PCSK9 Inhibitors in Real-world Practice: Analysis of Data from 314 Patients and 2 Years of Experience in a Center of Preventive Cardiology.

PURPOSE OF REVIEW: PCSK9 inhibitors have been shown to be the most effective class of drugs modifying the levels of LDL-cholesterol as the main risk factor for atherosclerotic cardiovascular disease. The aim of this paper is to assess the effect of monoclonal antibodies on lipid and lipoprotein metabolism in real-world practice. RECENT FINDINGS: The outcome trials showed effective reduction of LDL-C by 56-62%. Landmark studies enrolling over a total of 46,000 patients with CHD in their medical history demonstrated the beneficial effect of both agents on cardiovascular morbidity and mortality. The data from real everyday clinical practice are very limited or missing. Even in real-world practice, PCSK9 inhibitors have been shown to be an effective, safe, and well-tolerated class of drugs with effects comparable with those reported from large randomized controlled trials.

Statin Intolerance in Clinical Practice.

PURPOSE OF REVIEW: In our pilot study, we aimed to determine how many patients with the statin intolerance history referred to the specialized center for the diagnostics and treatment of lipoprotein metabolism disorders really suffer from a complete statin intolerance. The purpose of the study was to prove that complete statin intolerance is overestimated and overdiagnosed, and with the detailed knowledge of the issue and patient approach, it is possible to find an appropriate statin treatment for the most of patients. RECENT FINDINGS: With the increasing number of statin users worldwide, the issue of statin intolerance has been a frequently discussed topic in recent years. There are many factors that play a role in the manifestation of statin intolerance (predisposing factors as age, sex, and some diseases), genetic factors leading to a different metabolism, drug-drug interactions, psychological reasons, and the negative influence of the mass media. However, it is estimated that true complete statin intolerance, defined by an intolerance of at least three statins at their usual lowest daily doses, occurs in approximately 3-6% of all statin users. In our pilot study, we conducted a retrospective analysis of 300 patients who were referred to the Center of Preventive Cardiology with a history of statin intolerance. During the follow-up treatment, 222 patients (74%) were able to use some statin (rosu-, atorva-, simva-, fluvastatin), and in 21% of the cases (63 patient), the target values according their CV risk level were even achieved. Only 78 patients (26%) were confirmed as being complete statin intolerant following a thorough therapeutic effort. The most tolerated statin was rosuvastatin.

Amaranth as a potential dietary adjunct of lifestyle modification to improve cardiovascular risk profile.

The aim of this review was to summarize data regarding amaranth as a potential component of lifestyle modification to improve cardiovascular risk profiles by modifying cardiovascular risk factors such as cholesterol, diabetes, and hypertension. PubMed was searched for appropriate articles. The main inclusion criteria for articles were as follows: interventions with amaranth; conducted in humans or animals or in vitro; and reported serum lipids and lipoprotein levels, and antidiabetic, antihypertensive, and antioxidant abilities. The outcome measures were changes in serum lipids and the presence of antidiabetic, antihypertensive, and antioxidant activity. A total of 33 articles were included herein. Regarding hypolipidemic activity, most studies investigated the effect of intervention with amaranth in animals, and fewer studies were performed in humans. Most studies in animal models demonstrated the ability of amaranth to decrease total cholesterol and low-density lipoprotein cholesterol. Pilot studies in humans were not convincing regarding amaranth's lipid-lowering activity. Based on this search, it is not clear which constituents are potentially responsible for the hypocholesterolemic effect of amaranth. Some authors tend to think that squalene can play a role in this effect, whereas others suggest that different components of amaranth are of greater importance (eg, sterols, oil fractions rich in fatty acids, proteins, amino acids, or fiber) for its hypocholesterolemic effect. It is possible that several constituents are jointly responsible for this action. Regarding the antidiabetic, antihypertensive, and antioxidant activities, most studies were performed in vitro and showed good potential for all three biological effects. Future research should focus on clarifying the effect of amaranth on high-density lipoprotein cholesterol, identifying the constituents responsible for these beneficial effects, and providing more data regarding its use in humans, ideally using randomized controlled trials. The antidiabetic, antihypertensive, and antioxidant activities found in vitro should be confirmed further in animal or human models.

Clinical Management of High and Very High Risk Patients with Hyperlipidaemia in Central and Eastern Europe: An Observational Study.

