Advantages of perindopril as monotherapy and combinations with indapamide compared to other ACE inhibitors in cardiovascular patients

Inhibitori angiotenzin konvertirajućeg enzima (ACE-inhibitori) imaju ključnu ulogu u liječnju bolesnika duž čitavog kardiovaskularnog kontinuma, od nekomplicirane arterijske hipertenzije do razvijene koronarne bolesti i bolesti srčanog mišića. Temeljem provedenih randomiziranih kliničkih studija može se zaključiti da uz temeljni antihipertenzivni učinak imaju značajni kardio i vazoprotektivni učinak. Bitno je napomenuti da se unutar klase ACE inhibitora, perindopril upravo ističe sa svojim značajnim učincima na poboljšanje funkcije endotela, zapravo inhbirajući patofiziološki proces od samoga početka. Logična je kombinacija perindoprila s diuretikom – indapamidom s obzirom da je njihov kombinirani učinak aditivan, odnosno rezultira optimalnom kontrolom renin angiotenzin-aldosteron sustava i snažnom antihipertenzivnom reakcijom. Perindopril i ramipril su jasno pokazali redukciju kardiovaskularnog rizika u randomiziranim kliničkim pokusima u skupini bolesnika sa stabilnom anginom pektoris, dočim kvinapril i trandolapril nisu imali navedeni učinak. Od svih kardiovaskularnih lijekova, ACE inhibitori imaju navišu razinu dokaza u smislu prevencije kardiovaskularnih događanja tijekom čitavog spektra kardiovaskularnih bolesti. Krkin perindopril, odnosno fiksna kombinacija perindoprila s indapamidom dostupna je u različitim dozama i pakiranjima što ga čini optimalnim izborom na tržištu.Angiotensin-converting enzyme (ACE) inhibitors play a key role in the treatment of patients along the entire cardiovascular continuum from uncomplicated hypertension to developed coronary artery disease and myocardial disease. Based on the conducted randomized clinical trials, we can conclude that they have a significant cardiac and vasoprotective effect in addition to the basic antihypertensive effect. It is important to note that within the class of ACE inhibitors, perindopril is characterized by its very significant effects on improvement of endothelial function, thereby inhibiting pathophysiological process from the outset. The combination of perindopril with the diuretic – indapamide is logical given that their combined effect is additive, that is, it results in an optimal control of the renin angiotensin-aldosterone system and strong anti-hypertensive reaction. Perindopril and ramipril have clearly demonstrated the reduction of cardiovascular risk in randomized clinical trials in the group of patients with stable angina pectoris, whereas quinapril and trandolapril did not show the above effect. Of all cardiovascular drugs, ACE inhibitors have the highest level of evidence in terms of prevention of cardiovascular events during the entire spectrum of cardiovascular diseases. Krka’s perindopril, or a fixed combination of perindopril with indapamide is available in different dosages and packaging, making it the optimal choice on the market

Advantages of perindopril as monotherapy and combinations with indapamide compared to other ACE inhibitors in cardiovascular patients

Inhibitori angiotenzin konvertirajućeg enzima (ACE-inhibitori) imaju ključnu ulogu u liječnju bolesnika duž čitavog kardiovaskularnog kontinuma, od nekomplicirane arterijske hipertenzije do razvijene koronarne bolesti i bolesti srčanog mišića. Temeljem provedenih randomiziranih kliničkih studija može se zaključiti da uz temeljni antihipertenzivni učinak imaju značajni kardio i vazoprotektivni učinak. Bitno je napomenuti da se unutar klase ACE inhibitora, perindopril upravo ističe sa svojim značajnim učincima na poboljšanje funkcije endotela, zapravo inhbirajući patofiziološki proces od samoga početka. Logična je kombinacija perindoprila s diuretikom – indapamidom s obzirom da je njihov kombinirani učinak aditivan, odnosno rezultira optimalnom kontrolom renin angiotenzin-aldosteron sustava i snažnom antihipertenzivnom reakcijom. Perindopril i ramipril su jasno pokazali redukciju kardiovaskularnog rizika u randomiziranim kliničkim pokusima u skupini bolesnika sa stabilnom anginom pektoris, dočim kvinapril i trandolapril nisu imali navedeni učinak. Od svih kardiovaskularnih lijekova, ACE inhibitori imaju navišu razinu dokaza u smislu prevencije kardiovaskularnih događanja tijekom čitavog spektra kardiovaskularnih bolesti. Krkin perindopril, odnosno fiksna kombinacija perindoprila s indapamidom dostupna je u različitim dozama i pakiranjima što ga čini optimalnim izborom na tržištu.Angiotensin-converting enzyme (ACE) inhibitors play a key role in the treatment of patients along the entire cardiovascular continuum from uncomplicated hypertension to developed coronary artery disease and myocardial disease. Based on the conducted randomized clinical trials, we can conclude that they have a significant cardiac and vasoprotective effect in addition to the basic antihypertensive effect. It is important to note that within the class of ACE inhibitors, perindopril is characterized by its very significant effects on improvement of endothelial function, thereby inhibiting pathophysiological process from the outset. The combination of perindopril with the diuretic – indapamide is logical given that their combined effect is additive, that is, it results in an optimal control of the renin angiotensin-aldosterone system and strong anti-hypertensive reaction. Perindopril and ramipril have clearly demonstrated the reduction of cardiovascular risk in randomized clinical trials in the group of patients with stable angina pectoris, whereas quinapril and trandolapril did not show the above effect. Of all cardiovascular drugs, ACE inhibitors have the highest level of evidence in terms of prevention of cardiovascular events during the entire spectrum of cardiovascular diseases. Krka’s perindopril, or a fixed combination of perindopril with indapamide is available in different dosages and packaging, making it the optimal choice on the market

