Obesity and Dyslipidemia.

PURPOSE OF REVIEW: This article sumarizes pathopysiological consequencies between obesity and dyslipidemia and aims to bring some practical approach. RECENT FINDINGS: Dyslipidemia is often present in individuals with obesity and simultaneusly, many obese individuals have lipid metabolism disorders. Especially the abdominal obesity increases the cardiometabolic risk because of the presence of atherogenic dyslipidemia while the total low density lipoprotein cholesterol (LDL-C) may be normal. LDL-C is the primary goal in dyslipidemia treatment. Apoliprotein B (Apo B) and non - high density lipoprotein cholesterol (non-HDL-C) should be estimated to precise the cardiovascular risk and represents the secondary goal in treatment. Weight loss either with diet or antiobestic medication induces the decrease in triglycerides (TG) and LDL-C and the increase in HDL-C. Composition of nutrients, esp. fatty acids, influences lipid levels. Bariatric surgery is efficient in weight loss and has a significant effect on serum lipids. Dyslipidemia and obesity present common diseases that must be managed to decrease the cardiovascular risk and the risk of obesity-related complications.

Preventive cardiology: Quo vadis?

Reflections of preventive cardiology history, it´s development and look to the future are mentioned. The main problems of primary and secondary prevention for atherosclerotic cardiovascular diseases are presented. New ways to the prevention improvement are sketched in the field of physician care, inside the whole society and throught the new technologies.

Advances of the contemporary treatment of hypertension and hypercholesterolemia by a new fixed combination.

Parallel occurrence of high blood pressure and high plasma cholesterol level is very frequent, in our population in 30 %, and brings multiplicative higher risk for atherosclerotic cardiovascular diseases. On the other hand the contemporary treatment of them reduces that risk synergically. New fixed combination pill of rosuvastatin and ramipril (Kastel) is very felicitous choice for patients with hypercholesterolemia and mild hypertension, in which two antihypertensive drugs are not required immediatelly.

New technology in the hypolipidemic drugs development. Inclisiran (LEQVIO).

The development of lipid modifying drugs was expanding during the past 30 years. Statins stay to be the first choice drugs in dyslipidemia treatment. Inhibitors of proprotein convertase subtilisin- kexin type 9 (PCSK9) enzyme in combination with statin and/or ezetimibe represent very effective therapy and better atherosclerotic cardiovascular disease (ASCVD) prevention. Antisense therapy based on oligonucleotides belongs to the new technology drugs. This therapy inhibits translation of some proteins important for the production of atherogenic lipid particles. Inclisiran is a small interfering RNA that suppresses translation of PCSK9 in the liver cells. It is applied subcutaneously twice a year and it represents a big chance for the improvement of ASCVD treatment and prevention.

Prediabetes.

Prediabetes is defined as impaired fasting glucose or impaired glucose tolerance. It often appears as a part of metabolic syndrome and then represents high cardiometabolic risk. The cornestones of prediabetes management and Type 2 diabetes and cardiovascular disease prevention are weight reduction and regular physical activity. Suitable drugs for prediabetic patients are mentioned.

How to treat arterial hypertension in obese patients?

Obesity (the most common metabolic disease) and arterial hypertension (the most common cardiovascular disease) are often occurring together, which brings very high cardiometabolic risk, i.e. risk for atherosclerotic vascular diseases and type 2 diabetes. Hypertension in obese patients is often resistant to drug treatment, represents the salt sensitive hypertension and many organ damages and other diseases are present. The common pathophysiological mechanisms of the both diseases are mentioned. Those mechanisms stimulate the development of macro- and micro-vascular complications and from those mechanisms arise the management of hypertension in obese patients. Combination of ACE inhibitor and metabolically neutral diuretic indapamide seems to be suitable for the pharmacological treatment of hypertension in obese patient.

“The higher the better” seems to be no longer true for HDL-cholesterol.

