Gábor Simonyi

[The pharmacological treatment of obesity: past, present and future].

Currently, obesity presents one of the biggest health problems. Management strategies for weight reduction in obese individuals include changes in life style such as exercise and diet, behavioral therapy, and pharmacological treatment, and in certain cases surgical intervention. Diet and exercise are best for both prevention and treatment, but both require much discipline and are difficult to maintain. Drug treatment of obesity offer a possible adjunct, but it may only have modest results, limited by side effects; furthermore, the weight lowering effects last only as long as the drug is being taken and, unfortunately, as soon as the administration is stopped, the weight is regained. These strategies should be used in a combination for higher efficacy. Drugs used to induce weight loss have various effects: they increase satiety, reduce the absorption of nutrients or make metabolism faster; but their effect is usually moderate. In the past, several drugs were used in the pharmacological therapy of weight reduction including thyroid hormone, dinitrophenol, amphetamines and their analogues, e.g. fenfluramine, At present, only orlistat is available in the long term treatment (≥ 24 weeks) of obesity as sibutramine and rimonabant were withdrawn form the market. Several new anti-obesity drugs are being tested at present, and liraglutide, a GLP-1 analogue (incretin mimetic), is the most promising one.

Diagnosis and discrimination of remote antero- and inferoseptal non-Q wave myocardial infarctions with body surface potential mapping

BACKGROUND Previous studies have shown that the diagnosis and localization of previous non-Q wave myocardial infarction (NQMI) is possible by body surface potential mapping (BSPM), but the criteria for the discrimination between anteroseptal and inferoseptal middle regions remain to be determined. METHODS BSPM using 63 unipolar leads was recorded in 119 patients with previous NQMI (36 to 76 years of age, average 61 years; 85 men). Localization of anteroseptal or inferior middle NQMI occurred in 70 cases (44 to 76 years of age, average 61 years, 53 men) by determining early anterior minimum potential with only slight negativity. In these cases, isopotential maps obtained at additional time points were investigated to discriminate between anteroseptal and inferoseptal NQMI. The clinical localization was based on the concordance of two of the following tests: wall motion disturbances on echocardiography, coronary angiogram and repolarization changes in the acute-phase electrocardiogram. RESULTS Two milliseconds before the appearance of the first anterior minimum, a more accentuated superior negativity indicated anteroseptal NQMI (32 of 70 cases), while a more pronounced inferior negativity indicated inferoseptal NQMI (38 of 70 cases). Fishers exact test showed statistically significant associations between the above BSPM localizations and the clinical localizations (P<0.001). Occlusion or stenosis of the expected infarct-related coronary artery was detected in all patients either as a single lesion or together with other coronary artery lesions. CONCLUSIONS The BSPM criteria proposed here are suitable to detect the most frequent NQMI localizations. The narrowing of the infarct-related coronary arteries, the left anterior descending or the posterior descending coronary artery, can be thus differentiated.

Non-ST elevation myocardial infarction: A new pathophysiological concept could solve the contradiction between accepted cause and clinical observations

UNLABELLED Non-ST elevation myocardial infarction (NSTEMI) and ST elevation infarction have many differences in their appearance and prognosis. A comprehensive search made us form a new hypothesis that a further cause also existsin NSTEMI: an acute, critical increase in the already existing high microvascular resistance in addition to the subtotal coronary artery occlusion. Various findings and studies can be interpreted only by our hypothesis: hemodynamic findings, ECG changes, autopsy reports and clinical observations (different long-time prognosis and different result of acute revascularization therapy in NSTEMI, similarities of NSTEMI with other clinical symptoms where increased microvascular resistance can be supposed without coronary artery disease). OBJECTIVE Despite similarities in the underlying pathologic mechanism non-ST elevation myocardial infarction(NSTEMI) and ST elevation infarction (STEMI) have many differences in their clinical presentation and prognosis. METHOD A systematic review of the literature about NSTEMI and the blood supply of the myocardium made us form a hypothesis that a further cause also exists in addition to the accepted cause of NSTEMI (subtotal coronaryartery occlusion): an acute, critical increase in an already existing high intramyocardial microvascular resistance. EVIDENCE Knowledge about microcirculation disturbances in ischemic heart disease and development of microcirculation damage can be fitted in our hypothesis. Various findings and studies can be interpreted only by our hypothesis: hemodynamic findings, ECG changes, autopsy reports and clinical observations about NSTEMI. The latest ones involve the different long-time prognosis and different result of acute revascularization therapy in STEMI and NSTEMI. Regarding the repolarization changes on the ECG NSTEMI shows similarities with other clinical symptoms where increased intramyocardial microvascular resistance can be supposed without coronary artery disease: false positive exercise stress test, supraventricular tachycardia, left ventricular strain and conduction disturbances. CONCLUSION The acute treatment of NSTEMI should aim to improve the blood inflow to the stiff myocardiumand/or impaired microvascular system and decrease the high microvascular resistance.

