Neopstruktivna koronarna bolest - klinička važnost, dijagnostika, liječenje i prijedlog nove patofiziološke klasifikacije

New data gathered from large clinical trials indicate that nonobstructive coronary artery disease (non-CAD) is a clinical entity that should not be ignored. It is estimated that 50% of female population undergoing coronarography are diagnosed with non-CAD. There is also an increase in the prevalence of non-CAD in both genders, which is probably due to gradual expanding of clinical indications for angiography in patients with angina. Furthermore, considering the increased mortality risk established recently, a prognosis of non-CAD is not benign as previously thought. However, the concept and definition of non-CAD remains elusive causing difficulties in diagnosis and treatment. One of the major shortcomings is the exclusion-based diagnosis of non-CAD. Furthermore, treatment of non-CAD still presents a great challenge and optimal therapy is yet to be determined. There are two major hypotheses explaining the pathophysiological mechanisms of non-CAD, i.e. ischemic hypothesis based on abnormal microvascular dysfunction and non-ischemic one based on altered pain perception. This review encompasses a broader spectrum of pathophysiological mechanisms of non-CAD, and proposes a new way of classification based on the major disorder involved: type I (ischemic mechanisms) and type II (non-ischemic mechanisms), depending on which mechanism predominates. Hopefully, this would provide new insights in the understanding of this disorder, thus leading to accurate and early diagnosis and successful treatment, especially considering the increased mortality risk in these patients.Novi podaci prikupljeni iz velikih kliničkih ispitivanja pokazuju da je neopstruktivna koronarna bolest (ne-OKB) klinički entitet koji se ne smije zanemariti. Procjenjuje se da se u 50% ženske populacije koja se podvrgava koronarografiji dijagnosticira ne-OKB. Također postoji povećanje učestalosti ne-OKB u oba spola, što je vjerojatno posljedica postupnog širenja kliničkih indikacija za koronarografiju u bolesnika s anginom pektoris. Nadalje, s obzirom na povećani rizik od smrtnosti koji je nedavno ustanovljen, prognoza ne-OKB nije dobroćudna kao što se ranije mislilo. Međutim, koncept i definicija ne-OKB ostaju nedovoljno definirani, što uzrokuje poteškoće kako u dijagnozi tako i u liječenju. Jedan od glavnih nedostataka je dijagnostika ne-OKB koja se temelji na dijagnozi isključivanja. Nadalje, liječenje ne-OKB i dalje predstavlja velik izazov, a optimalnu terapiju tek treba odrediti. Postoje dvije glavne hipoteze koje objašnjavaju patofiziološke mehanizme ne-OKB. Ishemijska hipoteza temelji se na mikrovaskularnoj disfunkciji, a neishemijska hipoteza na promijenjenoj percepciji boli. Ovaj pregledni članak obuhvaća širok spektar patofizioloških mehanizama ne-OKB i predlaže novi način klasifikacije temeljen na glavnom poremećaju koji je uključen u patofiziologiju: tip I. (ishemijski mehanizam) i tip II. (ne-ishemijski mehanizam), ovisno o tome koji mehanizam prevladava. Nadamo se da će to omogućiti nove spoznaje u razumijevanju ovoga poremećaja, što dovodi do točne i rane dijagnoze i uspješnog liječenja, osobito s obzirom na povećani rizik smrtnosti kod ovih bolesnika

Povezanost koštane mineralne gustoće i sastavnica metaboličkog sindroma u postmenopauzalnih žena sa šećernom bolešću tipa 2

