Coronary Microvascular Dysfunction and Hypertension: A Bond More Important than We Think.

Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-induced morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly that with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD and also to investigate and guide the treatment of additional complications that can affect further prognosis. This comprehensive review provides insight into the main pathophysiological mechanisms of CMD in hypertensive patients, offering an integrated diagnostic approach as well as an overview of currently available therapeutical modalities.

Psychosocial Stress and Risk of Myocardial Infarction: A Case-Control Study in Belgrade (Serbia).

BACKGROUND: The purpose of this study was to investigate which psychosocial risk factors show the strongest association with occurrence of myocardial infarction (MI) in the population of Belgrade in peacetime, after the big political changes in Serbia. METHODS: A case-control study was conducted involving 154 consecutive newly diagnosed patients with MI, and 308 controls matched by gender, age, and place of residence. RESULTS: According to conditional logistic regression analysis, after adjustment for conventional coronary risk factors, the odds ratios (95% confidence intervals) for work-related stressful events, financial stress, deaths and diseases, and general stress were 3.78 (1.83-7.81), 3.80 (1.96-7.38), 1.69 (1.03-2.78), and 3.54 (2.01-6.22), respectively. Among individual stressful life events, the following were independently related to MI: death of a close family member, 2.21 (1.01-4.84); death of a close friend, 42.20 (3.70-481.29); major financial problems, 8.94 (1.83-43.63); minor financial problems, 4.74 (2.02-11.14); changes in working hours, 4.99 (1.64-15.22); and changes in working conditions, 30.94 (5.43-176.31). CONCLUSIONS: During this political transition period , stress at work, financial stress, and stress in general as they impacted the population of Belgrade, Serbia were strongly associated with occurence of MI.

Homocysteine Blood Levels and Mandatory Folic Acid Fortification in Serbia.

INTRODUCTION/OBJECTIVE: The current study aims to investigate the blood Hcy levels in patients with CAD and hypertension in Serbia, a country with a high incidence and mortality of both diseases. METHODS: The level of Hcy in the Serbian population was assessed in 123 patients with chronic coronary artery disease (CAD) and hypertension. There were 53 patients with chronic CAD and 70 patients with hypertension (HTA), but without CAD. RESULTS: The Hcy levels were high in both groups of patients (the mean Hcy level of 16.0 ± 7.0 µmol/L) without a statistical difference between the patients in the CAD (14.9 ± 7.3 µmol/L) and hypertension (16.7 ± 6.7 µmol/L) groups. Hypercholesterolemia was found in 81% of the patients with CAD and 92.0% of the patients with HTA, as a common concern across both clinical conditions. It was also found that not a single conventional risk factor (diabetes, hypertension, the smoking status, the family history of CAD, and hyperlipidemia) may individually influence Hcy levels. By contrast, the low levels of vitamin B12 may be related to the high levels of Hcy. CONCLUSION: Given the fact that it is known that various factors interact and influence Hcy levels and associated cardiovascular risks, specific dietary habits, lifestyle and the other Serbia-specific possible factors were done.

Coronary revascularization and sex differences in cardiovascular mortality after myocardial infarction in 12 high and middle-income European countries.

BACKGROUND: Existing data on female sex and excess cardiovascular mortality after myocardial infarction (MI) mostly come from high-income countries (HICs). This study aimed to investigate how sex disparities in treatments and outcomes vary across countries with different income levels. METHODS: Data from the ISACS-Archives registry included 22 087 MI patients from 6 HICs and 6 middle-income countries (MICs). MI data were disaggregated by clinical presentation: ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). The primary outcome was 30-day mortality. RESULTS: Among STEMI patients, women in MICs had nearly double the 30-day mortality rate of men (12.4% versus 5.8%; adjusted risk ratio [RR] 2.30, 95% CI 1.98-2.68). This difference was less pronounced in HICs (6.8% versus 5.1%; RR 1.36, 95% CI 1.05-1.75). Despite more frequent treatments and timely revascularization in MICs, sex-based mortality differences persisted even after revascularization (8.0% versus 4.1%; RR 2.05, 95% CI, 1.68-2.50 in MICs and 5.6% versus 2.6%; RR 2.17, 95% CI 1.48-3.18) in HICs. Additionally, women from MICs had higher diabetes rates compared to HICs (31.8% versus 25.1%, standardized difference = 0.15). NSTEMI outcomes were relatively similar between sexes and income groups. CONCLUSIONS: Sex disparities in mortality rates following STEMI are more pronounced in MICs compared to HICs. These disparities cannot be solely attributed to sex-related inequities in revascularization. Variations in mortality may also be influenced by sex differences in socioeconomic factors and baseline comorbidities.