INTRODUCTION: A retrospective/prospective observational study was conducted to explore the current management of hyperlipidaemia in high-risk (HR) and very high risk (VHR) patients in central/eastern Europe and Israel. METHODS: The study enrolled adult patients who were receiving lipid-lowering therapy and attending a specialist (cardiologist/diabetologist/lipidologist) or internist for a routine visit at 57 sites (including academic/specialist/internal medicine centres) across Bulgaria, Croatia, Czech Republic, Israel, Poland, Romania and Slovakia. Data were collected from medical records, for the 12 months before enrolment, with/without ≤ 6 months' additional prospective follow-up. RESULTS: A total of 1244 patients, mean (SD) age 63.3 (11.3) years were included (307 with familial hypercholesterolaemia (FH), 943 secondary prevention patients). Almost all patients (98.1%) were receiving statins (76.7% monotherapy/21.4% combined therapy), with 53.1% receiving high-intensity statin therapy: 127 patients (10.2%) had adverse events attributed to statin intolerance. Mean (SD) low density lipoprotein cholesterol (LDL-C) levels were 3.3 (1.7) mmol/L at the first, and 2.7 (1.3) mmol/L at the last, visit of the retrospective phase of observation, with little change during the prospective phase. Less than one-quarter (23.8%; 95% CI 17.29-31.45%) of HR patients and less than half (42.0%; 39.05-44.98%) of VHR patients achieved their risk-based LDL-C targets of < 2.5 and < 1.8 mmol/L, respectively. Less than 15% of FH patients reached these targets (10.9% (5.6-18.7%) of HR and 12.1% (8.0-17.4%) of VHR patients). The revised 2016 ESC/EAS target for HR patients (2.6 mmol/L) was met by 28.5% (21.44-36.38%) of HR patients overall. Almost one-half of patients (42.1%) experienced one or more cardiovascular events during observation. CONCLUSION: Our findings confirm that, despite widespread statin use, a substantial proportion of patients treated for hyperlipidaemia in central/eastern Europe and Israel, particularly those with FH, do not reach recommended LDL-C targets, thus remaining at risk of cardiovascular events. FUNDING: Amgen (Europe) GmbH.

A comprehensive guidelines-based approach reduces cardiovascular risk in everyday practice: the VARO study.

INTRODUCTION: The aim of study was to investigate the possibility of cardiovascular risk improvement through systematic identification of high-risk individuals and treatment in accordance with current guidelines using modern therapy in daily clinical practice. MATERIAL AND METHODS: Two hundred and sixty-three physicians participated in the study. The physicians were asked to screen for cardiovascular risk factors in patients presenting with unrelated problems and to re-evaluate the attainment of treatment goals in those with already known risk factors. Each physician enrolled up to 20 consecutive patients with hypertension and/or hyperlipidemia. A total of 3015 patients were included. Cardiovascular risk was assessed using the SCORE system. Risk factors were treated in accordance with current national guidelines. The therapy of hyperlipidemia and hypertension was preferentially based on rosuvastatin, amlodipine and valsartan. Further medication was at the discretion of the attending physician. Patients were examined at baseline and after 3 and 6 months. RESULTS: The principal result is that global cardiovascular risk decreased by 35% (from 8.9 ±6.4 to 5.9 ±4.4, p < 0.001). Systolic and diastolic blood pressure decreased by 12.5% (from 152 ±18 to 133 ±11, p < 0.001) and 11.4% (from 88 ±11 to 78 ±7, p < 0.001). The level of total cholesterol decreased 21% (from 6.3 ±1.2 to 5.0 ±0.9, p < 0.001) and the concentration of LDL-C decreased 28% (from 3.9 ±1.1 to 2.8 ±0.8, p < 0.001). HDL-C increased by 7% (from 1.43 ±0.58 to 1.53 ±0.56, p < 0.001) and triglycerides decreased by 25% (from 2.4 ±1.3 to 1.8 ±0.9, p < 0.001). Blood pressure and LDL-C target values were reached in 68% and 34%of patients, respectively. CONCLUSIONS: The VARO study demonstrates that in daily practice settings, both individual risk factors and global cardiovascular risk are significantly improved through the systematic identification of high-risk individuals and their treatment in accordance with current guidelines using modern pharmacotherapy.

[Hypolipidemic and antihypertensive therapy in diabetic patients in the Czech Republic: notes on the VZP (General Health Insurance Company) Data]. / Terapie diabetiku hypolipidemiky a antihypertenzivy v Ceské republice: poznámky k datum VZP.