It is very well known from the old epidemiological population studies, that HDL-cholesterol (HDL-C) was in a negative association with coronary events risk. New studies have occurred during the last 10 years that the mentioned association has in fact the U-shaped curve, i.e. lower and higher levels of HDL-C then the optimal one are in an exponential increasing risk. The association of high HDL-C levels with cardiovascular risk is not explained clearly. There might be a hypothesis concerning a change of function of large HDL particles riched of cholesterol esters, which become to be cholesterol donors for the arteries. Key words: cardiovascular risk - HDL-cholesterol - HDL particles.

A summary of the EAS consensus concerning the causal relationship between low-density lipoproteins and atherosclerotic cardiovascular diseases, prepared by the Board of the Czech Society for Atherosclerosis.

This article summarised opinion of the European Society for Atherosclerosis on the causal relationship between low density lipoprotein (LDL) and the development of atherosclerosis. The fact that there is a clear causal relationship between the LDL concentration and the development of atherosclerotic cardiovascular disease (ASKVO) is evidenced by congenital lipid metabolism disorders and results of prospective epidemiological studies, Mendelian randomized trials, and randomized controlled trials. It is documented that the effect of LDL exposure on ASKVO development is cumulative; the additive effect of other risk factors is also discussed. In conclusion the facts, underlying the rational approach to the therapy of patients with dyslipidemia, are summarized. Key words: atherosclerotic cardiovascular disease - LDL - low density lipoprotein - EAS.

A multicentre study on unattended automated office blood pressure measurement in treated hypertensive patients.

AIMS: Unattended automated office blood pressure (uAutoOBP) may eliminate white-coat effect. In the present study, we studied its relationships to attended office blood pressure (BP) and ambulatory BP monitoring (ABPM). MATERIAL AND METHODS: Stable treated hypertensive subjects were examined in four Czech academic hypertension centres. uAutoOBP was measured with the BP Tru device; attended BP was measured six times: three times with auscultatory method (AuscOBP) by the physician followed optionally by three oscillometric measurements (OscOBP). ABPM was performed within one week from the clinical visit. RESULTS: Data on 172 subjects aged 63.7 ± 12.4 years with AuscOBP 127.6 ± 12.1/77.6 ± 10.0 mm Hg are reported. uAutoOBP was by 8.5 ± 9.0/3.0 ± 6.1 mm Hg lower than AuscOBP. The AuscOBP-uAutoOBP difference increased with the AuscOBP level and it did not depend on any other factor. OscOBP differed by 8.6 ± 8.6/1.9 ± 5.7 mm Hg from uAutoOBP. 24-hour mean BP was by 4.2 ± 12.1/3.5 ± 7.8 mm Hg lower than AuscOBP and by 4.3 ± 11.0/0.5 ± 6.9 mm Hg higher than uAutoOBP; the correlation coefficients of 24-hour mean BP with AuscOBP and with uAutoOBP did not differ (p for difference ≥.13). In the lowest BP group (systolic AuscOBP <120 mm Hg or diastolic AuscOBP <70 mm Hg), both AuscOBP and uAutoOBP were lower than 24-hour mean BP, while in the highest BP group (systolic AuscOBP ≥140 mm Hg or diastolic AuscOBP ≥90 mm Hg), they were higher. CONCLUSIONS: Compared to uAutoOBP, attended BP measurement gives higher values, both when measured with auscultatory or oscillometric method. Inter-individual variability of AutoOBP - uAuscOBP difference, as well of uAutoOBP - ABPM difference, is large. We did not prove that uAutoOBP would be associated to 24-hour ambulatory BP more closely than attended BP.

Diagnosis of heart failure: the new classification of heart failure.

Heart failure (HF) is a clinical syndrome characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and periphe-ral oedema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress. Natriuretic peptides have a significant nega-tive predictive value for excluding of heart failure. Echocardiography is the most important imaging method in heart failure. The new classification distinguishes HF by left ventricule ejection fraction (LV EF) into 3 groups: HF with preserved EF - HFpEF with LV EF ≥ 50 %, mid-range EF - HFmrEF with LV EF 40-49 % and HF with reduced EF - HFrEF with LV EF < 40 %. A quantity of examination methods is available in heart failure diagnosis and treatment. Key words: classification - diagnosis - echocardiography - heart failure - natriuretic peptides.

