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Aims Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI. Methods and results We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0–10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0–8.0%), 6.7% (5.0–8.0%), 5.9% (4.0–7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0–6.0%) vs. 17% (14–19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14–21%), 8.2% (6.0–10%), 9.1% (6.0–11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0–5.0%) vs. 5.0% (4.0–6.0%)]. Age [odds ratio (OR) 1.33, P = 0.04], female gender (OR 1.47, P = 0.007), Asian and Black race (P Conclusion Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.

Ivan Pećin,1,2 Željko Reiner1,2 1Zagreb School of Medicine, University of Zagreb, Zagreb, Croatia; 2Division of Metabolic Diseases, Department of Internal Medicine, University Hospital Center, Zagreb, CroatiaCorrespondence: Željko ReinerDivision of Metabolic Diseases, Department of Internal Medicine, University Hospital Center Zagreb Kispaticeva 12, Zagreb, 10 000, CroatiaTel + 385 1 2388772Fax + 385 1 2388623Email zreiner@kbc-zagreb.hrAbstract: Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in most developed countries and even more in developing countries. Dyslipidemia is a well known main risk factor for ASCVD. Lipid-lowering treatment, particularly lowering LDL-cholesterol (LDL-C), can decrease the risk for ASCVD. New data and guidelines based upon them suggest that we should go with LDL-C levels as low as we can. Therefore, conventional lipid lowering agents (statins and statins+ezetimibe) are not enough mainly because of poor compliance and statin intolerance which is in the real world mostly pseudo-intolerance. PCSK9 inhibitors provided a new hope to further decrease LDL-C but are still expensive, they have to be injected subcutaneously twice a month and their long-lasting adverse effects are not known. Therefore, there is a constant need to develop novel, more potent, more safe, less expensive, more user friendly regimens of hypolipemic agents (bempedoic acid, selective PPAR alpha receptor modulators etc). One of the ways to overcome poor compliance and increase the potency of therapy with less adverse effects are fixed combinations of established drugs (statin+ezetimibe). The future of hypolipemic agents is based on antisense therapy, ie. the use of specific oligonucleotide sequences blocking the translation of the selected protein (targeting apolipoprotein CIII, lipoprotein (a), apolipoprotein B) or RNA silencing technique (PCSK9 mRNA) and are in various stages of clinical trials. Some of them are almost ready to use in everyday clinical practice. High risk and very high risk patients (eg. familial hypercholesterolemia, familial severe chylomicronemia syndrome) will benefit most. The aim of this review is to inform about novel hypolipemic agents – potent and safe drugs for dyslipidemia which should reduce the risk of ASCVD.Keywords: dyslipidemia, novel hypolipemic drugs, cardiovascular risk, LDL-cholesterol, triglycerides, inclisiran, PCSK9 inhibitors, pemafibrate, bempedoic acid, ANGPTL3, pelacarsen

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non–lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction. © 2018 American College of Cardiology Foundation

Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed. © 2018 Elsevier B.V.

Dijagnostički izazovi i liječenje nasljednih bolesti stvaranja energije u mitohondrijima

Prati se unos soli u Hrvatskoj. CRASH

Naši rezultati ukazuju na moguću povezanost aktivnosti PChE s metaboličkim sindromom i razvojem kardiovaskularnih bolesti. Iako uzročno-posljedična veza između aktivnosti PChE i pojedinih komponenata metaboličkog sindroma još nije razjašnjena, ukoliko se ove pretpostavke pokažu točnima, aktivnost PChE mogla bi postati zasebni pokazatelj stupnja inzulinske rezistencije i rizika od razvoja ateroskleroze.

ESR1, LPL, and APO E genetic polymorphic variants could represent predictive genetic risk markers for lipid status and obesity in young healthy subjects.

Genske polimorfne varijante ESR1, LPL i APO E mogli bi predstavljati prediktivne genske biljege za status lipida i pretilosti u mladih zdravih ispitanika. Mediteranski tip prehrane je također važan pozitivan faktor kod abdominalne pretilosti.

There is wide diversity of etiologies of perforation classified as nontraumatic spontaneous small intestine perforation.

Fabry disease is a rare, X-linked recessive lysosomal storage disease caused by a deficiency of the lysosomal enzyme α-galactosidase A.

Pompse disease or acid maltase deficiency or glycogenosis type II is rare lysosomal storage disease due to the mutations of acid alpha-glucoside gene (GAA) on chromosome 17q25.

Varijacije i povezanost s pretilošću i statusom lipida.

Visok unos kuhinjske soli važan je faktor rizika za bubrežne i kardiovaskularne bolesti.

