LDL-C: The Only Causal Risk Factor for ASCVD. Why Is It Still Overlooked and Underestimated?

PURPOSE OF REVIEW: Low-density lipoprotein cholesterol (LDL-C) is the most important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). This article reviews why LDL-C remains overlooked and underestimated despite numerous studies that have proved its role. RECENT FINDINGS: Recently published EAS/ESC Guidelines for dyslipidemia and EAS Guidelines for prevention set new targets for LDL-C levels in primary and secondary prevention of ASCVD. These guidelines are based on data from large studies and meta-analyzes that have shown that lower LDL-C also means lower cardiovascular event rates. Real-life experience published in registries worldwide has shown us that the guidelines have not been translated to everyday clinical practice, meaning that a significant number of patients are undertreated and have LDL-C levels well above target. Potential reasons for the abovementioned are poor adherence and education of the patient and physician and health care system related factors. Implementation of the latest version of guidelines will require continuous patient and physicians education, as well as a shared decision-making process between physician and patient.

The Impact of the International Cooperation On Familial Hypercholesterolemia Screening and Treatment: Results from the ScreenPro FH Project.

PURPOSE OF REVIEW: Familial hypercholesterolemia (FH) is often perceived and described as underdiagnosed and undertreated, though effective treatment of FH is available. Owing to the mentioned facts, it is ever more imperative to screen and treat FH patients. Subsequent to the identification of patients, the project focuses on the improvement of their prognoses. The ScreenPro FH project was established as a functional international network for the diagnosis, screening, and treatment of FH. Individual countries were assigned goals, e.g., to define the actual situation and available treatment. With "central support," more centers and countries participated in the project. Subsequently, individual countries reported the results at the beginning and end of the project. Collected data were statistically evaluated. RECENT FINDINGS: The increasing number of patients in databases, from 7500 in 2014 to 25,347 in 2018, demonstrates the improvement in overall effectiveness, as well as an increase in the number of centers from 70 to 252. Before all, LDL-C decreased by 41.5% and total cholesterol by 32.3%. As data from all countries and patients were not available at the time of the analysis, only those results from 10 countries and 5585 patients at the beginning of the project and at the time of writing are included. Our data are quite positive. However, our results have only limited validity. Our patients are far from the target levels of LDL-C. The situation can be improved with the introduction of new therapy, PCSK9-i, evolocumab, and alirocumab. International cooperation improved the screening of FH and finally led to an improvement in cardiovascular risk.

ScreenPro FH - Screening Project for Familial Hypercholesterolemia in Central, Southern and Eastern Europe: Rationale and Design.

Familial hypercholesterolemia (FH) is a genetic disorder with well-known genetic transmission and clinical course. Despite great recent progress, FH is still underestimated, under-diagnosed and thus undertreated. Furthermore it represents a significant healthcare challenge as a common risk factor for the premature development of coronary heart disease. The ScreenPro FH Project is an international network project aiming at improving complex care - from timely screening, through diagnosis to up-to-date treatment of familial hypercholesterolemia in Central, Eastern and Southern Europe. An important task for the project is to harmonise and unify diagnostic and therapeutic approaches in participating countries, where the situation differs from country to country. Countries with more experience should serve as a model for countries developing the FH network.Key words: diagnosis - familial hypercholesterolemia - screening - treatment optimization.

ScreenPro FH - Screening Project for Familial Hypercholesterolemia in Central, Southern and Eastern Europe: Basic Epidemiology.

INTRODUCTION: Despite great recent progress, familial hypercholesterolemia (FH) is still underestimated, under-diagnosed and thus undertreated worldwide. We have very little information on exact prevalence of patients with FH in the Central, Eastern and Southern Europe (CESE) region. The aim of the study was to describe the epidemiological situation in the CESE region from data available. METHODS: All local leaders of the ScreenPro FH project were asked to provide local data on (a) expert guess of FH prevalence (b) the medical facilities focused on FH already in place (c) the diagnostic criteria used (d) the number of patients already evidenced in local database and (e) the availability of therapeutic options (especially plasma apheresis). RESULTS: With the guess prevalence of FH around 1 : 500, we estimate the overall population of 588 363 FH heterozygotes in the CESE region. Only 14 108 persons (2.4 %) were depicted in local databases; but the depiction rate varied between 0.1 % and 31.6 %. Only four out of 17 participating countries reported the the LDL apheresis availability. CONCLUSION: Our data point to the large population of heterozygous FH patients in the CESE region but low diagnostic rate. However structures through the ScreenPro FH project are being created and we can hope that the results will appear soon.Key words: diagnosis - epidemiology - familial hypercholesterolemia - screening.

