Lege Artis Medicinae

[ACE Inhibitor for Everyone?]

CZURIGA István

OCTOBER 20, 2001

Lege Artis Medicinae - 2001;11(10)

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Matrix metalloproteinases (MMPs), which are synthesized by many cell groups and responsible for the destruction of matrix proteins, and endogen tissue inhibitors of MMPs (TIMPs) have a role in the pathogenesis of Multiple Sclerosis (MS) by affecting the blood-brain barrier. We aimed to investigate the role of MMPs and TIMPs in the immunopathogenesis and in the course of multiple sclerosis (MS). We enrolled 25 relapsing remitting MS patients, who had a definite MS diagnosis according to McDonald criteria and 25 healthy subjects similar for age and gender as control group. MMP-9- and TIMP-1 levels were measured twice in patient group (one time during an attack and one in remission) and once in healthy subjects. MMP-9- and TIMP-levels of patients during attack and remission period and MMP-9/TIMP-1 ratio were found significantly higher than in the control subjects. In patient group MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratio during attacks were not significantly different than during remission period. However, when subdivided according to their number of attacks, patients with 2 attacks had significantly higher levels during attack period comparing to remission period (p<0.05); in case of patients with more than 2 attacks did not have a statistically significant difference in attack and remission periods. Matrix metalloproteinases are important actors in MS immunopathogenesis, particularly in the early period and inhibitor agents for these enzymes can be used as a treatment option.

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[Acute respiratory syndrome with various signs and outcomes caused by the SARS-CoV-2 virus is the biggest challenge facing health systems worldwide today. The renin-angiotensin-aldosterone and kinin-kallikrein systems and within these two endopeptidases (ACE and ACE2) play a crucial role in the developing clinical feature of COVID-19. Adverse effects of the ACE-stimulated Ang II/AT1R axis (oxidant, pro-inflammatory effect, vasoconstriction) are counterbalanced by the ACE2-induced AT2R and MasR activities (antioxidant, anti-inflammatory effect, vasodilation). The severity of SARS-CoV-2 pneumonia and systemic inflammation explains the impairment of ACE2 (as an important defence factor of the lungs) caused by the biding spike protein of the SARS-CoV-2, which decreases the ACE2 levels. In parallel, bradykinin production also increases and intensifies the SARS-CoV-2-induced cytokine storm through the BKB1 and BKB2 receptors. Since the RAAS inhibitors (ACEI, ARB) affect the two regulatory systems and enzymes at different sites and to different degrees, their role must urgently have been clarified in the COVID-19 since their use is essential and general of many population-wide diseases (hypertension, cardiovascular, renal and metabolic conditions). Based on pathophysiological and experimental data, it is reasonable to hypothesize that in COVID-19 with comorbidities, especially in the elderly, the decreased ACE2 expression may be restored by RAAS inhibitors and the missed or reduced protective effect may be revitalised. This protective effect applies to both RAAS inhibitors. Clinical trials clearly support the declared opinion of many international societies that the use of RAAS inhibitors does not increase the risk of the occurrence of SARS-CoV-2 in itself let alone the severe and critical cases. Accordingly, initiated RAAS inhibitor therapy not only may rather must be continued during the development of COVID-19.]

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NÁDRÓ Bíborka, DIÓSZEGI Ágnes, KOVÁCS Beáta, PARAGH György, PÁLL Dénes, HARANGI Mariann

[Familial hypercholesterolemia (FH) is an inherited defect of cholesterol metabolism characterized by high plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease risk. Prevalence of hypertension in FH is not clarified, but its appearance is independent risk factor for the development of cardiovascular disease. Therefore, optimal treatment has a major priority in this high-risk population. We aimed to investigate the lipid parameters and evaluate the presence of hypertension and its treatment characteristics in 86 newly diagnosed, untreated heterozygous FH patients (27 males, 59 females, mean age 53.6±13.4 years). We diagnosed FH by using the Dutch Lipid Clinic Network criteria. The mean TC level was 8.49±1.7 mmol/l, the mean LDL-C level was 6.11±1.5 mmol/l, the mean high-density lipoprotein cholesterol (HDL-C) level was 1.62±0.5 mmol/l, while the median lipoprotein (a) level was 301 mg/l. We diagnosed 33 FH patients (38.4%) with hypertension. Beta blockers were used in 23, ACE-inhibitors in 13, ARBs in 12, calcium channel blockers in 9, and HCT in 11 cases. 11 patients was treated with monotherapy, for 10 patients double, for 11 patients triple, while for 1 patient quadruple combined antihypertensive therapy was administered. Based on our results, hypertension might be underdiagnosed in this specific patient population. Neither the types nor the combination patterns of blood pressure lowering agents are in line with current guidelines. Up to date screening and treatment of hypertension should be worth considering in this extremely high risk population with enhanced atherosclerosis.]

