USE OF FIXED COMBINATIONS OF RAMIPRIL AND HYDROCHLOROTHIAZIDE IN PATIENTS WITH ARTERIAL HYPERTENSION AND HIGH OR VERY HIGH CARDIOVASCULAR RISK (OPTIMIST 2 STUDY): RESULTS OF THE NONCOMPARATIVE STUDY

Aim. To evaluate efficacy and safety of treatment with fixed combination of ramipril and hydrochlorothiazide in patients with arterial hypertension (HT) 2-3 degree and high or very high cardiovascular risk in clinical practice. Material and methods. Patients with HT 2-3 degree and high or very high cardiovascular risk who had not reached target blood pressure (BP) levels with previous therapy (n=427) were included in open-label non-comparative multicenter phase IV study. Patients were treated with fixed combination of ramipril and hydrochlorothiazide during 8 weeks. The drug dose was increased and/or amlodipine was added in case of insufficient antihypertensive effect. Achievement of the target BP level (<130/80 mmHg) and therapy safety were assessed. Results. 420 patients (98.4%) completed the study. After 8 weeks 273 (65%) patients had a two-component therapy (fixed combination of ramipril and hydrochlorothiazide), 147 (35%) patients — triple therapy (ramipril, hydrochlorothiazide and amlodipine). The target BP level was achieved in 408 (97.14%) patients and it was not reached in 12 (2.86%) patients. 7 patients were dropped out from the study: 4 — because of adverse events (dry cough), 3 — due to violation of study protocol. Both patients and doctors considered fixed ramipril and hydrochlorothiazide combination as effective and well tolerable one.  Conclusion. Ramipril and hydrochlorothiazide fixed combination provides an achievement of the target BP level in the most of HT patients

EXPERIENCE OF RAMIPRIL (HARTIL) USAGE IN PATIENTS WITH HIGH CARDIOVASCULAR RISK (THE OPTIMIST STUDY)

Aim. To evaluate efficacy and safety of ramipril (Hartil, Egis) in treatment of patients with different cardiovascular risk (according to arterial hypertension (HT) risk stratification) in real clinical practice.Material and methods. 998 patients (424 men and 574 women; aged 57,4±0,4 y.o.) with HT; with combination of HT and ischemic heart disease; with ischemic heart disease and high normal blood pressure (BP) were included in the open non-control non-comparative multicenter phase IV study. The anamnesis data collection, physical examination, evaluation of risk factors, the target organ damage, the associated cardiovascular diseases, total cardiovascular risk, previous therapy, and also BP measurement were performed. All patients received ramipril within 8 weeks additionally to previous antihypertensive therapy. The BP measurement was performed initially, after 4 and 8 weeks of therapy. Achievement of target BP level (BP&lt;140/90 or &lt;130/80 mm Hg in patients of high or very high cardiovascular risk) was used as efficacy criterion.Results. 790 (82,1%) hypertensive patients used antihypertensive therapy before the study. 675 (85,4%) patients received ACE inhibitors, 435 (55%) patients - beta-blockers, 230 (29,1%) patients - calcium channel blockers, 420 (53,2%) patients – diuretics and 28 (3,5%) patients - angiotensin II receptor blockers. Ramipril additionally to previous therapy provided achievement of target BP in 69,4% of patients with high and in 64,8% of patients with very high cardiovascular risk.Conclusion. Addition of a ramipril to the treatment of patients with high and very high cardiovascular risk increases efficacy of the therapy.</p

EXPERIENCE OF RAMIPRIL (HARTIL) USAGE IN PATIENTS WITH HIGH CARDIOVASCULAR RISK (THE OPTIMIST STUDY)

Aim. To evaluate efficacy and safety of ramipril (Hartil, Egis) in treatment of patients with different cardiovascular risk (according to arterial hypertension (HT) risk stratification) in real clinical practice.Material and methods. 998 patients (424 men and 574 women; aged 57,4±0,4 y.o.) with HT; with combination of HT and ischemic heart disease; with ischemic heart disease and high normal blood pressure (BP) were included in the open non-control non-comparative multicenter phase IV study. The anamnesis data collection, physical examination, evaluation of risk factors, the target organ damage, the associated cardiovascular diseases, total cardiovascular risk, previous therapy, and also BP measurement were performed. All patients received ramipril within 8 weeks additionally to previous antihypertensive therapy. The BP measurement was performed initially, after 4 and 8 weeks of therapy. Achievement of target BP level (BP&lt;140/90 or &lt;130/80 mm Hg in patients of high or very high cardiovascular risk) was used as efficacy criterion.Results. 790 (82,1%) hypertensive patients used antihypertensive therapy before the study. 675 (85,4%) patients received ACE inhibitors, 435 (55%) patients - beta-blockers, 230 (29,1%) patients - calcium channel blockers, 420 (53,2%) patients – diuretics and 28 (3,5%) patients - angiotensin II receptor blockers. Ramipril additionally to previous therapy provided achievement of target BP in 69,4% of patients with high and in 64,8% of patients with very high cardiovascular risk.Conclusion. Addition of a ramipril to the treatment of patients with high and very high cardiovascular risk increases efficacy of the therapy

Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations.