Diabetes mellitus type 2 is associated with greater bone mineral density (BMD) due to obesity, although rapid bone loss observed over time could be explained by elevated chronic inflammation. The objective of this study was to investigate the relationship between central adiposity and hyperinsulinemia, as well as inflammation markers with vertebral and femoral BMD and bone turnover markers in postmenopausal women with type 2 diabetes. Femoral and vertebral BMD, osteocalcin, pyrilinks D, beta-CrossLaps (B-CTx), insulin, C-reactive protein (CRP), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) were measured in 114 postmenopausal female patients with diabetes type 2. The patients of similar age, HbA1c levels and diabetes duration were divided into 2 groups based on their body mass index (BMI) values: lower or equal to 27 kg/m2(31 patients) and higher than 27 kg/m2(83 patients). Lower levels of osteocalcin (p=0.001), B-CTx (p=0.000007) and pyrilinks D (p=0.0365), and higher femoral BMD (p=0.00006), insulin level (p=0.0002), PAI-1 (p=0.00000) and CRP (p=0.002) were found in the overweight group. There were no significant differences in vertebral BMD and fibrinogen. Osteocalcin and B-CTx showed inverse correlation, and femoral BMD positive correlation with waist circumference, insulin level and PAI-1. This suggests that abdominal obesity and hyperinsulinemia as components of the metabolic syndrome could increase femoral BMD by lowering bone rate. In addition, the only inflammation marker linked with femoral BMD was PAI-1, which is associated with increased mineralization of cortical bone in mouse models.Šećerna bolest tipa 2 povezana je s većom koštanom mineralnom gustoćom (bone mineral density, BMD) zbog debljine, iako se zamijećeni ubrzani gubitak koštane mase tijekom vremena može objasniti prisustvom kronične upale. Cilj ovoga istraživanja bio je utvrditi povezanost biljega koštane pregradnje i koštane gustoće s centralnom debljinom, hiperinzulinemijom kao i upalnim biljezima u postmenopauzalnih žena sa šećernom bolešću tipa 2. U 114 ispitanica izmjerena je koštana gustoća kralježnice i kuka, određeni su osteokalcin, pirilinks D, beta-CrossLaps (B-CTx), inzulin, C-reaktivni protein (CRP), fibrinogen i inhibitor aktivatora plazminogena-1 (PAI-1). Ispitanice slične dobi, podjednakog trajanja dijabetesa te HbA1c bile su podijeljene u dvije skupine prema indeksu tjelesne mase (ITM): niži ili jednaki 27 kg/m2(31 ispitanica) te veći od 27 kg/m2 (83 ispitanice). Niže vrijednosti osteokalcina (p=0,001), B-CTx (p=0,000007) i pirilinksa D (p=0,0365) te više vrijednosti košane gustoće kuka (p=0,00006), inzulina (p=0,0002), PAI-1 (p=0,0000) i CRP (p=0,002) utvrđene su u skupini s prekomjernom tjelesnom težinom. Nije bilo statistički značajne razlike u koštanoj gustoći kralježnice i vrijednosti fibrinogena. Osteokalcin i B-CTx su negativno korelirali, dok je BMD kuka bio u pozitivnoj korealciji s opsegom struka, inzulinom i PAI-1. Ovi rezultati upućuju na to da sastavnice metaboličkog sindroma, centralna debljina i hiperinzulinemija utječu na povećanje koštane gustoće kuka inhibirajući koštanu pregradnju. Jedini upalni biljeg povezan s BMD kuka bio je PAI-1 koji povećava mineralizaciju kortikalne kosti na mišjem modelu

Hepatitis C–Associated Diabetes Mellitus

Diabetes type 2 mellitus (T2DM) is the most common extrahepatic association of hepatitis C virus (HCV) infection. Substantial research has suggested that insulin resistance (IR) has crucial importance in development of type 2 diabetes in HCV-infected patients. Several pathophysiological mechanisms are proposed, such as direct effect of HCV proteins on inhibition of the insulin-signaling pathway inducing central insulin resistance (IR), while overproduction of inflammatory cytokines and increased lipolysis promote peripheral IR. IR in HCV-infected patients is associated with impaired sustained virologic response (SVR) and higher incidence of hepatocellular carcinoma (HCC). Some, but not all, studies have shown improvements in achieving SVR in patients with interferon/ribavirin (RBV) therapy co-treated with metformin or pioglitazone as well as beneficiary effect on the incidence of hepatocellular carcinoma. Recent studies indicate that response to the new direct-acting antiviral (DAA) treatments is unaffected by insulin resistance thus diminishing importance of IR in the new era of DAA. Additionally, viral eradication by DAAs has been shown to ameliorate insulin resistance, attenuating the risk of new-onset diabetes type 2. However, those metabolic improvements are sustainable long after the treatment remains unclear

Pharmacogenomic Testing in the Era of Patient-Tailored HCV Treatment

Hepatitis C affects approximately 180 million people worldwide, with 3–4 million newly infected each year. Hepatitis C virus (HCV) has been classified into seven different genotype categories, wherein HCV genotype 1 (HCV-1) is the most prevalent. To date, there is still no vaccine available against HCV infection. Until recently, combination therapy of pegylated interferon-a (PegIFN) and ribavirin (RBV) has been the standard of care. Nevertheless, for many patients, particularly those infected with HCV genotype 1 (HCV-1), this treatment has resulted with unsatisfactory treatment response rates and high adverse drug reaction (ADR) rates. Many clinical factors, including pharmacogenetics, influence the treatment response rate. This review focuses on the association between pharmacogenetics and HCV antiviral therapy in patients infected with HCV genotype 1 and other genotypes (GT); patients reinfected with HCV after liver transplantation; and patients coinfected with HCV and human immunodeficiency virus. Data considering triple therapy in HCV-infected patients are also reviewed. Additionally, various genetic polymorphisms, with an emphasis to IL-28B, and their association with pharmacogenetic testing in HCV are discussed