Lijekovi izbora za takve oblike dislipidemije su fibrati, poglavito fenofibrat, ili eventualno nijacin (zbog nuspojava i složenog doziranja ga bolesnici nerado uzimaju) te gdjegda etilni esteri omega-3 masnih kiselina koji su registrirani kao lijekovi i također smanjuju trigliceride. Svi se ovi lijekovi mogu kombinirati sa statinima ako istodobno treba postići i značajnije smanjenje ukupnog i LDL kolesterola.

Naš preliminarni rezultati pokazuju kako je unos kuhinjske soli značajno iznad preporučenih 5 g NaCl. Razlike između muškaraca i žena, te između ruralne i urbane populacije ukazuju na potrebu prilagođenog pristupa u mjerama primarne prevencije.

Loše životne navike se gomilaju u bolesnika sa arterijskom hipertenzijom. Nadamo se kako će CRASH inicijativa povećati svjesnost i poboljšati liječenje u bolesnika sa povišenim kardiovaskularnim rizikom.

Radi se o važnosti medicinskih sestara u nacionalnoj kampanji za smanjenje unosa soli.

Antagonisti beta adrenergičkih receptora (beta blokatori) nedvojbeno spadaju među najdjelotvornije antihipertenzive, a važni su osobito u sekundarnoj prevenciji infarkta miokarda. indicirani su i u zatajivanju srca te nekim aritmijama.

Hiperkolesterolemija, tj. povećani ukupni i LDL kolesterol glavni su čimbenik rizika za koronarnu bolest i infarkt miokarda. lijekovi izbora za hiperkolesterolemiju su statini.

Fabryeva bolest pripada skupini rijetkih nasljednih metaboličkih bolesti, iz grupe lizosomskih bolesti nakupljanja. Prevalencija ove bolesti je u Europskoj populaciji 1:117.000. bolest je posljedica nedostatka enzima alfa-galaktozidaze A te nakupljanja glukosfingolipida, prvenstveno globotriazilceramida (GL-3) u različitim tkivima.

Budući da su kardiovaskularne bolesti najčešći uzrok smrtnosti i pobola u razvijenim zemljama, uključujući i Hrvatstku, nedvojbena je potreba da se učine maksimalni napori kako bi se uspješnije spriječio njihov nastanak i napredovanje. Pojam prevencija kardiovaskularnih bolesti odnosi se na sveukupnost mjera i načina liječenja koji se poduzimaju da se spriječi pojava kardiovaskularnih događaja.

Ako se dijetom i fibratima ne uspiju postići željene vrijednosti triglicerida u krvi, može se uz njih davati još i neki od pripravaka ribljih višestruko nezasićenih omega-3 masnih kiselina (najbolje u obliku etilnih estera) ali u dozi od 3-4 g dnevno jer manje doze koje proizvođači tih pripravaka ponekad savjetuju nisu djelotvorne.

The aim of the study was to assess the relationship between systolic blood pressure during maximal treadmill test (SBP9mtt)) and flow-mediated vasodilation (FMD). Abnormal rise of SBP(mtt) is the phenomenon more frequent in hypertensive persons but it could be found in normotensive subjects too. 199 subjects referred to treadmill test were enrolled in the study. Four groups were formed: hypertensives with abnormal SBP(mtt) (group A), hypertensives with normal SBP(mtt) (group B), normotensives with abnormal SBP(mtt) (group C) and normotensives with normal SBP(mtt) (group D). Rise of SBP(mtt) above 200 mmHg was considered abnormal reaction. Simple linear regression analysis showed significant inverse relationship between SBP(mtt) and FMD (F = 20.2036, p < 0.001, R2 = 0.0956). Mean FMD index was worst in hypertensive subjects with abnormal SBP(mtt) (group A), followed by normotensives with abnormal SBP(mtt) (group C), hypertensives with normal SBP(mtt) (group B) and the best was in normotensives with normal SBP(mtt) (3.56 +/- 5.17, 4.19 +/- 5.14, 6.81 +/- 8.43 and 10.92 +/- 7.48%, respectively). In multivariate regression analysis FMD showed significant association with abnormal SBP(mtt) (p < 0.001) along with brachial artery diameter (p < 0.001), male gender (p < 0.001), but not with hypertension (p = 0.073), BMI (p = 0.137) and total cholesterol (p = 0.23) (coefficients: -0.26, -0.40, -0.27, -0.13, -0.11 and -0.07, respectively). There was a significant inverse relationship between SBP(mtt) and FMD. An impairment of FMD exists in normotensive subjects with abnormal SBP(mtt). In hypertensives with abnormal SBP(mtt) an additional impairment of FMD exists when compared to hypertensives with normal SBP(mtt). Abnormal SBP(mtt) should be taken into account in global cardiovascular risk assessment.

