New Drugs for Lowering LDL-Cholesterol.

LDL-Cholesterol (LDL-C) is a well-known risk factor for cardiovascular disease. Although statins are the mainstream treatment for lowering LDL-C level, additional LDL-lowering therapies are needed to reduce residual cardiovascular risk, especially in patients at very high risk, or with hereditary lipid disorderes or statin intolerance. The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator for LDL-Receptor activity and an attractive target for the treatment of hypercholesterolaemia. From its discovery in 2003, several therapeutic approaches to the inhibition of PCSk9 have been proposed. Monclonal antibodies that bind to PCSJ9 received marketing approval in 2015 (alirocumab and evolucumab) or are being evaluated in phase III trials (bococizumab). Many other molecules are in preclinical studies, phase I or II clinical trials. Another point of interest carefully investigated is the cardiovascular benefit of reducing LDL-C using these new molecules. High hopes are invested in them.

Rare Cause of Rhabdomyolysis - Case Report.

Rhabdomyolysis, a syndrome caused by injury to the skeletal muscles, is a condition associated with various signs ranging in from asymptomatic elevation of serum creatine-kinase to acute kidney injury, abnormal heart rate and rhythm, coma and even death. We report the case of a 52-year-old woman who developed rhabdomyolysis following an epileptic seizure. Because a single epileptic seizure does not commonly cause rhabdomyolysis, we tried to identify other contributing factors. The only finding was an electrolyte imbalance due to vomiting. This case had a favorable outcome. Our report highlights the importance of considering rhabdomyolysis in a patient with a recent epileptic seizure, especially when several trigger factors for rhabdomyolysis act simultaneously in the same patient.

New Nitric Oxide Donors With Therapeutic Potential.

Nitric oxide (NO), formerly known as the endothelium-derived relaxing factor, is a mediator with a key role in the body, both in the central nervous system and in periphery. NO is synthesized by several cell types, where it acts as an autocrine and paracrine signaling molecule. Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. In order to overcome the limitations linked with the use of nitric oxide and specially to increase the release of the radical in the targeted area, promising therapeutic strategies have been implemented, based on specific technologies which create releasing agents and vehicles for nitric oxide. Organic nitrites are the most known NO donor drugs, used especially in the treatment of cardiovascular diseases. In recent years, technological advances have allowed obtaining variations synthetic derivatives (such as diazeniumdiolates, S-nitrosothiols), which can generate NO in a controlled mode in the body and to chemically stabilize it; these compounds were studied with promising results in various animal models of vasospasm and pulmonary hypertension. Another high value therapeutic path is represented by the development of hybrid drugs (new nonsteroidal anti-inflammatory NO donor agents), with practical applications in inflammatory disorders accompanied by pain. Also, there is increasing evidence of the existence of NO donors with important antioxidant and hepatoprotective effects.

Thyroid dysfunction and ischemic heart disease--clinical correlations, progressive implications and impact on the prognosis.

UNLABELLED: Thyroid dysfunctions are associated with systolic and diastolic heart dysfunction, hypertension, rhythm disorders, etc. Clinically significant hyperthyroidism and hypothyroidism may have an impact on the patients with ischemic heart disease. OBJECTIVES: Investigation of the risk of developing ischemic heart disease, of the evolution and prognosis in relation to the entire spectrum of thyroid dysfunctions. MATERIALS AND METHODS: All participants included in the study were selected from among subjects with heart disorders who were controlled with concern to the thyroid hormonal condition and who hadn't been treated previously for thyroid functional disorders. Based on these criteria we defined a study group made out of 791 subjects, divided into five lots based on the level of thyroid hormones. Once the group was formed, we conducted evaluations of the cardiovascular and thyroid status at 6 and 12 months, respectively. RESULTS: In the witness lot, during monitoring 49% of the patients showed an ischemic heart disease. The main risk factors were: heart frequency of over 80 beats/min (RR = 1.83), age over 60 (RR = 1.47), female sex (RR = 1.21) and values of triglycerides over 160 mg/dl (RR = 1.23). In the group of patients with overt clinic hyperthyroidism, during monitoring 46.1% showed ischemic heart disease. The main risk factors were: heart frequency over 80 beats/min (RR = 2.41), age over 60 (RR = 1.67), high level of LDL-cholesterol (RR = 1.53) and female sex (RR = 1.31). Among the patients with overt clinical hyperthyroidism, during monitoring 53.3% showed ischemic heart disease. The main risk factors identified were: heart frequency over 80 beats/min (RR = 2.01), age over 60 (RR = 1.42), high levels of triglycerides (RR = 1.42) and LDL-cholesterol (RR = 1.32), as well as the presence of hypertension in the health records (RR = 1.31). CONCLUSIONS: Thyroid dysfunction is a common clinical condition with a key role in the regulation of the cardiovascular system and may contribute to the evolution of the ischemic heart disease and which should be taken into consideration when patients with heart disease are treated. In this light, thyroid function needs to be evaluated for all patients with a risk for ischemic heart disease.