Comparison of intubation condition and the quality of muscle relaxation between rocuronium and vecuronium using "timing principle".

Aim To compare the quality of the conditions for endotracheal intubation and muscle relaxation between rocuronium bromide and vecuronium bromide using the ''timing principle'' method for induction in anaesthesia. The "timing principle" includes the administration of muscle relaxants before the hypnotic agent during induction in anaesthesia. Method Sixty patients who had undergone elective surgery were randomly allocated into two equal groups using muscle relaxants: rocuronium (group R) and vecuronium (group V). The intubation conditions were assessed using Cooper's scoring system, based on jaw relaxation, vocal cords position and response to intubation. The quality of muscle relaxation was evaluated by recording the time of clinical weakness, a count of ''train of four'' (TOF) twitches at intubation, the time of loss TOF response and duration of direct laryngoscopy. Results The intubation conditions were excellent in 100% of patients in the group R versus excellent in 80% and good in 20% of patients in the group V (p<0.05). The time of clinical weakness was statistically significantly shorter in the group R than in the group V (p<0.000). The time of loss of TOF response was statistically significantly shorter in the group R (p<0.000). The absence of TOF twitches (the level of muscle relaxation of 100%) at intubation recorded in 25 (83.3%) patients in the group R versus five (16.7%) patients in the group V (p<0.000). Duration of direct laryngoscopy did not significantly differ between the groups. Conclusion Rocuronium bromide provides better intubation conditions and greater quality of muscle relaxation than vecuronium bromide using ''timing principle'' technique.

Evaluation of risk markers fluctuation during an initial therapy with rosiglitazon in patients suffering from metabolic syndrome.

The aim of this study was to examine the effects of hypoglycaemic drug-agonists of PPAR-gama receptors-rosiglitazone (Avandia,4 mg - Glaxo Smith Kline) on values of wide-spread risk - markers-fibrinogen, C-reactive protein and uric acid and glicolysated haemoglobin HbA1C as parameter of metabolic control .We included fourty patients with criteria for metabolic syndrome and evaluated results into groups of diabetic and prediabetic patients according to criteria of IDF (International Diabetic Federation)These risk markers and glicolysated haemoglobin HbA1C were observed at the start of therapy, then after four, eight and twelve weeks and results were compared and statistically calculated. Three months initial therapy with rosiglitazone significantly reduced values of HbA1C, fibrinogen and CRP but not uric acid in prediabetic patients.Rosiglitazone initial three months therapy significantly reduced HbA1C, fibrinogen and uric acid, but not CRP in diabetic patients.

Cardiac sarcoidosis mimicking Takotsubo syndrome.

An unusual case of cardiac sarcoidosis is described. A woman with biopsy proven lung sarcoidosis was presented on admission in hospital as ventricular tachycardia and non Q myocardial infarction. Ultrasound of the heart and coronarography examination presented Takotsubo syndrome, "ballooning heart", and normal blood vessels. Cardiac sarcoidosis and Takotsubo syndrome are diseases where definitive etiological factor was not found. This case report suggests the existence of their similar pathogenesis. As far as we know, this is the first described connection between Takotsubo syndrome and cardiac sarcoidosis.

Familial hypercholesterolemia screening program in Bosnia and Herzegovina and cardiovascular morbidity.