[Epidemiology of hypercholesterolemia]. / Epidemiologie hypercholesterolemie.

Hypercholesterolemia is one of the most important risk factors of cardiovascular (CV) disease. Epidemiology follows the prevalence, the incidence and the possibilities of risk factors or diseases intervention. A review of observation epidemiologic studies, pharmacotherapy and treatment perspectives is presented. The first epidemiologic studies, e.g. the Framingham Heart Study or MRFIT showed hyperlipidemia is associated with the incidence of CV disease. The North Karelia Project showed the intervention of CV risk factors is useful on population-based principles. Interventional studies with statins showed the usefulness of LDL cholesterol lowering to decrease CV morbidity and mortality and also total mortality. Anyway, the control of CV risk factors is unsatisfactory.Key words: epidemiology - hypercholesterolemia - intervention.

[Metabolic syndrome and the role of the polypill in the prevention of its complications]. / Metabolický syndrom a postavení polypilu v prevenci jeho komplikací.

The first mention concerning occurrence of cardiometabolic risk factors together appeared 100 years ago. Metabolic syndrome brings 5times higher risk for type 2 diabetes development and 2-3tímes higher cardiovascular (CV) risk in comparison to the subjects without that syndrome. Healthy life habits and rational pharmacotherapy of hypertension, dyslipidemia and hyperglycemia represent an effective way for high cardiometabolic risk reduction. The problem are patient´s low adherence and persistence to the recommendation and pharmacotherapy. Right now polypill (fixed combination of antihypertensives and lipid modifying drugs) are solving in the CV disease prevention. However sufficient evidence exist in the secondary CV prevention, some gap of knowledge is persisting in the primary CV prevention. Right combination of drugs in the polypill might be a suitable solving of CV disease and diabetes prevention for the patients with metabolic syndrome.Key words: cardiometabolic risk - cardiovascular disease prevention - metabolic syndrome - polypill.

[Obesity paradoxes]. / Paradoxy obezity.

Obesity (esp. abdominal type) was still considered as a risk factor for cardiovascular disease. During the last decade has a new phenomenon appeared: "obesity paradox", i.e. patients with high BMI die less frequently than patients with low BMI. Obesity paradox was described first in patients with chronic renal failure, heart failure or in oncological patients, later on in patients with cardiovascular disease and now also in patients with type 2 diabetes. In comparison with population studies, BMI associated with low cardiovascular mortality in patients with Type 2 diabetes is shifted to the higher level than in subjects from general population. Mechanisms of obesity paradox is not yet clarified.

[The common position of the Czech professional associations on the consensus of the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine regarding investigation on blood lipids and interpretation of their levels]. / Spolecné stanovisko ceských odborných spolecností ke konsenzu European Atherosclerosis Society a European Federation of Clinical Chemistry and Laboratory Medicine k vysetrování krevních lipidu a k interpretaci jejich hodnot.

The aim of this opinion is to summarize and to comment the consensus of the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine, which covers two main areas: 1) whether it is necessary / required to be fasting or non-fasting before blood sampling for lipids measurement, and what are the changes in the concentration of blood lipids during the day; 2) What decision limits (cut off value) of lipids and lipoproteins should be reported from laboratories and what is the recommended procedure for people with extreme / critical blood lipid values. Following parameters are discused: total cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein(a). This opinion should be the object of interest both for professionals in clinical laboratories and for physicians in hospitals and out-patients departments.Key words: apolipoproteins - blood collection - cholesterol - laboratory testing - lipoprotein(a) - cut off limits - triglycerides.