The importance of clinical prediction models in non-fatal pulmonary embolism: an analysis of the best known clinical scores.

The clinical evaluation in pulmonary embolism (PE) is the first instrument used by practitioners in the management of this potentially fatal pathology. The necessity of develop- ing certain valid and especially affordable practical instruments has led to the emergence of various clinical prediction models. The purpose of this paper is to analyze the main clinical scores, as a diagnostic or a prognostic tool, with their strengths and weaknesses. The PESI score, while relatively recent, remains the most investigated and validated prognostic score for the identification of the mortality risk and major adverse events, with economic implications of health services reduction costs through the accurate identification of patients with a low risk who are candidates of early hospital discharge. The simplified Geneva score (with a similar accuracy as the Geneva one) identifies a high or low PE probability, especially in combination with D-dimers, with a prognosis value as well. The Wells and simplified Wells scores identify the high or low probability, being improved by the level of D-dimers, having similar results with the Geneva score. The LR-PED score, conceived as an identification score for low risk, uses biochemical and electrocardiographic markers, but is less validated. The Vienna Prediction Model is another system for the evaluation of the recurrence in which the level of D-dimers is the main prediction factor. Other scores were evaluated with a statistically low significance. The Geneva and the PESI scores remain the most valuable instruments of diagnosis and clinical prognostic, respectively.

[Aggressive nature of rheumatic arthritis with citrullinated cyclic peptide antibodies]. / Caracterul agresiv al artritei reumatoide cu anticorpi anti peptid ciclic citrulinat prezenti.

UNLABELLED: Numerous studies demonstrate the high specificity (90-98%) of the anticyclic citrullinated antibodies (antiCCP) in rheumatoid arthritis (RA) and their correlation with the erosive arthritis, these antibodies being a disease activity marker and a prognostic factor. MATERIAL AND METHODS: A total of 53 RA patients (48 women, 5 men), mean age 47.3 years old, diagnosed according to the ACR criteria were evaluated. The clinical evaluation was centered upon: tender joint count, swollen joint count, patient pain (VAS), morning stiffness and disease activity score (DAS28). The laboratory tests had in view: the inflammatory syndrome, blood count, immunological syndrome (antinuclear antibodies, rheumatoid factor, antiCCP antibodies), radiographs of the hands and feet. RESULTS: The high levels of the anti-CCP antibodies founded in 28 patients with RA were correlated with severity of the inflammatory syndrome, the immunological abnormalities and with the precocity appearance of the joint erosions. CONCLUSIONS: The presence of the anti-CCP antibodies at patients with RA are correlated with severe joint destruction and it represents a marker of the disease activity and progression.

[Assessment of left atrial remodeling in atrial fibrillation]. / Evaluarea remodelarii atriului stâng in fibrilatia atriala.