Traditional risk factors and premature acute coronary syndromes in South Eastern Europe: a multinational cohort study.

Background: The age-standardized death rates under 65 years from ischemic heart disease in South Eastern Europe are approximately twice as high than the Western Europe average, but the reasons are not completely recognized. The aim of the present study was to address this issue by collecting and analyzing data from a large, multinational cohort. Methods: We enrolled 70,953 Caucasian patients with first acute coronary syndrome, from 36 urban hospital in 7 South Eastern European countries and assessed their life expectancy free of acute coronary syndrome and mortality within 30 days after hospital admission from acute coronary syndrome as estimated in relation to dichotomous categories of traditional risk factors (current smoking, hypertension, diabetes and hypercholesterolemia) stratified according to sex. Findings: Compared with patients without any baseline traditional risk factors, the presence of all four risk factors was associated with a 5-year shorter life expectancy free of acute coronary syndrome (women: from 67.1 ± 12.0 to 61.9 ± 10.3 years; r = -0.089; p < 0.001 and men: from 62.8 ± 12.2 to 58.9 ± 9.9 years; r = -0.096; p < 0.001). Premature acute coronary syndrome (women <67 years and men <63 years) was remarkably related to current smoking and hypercholesterolemia among women (RRs: 3.96; 95% CI: 3.72-4.20 and 1.31; 95% CI: 1.25-1.38, respectively) and men (RRs: 2.82; 95% CI: 2.71-2.93 and 1.39; 95% CI: 1.34-1.45, respectively). Diabetes was most strongly associated with death from premature acute coronary syndrome either in women (RR: 1.52; 95% CI: 1.29-1.79) or men (RR: 1.63; 95% CI: 1.41-1.89). Interpretation: Public health policies in South Eastern Europe should place significant emphasis on the four traditional risk factors and the associated lifestyle behaviors to reduce the epidemic of premature ischemic heart disease. Funding: None.

Early coronary revascularization among "stable" patients with non-ST-segment elevation acute coronary syndromes: the role of diabetes and age.

AIMS: To investigate the impact of an early coronary revascularization (<24 hours) compared with initial conservative strategy on clinical outcomes in diabetic patients with non-ST elevation acute coronary syndrome (NSTE-ACS) who are in stable condition at hospital admission. METHODS AND RESULTS: The ISACS-TC database was queried for a sample of diabetic and nondiabetic patients with diagnosis of NSTE-ACS. Patients with cardiac arrest, hemodynamic instability, and serious ventricular arrhythmias were excluded. The characteristics between groups were adjusted using logistic regression and inverse probability of treatment weighting models. Primary outcome measure was all cause 30-day mortality. Risk ratios (RRs) and odds ratios (ORs) with their 95% CIs were employed. Of the 7,589 NSTE-ACS patients identified, 2,343 were diabetics. The data show a notable reduction in mortality for the elderly (> 65 years) undergoing early revascularization compared to those receiving an initial conservative strategy both in the diabetic (3.3% versus 6.7%; RR: 0.48; 95% CI: 0.28-0.80) and nondiabetic patients (2.7% versus 4.7%: RR: 0.57; 95% CI: 0.36-0.90). In multivariate analyses, diabetes was a strong independent predictor of mortality in the elderly (OR: 1.43; 95% CI: 1.03-1.99), but not in the younger patients OR: 1.04; 95% CI: 0.53-2.06). CONCLUSIONS: Early coronary revascularization does not lead to any survival advantage within 30 days from admission in young NSTE-ACS patients who present to hospital in stable conditions with and without diabetes. An early invasive management strategy may be best reserved for the elderly. Factors beyond revascularization are of considerable importance for outcome in elderly diabetic subjects with NSTE-ACS. REGISTRATION: ClinicalTrials.gov: NCT01218776.

Risks for first nonfatal myocardial infarction in Belgrade.

