Hypertension and nephrology

[Hypertensive and cardiovascular risks of nonsteroidal antiinflammatory drugs]

FARSANG Csaba, BEDROS J. Róbert, ALFÖLDI Sándor

SEPTEMBER 21, 2012

Hypertension and nephrology - 2012;16(03-04)

[Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most frequently used medicines. During the last ten years several original publications, reviews and meta-analyses were published on the cardiovascular safety of NSAIDs and the results underlined their potentially harmful cardiovascular side effects. It can also be emphasized that there are substantial differences between different compounds, and the CV risk does not depend on the ratio of COX-1/COX-2 selectivity. Cardiovascular risk can be increased by all NSAIDs and paracetamol with the possible exception of naproxen and probably aceclofenac.]

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[The apparatus which controls our kidney too. - Part 1]

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[The series gives a brief overview on the discovery of the juxtaglomerular apparatus (JGA), an interesting story, as well as on details of its structure and function down to the molecular level. The discovery of JGA, i.e., a phylogenetically ancient organ, is a fine example of the close morphological and functional correlations characteristic of living organisms. Presented are the JGA related misconcepts and the underlying theoretical and practical difficulties. Utilization of the most modern methods, such as atomic force microscopy, as well as the in vivo multiphoton laser microscopy revealed previously unrecognized phenomen highlighting the ambiguities of textbook information, accepted paradigms. The author is looking for relationship between the new and provocative theoretical research and clinical consequences of pharmacological interventions. He shows that JGA is not only a participant of the salt-water balance and blood pressure regulation, but it can also play a significant role in the pathogenesis of the major public diseases. Finally, he makes an attempt to analyze the current research directions that predict some potential scientific discoveries and describe some general lessons from his own research career.]

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[Is there a role of triple combination in the therapy of hypertension? - Antihypertensive efficiency of perindopril-amlodipine-indapamide]

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[Blood pressure reduction to target level decreases cardiovascular morbidity and mortality. However, in the vast majority of cases, this can be achieved only with a (multiple) combination regimen. The primary objective of the PAINT (Perindopril- Amlodipine plus Indapamide Combination for Controlled Hypertension Non-intervention Trial) study was to evaluate the efficacy of combination therapy with perindopril, amlodipine, and indapamide in patients who had not reached target blood pressure with their pre-existing therapy. Secondary objectives included the monitoring of metabolic parameters and the number of antihypertensive tablets taken by the subjects. In this subgroup-analysis we involved 126 patients (74 females and 52 males, mean age 59.8±12.5 years) who had a valid 24-hour ambulatory blood pressure monitoring both at baseline and at the end of the 4-months follow-up. At the beginning of the study none of the subjects reached blood pressure target despite taking on average 2.4±1.4 antihypertensive drugs. During the study, the subjects received the combination of amlodipine, perindopril, and indapamide instead of their pre-existing antihypertensive regimen. 24-hour mean systolic blood pressure decreased from 139.2±13.4 mmHg to 126.5±12.9 mmHg (p<0.01), as well as mean diastolic blood pressure from 77.3±11.3 mmHg to 71.1±8.7 mmHg (p<0.01). Heart rate remained unchanged. Blood pressure reduction was statistically significant both during the day and the night. We found significant blood pressure reduction in all hours (10.1-15.4/5.1-7.8 mmHg; p<0.001). Hyperbaric impact decreased from 366.9±251.1 mmHg × hour to 166.2±185.4 mmHg × hour (p<0.01) for systolic blood pressure, and from 112±130.6 mmHg × hour to 41.6±65.6 mmHg × hour (p<0.01) for diastolic blood pressure. We also could observe favourable changes in metabolic parameters, not only in lipids, but also in blood sugar level. The mean number of tablets taken by the subjects increased from 2.4 to 2.9, but this led to a significantly improved control of blood pressure. Triple combinations of state-of-the-art antihypertensive agents - such as of perindopril, amlodipine and indapamide - ensure effective blood pressure control in sufficiently compliant patients.]

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[Only few such outstanding physicians lived, whose achievements and personality influenced the development of the Hungarian nephrology as remarkably as professor István Taraba did. He started his university career as an experimental researcher at the Institute of Physiology on Semmelweis University, Budapest, then at the age of 34, after completing his Ph.D thesis, decided to treat patients to utilize his acquired knowledge in the field of renal failure’s pathophysiology. This way he devoted himself to cure patients with kidney failure being in very poor circumstances at that time. Besides his daily clinical activity, he accomplished outstanding organizing work in establishing and leading the Hungarian Nephrology Society, and also in initiating specialty training for nephrologists and nephrology nurses. The hallmark of his professional work was that in spite of extremely adverse circumstances he forced to improve the quality of dialysis treatment to approach European standards. Among the renal replacement treatment modalities- antecedently to his age - he respected peritoneal dialysis equal to hemodialysis, and attempted to popularize it in his country. Under his leadership the Nephrology Department of Margit Hospital in Budapest became the therapeutic and educational centre of Hungarian nephrology. His achievements have been acknowledged internationally, and his early death is substantial loss for Hungarian nephrology as a whole. It was a great honour to me to work beside him during the whole period he spent in the Margit Hospital, and since March of 1997 I have the opportunity to lead the department he had established in his intellectuality.]

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[Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most frequently used medicines all over the world. In the year 2012 in the LAM, we summarized data on cardiovascular (CV) safety of these drugs. We emphasized that all NSAIDs may potentially be harmful on the CV system, as they can increase the blood pressure, the risk of coronary events (angina, myocardial infarction), and that of stroke, as well as they may deteriorate renal functions. We also outlined that in this respect there are substantial differences between different compounds, and the CV risk does not depend on the ratio of COX- 1/COX-2 selectivity. The newly available data of original papers and metaanalyses shed light on further details. Even naproxen which drug was previously considered the less harmful on CV system can increase the risk of blood pressure, stroke, and gastrointestinal (GI) complications. We have to emphasize that the most important risk of NSAIDs is still the GI bleeding. This adverse effect is significantly less for drugs which are more selective for COX-2 than COX-1 enzyme, but other, pleiotropic effects can also beneficially modify the GI as well as the CV risk. E.g. the aceclofenac was found to be among NSAIDs with the less adverse effects on GI system and is also among those having the less CV risk.]