Diagnostic value of body surface potential mapping in assessment of the coronary artery lesion after angina pectoris and without repolarization changes on the electrocardiogram

BACKGROUND The body surface potential mapping (BSPM) method is sensitive in detecting minor electrical potential abnormalities, but its diagnostic value is unclear in detection and localization of significant coronary artery lesion (CAL) in patients after angina pectoris and without ischemic electrocardiogram abnormalities at the time of the BSPM record. METHODS AND RESULTS Characteristic features and quantitative parameters of the isopotential maps during the depolarization were evaluated and compared with the result of coronary angiography in 228 patients (164 males; age, 61.6 +/- 9.5 years). Twenty-three of them had their first angina, but the others had a history of earlier angina, unstable angina, non-ST-elevation infarction. Fifty-nine healthy subjects (32 males; age, 53.3 +/- 12.2 years) served as control. The diagnostic power was high in detection of CAL among patients with previous ischemic events, but it was low in first angina. The accuracy of the CAL localization by multiple regression was different: at 90% specificity level, the sensitivity was near 80% for right/posterior descending CAL and slightly more than 60% for left anterior descending CAL but only 19% for first marginal/first diagonal CAL. CONCLUSIONS The BSPM changes during the depolarization could well indicate CAL only after previous ischemic events. Sensitivity and specificity of the CAL localization depended on the extension and location of the underlying myocardium damage.

Ramipril + amlodipine and ramipril + hydrochlorothiazide fixed-dose combinations in relation to patient adherence

Objective To compare 1-year treatment adherence of ramipril + amlodipine and ramipril +hydroclorothiazide fixed-dose combination therapies in patients with hypertension. Methods Data were extracted from the database of the National Health Insurance Fund of Hungary. Treatment adherence was modelled using survival analysis. Results At 2 months after initiation of treatment, 42% of patients using ramipril +hydrochlorothiazide (n = 28,800) had discontinued treatment, compared with 0% of patients using ramipril + amlodipine (n = 10,295). At 1 year, treatment adherence was 29% in the ramipril + hydrochlorothiazide group and 54% in the ramipril + amlodipine group. The hazard ratio for discontinuing ramipril + hydrochlorothiazide vs ramipril + amlodipine was 2.318 (95% confidence intervals 2.246, 2.392). Conclusion Ramipril + amlodipine had significantly higher 1-year treatment adherence than ramipril + hydrochlorothiazide in patients with hypertension.

Significance of patient adherence in cardiovascular therapy

The appropriate cooperation of patients is very important during therapy. The term of compliance used earlier for the definition of patient´s cooperation refers to a sub- or over-ordination of the relationship betwees physicians and patients. Nowadays the term of adherence is used, which suggests a higher level of patient cooperation because it assumes an active contribution of the patient. The adherence of patients to cardiocascular medical therapy in developed countries is just 50%, and this indicates that half of the patients do not take the prescribed medication. Because of the lack of medication, morbidity and mortality are increasing. There can be many reasons for the lack of patient cooperation, which should be taken account during medical treatment. Improving patient adherence can decrease the risk for complications and progression of the disease, which can improve health condition and reduce health care and social costs.