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Controversy exists as to whether the deletion/deletion (DD) genotype of angiotensin l-converting enzyme (ACE) gene polymorphism is associated with coronary heart disease (CHD). There are only a few studies dealing with this issue in the elderly, also with controversial results. The aim of this study was the assessment of correlation between genetic markers and the risk of CHD in the elderly. The results indicated DD genotype importance for CHD in the elderly as proven by discriminant analysis (chi2 = 25.77; df = 16; p = 0.0620). However, the use of univariate method demonstrated no correlation between DD genotype of ACE gene polymorphism and coronary artery disease. D allele of ACE gene was associated with higher activities of ACE plasma. A weak, but increased risk of MI is associated with high frequency of DD genotype in the elderly. Strong correlation between ACE polymorphism and ACE plasma activities was demonstrated.

Povećana koncentracija ukupnog i LDL - kolesterola u serumu najvažniji je čimbenik rizika od kardiovaskularne bolesti. U nizu je kliničkih ispitivanja dokazano da se davanjem estera biljnih sterola ili stanola može djelotvorno smanjiti previsoka koncentracija ukupnog i LDL - kolesterola.

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Prikazani su rezultati pozitivnih učinaka adjuvantnog liječenja antiestrogenom tamoksifenom na razine serumskih lipida i lipoproteina.

Endogenous sex hormones, lipoproteins and atherosclerosis

Drugo izvješće i evaluacija rizičnih čimbenika u općoj populaciji Hrvatske.

Promicanje zdravlja hrvatskog pučanstva.

Privatizacija zdravstva u zemljama u tranziciji

Autori analiziraju nalaze pregleda metodom kompjutorizirane tomografije abdomena kod 7 bolesnika s Hodgkinovim limfomima i 7 bolesnika s non-Hodgkin limfomima. Prema mišljenju autora kompjutorizirana tomografija kao neinvazivna metoda može biti od koristi u dijagnostici raširenosti malignih limfoma. Lako se mogu izvoditi kontrolni pregledi.

Rad se bavi sa policističnom bolesti bubrega

rad istražuje paraproteinemiju

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rad razmatra evoluciju mitohondrija

Etiopatogenetska podjela cističnih promjena bubrežnog parenhima s posebnim osvrtom na urođene promjene

Procjenjuje se da više od milijarde ljudi diljem svijeta ima niske koncentracije vitamina D zbog čega se s pravom govori o „pandemiji“ hipovitaminoze D te se razmatraju teške posljedice za javno zdravstvo. Geografski položaj Republike Hrvatske, posebice kontinentalnog dijela zemlje, čimbenik je rizika od pojave nedostatka vitamina D u populaciji. Cilj je ovih smjernica pružiti kliničarima jasan i jednostavan alat za prevenciju, prepoznavanje i liječenje nedostatka vitamina D u zdravoj populaciji i u različitih skupina bolesnika. Ove su smjernice nastale suradnjom kliničara različitih disciplina koji se bave brojnim aspektima skrbi o bolesnicima u riziku od razvoja nedostatka vitamina D. Utemeljene su na dokazima, prema sustavu GRADE (engl. Grading of Recommendations, Assessment, Development and Evaluation) koji uz snagu dokaza opisuje i razinu preporuke. Temeljni zaključci ovih smjernica odnose se na preporučenu populacijsku koncentra­ciju vitamina D u krvi koja iznosi 75 – 125 nmol/L te na definiranje preventivnih i terapijskih doza vitamina D za postizanje njegovih preporučenih koncentracija, It is estimated that over one billion of people around the globe have low serum values of vitamin D, therefore, we can consider vitamin D deficiency as a pandemic and public health problem. Geographic position of Croatia, especially the continental part of the country, is a risk factor for the development of deficiency of vitamin D in the population. The aim of these guidelines is to provide the clinicians with easy and comprehensive tool for prevention, detection and therapy of vitamin D deficienncy in healthy population and various groups of patients. They were made as a result of collaboration of clinicians of different backgrounds who are dealing with patients at risk of vitamin D deficiency. These guidelines are evidence-based, according to GRADE-system (Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendation. The main conclusions address the recommended serum vitamin D values in the population which should be between 75 and 125 nmol/L and defining recommended preventive and therapeutic dosages of vitamin D in order to reach the adequate levels of serum vitamin D.

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), “lower is better for longer”, and the recent data have strongly emphasized the need of also “the earlier the better”. In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual’s calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an ‘Extremely High Risk’ group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardio-vascular risk in these patients.