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.

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.

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.

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.

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.

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.

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.

Smoking and sex differences in first manifestation of cardiovascular disease.

BACKGROUND AND AIMS: An increasing proportion of women believe that smoking few cigarettes daily substantially reduces their risk of developing cardiovascular (CV) related disorders. The effect of low intensity smoking is still largely understudied. We investigated the relation among sex, age, cigarette smoking and ST segment elevation myocardial infarction (STEMI) as initial manifestation of CV disease. METHODS: We analyzed data of 50,713 acute coronary syndrome patients with no prior manifestation of CV disease from the ISACS-Archives (NCT04008173) registry. We compared the rates of STEMI in current smokers (n = 11,530) versus nonsmokers (n = 39,183). RESULTS: In the young middle age group (<60 years), there was evidence of a more harmful effect in women compared with men (RR ratios: 1.90; 95% CI: 1.69-2.14 versus 1.68; 95% CI: 1.56-1.80). This association persisted even in women who smoked 1 to 10 packs per year (RR ratios: 2.02; 95% CI: 1.65 to 2.48 versus 1.38; 95% CI: 1.22 to 1.57). In the older group, rates of STEMI were similar for women and men (RR ratios: 1.36; 95% CI: 1.22-1.53 versus 1.39; 95% CI: 1.28-1.50). STEMI was associated with a twofold higher 30-day mortality rate in young middle age women compared with men of the same age (odds ratios, 5.54; 95% CI, 3.83-8.03 vs. 2.93; 95% CI, 2.33-3.69). CONCLUSIONS: Low intensity smoking provides inadequate protection in young - middle age women as they still have a substantially higher rate of STEMI and related mortality compared with men even smoking less than 10 packs per year. This finding is worrying as more young - middle age women are smoking, and rates of smoking among young-middle age men continue to fall.

Aspirin for primary prevention of ST segment elevation myocardial infarction in persons with diabetes and multiple risk factors.

BACKGROUND: Controversy exists as to whether low-dose aspirin use may give benefit in primary prevention of cardiovascular (CV) events. We hypothesized that the benefits of aspirin are underevaluated. METHODS: We investigated 12,123 Caucasian patients presenting to hospital with acute coronary syndromes as first manifestation of CV disease from 2010 to 2019 in the ISACS-TC multicenter registry (ClinicalTrials.gov, NCT01218776). Individual risk of ST segment elevation myocardial infarction (STEMI) and its association with 30-day mortality was quantified using inverse probability of treatment weighting models matching for concomitant medications. Estimates were compared by test of interaction on the log scale. FINDINGS: The risk of STEMI was lower in the aspirin users (absolute reduction: 6·8%; OR: 0·73; 95%CI: 0·65-0·82) regardless of sex (p for interaction=0·1962) or age (p for interaction=0·1209). Benefits of aspirin were seen in patients with hypertension, hypercholesterolemia, and in smokers. In contrast, aspirin failed to demonstrate a significant risk reduction in STEMI among diabetic patients (OR:1·10;95%CI:0·89-1·35) with a significant interaction (p: <0·0001) when compared with controls (OR:0·64,95%CI:0·56-0·73). Stratification of diabetes in risk categories revealed benefits (p interaction=0·0864) only in patients with concomitant hypertension and hypercholesterolemia (OR:0·87, 95% CI:0·65-1·15), but not in smokers. STEMI was strongly related to 30-day mortality (OR:1·93; 95%CI:1·59-2·35). INTERPRETATION: Low-dose aspirin reduces the risk of STEMI as initial manifestation of CV disease with potential benefit in mortality. Patients with diabetes derive substantial benefit from aspirin only in the presence of multiple risk factors. In the era of precision medicine, a more tailored strategy is required. FUNDING: None.

Sex Differences in Modifiable Risk Factors and Severity of Coronary Artery Disease.

Background It is still unknown whether traditional risk factors may have a sex-specific impact on coronary artery disease (CAD) burden. Methods and Results We identified 14 793 patients who underwent coronary angiography for acute coronary syndromes in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries; Clini​calTr​ials.gov, NCT01218776) registry from 2010 to 2019. The main outcome measure was the association between traditional risk factors and severity of CAD and its relationship with 30-day mortality. Relative risk (RR) ratios and 95% CIs were calculated from the ratio of the absolute risks of women versus men using inverse probability of weighting. Estimates were compared by test of interaction on the log scale. Severity of CAD was categorized as obstructive (≥50% stenosis) versus nonobstructive CAD. The RR ratio for obstructive CAD in women versus men among people without diabetes mellitus was 0.49 (95% CI, 0.41-0.60) and among those with diabetes mellitus was 0.89 (95% CI, 0.62-1.29), with an interaction by diabetes mellitus status of P =0.002. Exposure to smoking shifted the RR ratios from 0.50 (95% CI, 0.41-0.61) in nonsmokers to 0.75 (95% CI, 0.54-1.03) in current smokers, with an interaction by smoking status of P=0.018. There were no significant sex-related interactions with hypercholesterolemia and hypertension. Women with obstructive CAD had higher 30-day mortality rates than men (RR, 1.75; 95% CI, 1.48-2.07). No sex differences in mortality were observed in patients with nonobstructive CAD. Conclusions Obstructive CAD in women signifies a higher risk for mortality compared with men. Current smoking and diabetes mellitus disproportionally increase the risk of obstructive CAD in women. Achieving the goal of improving cardiovascular health in women still requires intensive efforts toward further implementation of lifestyle and treatment interventions. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01218776.