UNLABELLED: Left atrial size, most frequently assessed for practical reasons by echocardiography, is important in clinical decision-making. Left atrium volume measurements allow an accurate assessment of asymmetric remodeling and reverse remodeling in atrial fibrillation (AF) patients. AIM: To assess a new method (CTEL2) derived from CT scan by ellipsoid formula (CTEL1) to measure LA volume, we compared the conventional echocardiography-ellipsoid method (EEL), as a reference, with CTEL1 and with the new method-CTEL2. MATERIAL AND METHOD: Left atrium volume was measured by EEL and CTEL2 in 40 consecutive pts (group 1, 56 +/- 12 years, 80% men) and by EEL and CTEL1, in another 46 consecutive patients (group 2, 58 +/- 11 years, 80% men) with AF. For measurements by CTEL2 we used the same formula as the ellipsoid method but as optimal view for the orthogonal dimensions were taken every time the last axial section just under the superior veins (atrialized in dilated left atrium). Usual, the dimensions are taken on the largest axial left atrium area. The correlation coefficients were compared by Z test with Fisher inverse tank transformation. RESULTS: Mean left atrium volume irrespective of methods was > 50 mL. We found a good and significant correlation between CTEL1 and EEL (r1 = 0.769; p < 0.001) but a much better between CTEL2 and EEL (r1 = 0.915; p < 0.001). Both r1 and r2 coefficients were significantly stronger for the correlation with CTEL2 and with CTEL1 (p = 0.016). CONCLUSIONS: This new technique evaluation for left atrium volume is adequacy and could avoid an overestimation or underestimation of LA remodelation assessment, as standard ellipsoid method, in specific situations as cardioversion or AF ablation.

[Corticosteroid resistance thrombocytopenia in connective tissue disorders and vasculitis]. / Trombocitopenii corticorezistente în bolile tesutului vasculo-conjunctiv.

In rheumatic diseases there can appear deteriorations of the thrombocytes number in the sense of increase or decrease of this number.Thrombocytosis has 3 major causes: (1) reactive or secondary thrombocytosis; (2) family thrombocytosis and (3) clonal thrombocytosis. Thrombocytopenia, that is, decrease of the thrombocytes number below 150000/mmc is unusually in rheumatic diseases. Their mechanism of production can be central and peripheral. In the connective tissue disorders and vasculitis thrombocytopenia can has different causes: (1) decrease thrombocytes production; (2) splenic platelets sequestration; (3) peripheral platelets consumption; (4) peripheral immune mediated destruction of platelets. Thrombocytopenia is present in the following rheumatic diseases: systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, Felty syndrome, vasculitis. Steroids are the conventional first line therapy for immune thrombocytopenia. Corticosteroid resistance can develop as a result of deteriorations that appear to the any level of pathway action of corticosteroids.

[Implications of some risk factors in degenerative valvular heart diseases]. / Studiu asupra implicarii unor factori de risc în valvulopatiile degenerative.

UNLABELLED: A retrospective study on 223 patients diagnosed with degenerative heart valvular lesions: 124 women with an average of 74.9 years old and 99 men with an average of 70.1 years old with the lower limit under 50 years old (one woman and one man) and upper limit over 80 years old (22 women and 11 men) revealed that 109 patients (48.8%) had arterial hypertension, 30 patients (13.4%) had diabetes mellitus, and 16 patients (7%) had obesity. Chronic alcoholism was present at 89 patients (39.9%), chronic tobacco consumption at 54 patients (24.2%), cholesterol value over 200mg/dl in 99 patients (44%) and triglycerides value over 150 mg/dl in 15 patients (6.6%). In the 15 patients with a sever form of aortic stenosis was discovered cholesterol value over 200 mg/dl as well as chronic tobacco use and alcoholism. CONCLUSION: Degenerative heart valvular disease represents a different process from arteriosclerosis, therefore the conventional risk factors of arteriosclerosis, can not be considered as having the same significance for degenerative heart diseases.

[Some aspects of degenerative mitral valve lesions encountered in medical practice]. / Date despre leziunile valvulare mitrale degenerative întâlnite în practica medicalâ.