[PCSK9 inhibitors - new possibilities in the treatment of hypercholesterolemia: For which patients will be indicated?Czech atherosclerosis society statement]. / PCSK9 inhibitory - nové moznosti v lécbe hypercholesterolemie: U koho budou indikovány?Stanovisko Ceské spolecnosti pro aterosklerózu.

First line drug for the treatment of hypercholesterolemia are statins, which reduce LDL-cholesterol up to 50 %; such reduction is sufficient for most patients to achieve the target values. The exceptions are patients with familial hypercholesterolemia and patients with statin intolerance. To achieve target LDL-cholesterol in these two groups of patients will be possible with new drugs - PCSK9 inhibitors, which decrease LDL-cholesterol by an additional 50-60 %. The first two PCSK9 inhibitors (alirocumab and evolocumab) already had been approved for clinical use by European regulatory authorities. The primary indication for combination statin with PCSK9 inhibitor should be undoubtedly patients with a confirmed diagnosis of familial hypercholesterolemia, who are treated in the Czech Republic primarily in specialized centers of MedPed project. Furthermore, this treatment should be available for other patients at very high risk of cardiovascular diseases, who cannot achieve target LDL-cholesterol (eg. for statins intolerance).

[What is the contribution of the review of the evidence on reducing macrovascular risk in patients with atherogenic dyslipidemia? Report on consensus of experts in the importance of the combined therapy by fenofibrate with statin]. / Co prinásí prehledný clánek o dukazech redukce makrovaskulárního rizika u pacientu s aterogenní dyslipidemií? Zpráva o konsenzu expertu o významu kombinované terapie fenofibrátem a statinem.

A meeting of European experts in cardiovascular (CV) disease and lipids was convened in Paris, November 2014, where an important problem of preventive cardiology--residual vascular risk done by atherogenic dyslipidemia (AD)--was discussed. On the basis of discussion have the experts summarised a consensus concerning AD, its CV risk and up to date evidence of combined therapy with statin and fenofibrate on CV risk. Atherogenic dyslipidemia should be the secondary aim of dyslipidemia treatment, because it is a reason of residual vascular risk. Non-HDL-cholesterol should be the secondary target of AD treatment, which is a most unexpensive and easiest marker of residual vascular risk. Combined therapy with statin and fenofibrate is safe, well tolerated and reduces plasma atherogenity and CV events in patients with AD and high CV risk, type 2 diabetes or metabolic syndrome.

[Residual cardiovascular risk markers]. / Markery reziduálního kardiovaskulárního rizika.

The European definition of biomarker is presented; it is a measurable factor, which reflects a physiological or pathological process in human body. There are also mentioned transferred meanings of the term marker used in different fields of medicine. The importance, categorization and calculation of global cardiovascular (CV) risk are explained in patients in primary prevention of CV disease (SCORE risk chart). Residual CV risk persists in patients in primary or secondary prevention of CV diseases treated according to current guidelines, even if their risk factors (blood pressure, LDL-cholesterol, glucose level) have achieved the recommended values. This residual risk was done by non-LDL dyslipidemia especially, so called atherogenic dyslipidemia (Residual Risk Reduction Initiative definition). Investigators of preventive EUROASPIRE studies assessed, that 5-year mortality from CV diseases was in a positive association with glucose level, smoking and total cholesterol. In our recent analysis, we have described among the Czech samples of EUROASPIRE studies I-IV, that BMI and prevalence of diabetes increase during the last 16 years very steeply. Patients with stable coronary heart diseases in combination with diabetes have had higher prevalence of residual risk markers (atherogenic dyslipidemia, atherogenic index of plasma described by M. Dobiasova and hypertriglyceridemic waist) than patients without diabetes. Except of prescription of statins, ACE inhibitors, antiaggregative or anticoagulative drugs was increasing, the residual CV risk was not changing during the followed period of 16 years.

Evolocumab is Initiated in Central and Eastern Europe at Much Higher LDL-C Levels Than Recommended in Guidelines: Results from the Observational HEYMANS Study.