Diabetes mellitus and in particular type 2 diabetes mellitus is one of the most important risk factors of cardiovascular disease. To influence cardiovascular risk there is enormous important not only positive influence of glycemia, but also the treatment of diabetic dyslipidemia and hypertension. The present work provides an analysis of lipid-lowering and antihypertensive therapy for all diabetics registered with General Health Insurance Company in the period 2010-2013. In this time 866,570 patients with diabetes mellitus registered with General Health Insurance Company were treated, the majority of them were diabetics independent on insulin. Approximately half of the patients were observed by dialectologists and half of them by the doctors of other specialization. Out of antihypertensive medi-cation, patients were most often treated by drugs that affect the renin-angiotensin system, as well as beta-blockers and diuretics. Prescription of the lipid-lowering therapy, especially prescription of statins, in accordance with the guidelines, is increasing, but remains insufficient (at 2013 43.6% diabetics treated by dialectologists and 51.3% diabetics treated by GP´s didn´t have lipid lowering therapy). Inadequate use of combination lipid-lowering therapy was recorded too, still represented mainly by combination of statin and fibrate, but in coming years we expect (based on the positive results of the subanalysis IMPROVE-IT study), an increase of combination therapy statin and ezetimibe.

[Prevention of cardiovascular diseases in clinical practice: is it possible to achieve improvement?]. / Prevence kardiovaskulárních onemocnení v bezné klinické praxi: lze dosáhnout zlepsení?

Prevention through evaluation and treatment of cardiovascular risk factors is an efficient approach to reduce the risk of cardiovascular events, however, the problem remains that the available treatment options are underused. Implementation of cardiovascular disease prevention guidelines into clinical practice is therefore important for decreasing the burden of cardiovascular disease in general population. However, there are many barriers to this process, including questionable relevance of scientific results for clinical practice, personal preferences and expertise of the doctors, patient attitudes, lack of time, and economical factors. All these factors need to be taken into account for any change in the clinical practice to be successful. With respect to cardiovascular disease prevention, insufficient screening for risk factors, inappropriate risk estimation and hesitation to keep to the guidelines-based treatment targets contribute most to inadequate control of risk factors, and this has been repeatedly demonstrated to be difficult to improve. In this context, our studies demonstrate that the emphasis on systematic application of the principles of cardiovascular prevention results in improved control of cardiovascular risk factors. Adequate support for transforming the guidelines-based knowledge into practicable habit appears therefore important for successful prevention of cardiovascular disease in clinical practice and may translate into substantial reduction of cardiovascular risk in general population.

APOE polymorphism as a potential determinant of functional fitness in the elderly regardless of nutritional status.

OBJECTIVES: Life expectancy is determined by a combination of genetic predisposition (~25%) and environmental influences (~75%). Nevertheless a stronger genetic influence is anticipated in long-living individuals. Apolipoprotein E (APOE) gene belongs among the most studied candidate genes of longevity. We evaluated the relation of APOE polymorphism and fitness status in the elderly. MATERIAL AND METHODS: We examined a total number of 128 subjects, over 80 years of age. Using a battery of functional tests their fitness status was assessed and the subjects were stratified into 5 functional categories according to Spirduso´s classification. Biochemistry analysis was performed by enzymatic method using automated analyzers. APOE gene polymorphism was analysed performed using PCR-RFLP. RESULTS: APOE4 allele carriers had significantly worse fitness status compared to non-carriers (p=0.025). Multiple logistic regression analysis showed the APOE4 carriers had higher risk (p=0.05) of functional unfitness compared to APOE2/E3 individuals. CONCLUSIONS: APOE gene polymorphism seems be an important genetic contributor to frailty development in the elderly. While APOE2 carriers tend to remain functionally fit till higher age, the functional status of APOE4 carriers deteriorates more rapidly.

Impact of apolipoprotein A5 variants on statin treatment efficacy.

AIMS: Despite the fact that statin treatment efficacy is very high, there are substantial differences in treatment effectiveness among individuals. It is supposed that genetic predisposition plays an important role in these differences, but the contribution of individual polymorphisms is poorly understood. So far, more than 30 genes have been examined with ambiguous results. Apolipoprotein A5 is an important determinant of plasma lipid concentrations and its genetic variation could account for some of the observed differences in the response to statin therapy. However, this has not been analyzed before. MATERIALS AND METHODS: We examined the putative association between APOA5 SNPs (c.-1131T>C, c.56C>G and c.457G>A) and efficacy during 3 months of statin treatment in 187 adult Caucasians. Patients were treated with low-dose (10 or 20 mg per day) simvastatin (46.3%), atorvastatin (40.5%) and lovastatin (13.2%). RESULTS: The decrease in cholesterol was not significantly associated with the type or dose of statin. Carriers of the APOA5 genotype TT-1131 (n = 154) benefited more from statin treatment when compared with the C-1131 allele carriers (n = 33) (Delta low-density lipoprotein cholesterol: -36.3 +/- 15.1% vs Delta low-density lipoprotein cholesterol: -29.9 +/- 12.5%; p < 0.005, Mann-Whitney test). This result was independent of sex, age, BMI and APOE polymorphism. CONCLUSION: Our results suggest that the APOA5 gene variants may play an important role in the pharmacogenetics of statin treatment.