In recent years, degenerative valvular heart diseases have the tendency to be equal in frequency with rheumatic valvular diseases. The maximum attention has been paid on the degenerative aortic stenosis as being a lesion with maximum frequency and a severe evolution. This study, given on the 18,391 admissions in the period 1997-2001, is a retrospective analysis and it is concerned with the degenerative mitral valvular lesions. Of the 223 patients with degenerative valvular heart lesions, 139 patients (62.3%) had degenerative aortic stenosis and 96 patients (38.5%) were diagnosed with degenerative mitral valvular lesions from which 30 patients have had no association with aortic valvular lesions while 66 patients have had such an association. The pointed out types of mitral lesions were: the mitral insufficiency in 59 patients, the mitral annular calcification without hemodynamic disease in 19 patients, the mitral stenosis in 9 patients and the mitral disease in 9 patients, too. The women were affected nearly 1.7 times more frequent than the men, with a maximum average age greater with four years for women but with a low minimal average age at 60 years for women and 52 years for men. The detailed analysis of this 96 cases had shown the presence of a cholesterol value over 200 mg/dl in 50 patients (52%), the diabetes mellitus of type II in 12 patients (12.5%), an association with HTA in 42 patients (43.7%), the cardiac insufficiency in 68 patients (70.8%), a permanent atrial fibrillation in 24 patients (25%), chronic myocardial infarct in 19 patients (19.7%) and disorders in the transmission of stimuli in 8 patients (8.3%). The degenerative mitral valvular lesions had occurred more and more frequently realizing more complex features under the mitral insufficiency predominance. Its frequent association with the degenerative valvular lesions determines the evolutive and therapeutic particulars that are dominated by the high gravity prognostic.

[Some aspects regarding degenerative mitral valvular lesions encountered in medical practice]. / Aspecte ale leziunilor valvulare degenerative mitrale întâlnite în practica medicala.

In the last years, the degenerative valvular heart diseases have the tendency to equalize in frequency the rheumatismal valvular diseases. The maximum attention has been paid on the degenerative aortic stenosis as being a lesion with maximum frequency and a severe evolution. This study, given on the 18391 admissions in the period 1997-2001, is a retrospective analyse and it is concerned with the degenerative mitral valvular lesions. Of the 223 patients with degenerative valvular heart lesions, 139 patients (62.3%) had degenerative aortic stenosis and 96 patients (38.5%) were diagnosed with degenerative mitral valvular lesions from which 30 patients have had no association with aortic valvular lesions while 66 patients have had such an association. The pointed out types of mitral lesions were: the mitral insufficiency in 59 patients, the mitral annular calcification without hemodynamic disease in 19 patients, the mitral stenosis in 9 patients and the mitral disease in 9 patients, too. The women was affected nearly 1.7 times more frequent than the men, with a maximum average age greater with four years for women but with a low minimal average age at 60 years for women and 52 years for men. The detailed analyse of this 96 cases had shown the presence of a cholesterol value over 200 mg/dl in 50 patients (52%), the diabetic mellitus of type II in 12 patients (12.5%), an association with HTA in 42 patients (43.7%), the cardiac insufficiency in 68 patients (70.8%), a permanent atrial fibrillation in 24 patients (25%), the chronical myocardiac infarct in 19 patients (19.7%) and disorders in the transmission of stimuli in 8 patients (8.3%). The degenerative mitral valvular lesions had occurred more and more frequently realizing more complex features under the mitral insufficiency predominance. Its frequent association with the degenerative valvular lesions determines the evolutive and therapeutic particularities that are dominated by the high gravity prognostic.

[Analysis of some clinical aspects of degenerative valvular heart diseases in medical practice]. / Analiza unor aspecte clinice ale valvulopatilor degenerative întâlnite în practica medicala.