BACKGROUND AND AIMS: We aimed to estimate the frequency of cardiovascular diseases in familial hypercholesterolemia (FH) patients in Bosnia and Herzegovina. METHODS: We screened lipid profiles in the hospital system during the period March 2008-November 2016, and included 307 patients with LDL>4.5 mmol/L. FH was diagnosed according to the Dutch Lipid Clinic Network (DLCN) criteria. Followed parameters were: the presence of coronary artery disease (CAD), premature CAD (defined as men<55yrs,women<65yrs), cerebral vascular disease (CVD). Patients were divided into 4 groups according to the DLCN criteria: Group1 - definite FH, Group2 - probable FH, Group 3 - possible FH, Group4 - unlikely FH. Patients with incomplete data and secondary causes of hyperlipidemia were not included. Statistical analysis was done using the SPSS software package Version 19.0. RESULTS: There were 307 patients. Group1 counted 16 patients; Group2, 56; Group3, 140, and Group4, 95. In Group1, CAD was diagnosed in 7 patients (43.75%); PCAD in 7 (43.75%); CVD in 2 (12.5%). In Group2, CAD was diagnosed in 25 patients (44.6%); PCAD in 23 (41.1%); and CVD in 8 (14.3%). In Group3, CAD was diagnosed in 64 cases (45.7%); PCAD in 29 (20.7%); and CVD in 47 (33.6%). In Group4, CAD was diagnosed in 19 patients (20%); PCAD in 3 (3.2%); and CVD in 73 (76.8%). CAD was significantly more present in Groups 1,2 and 3 compared with Group4. Occurrence of PCAD was statistically significant in patients with definite and probable FH compared with Groups 3 and 4 (p < 0.05). There was a significant difference in the appearance of CVD in Group4 compared with Groups 1,2 and 3. CONCLUSIONS: Definitive and possible FH groups were strongly associated with PCAD and CAD, while CVD was significantly higher in the unlikely FH group. Screening program and worldwide information exchange are essential to spread the knowledge about FH prevalence.

Influence of C-reactive protein on the occurrence and assessing of albuminuria severity in diabetics.

Aim To asses relation of serum high sensitive C-reactive protein (hsCRP) level with albumin concentration in daily urine in patients with diabetes mellitus type 2 (T2DM). Methods The prospective study included 69 patients with T2DM, both sexes (24 males, 45 females), aged 30-82 years. They were divided into two groups: patients with T2DM and normoalbuminuria(T2DM-NA; n=40) and patients with T2DM and microalbuminuria (T2DM-MA; n=29). Patients were hospitalized at the Department of Internal Medicine, Cantonal Hospital Zenica, in the period January-April 2014. Immunonephelometry measurement of hsCRP was performed on the Nephelometer Analyzer BN II (Siemens, Germany). Results Frequency of patients in T2DM-NA and T2DM-MA groups was not significantly different in relation to sex and age. There was significant difference in relation to duration of diabetes ( p=0.001). Average glucose and HbA1c levels were significantly higher in T2DM-NA group comparing to T2DM-MA group (p=0.008 and p=0.047, respectively). Serum creatinine (p=0.011),urea (p=0.009) and hsCRP (p=0.005) were significantly higher in T2DM-MA group compared to T2DM-NA group. Urinary albumin showed significantly positive correlation with the hsCRP (rho=0.286; p=0.017), urea (rho=0.503) and creatinine (rho=0.438) (p < 0.0005). A one unit (mg/L) increase in hsCRP concentration was associated with 11.5% increase of odds of microalbuminuria OR=1.115; 95% CI 1.014-1.225; p=0.025). Conclusion Significantly higher values of serum hsCRP in patients with type 2 diabetes mellitus and microalbuminuria in comparison to those with normoalbuminuria as well as the correlation of values of inflammatory marker with urinary albumin implicate a low grade inflammation in the progression of diabetic nephropathy.

Acute heart failure after myocardial infarction.

We compared two groups of patients after acute myocardial infarction. First group was treated with fibrinolytics and they were hospitalized within six hours from the beginning of the first chest-symptoms, and second group that did not come within optimal time was treated with anticoagulants only. The patients were classified according to Killip-classification, shock-index and TIMI-risk-score after myocardial infarction. Results prove great benefit of fibrinolytic therapy in optimal time, concerning both keeping myocardial muscle mass and myocardial pump function.

Echocardiographic monitoring of patients with heart failure.

Twenty seven patients diagnosed as having systolic heart failure with Ejection Fraction (EF) of less than 40% by echocardiography were monitored over a period of 3 years. The monitored parameters included clinical symptoms, diastolic dysfunction, therapies and survival during three years of treatment. The results indicate a beneficial effect of treatment with high doses of ACE-inhibitors, spironolactone and beta-blockers in improving clinical symptoms and diastolic function. The survival rate was similar to that in the developed European countries.

The Patterns of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Use in Patients with Atrial Fibrillation in Seven Balkan Countries: a Report from the BALKAN-AF Survey.

INTRODUCTION: Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs). METHODS: A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants). RESULTS: Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20-3.56], rhythm control (OR 1.64, 1.25-2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51-3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis. CONCLUSIONS: NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.

