Publications by authors named "Dragan Lovic"

51 Publications

Potential for optimizing management of obesity in the secondary prevention of coronary heart disease.

Eur Heart J Qual Care Clin Outcomes 2021 Jul 27. Epub 2021 Jul 27.

Department of Medicine, Solna, Karolinska Institutet, FoU - Tema Hjärta och Kärl, S1:02, Karolinska Universitetssjukhuset/Solna, SE-171 76, Stockholm, Sweden.

Aims: Prevention guidelines have identified the management of obese patients as an important priority to reduce the burden of incident and recurrent cardiovascular disease. Still, studies have demonstrated that over 80% of patients with coronary heart disease (CHD) fail to achieve their weight target. Here, we describe advice received and actions reported by overweight CHD patients since being discharged from hospital and how weight changes relate to their risk profile.

Methods And Results: Based on data from 10 507 CHD patients participating in the EUROASPIRE IV and V studies, we analysed weight changes from hospital admission to the time of a study visit ≥6 and <24 months later. At hospitalization, 34.9% were obese and another 46.0% were overweight. Obesity was more frequent in women and associated with more comorbidities. By the time of the study visit, 19.5% of obese patients had lost ≥5% of weight. However, in 16.4% weight had increased ≥5%. Weight gain in those overweight was associated with physical inactivity, non-adherence to dietary recommendations, smoking cessation, raised blood pressure, dyslipidaemia, dysglycaemia, and lower levels of quality of life. Less than half of obese patients was considering weight loss in the coming month.

Conclusions: The management of obesity remains a challenge in the secondary prevention of CHD despite a beneficial effect of weight loss on risk factor prevalences and quality of life. Cardiac rehabilitation programmes should include weight loss interventions as a specific component and the incremental value of telehealth intervention as well as recently described pharmacological interventions need full consideration.
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http://dx.doi.org/10.1093/ehjqcco/qcab043DOI Listing
July 2021

Contraindications differ widely among Beta Blockers and Ought to be Cited for an Individual Drug, Not for the Entire Class.

Curr Pharm Des 2021 Jul 16. Epub 2021 Jul 16.

Faculty of Medicine, University of Niš, Serbia.

Beta-blockers (BBs) have significant side effects that contribute to low adherence and persistence. Therefore, the optimal choice of BB is a vital mode to prevent BB's side effects, leading to an increase in compliance, which can improve the outcomes in BBs' evidence-based indications such as acute myocardial infarction, heart failure, etc. The paper aims to suggest an improved method of reporting contraindications for BBs. We used a search of the following indexing databases: SCOPUS and PubMed, and web search engine Google Scholar to identify guidelines on arterial hypertension (HTN). HTN guidelines published during the last two decades were analyzed (from 2000 to 2020). Some of the contraindications (e.g., bradycardia, acute heart failure) are true for every BB. However, some contraindications do not belong to the whole BB class. For example, propranolol and carvedilol are contraindicated in chronic obstructive lung disease, but nebivolol and bisoprolol are not. To our knowledge, there is a lack of guidelines citing contraindications for individual BBs because they vary a lot within the class of BBs. We suggest that contraindications specific for some BBs (i.e., not for the whole class) ought to be listed with the exact name(s) of the individual BBs. In this way, we may decrease the number of wrong choices among BBs and consequently increase drug adherence (which is currently worse for the class of BBs than for most of the other antihypertensive drugs). It is an approach to improve both primary medical education and guidelines.
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http://dx.doi.org/10.2174/1381612827666210716162130DOI Listing
July 2021

Certain beta blockers (e.g., bisoprolol) may be reevaluated in hypertension guidelines for patients with left ventricular hypertrophy to diminish the ventricular arrhythmic risk.

J Hum Hypertens 2021 Jul 2;35(7):564-576. Epub 2021 Mar 2.

Institute for Cardiovascular Diseases of Vojvodina, Sremska Kamenica & Medical Faculty Novi Sad, Novi Sad, Serbia.

Hypertensive left ventricular hypertrophy (HTN LVH) is associated with almost threefold increased risk of ventricular tachycardia (VT)/ventricular fibrillation (VF). Furthermore, HTN LVH increases the risk of sudden cardiac death (SCD). The reverse LV remodeling due to efficient antihypertensive therapy lowers the incidence rates of cardiovascular events and SCD and the vast majority of available arterial hypertension (HTN) guidelines recommend renin angiotensin system (RAS) blockers and calcium channel blockers (CCBs) for HTN LVH aiming for LVH regression. On the other hand, beta blockers (BBs) as a class are not recommended in HTN LVH due to their insufficient capacity to reverse LVH remodeling even though they are recommended as the first-line drugs for prevention/treatment of VT/VF (in general, unrelated to HTN LVH). Moreover, BBs are the best antiarrhythmic (against VT/VF) among antihypertensive drugs. Despite that, BBs are currently not recommended for LVH treatment in HTN Guidelines. It is important to prevent VT/VF in patients at high risk, such as those with HTN LVH. Therefore, certain BBs (such as Bisoprolol) may be reevaluated in guidelines for HTN (in the section of HTN LVH).
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http://dx.doi.org/10.1038/s41371-021-00505-8DOI Listing
July 2021

Prediction of recurrent event in patients with coronary heart disease: the EUROASPIRE Risk Model.

Eur J Prev Cardiol 2020 Dec 29. Epub 2020 Dec 29.

Department of Public Health and Primary Care, Ghent University, C. Heymanslaan 10, 9000 Gent, Belgium.