UNLABELLED: In a period of 5 years there were 18,391 admissions; out of them 1129 cases were diagnosed with valvular lesions: 223 (19.7%) were degenerative valvular heart disease, 608 (53.8%) had rheumatismal valvular lesions, 7 (0.6%) had congenital valvular lesions and 291 cases (25.7%) had valvular lesions of other etiologies. Out of the 223 cases with degenerative valvular lesions, 99 cases (44.4%) were men with an average age of 70.1 years old and 129 were women (55%) with an average age of 74.9 years old. The calcific aortic valve stenosis was encountered in 139 patients (62.3%), the aortic insufficiency was diagnosed in 19 patients (8.5%), the mitral insufficiency 49 patients (21.9%) and the mitral stenosis in 10 patients (4.4%) the other patients having either aortic or mitral valvular disease. The combination of an aortic stenosis with a mitral insufficiency was diagnosed in 46 cases (20.6%) from the 223. Only 14 patients were asymptomatic, most of them having heart failure (namely, 178 patients i.e. 78%) with or without angine pectoris or effort vertigo, or they had only effort angina, vertigo or effort sincope. Rhythm disorders happened in 59 patients (26.4%) while disorders in the transmission of the stimuli were diagnosed in 14 patients (5.2%). Two patients died due to cardiac causes. CONCLUSION: Rheumatismal valve disease are nearly 2.5 times more frequent than degenerative valve disease and they became a practical reality, which is claimed by its continuously increasing frequency, by a variety of lesional aspects and by implications on the heart, and by it, presence in an age group were arteriosclerosis cumulates its risk factors.

Statistical epidemiological screening methods assessing certain biochemical markers.

The epidemiological studies have shown that it is difficult to define a "normal" value for the serum concentration of some biochemical markers with predictive significance for cardiovascular diseases (CVDs) as follows: total cholesterol (TC), total lipids (TL), triglycerides (TG), glycemia (G), and urea (U). Our study establishes the mean and limit values of the normality for the above mentioned markers, in an adult population from the Iasi City, using the epidemiological screening method. The employed methodology includes the records of the results of 2788 biochemical determinations during a period of 5 years, in order to assess the state of health of the population, as well the data working up and interpretation by means of the EpiInfo computer program. By testing a series of "normal" limits, the values found with apparent healthy persons (n = 2691) and persons previously diagnosed with diabetes mellitus or CVDs (n = 97) were analyzed in a differentiated way. In the sample of apparent healthy individuals, with the age between 20 and up to 60, the mean values were: 210 mg% for TC; 6.74 g@1000--TL; 125.74 mg%--TG; 0.91 g%--G and 0.34 g%--U. Satisfactory correlations (correlation coefficient-"r") of age with the values of TC (r = 0.38); TG (r = 0.26) and G (r = 0.23) comparatively with U (r = 0.15) or TL (r = 0.14) were noticed. The comparison of the mean values between males and females did not reveal a significant difference (p > 0.05) for any of the assessed constants. The clinical and community studies of the CVD risk assessed in the Iasi City area will have to be referred to the registered and analyzed values of this epidemiological screening in the interpretation of some biochemical markers data.

[Cardio-thoracic index: marker of the clinical course of alcoholic dilated cardiomyopathy]. / Indicele cardiotoracic--marker al evolutiei cardiomiopatiei dilatative alcoolice.

Alcoholic cardiomyopathy (ACM), a principal form of secondary dilated cardiomyopathy, can ensue from heavy consumption of alcohol over a long period of time. In harmful consumption, alcohol and its metabolites has a toxic effect on heart muscle cells. The clinical features include dilatation of the left ventricle, poor myocardial contractility and symptoms of heart failure. The heart and lung X-ray examination is required in all disease stages. The information gathered from this cheap and noninvasive investigation method, are very important in the diagnosis algorithm. In the ACM stages beginning, before the installation of the heart failure symptoms, it is possible to found normal dimensions of the heart, which is compatible with the alcoholic cardiomyopathy diagnosis. Specific for dilated alcoholic cardiomyopathy is the reversible character of cardiomegaly, objectified through the reduction of the cardio-thoracic index in conditions of alcohol abstinence and adequate treatment of the heart failure.

[Comparing population means using the ANOVA method]. / Compararea mediilor populatiilor folosind statistica ANOVA.

ANOVA is the abbreviation of the ANalysis Of Variance. It was developed for inferences concerning more than two populations. The tested hypothesis is the equality of the means of several normal populations. Some mathematical aspects are presented and also advantages and drawbacks of the method are marked out. Finally a practical example (implementing the ANOVA test) using the SPSS statistical software and also Microsoft Excel are shown.