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[Data on blood pressure over two years in resistant hypertensive patients with lett brain stem microvascular decompression]

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[In the background of resistant hypertension (RHT) the neurovascular pulsatile compression (NVPC) of the left rostral ventrolateral medulla may play a role. In these cases a microvascular decompression (MVD) may decrease the blood pressure (BP). The aim of this work was to investigate how the BP has changed after the MVD in the operated patients recorded at the farthest time from the MVD up to maximum 31 December 2016. We have retrospectively collected data from 9 patients whose follow-up data fór 2 years has already been published earlier. Data collection was carried out from the patient register program of the University of Szeged Albert-Szent Györgyi Clinical Centre. The MVDs were performed between 2000 and 2004. The mean follow-up time was 11.1±4.6 years. Both the systolic and the diastolic BPs were significantly lower at the time of last record compared to the BPs at the time of MVD (systolic BP 211±40 vs. 135±20 mmHg, p=0.003; diastolic BP 116±17 vs. 81±14 mmHg, p=0.007). Last recorded BPs compared to the 24-month data alsó were lower bút nőt signffi- cantly (systolic BP 148±32 vs. 135±20 mmHg, p=0.25; diastolic BP 96 vs. 85 mmHg, p=0.11). The mean number of antihypertensives at the last Office visít was nőt sig- nificantly higher compared to MVD (5.9±1.4 vs. 6.3±1.5; p=0.5) bút signfficantly increased compared to MVD +1 month data (4.7±0.9vs. 6.3±1.5; p=0.03). These results confirmed our previous opinion that in severe RHT nőt respond- ing to conventional therapy an MVD of the left side NVPC could be a therapeutic option and may guarantee a long-lasting BP reduction. Evén if the number of antihypertensives increased in the meantime, as they still responded better to therapy. ]

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[When should antihypertensive be taken: in the morning and/or evening? Chronopharmacotherapy of hypertension in practice]

SZAUDER Ipoly

[The circadian (24-hour) variability of blood pressure (BP) is influenced by constant and variable (external and internal) factors. With this in mind and by determining the type of hypertension with a 24-hour blood pressure monitoring (ABPM), individual chronopharmacological (chronopharmacotherapy) treatment can be planned. There are significant differences in the chronokinetics of antihypertensive drugs administered at different times. Their therapeutic range and efficacy depend significantly on their circadian timing. Although the most modern antihypertensives have a 24-hour effect, they are not able to lower blood pressure at all times. Morning intake of ACE inhibitors, ARB-s, alpha-blockers mainly affect the afternoon and early evening rise, while evening intake reduces nocturnal and morning rise. Calcium channel blockers, beta-blockers (except carvedilol and labetolol), do not affect the circadian blood pressure profile. Therefore, in nondipper hypertension or in the case of morning rise, the twice daily morning and evening administration is more effective than the single morning administration. (Usually a lower dose is sufficient in the evening.) Adequate control of nocturnal or morning blood pressure elevations can be achieved with medication taken in the evening. According to the relevant studies the conclusion is that there is no convincing evidence that the administration of BP-lowering drugs in the evening provides any significant advantage in terms of quality of BP control, prevention of target organ damage or reduction of cardiovascular events, so evening intake only is not recommended. In particular the administration of antihypertensive drugs at bedtime, especially in the case of elderly patients may cause excessive BP fall at night with increased risk of silent cerebral infarct and the myocardial ischemia in patients with coronary heart disease.]