Purpose: We examined clinical characteristics and low-density lipoprotein cholesterol (LDL-C) lowering in patients initiating evolocumab in real-world practice in a Central and Eastern European (CEE) cohort from the pan-European HEYMANS study. Methods: Patients from Bulgaria, Czech Republic, and Slovakia were enrolled at initiation of evolocumab (baseline) as per local reimbursement criteria. Demographic/clinical characteristics, lipid-lowering therapy (LLT) and lipid values were collected from medical records for ≤6 months before baseline and ≤30 months after evolocumab initiation. Results: Overall, 333 patients were followed over a mean (SD) duration of 25.1 (7.5) months. At initiation of evolocumab, LDL-C levels were markedly elevated in all three countries, with a median (Q1, Q3) LDL-C of 5.2 (4.0, 6.6) mmol/L in Bulgaria, 4.5 (3.8, 5.8) mmol/L in the Czech Republic, and 4.7 (4.0, 5.6) mmol/L in Slovakia. Within the first three months of evolocumab treatment, LDL-C levels were reduced by a median of 61% in Bulgaria, 64% in the Czech Republic, and 53% in Slovakia. LDL-C levels remained low throughout the remaining period of observation. The 2019 ESC/EAS guideline-recommended risk-based LDL-C goals were attained by 46% of patients in Bulgaria, 59% in the Czech Republic, and 43% of patients in Slovakia. LDL-C goal attainment was higher in patients receiving a statin ± ezetimibe-based background therapy (Bulgaria: 55%, Czech Republic: 71%, Slovakia: 51%) compared to those receiving evolocumab alone (Bulgaria: 19%, Czech Republic: 49%, Slovakia: 34%). Conclusion: In the HEYMANS CEE cohort, patients initiated on evolocumab had baseline LDL-C levels approximately three-fold higher than guideline-recommended thresholds for PCSK9i initiation. Risk-based LDL-C goal attainment was highest in patients receiving high-intensity combination therapy. Lowering the LDL-C reimbursement threshold for PCSK9i initiation would allow more patients to receive combination therapy, thus improving LDL-C goal attainment. Trial registration: ClinicalTrials.gov (NCT02770131; registration date: 27 April 2016).

High-sensitivity C-reactive protein and the hypertriglyceridemic waist in patients with type 2 diabetes and metabolic syndrome.

BACKGROUND: High-sensitivity C-reactive protein is an important biomarker of systemic inflammation. We studied the contribution to cardiovascular risk of increased high-sensitivity C-reactive protein in patients with type 2 diabetes with or without concomitant metabolic syndrome. MATERIAL/METHODS: The series included 381 patients (199 men, 182 women; median age, 66 years; age range, 50-80 years) with a mean duration of type 2 diabetes of 9+/-8 years. Standard physical examinations and laboratory investigations were administered to all patients. Modified National Cholesterol Education Program III criteria for defining the metabolic syndrome were used. High-sensitivity C-reactive protein was estimated by immunoturbidimetry and other laboratory tests using standard methods. RESULTS: High-sensitivity C-reactive protein correlated (Spearman's correlation) significantly positively with body mass index and waist size, fasting plasma triglyceride levels, apolipoprotein-B, gamma glutamyl transferase, homeostasis model assessment of insulin resistance, and fibrinogen, and negatively with high-density lipoprotein cholesterol. However, only waist, fibrinogen, apolipoprotein-B, plasma glucose, and gamma glutamyl transferase levels appeared to be associated with high-sensitivity C-reactive protein on multiple logistic regression model analyses. In those diabetic patients with concomitant metabolic syndrome, the hypertriglyceridemic waist appeared to be a major factor for an increased high-sensitivity C-reactive protein concentration. CONCLUSIONS: The hypertriglyceridemic waist contributes to the metabolic syndrome and most likely is an important factor increasing high-sensitivity C-reactive protein levels and consequently, relative coronary risk in patients with type 2 diabetes of any sex and age.