Red blood cell distribution width as a prognostic marker of mortality in patients on chronic dialysis: a single center, prospective longitudinal study

Aim To determine if red cell distribution width (RDW) is associated with all-cause mortality in patients on chronic dialysis and to evaluate its prognostic value among validated prognostic biomarkers. Methods This is a single center, prospective longitudinal study. At the time of inclusion in January 2011, all patients were physically examined and a routine blood analysis was performed. A sera sample was preserved for determination of NT-pro-brain natriuretic peptide (NT-pro-BNP) and eosinophil cationic protein. Carotid intima media thickness (IMT) was also measured. Following one year, all-cause mortality was evaluated. Results Of 100 patients, 25 patients died during the follow- up period of one-year. Patients who died had significantly higher median [range] RDW levels (16.7% [14.3-19.5] vs 15.5% [13.2-19.7], P < 0.001. They had significantly higher Eastern Cooperative Oncology Group (ECOG) performance status (4 [2-4] vs 2 [1-4], P < 0.001), increased intima-media thickness (IMT) (0.71 [0.47-1.25] vs 0.63 [0.31-1.55], P = 0.011), increased NT-pro-BNP levels (8300 [1108-35000] vs 4837 [413-35000], P = 0.043), and increased C-reactive protein (CRP) levels (11.6 [1.3-154.2] vs 4.9 [0.4-92.9], P < 0.001). For each 1% point increase in RDW level as a continuous variable, one-year all cause mortality risk was increased by 54% in univariate Cox proportional hazard analysis. In the final model, when RDW was entered as a categorical variable, mortality risk was significantly increased (hazard ratio, 5.15, 95% confidence interval, 2.33 to 11.36) and patients with RDW levels above 15.75% had significantly shorter survival time (Log rank P < 0.001) than others. Conclusions RDW could be an additive predictor for allcause mortality in patients on chronic dialysis. Furthermore, RDW combined with sound clinical judgment improves identification of patients who are at increased risk compared to RDW alone

Carotid Endarterectomy Unexpectedly Resulted in Optimal Blood Pressure Control

Resistant hypertension is defined as hypertension that remains above 140/90 mmHg despite the provision of three or more antihypertensive drugs in a rational combination at full doses and including a diuretic. It is associated with adverse clinical outcome and therefore requires aggressive medical treatment. We present a case of 70-year-old woman who was treated for resistant hypertension with a diuretic, ACE-inhibitor, calcium channel blocker, and with centrally acting antihypertensive, moxonodine. Despite of aggressive medical treatment her blood pressure remained above 160/90 mmHg continuously. Large diagnostic workup excluded common causes of secondary hypertension, but revealed significant carotid stenosis present on left internal carotid artery. Carotid endarterectomy was performed in order to improve cerebrovascular prognosis, but unexpectedly resulted in optimal control of her blood pressure. Two months after operation patient was on only one antihypertensive drug, having blood pressure below 130/85 mmHg. We suggest that in selected patients resistant hypertension could be associated with carotid stenosis and carotid sinus baroreceptor dysfunction. For definite conclusions further studies are warranted