Aims: Most patients with established atherosclerotic cardiovascular disease (CVD) are at very high risk for developing recurrent events. Since this risk varies a lot between patients there is a need to identify those in whom an even more intensive secondary prevention strategy should be envisaged. Using data from the EUROASPIRE IV and V cohorts of coronary heart disease (CHD) patients from 27 European countries, we aimed at developing and internally and externally validating a risk model predicting recurrent CVD events in patients aged < 75 years.

Methods And Results: Prospective data were available for 12 484 patients after a median follow-up time of 1.7 years. The primary endpoint, a composite of fatal CVD or new hospitalizations for non-fatal myocardial infarction (MI), stroke, heart failure, coronary artery bypass graft, or percutaneous coronary intervention (PCI), occurred in 1424 patients. The model was developed based on data from 8000 randomly selected patients in whom the association between potential risk factors and the incidence of the primary endpoint was investigated. This model was then validated in the remaining 4484 patients. The final multivariate model revealed a higher risk for the primary endpoint with increasing age, a previous hospitalization for stroke, heart failure or PCI, a previous diagnosis of peripheral artery disease, self-reported diabetes and its glycaemic control, higher non-high-density lipoprotein cholesterol, reduced renal function, symptoms of depression and anxiety and living in a higher risk country. The model demonstrated excellent internal validity and proved very adequate in the validation cohort. Regarding external validity, the model demonstrated good discriminative ability in 20 148 MI patients participating in the SWEDEHEART register. Finally, we developed a risk calculator to estimate risks at 1 and 2 years for patients with stable CHD.

Conclusion: In patients with CHD, fatal and non-fatal rates of recurrent CVD events are high. However, there are still opportunities to optimize their management in order to prevent further disease or death. The EUROASPIRE Risk Calculator may be of help to reach this goal.
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http://dx.doi.org/10.1093/eurjpc/zwaa128DOI Listing
December 2020

Lifestyle, psychological, socioeconomic and environmental factors and their impact on hypertension during the coronavirus disease 2019 pandemic.

J Hypertens 2021 06;39(6):1077-1089

Department of Hypertension, National Institute of Cardiology, Warsaw, Poland.

Summary: The coronavirus disease 2019 (COVID-19) pandemic considerably affects health, wellbeing, social, economic and other aspects of daily life. The impact of COVID-19 on blood pressure (BP) control and hypertension remains insufficiently explored. We therefore provide a comprehensive review of the potential changes in lifestyle factors and behaviours as well as environmental changes likely to influence BP control and cardiovascular risk during the pandemic. This includes the impact on physical activity, dietary patterns, alcohol consumption and the resulting consequences, for example increases in body weight. Other risk factors for increases in BP and cardiovascular risk such as smoking, emotional/psychologic stress, changes in sleep patterns and diurnal rhythms may also exhibit significant changes in addition to novel factors such as air pollution and environmental noise. We also highlight potential preventive measures to improve BP control because hypertension is the leading preventable risk factor for worldwide health during and beyond the COVID-19 pandemic.
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http://dx.doi.org/10.1097/HJH.0000000000002770DOI Listing
June 2021

Routine assessment of cognitive function in older patients with hypertension seen by primary care physicians: why and how-a decision-making support from the working group on 'hypertension and the brain' of the European Society of Hypertension and from the European Geriatric Medicine Society.

J Hypertens 2021 01;39(1):90-100

Center for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, Serviço de Medicina Interna do Hospital da Senhora da Oliveira, Guimarães.

: The guidelines on hypertension recently published by the European Societies of Hypertension and Cardiology, have acknowledged cognitive function (and its decline) as a hypertension-mediated organ damage. In fact, brain damage can be the only hypertension-mediated organ damage in more than 30% of hypertensive patients, evolving undetected for several years if not appropriately screened; as long as undetected it cannot provide either corrective measures, nor adequate risk stratification of the hypertensive patient.The medical community dealing with older hypertensive patients should have a simple and pragmatic approach to early identify and precisely treat these patients. Both hypertension and cognitive decline are undeniably growing pandemics in developed or epidemiologically transitioning societies. Furthermore, there is a clear-cut connection between exposure to the increased blood pressure and development of cognitive decline.Therefore, a group of experts in the field from the European Society of Hypertension and from the European Geriatric Medicine Society gathered together to answer practical clinical questions that often face the physician when dealing with their hypertensive patients in a routine clinical practice. They elaborated a decision-making approach to help standardize such clinical evaluation.
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http://dx.doi.org/10.1097/HJH.0000000000002621DOI Listing
January 2021

Diabetic Cardiomyopathy: Clinical and Metabolic Approach.

Curr Vasc Pharmacol 2021 ;19(5):487-498

Clinic for Internal Diseases Intermedica, Singidunum University Nis, Jovana Ristica 20/III-2, 1800 Nis, United States.

Background: Having in mind that diabetes mellitus (DM) and obesity are some of the greatest health challenges of the modern era, diabetic cardiomyopathy (DCM) is becoming more and more recognized in clinical practice. Main Text: Initially, DM is asymptomatic, but it may progress to diastolic and then systolic left ventricular dysfunction, which results in congestive heart failure. A basic feature of this DM complication is the absence of hemodynamically significant stenosis of the coronary blood vessels. Clinical manifestations are the result of several metabolic disorders that are present during DM progression. The complexity of metabolic processes, along with numerous regulatory mechanisms, has been the subject of research that aims at discovering new diagnostic (e.g. myocardial strain with echocardiography and cardiac magnetic resonance) and treatment options. Adequate glycaemic control is not sufficient to prevent or reduce the progression of DCM. Contemporary hypoglycemic medications, such as sodium-glucose transport protein 2 inhibitors, significantly reduce the frequency of cardiovascular complications in patients with DM. Several studies have shown that, unlike the above-stated medications, thiazolidinediones and dipeptidyl peptidase-4 inhibitors are associated with deterioration of heart failure.