[Treatment with angiotensin conversion enzyme inhibitors in heart failure]. / Tratamentul cu inhibitori ai enzimei de conversie a angiotensinei în insuficienta cardiaca.

The appearance of the Angiotensine Conversion Enzyme Inhibitors represents one of the most important events in cardio-vascular therapy, being much utilized in the last few years. The present study had as a main aim the evaluation of the benefit of the treatment with ACE Inhibitors in heart failure. Analyzing the results obtained, we can appreciate that ACE Inhibitors have a real benefit in patients with heart failure, improving the performance of physical effort and the life quality.

[The implications of thromboembolism in chronic heart failure]. / Implicatiile tromboembolismului în insuficienta cardiaca cronica (ICC).

The goal of investigation was to determine whether long-term anticoagulant therapy influences the mortality rate in CHF. The method consisted in the calculation of the annual death rate of the patients with CHF class III-IV NYHA: group A (controls)--who did not receive anticoagulant or antiplatelet therapy; group B--treated with Acenocumarol or Aspirin. The results show in group A, which included 150 patients, during the 5-year interval under study 30 deaths, representing an annual death rate of 4%. In group B, which included 325 patients of which 75 treated with Acenocumarol and 250 patients with aspirin, 20 deaths were recorded during the same 5-year interval, representing an annual death rate of 1.2%. Thus, the mortality risk proved to be 70% lower in group B than in the control group. It came out that the main mechanism of death in CHF is thrombembolism and in this circumstance anticoagulant or antiplatelet therapy would be essential.

[Enzymatic markers in the alcoholic cardiomyopathy]. / Markeri enzimatici în cardiomiopatia alcoolica.

Alcoholic cardiomyopathy can ensue from heavy consumption of alcohol over a long period of time. The clinical features include dilatation of the left ventricle, poor myocardial contractility with reduced left ventricular ejection volume, raised tissue enzymes. In numerous experimental data has been observed increased generation of oxygen and ethanol free radicals, indicate that free radicals are implied in myocardial and hepatic damage. Ethanol administration also elicits hepatic disturbances in the availability of antioxidant defense. The resulting antioxidative stress leads to enhanced lipid peroxidation and can also affect other important cellular component.

[Nebivolol treatment in essential arterial hypertension]. / Tratamentul cu nebivolol în hipertensiunea arteriala esentiala.

Nebivolol is a lipophilic beta 1-blocker. It is devoid of intrinsic sympathomimetic or membrane stabilising activity but appears to have nitric oxide-mediated vasodilatory effects. Nebivolol 5 mg once daily is well tolerated in patients with hypertension. Adverse events are infrequent, transient and mild to moderate. Those reported most often include headache, fatigue, paraesthesias and dizziness. Several studies reported no signs of orthostatic hypotension with Nebivolol.

[Neurological manifestations on collagenoses]. / Manifestari neurologice în colagenoze.

Collagen diseases are precipitated by very different etiologic factors, but have a common pathogenic mechanism--autoimmune, which evolves chronically and progressively involving new territories. The initial and main pathologic lesions are vascular arterial ischemic (and, according to the prevalently involved territory, the type of disease results: PAN--medium-sized and small arterioles; scleroderma--small arterioles and capillaries), and the secondary ones are the result of ischemia with plurivisceral involvement. Neurological dysfunctions were detected in about 50% of collagen diseases diagnosed during a 25 year interval in the IIIrd Medical Clinic of Iasi. The neurological manifestations were inaugural in 10% (in SLE) to 46.4% (in PAN) of the cases, the remainder occurring during the course of collagenosis, more commonly at 3-5 years and before death. Peripheral nervous system involvement (mainly polyneuritis) has prevailed, the central nervous system involvement being more rare and often fatal. Long-term corticosteroid therapy was followed by full or partial remission of peripheral nervous dysfunctions, but had transient effects or was ineffective on the central nervous ones.