Hypertension in the elderly

Arterijska hipertenzija (AH) u starijih osoba predstavlja veliki javnozdravstveni problem zbog visoke prevalencije i trenda starenja svjetske populacije. Najčešće se radi o izoliranoj sistoličkoj hipertenziji (90% bolesnika iznad 70 godina) te se kod osoba starije životne dobi kao najbitniji čimbenici rizika izdvajaju vrijednosti tlaka pulsa i sistoličkog tlaka. Patofiziološki u podlozi su brojne strukturne (gubitak elastičnosti velikih krvnih žila, smanjena rastezljivost, porast brzine pulsnog vala) i funkcionalne (endotelna disfunkcija, smanjena osjetljivost beta receptora, smanjena funkcija baroreceptora, osjetljivost na sol) promjene. Liječenje AH u starijih do sada je bilo veliki izazov jer nije bilo dovoljno studija koje su se bavile tom populacijom, što se promijenilo objavom rezultata studije HYVET. Ova je studija uključila najstarije bolesnike (iznad 80 godina) te je dokazala kako sniženje vrijednosti arterijskog tlaka za 15/6 mmHg dovodi do značajno manje opće smrtnosti (21%), kardiovaskularne smrtnosti (23%), incidencije moždanog udara (30%) i srčanog zatajivanja (64%). Kao lijek prvog izbora u starijoj populaciji izdvojili bismo tijazidski diuretik, a budući ti pacijenti većinom zahtijevaju višestruku terapiju izdvojili bismo blokatore kalcijskih kanala ili ACE inhibitore. Naravno i komorbiditeti određuju osnovnu ili dodatnu terapiju.Hypertension in the elderly is a major public health problem due to high prevalence and the world population ageing trend. Most often it is the isolated systolic hypertension (90% of patients over 70 years of age) that is concerned. Furthermore, pulse pressure and systolic pressure are the most important risk factors in elderly persons. Pathophysiologically, there is a great number of structural (loss of elasticity of large blood vessels, decreased elasticity, increased pulse wave velocity) and functional (endothelial dysfunction, decreased sensitivity of beta receptors, decreased baroreceptor function, sensitivity to salt) changes in the background. Treatment of hypertension in the elderly has so far been a big challenge, because there were not enough studies that have dealt with this population. Now this has changed after results of the HYVET study have been published. HYVET study included the oldest patients (above 80 years of age) and has proven that lowering pressure by 15/6 mmHg, leads to significantly lower overall mortality (21%), cardiovascular mortality (23%), incidence of stroke (30%) and heart failure (64%). We emphasize thiazide diuretic as the first choice drug in the elderly population, and since these patients usually require multiple treatment, we emphasize calcium channel blockers or ACE inhibitors. Comorbidities, naturally, determine the basic or additional therapy

Hypertension in the elderly

Arterijska hipertenzija (AH) u starijih osoba predstavlja veliki javnozdravstveni problem zbog visoke prevalencije i trenda starenja svjetske populacije. Najčešće se radi o izoliranoj sistoličkoj hipertenziji (90% bolesnika iznad 70 godina) te se kod osoba starije životne dobi kao najbitniji čimbenici rizika izdvajaju vrijednosti tlaka pulsa i sistoličkog tlaka. Patofiziološki u podlozi su brojne strukturne (gubitak elastičnosti velikih krvnih žila, smanjena rastezljivost, porast brzine pulsnog vala) i funkcionalne (endotelna disfunkcija, smanjena osjetljivost beta receptora, smanjena funkcija baroreceptora, osjetljivost na sol) promjene. Liječenje AH u starijih do sada je bilo veliki izazov jer nije bilo dovoljno studija koje su se bavile tom populacijom, što se promijenilo objavom rezultata studije HYVET. Ova je studija uključila najstarije bolesnike (iznad 80 godina) te je dokazala kako sniženje vrijednosti arterijskog tlaka za 15/6 mmHg dovodi do značajno manje opće smrtnosti (21%), kardiovaskularne smrtnosti (23%), incidencije moždanog udara (30%) i srčanog zatajivanja (64%). Kao lijek prvog izbora u starijoj populaciji izdvojili bismo tijazidski diuretik, a budući ti pacijenti većinom zahtijevaju višestruku terapiju izdvojili bismo blokatore kalcijskih kanala ili ACE inhibitore. Naravno i komorbiditeti određuju osnovnu ili dodatnu terapiju.Hypertension in the elderly is a major public health problem due to high prevalence and the world population ageing trend. Most often it is the isolated systolic hypertension (90% of patients over 70 years of age) that is concerned. Furthermore, pulse pressure and systolic pressure are the most important risk factors in elderly persons. Pathophysiologically, there is a great number of structural (loss of elasticity of large blood vessels, decreased elasticity, increased pulse wave velocity) and functional (endothelial dysfunction, decreased sensitivity of beta receptors, decreased baroreceptor function, sensitivity to salt) changes in the background. Treatment of hypertension in the elderly has so far been a big challenge, because there were not enough studies that have dealt with this population. Now this has changed after results of the HYVET study have been published. HYVET study included the oldest patients (above 80 years of age) and has proven that lowering pressure by 15/6 mmHg, leads to significantly lower overall mortality (21%), cardiovascular mortality (23%), incidence of stroke (30%) and heart failure (64%). We emphasize thiazide diuretic as the first choice drug in the elderly population, and since these patients usually require multiple treatment, we emphasize calcium channel blockers or ACE inhibitors. Comorbidities, naturally, determine the basic or additional therapy