The aim of this study was to investigate which one among possible risk factors are independently related to first nonfatal myocardial infarction (MI) in Belgrade population. Case-control study was conducted in Belgrade during the period 2005-2006. Case group comprised 100 subjects 35-80 years old who were hospitalized because of first nonfatal MI at the coronary care unit in Urgent Center, Belgrade. Control group consisted of 100 persons chosen among patients treated during the same period at the Institute of Rheumatology, Institute for Gastroenterology, and Clinic for Orthopedics, Belgrade, Serbia. Cases and controls were individually matched by sex, age (+/- 2 years) and place of residence (urban/rural communities of Belgrade). According to the multivariate analysis risk factors for MI occurrence were "good" socioeconomic conditions (OR = 2.76), total alcohol consumption (OR = 2.62) and consumption of brandy (OR = 6.73), stressful life events taken together (OR = 3.13) and stress because of close relative Ns death (OR = 3.35), great financial problems (OR = 31.64) and small financial problems (OR = 8.47), hypertension (OR = 2.39), MI among all relatives (OR = 3.66), MI in father (OR = 6.24), and low level of high density lipoprotein cholesterol (OR = 152.41). Amateur sport activity in the past was negatively associated with MI development. The results obtained are mainly in accordance with other studies results and can be of help in development of strategy for coronary heart disease prevention in Serbia.

Clinical determinants of ischemic heart disease in Eastern Europe.

Cardiovascular inequalities remain pervasive in the European countries. Disparities in disease burden is apparent among population groups based on sex, ethnicity, economic status or geography. To address this challenge, The Lancet Regional Health - Europe convened experts from a broad range of countries to assess the current state of knowledge of cardiovascular disease inequalities across Europe. This report presents the main challenges in Eastern Europe. There were pronounced variations in cardiovascular disease mortality rates across Eastern European countries with a remarkably high disease burden in the North-Eastern Europe. There were also significant differences in access and delivery to healthcare and unmet healthcare needs. Addressing the cardiovascular determinants of health and reducing health disparities in its many dimensions has long been a priority of the European Parliament's work through resolutions and by financing pilot projects. Yet, despite these efforts, few large-scale studies have been conducted to examine the feasibility of reducing cardiovascular disparities in Eastern Europe. There is an urgent need for improved data, measurements, reporting, and comparisons; and for dedicated, collaborative research. There is also a need for a broader understanding of the typology of actions needed to tackle cardiovascular inequalities and a clear political will.

Sex Differences in Heart Failure Following Acute Coronary Syndromes.

Background: There have been conflicting reports regarding outcomes in women presenting with an acute coronary syndrome (ACS). Objectives: The objective of the study was to examine sex-specific differences in 30-day mortality in patients with ACS and acute heart failure (HF) at the time of presentation. Methods: This was a retrospective study of patients included in the International Survey of Acute Coronary Syndromes-ARCHIVES (ISACS-ARCHIVES; NCT04008173). Acute HF was defined as Killip classes ≥2. Participants were stratified according to ACS presentation: ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS). Differences in 30-day mortality and acute HF presentation at admission between sexes were examined using inverse propensity weighting based on the propensity score. Estimates were compared by test of interaction on the log scale. Results: A total of 87,812 patients were included, of whom 30,922 (35.2%) were women. Mortality was higher in women compared with men in those presenting with STEMI (risk ratio [RR]: 1.65; 95% CI: 1.56-1.73) and NSTE-ACS (RR: 1.18; 95% CI: 1.09-1.28; P interaction <0.001). Acute HF was more common in women when compared to men with STEMI (RR: 1.24; 95% CI: 1.20-1.29) but not in those with NSTE-ACS (RR: 1.02; 95% CI: 0.97-1.08) (P interaction <0.001). The presence of acute HF increased the risk of mortality for both sexes (odds ratio: 6.60; 95% CI: 6.25-6.98). Conclusions: In patients presenting with ACS, mortality is higher in women. The presence of acute HF at hospital presentation increases the risk of mortality in both sexes. Women with STEMI are more likely to present with acute HF and this may, in part, explain sex differences in mortality. These findings may be helpful to improve sex-specific personalized risk stratification.

Relationship Between Azithromycin and Cardiovascular Outcomes in Unvaccinated Patients With COVID-19 and Preexisting Cardiovascular Disease.

Background Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID-19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events. Methods and Results This study was conducted using data from the ISACS-COVID-19 (International Survey of Acute Coronavirus Syndromes-COVID-19) registry. Patients with a confirmed diagnosis of SARS-CoV-2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30-day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06-2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69-1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42-0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75-2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other (Pinteraction=0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34-3.90]). Conclusions These findings suggest that azithromycin use in patients with COVID-19 and prior history of CVD is significantly associated with an increased risk of AHF and all-cause 30-day mortality. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05188612.

