Lege Artis Medicinae

[Anti-atherosclerotic effects of Ca-antagonists in the light of new clinical data]


SEPTEMBER 10, 2001

Lege Artis Medicinae - 2001;11(08-09)

[Based on in vitro and animal research, it has been found that calcium antagonist drugs are capable of inhibiting directly the atherosclerotic process. In spite of their advantegous antiatherosclerotic effect, the fast-release, first-generation dihydropyridines had an unfortunate effect on the number of newly developed myocardial infarctions and on cardiovascular mortality. New, controlled clinical studies have found long acting calcium antagonists to decrease significantly the progression of the atherosclerosis in the carotid artery - verified with B-mode ultrasound scans - and the appearance of cardiovascular clinical events, when either proven coronary sclerosis (PREVENT, CAPARES studies) or hypertension (INSIGHT, ELSA, VHAS) was present. If further clinical trials (CAMELOT, NORMALISE - now under way) justify these promising clinical data, then long-acting calcium channel blockers may become new and significant tools in the prevention of the progression and clinical complications of atherosclerotic disease.]



Further articles in this publication

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[Congress of ASH, 2001.]


Lege Artis Medicinae

[Endothel dysfunction and hypertension]


[In the past two decade numerous data has been collected about the role of endothelium in the development of several cardiovascular disorders i.e. hypertension, congestive heart failure and atherosclerosis. Endothelial cells had been thought to be passive barriers only, but it turned out that through paracrine and autocrine hormone secretion they take part in modulating and regulating the vasodilator and vasoconstrictor effects being directed to vascular smooth muscle cells. The intact endothelium prevents the adhesion of platelets and monocytes, the platelet aggregation, as well as the migration and proliferation of vascular smooth muscle cells. It has been shown that both in experimental and human hypertension the endothelial function i.e. the so-called endothel-dependent vasodilatation is damaged, being the main feature of endothelial dysfunction. In spite of extensive research it is not clear whether endothelial dysfunction is a cause or a consequence of hypertension, with exact pathomechanism being also unclear. Methods, by which this important parameter could be precisely measured are under development. Researchers also examine whether recently used antihypertensive agents could improve or eliminate endothelial dysfunction and whether this effect may offer benefit to patients in terms of morbidity and mortality. This article attempts to summarize the most up-to-date information about the endothelial dysfunction research.]

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[Risk to the fetus in the light of new data]

BODA Domokos

[Extensive research efforts based on principles of evidence-based medicine have helped lately to accumulate large amount of information on the risks to the fetus during pregnancy. As a result, the standpoints concerning risks to the fetus have become more precise in many respects. A number of earlier assumptions have been proven to be exaggerated or unfounded and the range of cases at risk has been narrowed down. This paper presents the most important data on potential risks to the fetus originating from hereditary factors, infections, maternal diseases, drugs, irradiation and special gestational anomalies. The data presented highlight the necessity of identifying the fetal damage during the pregnancy unequivocally, based exclusively on evidence of probative force and with realistic appraisal of the danger of any existent fetal damage.]

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[Wegener’s granulomatosis: diagnostic questions]

CSISZÉR Eszter, SOLTÉSZ Ibolya, FÜZESI Katalin

[INTRODUCTION - Wegener’s granulomatosis is a disease of unknown origin classified as an immune vasculitis. The main pathologic feature is necrotising granulomatous small vessel vasculitis. Clinically the upper and/or lower airways are affected most often as well as the kidneys in the generalised form. The highly specific antineutrophil cytoplasmic antibodies have diagnostic significance beside the pathology and clinical symptoms. PATIENTS AND METHODS - We have studied the clinical and diagnostic characteristics of 15 cases diagnosed in our centre from the last 25 years. All patients had pulmonary manifestation. We analysed the organ involvement, clinical signs indicating the diagnosis, chest radiography, chances for biopsies of diagnostic significance and the difficulties of differential diagnostics. RESULTS - The diagnosis was made based on histological samples from the upper airways in three cases and from the lower airways in six cases (in four cases the bronchoscopic biopsies were diagnostic, in two patients thoracotomy was necessary). In six cases, clinical signs and typical organ manifestations were the basis of the diagnosis. CONCLUSION - This very rarely occurring disease which is difficult to recognise requires pulmonological examination due to the involvement of lungs. If this diagnosis comes to mind - based on findings of bilateral, multiplex, round pulmonal shadows with cavitation - the pulmonologist should search for other organ manifestations and involve respective specialists. Ideally, diagnosis is established by histopathology or by positive cytoplasmic antineutrophil cytoplasmic antibodies.]

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[Paradigm changes in psychiatrics]


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Related contents

Hypertension and nephrology

[Evaluation of arterial stiffness in children. Guidelines for the practice]

CSEPREKÁL Orsolya, KIS Éva, SZABÓ J. Attila, REUSZ György

[Assessment of early atherosclerosis and decreased arterial elasticity to recognise the cardiovascular dysfunction in high-risk patients has gained importance in the past decade. Since 1990, more than 630 papers have been published in the adult and pediatric literature. Methods of early risk assessment in adults are well determined in international recommendations. The aim of the present work is to review the suggestions of the American Heart Association helping us to find the most appropriate method for the non invasive methods of cardiovascular assessment of young adults and children. Furthermore, multicentric studies should be conducted to create a Framingham like score system for pediatric patients, to render cardiovascular risk assessment much easier for the every day routine.]