Conclusion: Imaging procedures, especially myocardial strain with echocardiography and cardiac magnetic resonance, are useful to identify the early signs of DCM. Research and studies regarding new treatment options are still "in progress".
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http://dx.doi.org/10.2174/1570161119999201102213214DOI Listing
January 2021

Hypertensive emergency is characterized by acute hypertension-mediated organ damage but also a life-threatening status.

Hypertens Res 2020 12 29;43(12):1457-1458. Epub 2020 Jun 29.

Faculty of Medicine, University of Nis, Nis, Serbia.

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http://dx.doi.org/10.1038/s41440-020-0501-6DOI Listing
December 2020

Electrocardiographic criteria which have the best prognostic significance in hypertensive patients with echocardiographic hypertrophy of left ventricle: 15-year prospective study.

Clin Cardiol 2020 Sep 3;43(9):1017-1023. Epub 2020 Jun 3.

Singidunum University School of Medicine, Clinic for Internal Diseases Intermedica, Nis, Serbia.

Background: Electrocardiography is the first-choice technique for detecting left ventricular hypertrophy in patients with arterial hypertension. It is necessary to know the probable outcome for every patient during the treatment, with the aim of improving cardiovascular event prevention.

Hypothesis: Certain electrocardiographic criteria for left ventricular hypertrophy may predict outcomes of patients with left ventricular hypertrophy during a 15-year follow-up.

Methods: Fifteen-year prospective study of 83 consecutive patients (53 male and 30 female; mean age 55.3 ± 8.1) with echocardiographic left ventricular hypertrophy (left ventricular mass index 170.3 ± 31.6 g/m ). Electrocardiographic left ventricular hypertrophy was determined by means of Gubner-Ungerleider voltage, Lewis voltage, voltage of R wave in aVL lead, Lyon-Sokolow voltage, Cornell voltage and Cornell product, voltage RV and RV ratio, Romhilt-Estes score, Framingham criterion and Perugia criterion.

Results: One or more composite events were registered in 32 (38.5%) patients during 15-year follow-up. Positive Lyon-Sokolow score (17.6% vs. 47.3%; P < 0.05), Lewis voltage (9.8% vs. 21.9%; P < 0.05), Cornell voltage (15.7% vs. 37.5%; P < 0.05), and Cornell product (9.8% vs. 34.4%; P < 0.01) were more frequent in a group of patients with composite events. Odd ratio for Cornell product was 4.819 (95% CI 1.486-15.627).

Conclusion: Patients with echocardiographic left ventricular hypertrophy who had positive Lewis voltage, Lyon-Sokolow voltage, Cornell voltage, and Cornell product showed worse 15-year outcome. The strongest predictor of cardiovascular events was positive result of Cornell product.
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http://dx.doi.org/10.1002/clc.23402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462184PMC
September 2020

Impending hypertensive emergency is frequently considered in guidelines, but neither defined nor explained.

Blood Press 2020 10 22;29(5):336-337. Epub 2020 May 22.

Faculty of Medicine, University of Nis, Nis, Serbia.

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http://dx.doi.org/10.1080/08037051.2020.1769467DOI Listing
October 2020

Beta blocker rebound phenomenon is important, but we do not know its definition, incidence or optimal prevention strategies.

Hypertens Res 2020 07 7;43(7):591-596. Epub 2020 May 7.

Community Health Centre Dr Sava Stanojevic, Trstenik, Serbia.

The aim of this review is to analyze whether there is a need for scientific information about the beta blocker (BB) rebound phenomenon; whether such information is available; and, if it is, how detailed is the BB rebound phenomenon explained in the guidelines and papers? A narrative review is used due to the lack of valid randomized clinical trials (RCTs) on the topic, which are needed for a meta-analysis. The BB rebound phenomenon can have dangerous consequences. The discontinuation of a BB leads to a fourfold increased risk of events related to coronary artery disease in hypertensive patients; it increases in-hospital mortality in heart failure patients; it can precipitate angina pectoris attack; and it increases the risk for death and rehospitalization in patients who survive acute myocardial infarction. Consequently, being considered in the guidelines, the BB rebound phenomenon is believed to be clinically relevant (by experts in the field). This is in sharp contrast with the lack of any additional relevant information about the BB rebound phenomenon in the various important guidelines. For example, we lack a consensus about the precise definition. Moreover, data about the incidence and optimal prevention strategies are lacking for the phenomenon (which is sometimes life-threatening). The BB rebound phenomenon is an additional reason why it is very important to test the prognosis of patients following the cessation of long-term medicaments in RCTs, particularly for BBs.
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http://dx.doi.org/10.1038/s41440-020-0449-6DOI Listing
July 2020

Unsolved Problem: (Isolated) Systolic Hypertension with Diastolic Blood Pressure below the Safety Margin.

Med Princ Pract 2020 7;29(4):301-309. Epub 2020 May 7.

Department for Cardiovascular Diseases, Clinical Center Nis, Nis, Serbia.