Sex differences and disparities in cardiovascular outcomes of COVID-19.

AIMS: Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men. METHODS AND RESULTS: This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71-0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90-1.42) and 0.86 (95% CI: 0.70-1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73-2.98; 3.85, 95% CI: 3.21-4.63; and 3.95, 95% CI: 3.04-5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94-1.67 vs. 0.83; 95% CI: 0.59-1.16, pinteraction = 0.04). CONCLUSIONS: Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications.

Impact of the combined left ventricular systolic and renal dysfunction on one-year outcomes after primary percutaneous coronary intervention.

BACKGROUND: The aim of this study was to assess the impact of combined left ventricular systolic dysfunction (LVSD) and renal dysfunction (RD) on 1-year overall mortality and major adverse cardiovascular events (MACEs) (comprising cardiovascular death, nonfatal renfarction, target vessel revascularization, and nonfatal stroke) in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). METHODS: One thousand three hundred ninety eight patients with first myocardial infarction, undergoing pPCI were divided into four groups according to the presence of LVSD (ejection fraction [EF] <40%) and/or baseline RD (estimated glomerular filtration rate <60 mL/min per m(2)): Group I (no LVSD and no RD); Group II (LVSD, no RD); Group III (RD, no LVSD); Group IV (LVSD + RD). RESULTS: One-year mortality rates in Groups I, II, III, and IV were 2.6%, 15.2%, 10.6%, and 34.2% and 1-year MACE rates were 5.7%, 19.5%, 17.1% and 35.7%, respectively. Patients in Groups II, III, and IV had an increased probability of 1-year overall mortality and MACE as compared to Group I. Overall mortality: Group II HR 2.1 (95% CI 1.1-4.2); Group III HR 2.1 (95% CI 1.1-4.1); Group IV HR 4.8 (95% CI 2.4-9.4); MACE: Group II HR 2.2 (95% CI 1.1-4.2); Group III HR 2.2 (95% CI 1.1-4.3); Group IV HR 5.1 (95% CI 2.6-10.1). The LVSD-RD combination was the strongest independent predictor for 1-year outcomes. CONCLUSIONS: The LVSD-RD combination is associated with an approximately five-fold increase in 1-year overall mortality and MACE after pPCI. The evaluation of the renal function in patients with LVSD represents a simple method which enables a more precise stratification of the risks related to the occurrence of adverse events in long-term patient follow-up.

Utility of lipoprotein-associated phospholipase A2 for prediction of 30-day major adverse coronary event in patients with the first anterior ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been suggested as an inflammatory marker of cardiovascular risk. The predictive value of Lp-PLA2 in ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) has not been established. The aim of this study was to determine whether plasma Lp-PLA2 is a predictor of a major adverse cardiac event (MACE) in patients with the first anterior STEMI treated by primary PCI. METHODS: This study consisted of 100 consecutive patients with first anterior STEMI who underwent primary PCI within 6 hours of the symptom onset. Plasma Lp-PLA2 level was measured on admission using a turbidimetric immunoassay (diaDexus, Inc., USA). The Receiver Operating Characteristic analysis was performed to identify the most useful Lp-PLA2 cut-off level for the prediction of MACE. The patients were divided into two groups according to the cut-off Lp-PLA2 level: high Lp-PLA2 group (> or = 463 ng/mL, n = 33) and low Lp-PLA2 group (< 463 ng/mL, n = 67). MACE was defined as cardiac death, non-fatal reinfarction, and target vessel revascularization. RESULTS: Patients in the high Lp-PLA2 group had significantly higher total-, LDL-cholesterol, apolipoprotein B levels, and significantly lower estimated glomerular filtration rates compared with the low Lp-PLA2 group. The incidence of 30-day mortality was 18.2% (6/33) in high Lp-PLA2 group, while in the low Lp-PLA2 group no patient died (p < 0.001). The 30-day MACE occurred in 24.2% of the high Lp-PLA2 group and 3% of the low Lp-PLA2 group (p = 0.001). Multiple logistic regression analysis identified the plasma Lp-PLA2 level as an independent predictor of MACE (OR 1.011, 95%CI 1.001 - 1.013, p = 0.037). CONCLUSIONS: In patients with first anterior STEMI treated by primary PCI, the plasma Lp-PLA2 level is an independent predictor of 30-day MACE.