TREATMENT OF ANEMIA IN CHRONIC KIDNEY DISEASE – POSITION STATEMENT OF THE CROATIAN SOCIETY FOR NEPHROLOGY, DIALYSIS AND TRANSPLANTATION AND REVIEW OF THE KDIGO AND ERPB GUIDELINES

Bubrežna anemija nastaje kao posljedica kronične bolesti bubrega (KBB), a pogoršava se s napredovanjem bolesti. Anemija može biti prvi znak bolesti bubrega. Sve bolesnike s KBB i anemijom potrebno je dijagnostički obraditi čime se može otkloniti druge uzroke bolesti. Dokazana je direktna povezanost koncentracije hemoglobina i stadija zatajenja bubrežne funkcije, a ranija pojava anemije učestalija je u dijabetičara. Rano liječenje anemije moglo bi usporiti napredovanje KBB. Anemija je neovisan činitelj rizika za razvoj srčano-žilnih bolesti u bolesnika s KBB. Liječenje anemije u bolesnika s KBB temelji se na smjernicama. Nedavno je skupina KDIGO (Kidney Disease: Improving Global Outcomes) objavila nove smjernice za liječenje anemije u KBB, a skupina ERBP (European Renal Best Practice) osvrt na te smjernice. Hrvatsko društvo za nefrologiju, dijalizu i transplantaciju (HDNDT) već godinama objavljuje vlastite smjernice koje se temelje na preporukama i pozitivnim iskustvima europskih i svjetskih stručnih društava, kao i na vlastitim iskustvima. Posljednja inačica hrvatskih smjernica objavljena je 2008. godine. Od tada do danas, temeljem brojnih istraživanja i kliničke prakse, došlo je do brojnih izmjena u suvremenom shvaćanju liječenja anemije u KBB. Slijedom navedenog, HDNDT objavljuje osvrt na posljednje preporuke međunarodnih stručnih društava, izražava svoj stav za liječenje anemije u KBB kao osnovu za nove smjernice prilagođene sadašnjem trenutku.Renal anemia is the result of chronic kidney disease (CKD) and deteriorates with disease progression. Anemia may be the first sign of kidney disease. In all patients with anemia and CKD, diagnostic evaluation is required. Prior to diagnosing renal anemia, it is necessary to eliminate the other possible causes. Direct correlation between the concentration of hemoglobin and the stage of renal failure is well known. Early development of anemia is common in diabetic patients. Correction of anemia may slow the progression of CKD. Anemia is an independent risk factor for developing cardiovascular disease in patients with CKD. Treatment of anemia in patients with CKD is based on current guidelines. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anemia in CKD patients and ERBP (European Renal Best Practice) group its position statement and comments on the KDIGO guidelines. The Croatian Society of Nephrology, Dialysis and Transplantation (HDNDT) has already published its own guidelines based on the recommendations and positive experience of European and international professional societies, as well as on own experience. The latest version of Croatian guidelines was published in 2008. Since then, on the basis of research and clinical practice, there have been numerous changes in the modern understanding of the treatment of anemia in CKD. Consequently, HDNDT hereby publishes a review of the recent recommendations of international professional societies, expressing the attitude about treating anemia in CKD as a basis for new guidelines tailored to the present time

Carotid endarterectomy unexpectedly resulted in optimal blood pressure control [Karotidna endarterektomija neočekivano rezultirala optimalnom kontrolom tlaka]