Urolithiasis and Osteoporosis: Clinical Relevance and Therapeutic Implications

Several clinical and epidemiological studies revealed increased bone turnover and lower bone mass in patients with urolithiasis. Bone mass loss is particularly evident in idiopathic calcium stone formers. However, pathogenetic mechanisms and factors implicated in bone loss in these patients are still unknown. Dietary calcium restriction, increased intake of salt and animal proteins, vitamin D receptor polymorphisms are likely risk factors, while role of inflammatory cytokines, osteopontin and prostaglandin mediated bone resorption is yet to be determined. Regarding treatment and prevention, it has been proven that calcium supplements and high calcium diet with the addition of potassium alkali have an important role in prevention and treatment of both, urolithiasis and osteoporosis. Thiazide diuretics reduce hypercalciuria in renal tubules, and in addition promote osteoblast differentiation. Finally, bisphosphonates, a commonly used drugs in treatement of osteoporosis, show the potential to inhibit calcium stone formation, whereas a possible protective effect of antioxidants in bone loss and renal injurie needs to be investigated further

Changing the Landscape of Hypertension Management With SGLT2i

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a newer class of drugs that have primarily been used in the treatment of type 2 diabetes. However, as new findings from clinical trials have become available, their indication has been expanded to include treatment of heart failure and chronic kidney disease without the presence of diabetes. The pathophysiological mechanisms of extraglycemic effects of SGLT2i are still being unraveled, but one of the most prominent consequences is a decrease in blood pressure, which has implications for hemodynamics and arterial stiffness. Recent findings indicate that this class of drugs has a beneficial effect on lowering nocturnal blood pressure (BP), with special importance in type 2 diabetes (DMT2), since unregulated nocturnal hypertension is associated with an increased incidence of cardiovascular (CV) events. In this mini-review, we have summarized current knowledge about the effects of SGLT2i on blood pressure, including office, home, and ambulatory BP, and potential implications for treatment of hypertension in diabetic and non-diabetic individuals, with positive effects on cardiorenal outcomes

Serumska vrijednost osteoprotegerina u bolesnika s kalcificirajućom aortnom stenozom u ovisnosti o zatajenju srca

The aim of the study was to assess the role of serum osteoprotegerin (OPG) as a biomarker in patients with aortic valve stenosis (AS) in relation to heart failure and symptomatic status. This was a case control study, which included 51 patients with AS and 39 control subjects. At the time of study enrolment, detailed medical history was obtained and all subjects underwent physical examination, chest x-ray and echocardiography. OPG levels were measured in all subjects, and serum N-terminal of the pro b-type natriuretic peptide (NT pro BNP) levels were determined in patients with AS. Serum OPG levels were elevated in patients with AS compared to control subjects (p=0.001). Pa-tients with heart failure due to AS had elevated serum OPG levels in comparison to patients without heart failure (p=0.001). A significant correlation between OPG and symptomatic status was observed in all patients with AS (p<0.001), however, it was not the case in patients without heart failure (p=0.425). There was a positive correlation between OPG and NT pro BNP concentrations with objective signs of heart failure on chest x-ray (p<0.001). Negative correlation of OPG concentrations with aortic valve area was present (p<0.040), as well as with left ventricular ejection fraction (p<0.001). Serum OPG could be a valuable biomarker in the evaluation of severity of calcified AS and serve as an additional indicator besides clinical presentation and echocardiography in the assessment of surgical treatment or aortic valve replacement.Cilj ove studije bio je ocijeniti ulogu osteoprotegerina (OPG) kao biljega u bolesnika sa stenozom aortnog srčanog za-liska u odnosu na prisutne simptome kao i stupanj srčanog zatajenja. U studiju je bio uključen 51 bolesnik s aortnom steno-zom (AS) i 39 kontrolnih ispitanika. Prije uključenja u studiju uzeta je detaljna anamneza, učinjen je fizikalni pregled, ren-tgenska snimka srca i pluća te ehokardiografija. OPG je određen u svih ispitanika, a N-terminalni nastavak pro b-tipa natriu-retskog peptida (NT pro BNP) bio je određen u bolesnika s AS. OPG je bio povišen u bolesnika s AS u odnosu na kontrolne ispitanike (p=0,001). Bolesnici sa srčanim zatajenjem zbog AS imali su povišene razine OPG-a u odnosu na bolesnike bez srčanog zatajenja (p=0,001). Značajna korelacija između OPG-a i simptomatskog statusa bila je zapažena u svih bolesnika s AS (p<0,001), ali to nije bio slučaj u bolesnika bez srčanog zatajenja (p=0.425). Zabilježena je i pozitivna korelacija između koncentracije OPG-a i NT pro BNP-a s objektivnim znakovima srčanog zatajenja na rentgenskoj snimci srca i pluća (p<0,001). Također je opažena negativna korelacija OPG-a i areje aortnog zaliska (p<0,040) te istisne frakcije lijeve klijetke (p<0,001). OPG bi mogao predstavljati vrijedan biljeg u procjeni težine kalcificirane AS te bi mogao poslužiti kao dodatni indikator prilikom odlučivanja o kirurškom liječenju ili zamjeni aortnog zaliska, naravno, uz kliničku prezentaciju i ehokardiografiju