The usefulness of myeloperoxidase in prediction of in-hospital mortality in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

BACKGROUND: The predictive value of myeloperoxidase (MPO) in ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) has not been established. The aim of the present study was to investigate MPO as a predictor of in-hospital mortality in STEMI patients treated by primary PCI. METHODS: Study population consisted of 189 STEMI patients having undergone primary PCI. Plasma MPO level was measured 24 hours after symptom onset using chemiluminescent microparticle immunoassay (Abbott Diagnostics, Germany). The Receiver Operating Characteristic analysis was performed to identify the most useful MPO cut-off level for the prediction of in-hospital mortality. The patients were divided into two groups according to the cut-off MPO level: high MPO group (> or = 840 pmol/L, n = 65) and low MPO group (< 840 pmol/L, n = 124). RESULTS: The high MPO group had significantly more frequent anterior wall infarctions (p < 0.001) and Killip class > 1 on admission (p = 0.013) as well as lower left ventricular ejection fraction (LVEF) (p = 0.011) and higher B-type natriuretic peptide (BNP) (p = 0.029) than the low MPO group. The incidence of in-hospital mortality was 5.8% and was significantly higher in the high MPO group (13.8%) than in the low MPO group (1.6%) (p = 0.001). Multiple logistic regression analysis identified the plasma MPO level as an independent predictor of in-hospital mortality (OR 3.88, 95% CI 1.13 - 13.34, p = 0.031). CONCLUSIONS: Plasma MPO level independently predicts in-hospital mortality in STEMI patients treated by primary PCI.

Temporal Trends in Acute Coronary Syndrome Mortality in Serbia in 2005-2019: An Age-Period-Cohort Analysis Using Data from the Serbian Acute Coronary Syndrome Registry (RAACS).

BACKGROUND: Cardiovascular diseases ranked first in terms of the number of deaths in Serbia in 2019, with 52,663 deaths. One fifth of those were from ischemic heart disease (IHD), and half of IHD deaths were from acute coronary syndrome (ACS). We present the ACS mortality time trend in Serbia during a 15-year period using the latest available data, excluding the COVID-19 pandemic. METHODS: The data on patients who died of ACS in the period from 2005 to 2019 were obtained from the National Statistics Office and processed at the Department of Prevention and Control of Non-communicable Diseases of the Institute of Public Health of Serbia. Number of deaths, crude mortality rates (CR) and age-standardized mortality rates (ASR-E) for the European population were analyzed. Using joinpoint analysis, the time trend in terms of annual percentage change (APC) was analyzed for the female and male population aged 0 to 85+. Age-period-cohort modeling was used to estimate age, cohort and period effects in ACS mortality between 2005 and 2019 for age groups in the range 20 to 90. RESULTS: From 2005 to 2019 there were 90,572 deaths from ACS: 54,202 in men (59.8%), 36,370 in women (40.2%). Over the last 15 years, the number of deaths significantly declined: 46.7% in men, 49.5% in women. The annual percentage change was significant: -4.4% in men, -5.8% in women. Expressed in terms of APC, for the full period, the highest significant decrease in deaths was seen in women aged 65-69, -8.5%, followed by -7.6% for women aged 50-54 and 70-74. In men, the highest decreases were recorded in the age group 50-54, -6.7%, and the age group 55-59, -5.7%. In all districts there was significant decline in deaths in terms of APC for the full period in both genders, except in Zlatibor, Kolubara and Morava, where increases were recorded. In addition, in Bor and Toplica almost no change was observed over the full period for both genders. CONCLUSIONS: In the last 15 years, mortality from ACS in Serbia declined in both genders. The reasons are found in better diagnostic and treatment through an organized network for management of ACS patients. However, there are districts where this decline was small and insignificant or was offset in recent years by an increase in deaths. In addition, there is space for improvement in the still-high mortality rates through primary prevention, which at the moment is not organized.

Concerns about the use of digoxin in acute coronary syndromes.