The problem of high systolic blood pressure (sBP) combined with low diastolic blood pressure (dBP) requires attention because sBP is directly and continuously related to the most important criterion, i.e., all-cause mortality, whereas dBP becomes inversely related to it after the age of 50-60 years. The European Society of Cardiology and European Society of -Hypertension (ESC/ESH) 2018 guidelines for hypertension (HTN) are helpful because they recommend a lower safety cut-off for in-treatment dBP. To prevent tissue hypoperfusion, these guidelines recommend that dBP should be ≥70 mm Hg during treatment. A patient with very elevated sBP (e.g., 220 mm Hg) and low dBP (e.g., 65 mm Hg) is difficult to treat if one strictly follows the guidelines. In this situation, the sBP is a clear indication for antihypertensive treatment, but the dBP is a relative contraindication (as it is <70 mm Hg, a safety margin recognized by the 2018 ESC/ESH guidelines). The dilemma about whether or not to treat isolated systolic hypertension (SH) patients with low dBP (<70 mm Hg) is evident from the fact that almost half (45%) remain untreated. This is a common occurrence and identifying this problem is the first step to solving it. We suggest that an adequate search and analysis should be performed, starting from the exploration of the prognosis of the isolated (I)SH subset of patients with a very low dBP (<70 mm Hg) at the beginning of already performed randomized clinical trials.
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http://dx.doi.org/10.1159/000508462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445659PMC
July 2021

Update of the position paper on arterial hypertension and erectile dysfunction.

J Hypertens 2020 07;38(7):1220-1234

University of Milano Bicocca, Milano, Italy.

: Sexual health is an integral part of overall health, and an active and healthy sexual life is an essential aspect of a good life quality. Cardiovascular disease and sexual health share common risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking) and common mediating mechanisms (endothelial dysfunction, subclinical inflammation, and atherosclerosis). This generated a shift of thinking about the pathophysiology and subsequently the management of sexual dysfunction. The introduction of phosphodiesterase type 5 inhibitors revolutionized the management of sexual dysfunction in men. This article will focus on erectile dysfunction and its association with arterial hypertension. This update of the position paper was created by the Working Group on Sexual Dysfunction and Arterial Hypertension of the European Society of Hypertension. This working group has been very active during the last years in promoting the familiarization of hypertension specialists and related physicians with erectile dysfunction, through numerous lectures in national and international meetings, a position paper, newsletters, guidelines, and a book specifically addressing erectile dysfunction in hypertensive patients. It was noted that erectile dysfunction precedes the development of coronary artery disease. The artery size hypothesis has been proposed as a potential explanation for this observation. This hypothesis seeks to explain the differing manifestation of the same vascular condition, based on the size of the vessels. Clinical presentations of the atherosclerotic and/or endothelium disease in the penile arteries might precede the corresponding manifestations from larger arteries. Treated hypertensive patients are more likely to have sexual dysfunction compared with untreated ones, suggesting a detrimental role of antihypertensive treatment on erectile function. The occurrence of erectile dysfunction seems to be related to undesirable effects of antihypertensive drugs on the penile tissue. Available information points toward divergent effects of antihypertensive drugs on erectile function, with diuretics and beta-blockers possessing the worst profile and angiotensin receptor blockers and nebivolol the best profile.
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http://dx.doi.org/10.1097/HJH.0000000000002382DOI Listing
July 2020

Nutraceuticals and blood pressure control: a European Society of Hypertension position document.

J Hypertens 2020 05;38(5):799-812

IRCCS Instituto Auxologico Italiano, University of Milano-Bicocca, Milano, Italy.

: High-normal blood pressure (BP) is associated with an increased risk of cardiovascular disease, however the cost-benefit ratio of the use of antihypertensive treatment in these patients is not yet clear. Some dietary components and natural products seems to be able to significantly lower BP without significant side effects. The aim of this position document is to highlight which of these products have the most clinically significant antihypertensive action and wheter they could be suggested to patients with high-normal BP. Among foods, beetroot juice has the most covincing evidence of antihypertensive effect. Antioxidant-rich beverages (teas, coffee) could be considered. Among nutrients, magnesium, potassium and vitamin C supplements could improve BP. Among nonnutrient-nutraceuticals, soy isoflavones could be suggested in perimenopausal women, resveratrol in insulin-resistant patients, melatonin in study participants with night hypertension. In any case, the nutracutical approach has never to substitute the drug treatment, when needed.
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http://dx.doi.org/10.1097/HJH.0000000000002353DOI Listing
May 2020

Long-lasting, resistant hypertension should be a part of the aortic dissection risk score.

Hypertens Res 2019 11 31;42(11):1836-1838. Epub 2019 Jul 31.

Institute for Treatment and Rehabilitation, Niska Banja, Serbia.

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http://dx.doi.org/10.1038/s41440-019-0305-8DOI Listing
November 2019

Blood pressure distribution and control in coronary patients from 24 European countries in the European Society of Cardiology EURoObservational Research Programme European survey of cardiovascular disease prevention and diabetes. EUROASPIRE IV Registry.

J Hypertens 2019 10;37(10):2015-2023

Department of Public Health and Primary Care, Ghent University, Ghent, Belgium.

Background: Hypertension is the most prevalent major independent risk factor for developing coronary heart disease (CHD). The present analysis aimed to assess blood pressure (BP) distribution and factors associated with insufficient BP control in coronary patients from 24 countries participating in the European Society of Cardiology (ESC) EURoObservational Research Programme (EORP) EUROASPIRE IV survey.