Resistant hypertension is defined as hypertension that remains above 140/90 mmHg despite the provision of three or more antihypertensive drugs in a rational combination at full doses and including a diuretic. It is associated with adverse clinical outcome and therefore requires aggressive medical treatment. We present a case of 70-year-old woman who was treated for resistant hypertension with a diuretic, ACE-inhibitor, calcium channel blocker, and with centrally acting antihypertensive, moxonodine. Despite of aggressive medical treatment her blood pressure remained above 160/90 mmHg continuously. Large diagnostic workup excluded common causes of secondary hypertension, but revealed significant carotid stenosis present on left internal carotid artery. Carotid endarterectomy was performed in order to improve cerebrovascular prognosis, but unexpectedly resulted in optimal control of her blood pressure. Two months after operation patient was on only one antihypertensive drug, having blood pressure below 130/85 mmHg. We suggest that in selected patients resistant hypertension could be associated with carotid stenosis and carotid sinus baroreceptor dysfunction. For definite conclusions further studies are warranted

Anti-citrullinated protein antibody and rheumatoid factor in patients with end-stage renal disease

Background: Patients with end-stage renal disease (ESRD) and on hemodialysis (HD) are at increased risk for developing rheumatoid arthritis (RA), as a result of defective immunity. Our aim was to examine if ESRD and the length of HD treatment impact the clinical utility of antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor (RF) as diagnostic tools for RA. Methods: We included 94 subjects in our study: 37 healthy volunteers and 57 patients with ESRD who had been undergoing HD for 1–12 years, and without confirmed RA. In order to test our hypothesis, we measured and correlated anti-CCP and RF as laboratory markers of RA. Results: Our study showed that there is no significant difference between values for anti-CCP (p=0.11) and RF (p=0.98) in control subjects as well as in patients undergoing HD, regardless of the length of time that patients had been undergoing HD treatment. Conclusions: Our study indicates that HD does not impair the specificity of anti-CCP and RF for RA in patients where the disease has not yet developed. Future prospective studies may show whether there is any use in determinating RF, and especially anti-CCP, as early predictors of RA in patients with ESRD who are at greater risk of developing this condition. Clin Chem Lab Med 2009;47:959–62.Peer Reviewe

Karotidna endarterektomija neočekivano rezultirala optimalnom kontrolom tlaka

Resistant hypertension is defined as hypertension that remains above 140/90 mmHg despite the provision of three or more antihypertensive drugs in a rational combination at full doses and including a diuretic. It is associated with adverse clinical outcome and therefore requires aggressive medical treatment. We present a case of 70-year-old woman who was treated for resistant hypertension with a diuretic, ACE-inhibitor, calcium channel blocker, and with centrally acting antihypertensive, moxonodine. Despite of aggressive medical treatment her blood pressure remained above 160/90 mmHg continuously. Large diagnostic workup excluded common causes of secondary hypertension, but revealed significant carotid stenosis present on left internal carotid artery. Carotid endarterectomy was performed in order to improve cerebrovascular prognosis, but unexpectedly resulted in optimal control of her blood pressure. Two months after operation patient was on only one antihypertensive drug, having blood pressure below 130/85 mmHg. We suggest that in selected patients resistant hypertension could be associated with carotid stenosis and carotid sinus baroreceptor dysfunction. For definite conclusions further studies are warranted.Rezistentna hipertenzija definirana je kao povišeni krvni tlak iznad 140/90 mmHg unatoč liječenju sa tri ili više antihpertenziva u racionalnoj kombinaciji uz uključeni diuretik. Asocirana je sa nepovoljnom kliničkom prognozom i zahtjeva agresivno liječenje. Prezentiramo slučaj 70-godišnje bolesnice koja je liječena od rezistentne hipertenzije sa diuretikom, ACE-inhibitorom, blokatorom kalcijskih kanala uz centralno djelujući antihipertenziv, moksonidin. Unatoč agresivnom liječenju njezin je tlak bio kontinuirano iznad 160/90 mmHg. Opsežna dijagnostička obrada isključila je uobičajene uzroke sekundarne hipertenzije, ali je otkrila značajnu stenozu lijeve karotide. Učinjena je karotidna endarterektomija sa ciljem da se poboljša cerebrovaskularna prognoza bolesnice, a kao neočekivani postoperativni nalaz javila se normotenzija bolesnice. Na temelju kliničke opservacije sugeriramo da u selekcioniranih bolesnika rezistentna hipertenzija može biti asocirana sa stenozom karotide i disfukcijom karotidnih baroreceptora. Za definitivne zaključke potrebne su kliničke studije