12/29 vs 3/31, p=0.001). Dyspnea is prevalent at group B (26/31 vs 21/29, p=0.01), and the resting heart rate is greater at the same group (89 +/- 19/min vs 74 +/- 14/min, p=0.02). Group A associates more frequent atherosclerotic neurologic and peripheric disease (7/29 vs 5/31 p=0.05 and respectively 6/29 vs 4/31, p=0.01). Although the ejection fraction has similar values (53.9 +/- 10% at group A and 53.8 +/- 14% at group B), the regional contractility abnormalities are more frequent at group A (17/29 vs 11/31, p=0.005). CONCLUSIONS: Old patients with chronic myocardial infarction are especially male gender, associate smoking, diabetes mellitus, other atherosclerotic neurological and peripheric diseases; the regional contractility disturbances are more prevalent at this group.

[Is physical training useful for elderly patients with ischemic heart disease?]. / Este antrenamentul fizic util la pacientii vârstnici cu disfunctie cardiaca ischemica?

UNLABELLED: The aim of the paper is the study of the effects of a supervised physical training at old patients with ischaemic heart disease. METHODS: 74 patients with ischaemic left ventricular dysfunction have been followed during a supervised physical training consisting of a daily programme of exercise over a period of 21 +/- 10 days. They were parted in Group A (n = 26) over 60 years old and Group B (n = 48) under this age. The heart rate (HR), systolic and diastolic heart pressure (SHP respectively DHP), the time-tension index (TTI) were registered during the rest, the peak intensity of exercise and the recovery. These parameters were compared in evolution at each group and also between the groups. RESULTS: At Group A, at the end of the period, SHP at the peak intensity decreased (from 146 +/- 19 to 137 +/- 14 mmHg, p = 0.01), also SHP in the recovery period (from 119 +/- 10 to 116 +/- 10 mmHg, p = 0.01) and HR during the recovery time (from 77 +/- 8/min to 73 +/- 6/min, p = 0.03). The total length of the session time increased (from 12 +/- 4 min to 21 +/- 6 min, p = 0.01) and also the duration of the peak exercise time (from 3.6 +/- 1.0 min to 7.7 +/- 2.9 min, p = 0.03), in the condition of maintaining a HR at the peak exercise of about 75-76% of the maximum HR obtained at a previous exercise testing. The improvement of the training parameters was similar with Group B, except the duration of the session, longer at the last group (21 +/- 6 min at Group A vs. 25 +/- 7 min at Group B, p = 0.02) and the duration of the peak intensity (7.7 +/- 1.0 min at Group A vs. 9.1 +/- 2.9 min at Group B, p = 0.02). CONCLUSIONS: Old patients with ischaemic left ventricular dysfunction improve their exercise capacity as well as the younger ones; the benefits of a supervised physical exercise are evident regardless of age.

[Osler--Rendu Disease: an example of a family clustering in a genetic disorder]. / Maladia rendu-osler: exemplu de agregare familiala a unei boli genetice.

The case of a 75 years old woman with hereditary hemorrhagic telangiectasia (HHT) is presented. This condition is an autosomal dominant mucocutaneous and visceral fibrovascular dysplasia in which telangiectasia, arteriovenous malformations and aneurysms may be widely distributed throughout the cardiovascular system. It is usually recognized as a "triad" of telangiectasia, recurrent epistaxis and a family history of the disorder.