Methods: EUROASPIRE IV is a cross-sectional study conducted in 2012-2013 in patients aged 80 years or less hospitalized for CHD with a follow-up visit at a median of 16 months later. Logistic regression analysis was applied to confirm factors associated with BP control defined as less than 140/90 mmHg for nondiabetic patients and less than 140/85 mmHg for diabetic patients.

Results: A total of 7998 patients (response rate, 48.7%) attended the follow-up visit. Complete data were available in 7653 participants (mean age 62.5 ± 9.6 years). The BP goal was achieved in 57.6%. Patients failing to achieve the BP goal were older, had higher BMI, had more often a history of coronary artery bypass grafting (CABG) and reported diabetes more frequently. Logistic regression confirmed the following independent significant predictors of not achieving the BP goal: a history of diabetes [odds ratio (OR) 1.75], obesity (OR 1.70 vs. normal BMI), overweight (OR 1.28 vs. normal BMI), age at least 65 years (OR 1.53) and CABG as the index event (OR 1.26 vs. acute MI).

Conclusion: EUROASPIRE IV found insufficient BP control in a large proportion of patients with stable CHD, with diabetes, increased BMI, older age and CABG as the index event being independent predictors of poor BP control.
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http://dx.doi.org/10.1097/HJH.0000000000002130DOI Listing
October 2019

The Growing Epidemic of Diabetes Mellitus.

Curr Vasc Pharmacol 2020 ;18(2):104-109

Cardiology Department, Asklepeion Hospital, Athens, Greece.

Background: During the past decades, the prevalence of diabetes (DM) has increased significantly, mainly as a result of continuous rise in the incidence of type 2 DM. According to World Health Organization statistics, >422 million adults globally were suffering from DM in 2014 and a continuous rise in DM prevalence is expected.

Objective: The present review considers recent epidemiological data providing worldwide estimates regarding the incidence of DM.

Methods: A comprehensive literature search was conducted to identify available data from epidemiological studies evaluating the current burden of DM.

Results: Over the past few decades the prevalence of DM has risen significantly in nearly all countries and may be considered as a growing epidemic. Urbanization and income status are major factors which influence current rates in the prevalence studies introducing interesting differences between several population groups.

Conclusion: Having recognized the global burden of DM, we now realize the urgent need for effective interventions. In order to monitor the public-health strategies and design effective future interventions we need reliable global estimates regarding the prevalence of DM.
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http://dx.doi.org/10.2174/1570161117666190405165911DOI Listing
September 2020

The Mechanisms of Actions of Aldosterone and its Antagonists in Cardiovascular Disease.

Curr Pharm Des 2018 ;24(46):5491-5499

Clinic for Internal Disease Intermedica, Cardiology department, Hypertension Center, Nis, Serbia.

Background: Aldosterone, through its actions on Mineralcorticosteroid Receptors (MR), controls fluid and electrolyte balance, but also exerts various direct deleterious actions on the vasculature. A number of aldosterone antagonists have been manufactured to reverse these effects.

Objective: A comprehensive review of the underlying mechanisms of the actions of aldosterone and its antagonists in cardiovascular disease.

Method: The relevant studies indexed in PubMed, Scopus and Google Scholar databases, published from 2003 to May 2018 were identified and reported.

Results: Aldosterone binds to MR, activating them as intracellular transcription factors. Moreover, aldosterone, through its actions on MR, as well as on another not fully explored class of receptors, triggers several signaling pathways that produce rapid, non-genomic actions. In the vasculature, all these changes favor the establishment of inflammation and cardiovascular dysfunction, which, in turn, lead to or exacerbate various cardiovascular diseases. Mineralcorticosteroid Antagonists (MRA) are compounds that antagonize the action of aldosterone on MR. Spironolactone was the first steroidal MRA to be commercially used. It showed beneficial clinical results, but also a number of adverse effects. The next generation of steroidal MRA, exhibited lower potency but did not induce many of these adverse reactions, due to their high selectivity for MR. The third generation of MRA compromises the newly introduced non-steroidal MRA, which have a completely different chemical structure, they induce different and more drastic changes to MR, they are much more specific and currently under clinical trials.

Conclusion: New MRA, which block the aldosterone induced pathways in the vasculature, hold promising results for the treatment of cardiovascular disease.
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http://dx.doi.org/10.2174/1381612825666190215100502DOI Listing
December 2019

Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: Results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry.

Eur J Prev Cardiol 2019 05 10;26(8):824-835. Epub 2019 Feb 10.

32 Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, Krakow, Poland.

Aims: The aim of this study was to determine whether the Joint European Societies guidelines on secondary cardiovascular prevention are followed in everyday practice.

Design: A cross-sectional ESC-EORP survey (EUROASPIRE V) at 131 centres in 81 regions in 27 countries.

Methods: Patients (<80 years old) with verified coronary artery events or interventions were interviewed and examined ≥6 months later.

Results: A total of 8261 patients (females 26%) were interviewed. Nineteen per cent smoked and 55% of them were persistent smokers, 38% were obese (body mass index ≥30 kg/m), 59% were centrally obese (waist circumference: men ≥102 cm; women ≥88 cm) while 66% were physically active <30 min 5 times/week. Forty-two per cent had a blood pressure ≥140/90 mmHg (≥140/85 if diabetic), 71% had low-density lipoprotein cholesterol ≥1.8 mmol/L (≥70 mg/dL) and 29% reported having diabetes. Cardioprotective medication was: anti-platelets 93%, beta-blockers 81%, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 75% and statins 80%.