Diagnostic value of the left atrial electrical potentials detected by body surface potential mapping in the prediction of coronary artery disease

BACKGROUND The electrocardiographic diagnosis of significant coronary artery stenosis (CAD) is often based on the investigation of the left ventricular repolarization changes during exercise ECG stress test (EST). Our aim was to prove that the electric activity of the left atrium can indicate the ischemic damage of the left ventricle, and furthermore, it is able to indicate CAD without exercise. METHODS AND RESULTS Patients with chest complaints but without evidence of acute coronary syndrome were investigated by EST and body surface potential mapping (BSPM, 63 leads). CAD was proven in 45 cases (32 men, years 40-76) and excluded in 50 cases (35 men, years 38-72) with coronary angiography. Left atrial electric potentials (EP-LA) before and after 0.08 mg sublingual nitroglycerine administration differed significantly (p<0.001) in the two groups. According to Fischer linear discriminant analysis, this difference in % (EP-LA(d%)) was the best separating parameter: below limit of -14.17% (CAD prevalence was considered) this parameter predicted CAD with 93% sensitivity, 100% specificity, >10 positive and 0.05 negative likelihood ratio (weighted for prevalence). The EST predicted CAD with 71% sensitivity, 78% specificity, 2.43 positive and 0.28 negative likelihood ratios. CONCLUSION The electrical activity changes of the left atrium seemed to be suitable to predict CAD as an EST-alternative resting method.

Az atorvastatin/amlodipin fix kombináció versus az atorvastatinterápia a terápiahűség tükrében

Absztrakt Bevezetes: A hypertonia es a dyslipidaemia modosithato cardiovascularis kockazati tenyezők. Hazankban a hypertonia es a dyslipidaemia egyarant nepbetegsegnek szamitanak. A celertekek elereseben a hatekony vegyuletek alkalmazasan tulmenően a betegek terapiahűsege alapvető fontossagu. Celkitűzes: Az atorvastatin/amlodipin fix kombinacio egyeves perzisztenciajanak osszehasonlitasa az atorvastatinterapiahoz kepest. Modszer: Az Orszagos Egeszsegbiztositasi Penztar adatbazisabol a venyforgalmi adatokra tamaszkodva 2012. oktober 1. es 2013. szeptember 30. kozotti időszakban első alkalommal atorvastatin/amlodipin fix kombinacio, illetve az atorvastatin hatoanyagu keszitmenyek barmely dozisanak receptjet kivalto betegeket valasztottak ki, akik a megelőző egy evben hasonlo terapiaban nem reszesultek. A perzisztencia modellezesere a tulelesanalizis klasszikus eszkoztarat alkalmaztak, ahol a „tulelesi” idő a gyogyszer szedesenek abbahagyasaig eltelt idő volt. A modellezeshez komplementer log-log link fuggve...

Device therapy of resistant hypertension

It is well known that hypertension is an independent cardiovascular risk factor. Treatment of hypertension frequently includes administration of three or more drugs. Resistant hypertension is defined when blood pressure remains above target value despite full doses (the patients maximum tolerated dose) of antihypertensive medication consisting of at least three different classes of drugs including a diuretic. Pharmacological treatment of hypertension is often unsuccessful despite the increasing number of drug combinations. Uncontrolled hypertension, however, increases the cardiovascular risk. Instrumental treatment of resistant hypertension is currently testing two major fields. One is the stimulation of baroreceptors in the carotid sinus and the other is radiofrequency ablation of sympathetic nerve fibers around renal arteries to reduce blood pressure in drug resistant hypertension.

Patient adherence in antihypertensive treatment

Hypertension is one of the most frequent chronic diseases as well as most important cardiovascular risk factors in developed countries. Blood pressure control to target levels can significantly decrease the risk for development of coronary artery disease, stroke, chronic renal disease and mortality. Adequately maintained blood pressure is very important in high risk patients. In the treatment of hypertension, life style therapy and drug treatment have essential roles. Further, patient adherence plays a significant part of the treatment, too. Importantly, about half of the patients only become adherent to antihypertensive therapy by the end of the first year treatment. Hence, non-adherence of patients is an important cause for resistant hypertension. Adherence is influenced by the complexity of drug regimen and characteristic of drug class, as well as age and gender of patients.