Therapeutic efficacy and toxicity of bolus application of chemotherapy protocol in the treatment of metastatic colorectal cancer.

AIM: To compare efficacy and toxicity of bolus application of chemotherapy protocol, oxaliplatin, fluorouracil (bolus), leucovorin (folfox) between two groups of patients in the therapy of metastatic colorectal carcinoma (mCRC). METHODS: A total of 63 patients were treated for mCRC in the period January 2009 - January 2010 at the Department of Oncology of the Cantonal Hospital Zenica, Bosnia and Herzegovina (first group, 30 patients) and at the Department of Oncology of the Clinical Hospital Centre Bezanijska kosa in Belgrade, Serbia, in the period January 2005 - January 2006 (second group, 33 patients). The patients were treated according the same protocol, i.v. bolus infusion, but in different day intervals (D), 1, 8, 15/28 days or D1-D5/28 days, respectively. In all patients the following factors were analyzed: tumor response, overall survival (OS), progression free survival, hematological and non-hematological toxicity . RESULTS: Colon was the primary localization in almost two thirds of patients. There was no statistically significant difference between the groups according to the age, hematological and non-hematological toxicity, as well as in achieved OS. Progression free survival expressed in months was in average 5 months though with a large range between minimal and maximal survival time. CONCLUSION: Both groups have shown equivalent efficacy to applied chemotherapy protocols. Overall survival in the two groups matched data from the literature. Further research should confirm success of the combination of chemotherapy protocols and their combination with the biological therapy.

Occurrence and morphological characteristics of cataracts in patients treated with general steroid therapy at Cantonal Hospital Zenica.

AIM: To determine the occurrence and morphological characteristics of cataracts and the impact of general steroid therapy on its occurrence. METHODS: A retrospective/prospective study was conducted on 90 patients who had been treated at the Cantonal Hospital Zenica with general steroid therapy. There were 30 patients whose general steroid therapy lasted shorter than 4 years and 30 patients on steroid therapy for more than 4 years. The remaining 30 patients were the control group. An examination of lens transparency and morphological characteristics of cataract was made by slit lamp with previously achieved mydriasis. RESULTS: A significant (p less than 0.05) occurrence of cataracts in patients taking general steroid therapy > 4 years and significantly more frequent occurrence of cataract in patients aged 60 years and over was found. Iatrogenic diabetes affects the occurrence of cataracts in addition to age and duration of therapy, especially in those who were on steroid therapy for more than 4 years. Steroid cataract was of subcapsular type according to its morphological characteristics. CONCLUSION: A possibility of cataract occurrence during or after the treatment with corticosteroids therapy should not be ignored. Subcapsular location of cataracts reduces work ability, normal daily activities and requires surgery. Ophthalmic examination should be an obligatory part of the preparation of patients for corticosteroids treatment. Control examinations should be repeated every six months during the therapy, and even more frequently if required.

Values of D-dimer test in the diagnostics of pulmonary embolism.

AIM: To establish a value of D-dimer and compare findings of elevated and normal values with the golden standard, computed tomography (CT) of lungs in patients who had symptoms indicating pulmonary thromboembolism (PTE) at admission. METHODS: This retrospective/prospective study was conducted at the Department of Internal Diseases of the Cantonal Hospital Zenica, Bosnia and Herzegovina. A sample included 80 patients with symptoms indicating PTE at the time of admission, D-dimers and CT scan of thoracic organs were performed. The patients were divided into two groups: 40 examinees with PTE confirmed by CT scan and 40 patients (control group) whose PTE was not confirmed by the CT scan. RESULTS: Sensitivity of D-dimer according to statistical calculation was 87.5%. Specificity of D-dimer was 57.5%. The chance of a patient to have PTE in case of elevated values of D-dimer was 3.58 higher than in patients with normal D-dimer values. The positive predicative value of D-dimer was 0.54, the negative predicative value was 0.75. Test accuracy was 57.5%. Values of D-dimer >0.83 using a ROC curve and present clinical symptoms of the disease have indicated further diagnostic examination according algorithm and a need for CT scan (of thoracic organs ) CONCLUSION: D-dimer is important in the diagnostics of PTE, high sensitivity and low specificity have been proven. A positive D-dimer test indicates the presence of PTE. However, the test is not reliable. In order to set a diagnosis it is necessary to visualize a blood clot by computed tomography of lungs.