Preeclampsia is a disorder that can occur during pregnancy and is one of the leading causes of death among pregnant women. This disorder occurs after the 20th week of pregnancy and is characterized by arterial hypertension, proteinuria, fetoplacental, and multiple organ dysfunctions. Despite the long history of studying preeclampsia, its etiology and pathogenesis remain poorly understood, and therapy is symptomatic. One of the factors of the disorder is believed to be misfolded proteins that are prone to form amyloid aggregates. The CRD tests, utilizing the binding of the amyloid-specific dye Congo red to urine components, demonstrate high efficiency in diagnosing preeclampsia. However, these tests have also been found to be positive in other disorders with proteinuria, presumably associated with concomitant amyloidosis. To assess the limitations of the CRD tests, we examined urine congophilia and protein components mediating Congo red positivity in patients with proteinuria, including preeclampsia, amyloid and non-amyloid nephropathies. We stained the urine samples and calculated congophilia levels. We also assessed the contribution of large protein aggregates to congophilia values using ultracentrifugation and determined the molecular weights of congophilic urinary proteins using centrifugal concentrators. All proteinuric groups demonstrate positive results in the CRD tests and congophilia levels were more than two times higher compared with the control non-proteinuric groups (p <0.01). There was a strong correlation between urine protein excretion and congophilia in amyloid nephropathy (rs = 0.76), non-amyloid nephropathies (rs = 0.90), and preeclampsia (rs = 0.90). Removal of large aggregates from urine did not affect the congophilia levels. Separation of urine protein fractions revealed congophilic components in the range of 30-100 kDa, including monomeric serum albumin. Our results indicate limitations of CRD tests in preeclampsia diagnostics in women with renal disorders and underscore the need for further research on the mechanisms of Congo red binding with urine components

The quantitative relationship between urine congophilia and proteinuria in three groups with nephropathies.

The Spearman rank-order correlation coefficients (Spearman’s correlation), 95% confidence intervals (C. I.), p values (t-test), and scatter charts with linear trend lines are shown for each group. AN, amyloid nephropathies; CRR, Congo red retention; NA, non-amyloid nephropathies; PE, preeclampsia.</p

All images used to generate the figures for this study.

All images used to generate the figures for this study.</p

Congophilia and protein composition in concentrated urine samples from women with uncomplicated pregnancy.

(A) From left to right: initial protein concentrations, protein amounts and CRRs for the four control urine samples (NP/130-134); procedure scheme; protein concentrations and total amounts of protein (weights and percentages of the initial amount) in the supernatant obtained by concentrating. (B) Mean CRRs of concentrated samples and HSA solutions at concentrations equal to concentrated samples are shown. (C) 10% polyacrylamide gel electrophoresis results for original and concentrated samples (1 μg of protein) are shown. BSA (2 μg) was applied to localize the putative HSA in the analyzed samples. Proteins in the gel are stained by Coomassie brilliant blue. BSA, bovine serum albumin; CF, centrifugation; CRR, Congo red retention; NP, control sample from a woman with uncomplicated pregnancy; RT, room temperature.</p

The representation of the CRD tests’ results.

The CRD membrane (A) and CRD paper (B) tests are shown. The representative images displayed are from five pregnant women with preeclampsia (1–5) and five control pregnant women (6–10).</p

Experimental data.

All data used to generate the results for this study. (XLSX)</p

Congophilia of urine samples and HSA solution after centrifugation on concentrators with cut-offs of 30 and 100 kDa.

(A) Samples before centrifugation (original samples) and after centrifugation (concentrates and filtrates) are analyzed using a membrane test. At the left, urine protein fractions are listed. (B) 10% polyacrylamide gel electrophoresis of urine samples with 15 μg of protein is shown. Proteins in the gel are stained by Coomassie brilliant blue. AL, Immunoglobulin light chain amyloidosis; HSA, human serum albumin; MW, molecular weight; PE, preeclampsia.</p