Učinak hipertireoze i antitiroidne terapije na koštanu gustoću - patofiziološki mehanizmi te kliničko značenje

Graves’ disease is an autoimmune disease characterized by excessive thyroid hormone production. One of the consequences of that state can be a decrease in bone mineral density (BMD). Graves’ disease is often treated with antithyroid drugs (ATD) as first line therapy, which can lead to disease remission. Moreover, recent data show that improvement in BMD can be expected. However, vitamin D deficiency can coexist along with Graves’ disease, which is also involved in the process of bone remodeling. It is still not known whether lower values of vitamin D can contribute to onset of Graves’ disease and if its supplementation might be helpful in therapy for hyperthyroidism. In the past couple of decades, osteopenia and osteoporosis have become a major health burden not only in post-menopausal women but also as a result of other diseases, leading to extensive research into various pathophysiological mechanisms responsible for bone remodeling. The Wnt (wingless integrated) signaling pathway is a very important factor in bone homeostasis, especially the canonical pathway. Present data indicate that stimulation of the Wnt pathway leads to bone mass increase and, in contrast, its inhibition leads to bone mass decrease. Hence, inhibitors of the canonical Wnt pathway became the focus of interest, in particular sclerostin and dickkopf 1 (DKK1). Hyperthyroidism and osteopenia/osteoporosis are quite common today and can coexist together or as separate entities. In this article, we aimed to give an overview of possible associations and potential mutual pathophysiological mechanisms.Gravesova bolest je autoimuna bolest karakterizirana prevelikom proizvodnjom hormona štitnjače. Jedna od posljedica toga stanja može biti sniženje mineralne gustoće kosti. Liječi se antitireoidnim lijekovima kao prvim izborom čime se može postići remisija bolesti. Postizanjem remisije, može se očekivati i poboljšanje mineralne gustoće kosti. No, uz Gravesovu bolest, može postojati i snižena vrijednost vitamina D koji je također važana za procese pregradnje kosti. Još je uvijek otvoreno pitanje mou li snižene vrijednosti vitamina D pridonijeti nastanku Gravesove bolesti i da li bi njegova supstitucija mogla pomoći u liječenju hipertireoze. Kako je smanjena mineralna gustoća kosti danas rasprostranjena širom svijeta, u prošlim desetljećima počeo se istraživati Wnt put. Ovaj put vrlo je važan za homeostazu kosti, osobito njegov dio koji se naziva kanonički put u kojem sudjeluju i sklerostin i dickkopf 1 kao inhibitori. Svi spomenuti čimbenici, odnosno stanja, danas su učestala i mogu postojati zajedno i odvojeno. Ovim člankom pokušali smo dati pregled moguće veze između njih

Impact of pharmacotherapeutic education on medication adherence and adverse outcomes in patients with type 2 diabetes mellitus: a prospective, randomized study

Aim To evaluate the impact of pharmacotherapeutic education on 30-day post-discharge medication adherence and adverse outcomes in patients with type 2 diabetes mellitus (T2DM). Methods The prospective, randomized, single-center study was conducted at the Medical Department of University Hospital Dubrava, Zagreb, between April and June 2018. One hundred and thirty adult patients with T2DM who were discharged to the community were randomly assigned to either the intervention or the control group. Both groups during the hospital stay received the usual diabetes education. The intervention group received additional individual pre-discharge pharmacotherapeutic education about the discharge prescriptions. Medication adherence and occurrence of adverse outcomes (adverse drug reactions, readmission, emergency department visits, and death) were assessed at the follow-up visit, 30 days after discharge.Results The number of adherent patients was significantly higher in the intervention group (57/64 [89.9%] vs 41/61 [67.2%]; χ2 test, P = 0.003]. There was no significant difference between the groups in the number of patients who experienced adverse outcomes (31/64 [48.4%] vs 36/61 [59.0%]; χ2 test, P = 0.236). However, higher frequencies of all adverse outcomes were consistently observed in the control group. Conclusion Pharmacotherapeutic education of patients with T2DM can significantly improve 30-day post-discharge medication adherence, without a significant reduction in adverse clinical outcomes