Conclusion: A large majority of coronary patients have unhealthy lifestyles in terms of smoking, diet and sedentary behaviour, which adversely impacts major cardiovascular risk factors. A majority did not achieve their blood pressure, low-density lipoprotein cholesterol and glucose targets. Cardiovascular prevention requires modern preventive cardiology programmes delivered by interdisciplinary teams of healthcare professionals addressing all aspects of lifestyle and risk factor management, in order to reduce the risk of recurrent cardiovascular events.
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http://dx.doi.org/10.1177/2047487318825350DOI Listing
May 2019

Incidence of cardiovascular events in patients with stabilized coronary heart disease: the EUROASPIRE IV follow-up study.

Eur J Epidemiol 2019 Mar 23;34(3):247-258. Epub 2018 Oct 23.

Department of Epidemiology and Population Studies, Faculty of Health Sciences, Jagiellonian University Medical College, Kracow, Poland.

The EUROASPIRE surveys (EUROpean Action on Secondary Prevention through Intervention to Reduce Events) demonstrated that most European coronary patients fail to achieve lifestyle, risk factor and therapeutic targets. Here we report on the 2-year incidence of hard cardiovascular (CV) endpoints in the EUROASPIRE IV cohort. EUROASPIRE IV (2012-2013) was a large cross-sectional study undertaken at 78 centres from selected geographical areas in 24 European countries. Patients were interviewed and examined at least 6 months following hospitalization for a coronary event or procedure. Fatal and non-fatal CV events occurring at least 1 year after this baseline screening were registered. The primary outcome in our analyses was the incidence of CV death or non-fatal myocardial infarction, stroke or heart failure. Cox regression models, stratified for country, were fitted to relate baseline characteristics to outcome. Our analyses included 7471 predominantly male patients. Overall, 222 deaths were registered of whom 58% were cardiovascular. The incidence of the primary outcome was 42 per 1000 person-years. Comorbidities were strongly and significantly associated with the primary outcome (multivariately adjusted hazard ratio HR, 95% confidence interval): severe chronic kidney disease (HR 2.36, 1.44-3.85), uncontrolled diabetes (HR 1.89, 1.50-2.38), resting heart rate ≥ 75 bpm (HR 1.74, 1.30-2.32), history of stroke (HR 1.70, 1.27-2.29), peripheral artery disease (HR 1.48, 1.09-2.01), history of heart failure (HR 1.47, 1.08-2.01) and history of acute myocardial infarction (HR 1.27, 1.05-1.53). Low education and feelings of depression were significantly associated with increased risk. Lifestyle factors such as persistent smoking, insufficient physical activity and central obesity were not significantly related to adverse outcome. Blood pressure and LDL-C levels appeared to be unrelated to cardiovascular events irrespective of treatment. In patients with stabilized CHD, comorbid conditions that may reflect the ubiquitous nature of atherosclerosis, dominate lifestyle-related and other modifiable risk factors in terms of prognosis, at least over a 2-year follow-up period.
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http://dx.doi.org/10.1007/s10654-018-0454-0DOI Listing
March 2019

New Horizons in the Pathogenesis, Pathophysiology and Treatment of Familial Hypercholesterolaemia.

Curr Pharm Des 2018 ;24(31):3599-3604

Centre of Cardiology, North Estonia Medical Centre, Tallinn, Estonia; Institute of Health Technologies, Tallinn University of Technology, Tallinn, Estonia.

Background: Familial Hypercholesterolaemia (FH) is an autosomal-dominant genetic disease and represents the most common genetic disorder: heterozygous 1/250 births, homozygous 1/300, 000 births. FH is characterized by high to very high low-density lipoprotein cholesterol (LDL-C), which is the main cause of increased incidence of premature atherosclerotic Cardiovascular Disease (CVD) or aortic stenosis.

Objective: The aim of the review was to investigate the pathogenesis and the pathophysiology of FH.

Results: The most common (60-80%) FH cause is mutations of the LDL Receptor (LDLR) protein (6 classes with a different number of receptors and functionality). Moreover, mutations in apolipoprotein B (APOB) (<5%) and gain-of-function mutations of proprotein convertase subtilisin/kexin type 9 genes (PCSK9) (<1%) contribute to its pathogenesis. An Autosomal Recessive Hypercholesterolaemia (ARH) is another cause, very rare (1/2.500 births), mainly in Sardinia. The remaining patients with a clinical diagnosis of monogenic hypercholesterolaemia do not present any known genetic cause. Since FH is a significant public health problem, early diagnosis and treatment are of utmost importance. Recent studies demonstrated the influence of the LDLR mutation type in the FH phenotype, associating a more severe clinical phenotype and worse advanced CVD in patients with null mutation than those with receptor-defective mutations. This analysis completes the adequate clinical diagnosis.

Conclusion: Both homozygous and heterozygous FH are related to mutations of LDLR (mainly), APOB, PCSK9, while other rare forms exist. All aberrations lead to the impaired removal of LDL-C from the blood leading to its accumulation and subsequent CVD earlier than in the general population.
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http://dx.doi.org/10.2174/1381612824666181009105305DOI Listing
November 2019

Should Cushing's Syndrome be Considered as a Disease with High Cardiovascular Risk in Relevant Guidelines?

Curr Vasc Pharmacol 2020 ;18(1):12-24

Health Centre Jagodina, Emergency Medical Service, Jagodina, Serbia.