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[Chlamydia pneumoniae in coronary arteries of young adults]


[INTRODUCTION - An association of Chlamydia pneumoniae (C. pneumoniae) with coronary heart disease has been found with seroepidemiological methods. This organism was demonstrated in atheromatous plaques by electron microscopy, immunohistochemistry, and polymerase chain reaction. MATERIAL AND METHODS - To better understand the significance of the presence of C. pneumoniae in atheromatous plaques, we examined coronary artery segments from young adults (15-34 years) with and without atherosclerosis. 74 samples of left anterior descending artery were examined immunohistochemically for the presence of C. pneumoniae by the monoclonal antibody RR402. RESULTS - C. pneumoniae was identified in the atheroma in 11 of 17 cases (65%) and in preatheroma in 6 of 15 cases (40%), in fatty streak in 7 of 23 cases (30%) and in intimal thickening in 1 of 14 cases (7%). C. pneumoniae was not found in the intimal and medial layer of the normal-appearing coronary arteries. C. pneumoniae was detected in the adventitia in 51 cases (67%) of the coronary arteries: in the normal arteries and initial lesions in 27 of 42 cases (63%), and in the advanced lesions in 24 of 32 cases (75%). Correlation was observed between the C. pneumoniae positive cases and cigarette smoking. CONCLUSION - Our results suggest that C. pneumoniae may relate to the severity of atherosclerosis in the youth, thus may initiate atherosclerotic injury or facilitate its progression along with other risk factors.]

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[New possibilities in treating hyperlipidemia]


[In the fight against atherosclerosis, statin therapy is one of the most important elements. On the basis of data from the past few years the clinical introduction of a more effective statin is not expected, however, in order to improve cardiovascular prevention further development of agents that reduce LDL-cholesterol levels more effectively than currently used statins is warranted. The need for the development of new cholesterol-lowering therapeutic options is also supported by the existence of statin intolerance. The currently available combination therapies do not provide additional mortality benefits compared with statin monotherapy. The new solutions include fourth-generation statin molecules that primarily aim to enhance the NO-donor capacity of statins, and to reduce their muscle toxicity. Certain compounds that affect cholesterol synthesis (squalene synthase inhibitors, MTP inhibitors, ACAT inhibitors) need to be further analysed because of the risk of side effects. The use of an antisense oligonucleotid that blocks the mRNA of apoB, the main protein on the LDL-particle and antibodies that inhibit the protein PCSK9 that promotes the intracellular breakdown of the LDL-receptor seems to be much more promising. Besides the lowering of LDLcholesterol level, studies have focused on the benefits of increasing HDL-cholesterol levels. Unfortunately, recently completed analyses show that new forms of the strong HDL-C increasing nicotinic acid have not provided any additional benefit when added to statin therapy. Similarly, the adverse effects associated with the promising CETP inhibitors and the lack of additional benefit when combined with statins question the significance of this drug class. The necessity for an absolute increase of HDL-cholesterol levels needs to be revised on the basis of new data, in other words, the exact role of the HDL particle in atherosclerosis needs to be further investigated.]

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[The atherosclerosis can not only be prevented, but also can be cured ]

MÁRK László

[The process of atherosclerosis nowadays plays an important role in the health care not just as a major cause of the most common cardiovascular diseases which lead to death, but also as a major factor in the loss of age-related elasticity in the blood vessels. Over the past two decades, large studies have shown that the treatment of high cholesterol levels can reduce the frequency of cardiovascular events and death and have confirmed the ability to reduce the already existing atherosclerotic plaque, which is almost unique in pharmacotherapy. Using lipid lowering therapy, if we do it properly, we can not only prevent vascular events, but can also cure atherosclerosis. Currently there are three drug groups (statins, ezetimibe and PCSK9- inhibitors), which have complete evidence that their use can reduce the number of cardiovascular events and plaque regression can be achieved. Despite many convincing clinical trials, lipid-lowering therapy is on the cardiovascular prevention palette in the just tolerated or forced applied category. In order to take advantage of its potentials at an appropriate level, as doctors, we have to approach to it by considering its importance. We should communicate to our patients that it’s about a life-long treatment, which not only can reduce the possibility of cardiovascular events, but also can slow down the aging process of the arteries. ]

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[Pathologist have recognized arterial calcification for over a century described also by Virchow in the 19th century. Vascular calcification, an active mechanism, involves a complex, regulated process of biomineralization resembling osteogenesis. Evidence indicates that proteins controlling bone mineralization are also involved in the regulation of vascular calcification. The atherosclerotic plaque calcification can be easily detected noninvasively with radiological methods currently available and it correlates with the amount of atherosclerotic plaque. Also, it serves as a surrogate measure for atherosclerosis, allowing preclinical detection of the disease. There are several examples for the relationship between hyperlipidaemia and increased loss of bone mass. It is not surprising that the base drugs for osteoporosis also have the characteristics for lowering vascular calcification and are antiatherogenous and antilipaemic drugs. The clinical importance ot these facts is that vascular calcification is associated with higher risk of cardiovascular events. In the summary, the authors review the four histopathological types of arterial calcification and the molecules and proteins involved in these processes.]