AIMS: The use of digitalis has been plagued by controversy since its initial use. We aimed to determine the relationship between digoxin use and outcomes in hospitalized patients with acute coronary syndromes (ACSs) complicated by heart failure (HF) accounting for sex difference and prior heart diseases. METHODS AND RESULTS: Of the 25 187 patients presenting with acute HF (Killip class ≥2) in the International Survey of Acute Coronary Syndromes Archives (NCT04008173) registry, 4722 (18.7%) received digoxin on hospital admission. The main outcome measure was all-cause 30-day mortality. Estimates were evaluated by inverse probability of treatment weighting models. Women who received digoxin had a higher rate of death than women who did not receive it [33.8% vs. 29.2%; relative risk (RR) ratio: 1.24; 95% confidence interval (CI): 1.12-1.37]. Similar odds for mortality with digoxin were observed in men (28.5% vs. 24.9%; RR ratio: 1.20; 95% CI: 1.10-1.32). Comparable results were obtained in patients with no prior coronary heart disease (RR ratio: 1.26; 95% CI: 1.10-1.45 in women and RR ratio: 1.21; 95% CI: 1.06-1.39 in men) and those in sinus rhythm at admission (RR ratio: 1.34; 95% CI: 1.15-1.54 in women and RR ratio: 1.26; 95% CI: 1.10-1.45 in men). CONCLUSION: Digoxin therapy is associated with an increased risk of early death among women and men with ACS complicated by HF. This finding highlights the need for re-examination of digoxin use in the clinical setting of ACS.

Reduced Heart Failure and Mortality in Patients Receiving Statin Therapy Before Initial Acute Coronary Syndrome.

BACKGROUND: There is uncertainty regarding the impact of statins on the risk of atherosclerotic cardiovascular disease (ASCVD) and its major complication, acute heart failure (AHF). OBJECTIVES: The aim of this study was to investigate whether previous statin therapy translates into lower AHF events and improved survival from AHF among patients presenting with an acute coronary syndrome (ACS) as a first manifestation of ASCVD. METHODS: Data were drawn from the International Survey of Acute Coronary Syndromes Archives. The study participants consisted of 14,542 Caucasian patients presenting with ACS without previous ASCVD events. Statin users before the index event were compared with nonusers by using inverse probability weighting models. Estimates were compared by test of interaction on the log scale. Main outcome measures were the incidence of AHF according to Killip class and the rate of 30-day all-cause mortality in patients presenting with AHF. RESULTS: Previous statin therapy was associated with a significantly decreased rate of AHF on admission (4.3% absolute risk reduction; risk ratio [RR]: 0.72; 95% CI: 0.62-0.83) regardless of younger (40-75 years) or older age (interaction P = 0.27) and sex (interaction P = 0.22). Moreover, previous statin therapy predicted a lower risk of 30-day mortality in the subset of patients presenting with AHF on admission (5.2 % absolute risk reduction; RR: 0.71; 95% CI: 0.50-0.99). CONCLUSIONS: Among adults presenting with ACS as a first manifestation of ASCVD, previous statin therapy is associated with a reduced risk of AHF and improved survival from AHF. (International Survey of Acute Coronary Syndromes [ISACS] Archives; NCT04008173).

Statins for primary prevention among elderly men and women.

AIMS: We undertook a propensity match-weighted cohort study to investigate whether statin treatment recommendations for statins translate into improved cardiovascular (CV) outcomes in the current routine clinical care of the elderly. METHODS AND RESULTS: We included in our analysis (ISACS Archives -NCT04008173) a total of 5619 Caucasian patients with no known prior history of CV disease who presented to hospital with a first manifestation of CV disease with age of 65 years or older. The risk of ST-segment elevation myocardial infarction (STEMI) was much lower in statin users than in non-users in both patients aged 65-75 years [14.7% absolute risk reduction; relative risk (RR): 0.55, 95% CI 0.45-0.66] and those aged 76 years and older (13.3% absolute risk reduction; RR: 0.58, 95% CI 0.46-0.72). Estimates were similar in patients with and without history of hypercholesterolaemia (interaction test; P-values = 0.24 and 0.35). Proportional reductions in STEMI diminished with female sex in the old (P for interaction = 0.002), but not in the very old age (P for interaction = 0.26). We also observed a remarkable reduction in the risk of 30 day mortality from STEMI with statin therapy in both age groups (10.2% absolute risk reduction; RR: 0.39; 95% CI 0.23-0.68 for patients aged 76 or over and 3.8% absolute risk reduction; RR 0.37; 95% CI 0.17-0.82 for patients aged 65-75 years old; interaction test, P-value = 0.46). CONCLUSIONS: Preventive statin therapy in the elderly reduces the risk of STEMI with benefits in mortality from STEMI, irrespective of the presence of a history of hypercholesterolaemia. This effect persists after the age of 76 years. Benefits are less pronounced in women. Randomized clinical trials may contribute to more definitively determine the role of statin therapy in the elderly.