A considerable amount of data supports a 1.8-7.4-fold increased mortality associated with Cushing's syndrome (CS). This is attributed to a high occurrence of several cardiovascular disease (CVD) risk factors in CS [e.g. adiposity, arterial hypertension (AHT), dyslipidaemia and type 2 diabetes mellitus (T2DM)]. Therefore, practically all patients with CS have the metabolic syndrome (MetS), which represents a high CVD risk. Characteristically, despite a relatively young average age, numerous patients with CS display a 'high' or 'very high' CVD risk (i.e. risk of a major CVD event >20% in the following 10 years). Although T2DM is listed as a condition with a high CVD risk, CS is not, despite the fact that a considerable proportion of the CS population will develop T2DM or impaired glucose tolerance. CS is also regarded as a risk factor for aortic dissection in current guidelines. This review considers the evidence supporting listing CS among high CVD risk conditions.
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http://dx.doi.org/10.2174/1570161116666181005122339DOI Listing
September 2020

Cost-effectiveness of optimized adherence to prevention guidelines in European patients with coronary heart disease: Results from the EUROASPIRE IV survey.

Int J Cardiol 2018 Dec 28;272:20-25. Epub 2018 Jun 28.

Department of Public Health, Ghent University, Ghent, Belgium.

Background: This study aims to assess the cost-effectiveness of optimized guideline adherence in patients with a history of coronary heart disease.

Methods: An individual-based decision tree model was developed using the SMART risk score tool which estimates the 10-year risk for recurrent vascular events in patients with manifest cardiovascular disease (CVD). Analyses were based on the EUROASPIRE IV survey. Outcomes were expressed as an incremental cost-effectiveness ratio (ICER).

Results: Data from 4663 patients from 13 European countries were included in the analyses. The mean estimated 10-year risk for a recurrent vascular event decreased from 20.13% to 18.61% after optimized guideline adherence. Overall, an ICER of 52,968€/QALY was calculated. The ICER lowered to 29,093€/QALY when only considering high-risk patients (≥20%) with decreasing ICERs in higher risk patients. Also, a dose-response relationship was seen with lower ICERs in older patients and in those patients with higher risk reductions. A less stringent LDL target (<2.5 mmol/L vs. <1.8 mmol/L) lowered the ICER to 32,591€/QALY and intensifying cholesterol treatment in high-risk patients (≥20%) instead of high-cholesterol patients lowered the ICER to 28,064€/QALY. An alternative method, applying risk reductions to the CVD events instead of applying risk reductions to the risk factors lowered the ICER to 31,509€/QALY.

Conclusion: Depending on the method used better or worse ICERs were found. In addition, optimized guidelines adherence is more cost-effective in higher risk patients, in patients with higher risk reductions and when using a less strict LDL-C target. Current analyses advice to maximize guidelines adherence in particular patient subgroups.
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http://dx.doi.org/10.1016/j.ijcard.2018.06.104DOI Listing
December 2018

Significance of asymptomatic hyperuricemia in patients after coronary events.

Scand J Clin Lab Invest 2018 07 27;78(4):312-317. Epub 2018 Apr 27.

f Veterans Affairs Medical Center Washington USA , Washington , DC , USA.

The goal of the present study was to determine the prevalence of hyperuricemia in patients with coronary artery disease (CAD), within three months after coronary events. Also, we aimed to determine whether the presence of hyperuricemia holds correlation with severe CAD, overall heart functioning and risk factors for CAD. The study included 505 consecutive CAD patients, 385 males and 120 females, aged 60.9 ± 9.6 years, with a mean body mass index (BMI) 28.0 ± 3.7 kg/m. All patients were admitted to specialized cardiovascular rehabilitation within three months post-acute myocardial infarction (AMI) without revascularization (32.6%), percutaneous coronary intervention (PCI) with myocardial infarction (32.1%) and with coronary bypass graft (35.3%). The mean value of serum acidum uricum (SUA) was 345.5 ± 100.3 µmol/L, where 115 (22.8%) patients had asymptomatic hyperuricemia. Patients with asymptomatic hyperuricemia had significantly higher average number of risk factors, lower HDL cholesterol and higher creatinine and triglycerides levels, lower ejection fraction (EF). Multivariate stepwise analysis revealed that five parameters were capable to predict SUA levels. We can conclude that in patients with CAD, SUA levels are independently associated with BMI, triglyceride and creatinine levels and negatively with EF. Thus, one can say that asymptomatic hyperuricemia is not significantly associated with the severity of CAD.
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http://dx.doi.org/10.1080/00365513.2018.1467035DOI Listing
July 2018

Blood pressure in acute ischemic stroke: challenges in trial interpretation and clinical management: position of the ESH Working Group on Hypertension and the Brain.

J Hypertens 2018 06;36(6):1212-1221

Department of Adult Neurology, Medical University of Gdansk, Gdansk, Poland.

: Altered blood pressure (BP) is a common phenomenon in acute ischemic stroke (AIS), with high BP being the most frequent scenario. The pathophysiology of BP changes in AIS is complex and only partially understood. The available evidence indicates that extremely high BP during AIS is associated with a poor outcome. Importantly, the observed relationship between BP and stroke outcome may or may not be causally related. Higher baseline BPs in focal cerebral ischemia may indicate preexisting hypertension, but may also be an effect of both nonspecific and stroke-related factors. Although antihypertensive therapy effectively reduces BP in AIS, studies on early BP lowering in AIS produce conflicting results in terms of functional outcome and mortality. Systematic reviews on BP management in AIS did not result in clinically applicable conclusions in general. However, the investigation on the effect of BP and its alterations in AIS are hampered by various important methodological issues. This position statement was prepared by a group of experts from the European Society of Hypertension and invited neurologists to discuss the main reasons for the discrepancies in the current evidence on the prognosis and treatment of altered BP in AIS which should be taken into account in future studies.
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http://dx.doi.org/10.1097/HJH.0000000000001704DOI Listing
June 2018

Sodium-glucose Cotransporter 2 Inhibitors: Potential Cardiovascular and Mortality Benefits.

Cardiovasc Hematol Disord Drug Targets 2018 ;18(2):114-119

Asklepeion General Hospital, Cardiology Department, Athens, Greece.

Background: The impact of overt diabetes and poor glycemic control on the risk of cardiovascular disease is well established. Among patients with type 2 diabetes, several studies demonstrated a significant increase in coronary artery disease-related death and cardiovascular events associated with HbA1c levels of greater than 7% compared with lower levels. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion.

Objectives: To summarize data on the potential mechanisms of SGLT-2 inhibition that could exert cardiovascular benefits in patients with diabetes mellitus.

Method: We conducted an in-depth literature search of SGLT-2 inhibitors and potential cardiovascular benefits and mechanisms that mediate those effects.

Results: In diabetes, expression of the SGLT-2 genes is up-regulated and renal threshold increased, resulting in increased glucose reabsorption from glomerular filtrate, reducing urinary glucose excretion and worsening hyperglycemia. SGLT-2 inhibition should offer potential cardiovascular protection in diabetic patients via attenuating hyperglycemia, blood pressure, body weight, hyperuricemia, and diabetic nephropathy.

Conclusion: The initial data of SGLT-2 inhibitors suggest beneficial effects on cardiovascular risk among patients with diabetes mellitus. Several mechanisms are hypothesized to mediate the abovementioned benefits. Future randomized, controlled studies are needed in order to unveil the contribution of each mechanism to these outcomes.
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http://dx.doi.org/10.2174/1871529X18666180227102137DOI Listing
March 2019

QTc dispersion and Cornell duration product can predict 10-year outcomes in hypertensive patients with left ventricular hypertrophy.

Clin Cardiol 2017 Dec 16;40(12):1236-1241. Epub 2017 Dec 16.

Department of Cardiology, Clinic for Internal Diseases Intermedica, Niš, Serbia; and Veterans Affairs Medical Center, Washington, District of Columbia.

Background: Persistent and adequate treatment of patients with arterial hypertension leads to more favorable disease outcome.

Hypothesis: Aside for the present left ventricular hypertrophy (LVH), there are other non-invasive parameters which can represent additional predictors of unfavorable prognosis in patients with essential arterial hypertension during the 10-year follow-up.

Methods: A hypertensive group with LVH (124 patients; age 57.0 ± 8.0; 84 males and 40 females) was included in the study and examined noninvasively. Patients used regular medication therapy during the follow-up period.

Results: During the 10-year follow-up period, unfavorable outcome was recorded for 40 (32.3%) patients. Patients with unfavorable outcome had higher baseline values of left ventricular mass index (178.9 ± 29.5 g/m vs 165.5 ± 29.5 g/m ; P < 0.05) and QTc dispersion (64.1 ± 24.7 ms vs 54.8 ± 19.4 ms; P < 0.05). Frequency of positive Cornell product was higher in the group of patients with unfavorable outcome (35% vs 22.2%; P < 0.01). Positive Lyon-Sokolow score did not show statistical significance (25% vs 11.9%; P = 0.06). Cornell product (β = 0.234; P < 0.01) and QTc dispersion >65 ms (β = 0.184; P < 0.05) had prognostic significance in LVH (multiple regression analysis: R = 0.314, R = 0.099, adjusted R = 0.084, standard error of the estimate = 0.449, P < 0.05).

Conclusions: Patients with a positive Cornell product and larger QTc dispersion had more unfavorable 10-year outcomes compared with other patients with LVH.
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http://dx.doi.org/10.1002/clc.22815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490563PMC
December 2017

Hypertension and cardiometabolic disease.

Front Biosci (Schol Ed) 2018 01 1;10:166-174. Epub 2018 Jan 1.

Clinic for internal disease Intermedica, Nis, Serbia,

Hypertension has  a central role in cardiometabolic disease and is usually associated with  metabolic disorders, such as insulin resistance, obesity, and dyslipidemia. Hyperinsulinemia may increase cardiovascular (CV) risk through its promotion of hypertension, which is possibly a result of chronic enhancement of sympathetic nervous system activity, stimulation of the renin-angiotensin-aldosterone system leading to increased renal tubular sodium reabsorption, modulating cation transport, or inducing vascular smooth muscle cell hypertrophy. The body mass index value is associated with hypertension, but additional analyses showed that the strongest link existed between visceral obesity and hypertension. In a cross-sectional study, we have already shown that pulse pressure (PP) amplification, heart rate (HR), and pulse valve velocity (PWV), but not augmentation index (Aix), are increased in patients with metabolic syndrome (MS). The basis of therapy for hypertension in MS lies in a changed way of life, involving caloric intake reduction, increased quality of food, increased physical activity, and medicamentous therapy. Such a therapy has a favorable impact not only on blood pressure (BP), but on all the components of MS, and is able to delay the onset of diabetes.
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http://dx.doi.org/10.2741/s506DOI Listing
January 2018
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