Prior Beta-Blocker Therapy for Hypertension and Sex-Based Differences in Heart Failure Among Patients With Incident Coronary Heart Disease.

The usefulness of ß-blockers has been questioned for patients who have hypertension without a prior manifestation of coronary heart disease or heart failure. In addition, sex-based differences in the efficacy of ß-blockers for prevention of heart failure during acute myocardial ischemia have never been evaluated. We explored whether the effect of ß-blocker therapy varied according to the sex among patients with hypertension who have no prior history of cardiovascular disease. Data were drawn from the ISACS (International Survey of Acute Coronary Syndromes)-Archives. The study population consisted of 13 764 patients presenting with acute coronary syndromes. There were 2590 patients in whom hypertension was treated previously with ß-blocker (954 women and 1636 men). Primary outcome measure was the incidence of heart failure according to Killip class classification. Subsidiary analyses were conducted to estimate the association between heart failure and all-cause mortality at 30 days. Outcome rates were assessed using the inverse probability of treatment weighting and logistic regression models. Estimates were compared by test of interaction on the log scale. Among patients taking ß-blockers before admission, there was an absolute difference of 4.6% between women and men in the rate of heart failure (Killip ≥2) at hospital presentation (21.3% versus 16.7%; relative risk ratio, 1.35 [95% CI, 1.10-1.65]). On the opposite, the rate of heart failure was approximately similar among women and men who did not receive ß-blockers (17.2% versus 16.1%; relative risk ratio, 1.09 [95% CI, 0.97-1.21]). The test of interaction identified a significant (P=0.034) association between sex and ß-blocker therapy. Heart failure was predictive of mortality at 30-day either in women (odds ratio, 7.54 [95% CI, 5.78-9.83]) or men (odds ratio, 9.62 [95% CI, 7.67-12.07]). In conclusion, ß-blockers use may be an acute precipitant of heart failure in new-onset coronary heart disease among women, but not men. Heart failure increases the risk of death. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04008173.

Sex-Related Differences in Heart Failure After ST-Segment Elevation Myocardial Infarction.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) complicated by symptoms of acute de novo heart failure is associated with excess mortality. Whether development of heart failure and its outcomes differ by sex is unknown. OBJECTIVES: This study sought to examine the relationships among sex, acute heart failure, and related outcomes after STEMI in patients with no prior history of heart failure recorded at baseline. METHODS: Patients were recruited from a network of hospitals in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776). Main outcome measures were incidence of Killip class ≥II at hospital presentation and risk-adjusted 30-day mortality rates were estimated using inverse probability of weighting and logistic regression models. RESULTS: This study included 10,443 patients (3,112 women). After covariate adjustment and matching for age, cardiovascular risk factors, comorbidities, disease severity, and delay to hospital presentation, the incidence of de novo heart failure at hospital presentation was significantly higher for women than for men (25.1% vs. 20.0%, odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.21 to 1.48). Women with de novo heart failure had higher 30-day mortality than did their male counterparts (25.1% vs. 20.6%; OR: 1.29; 95% CI: 1.05 to 1.58). The sex-related difference in mortality rates was still apparent in patients with de novo heart failure undergoing reperfusion therapy after hospital presentation (21.3% vs. 15.7%; OR: 1.45; 95% CI: 1.07 to 1.96). CONCLUSIONS: Women are at higher risk to develop de novo heart failure after STEMI and women with de novo heart failure have worse survival than do their male counterparts. Therefore, de novo heart failure is a key feature to explain mortality gap after STEMI among women and men.

Sex-Specific Treatment Effects After Primary Percutaneous Intervention: A Study on Coronary Blood Flow and Delay to Hospital Presentation.

Background We hypothesized that female sex is a treatment effect modifier of blood flow and related 30-day mortality after primary percutaneous coronary intervention ( PCI ) for ST -segment-elevation myocardial infarction and that the magnitude of the effect on outcomes differs depending on delay to hospital presentation. Methods and Results We identified 2596 patients enrolled in the ISACS - TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry from 2010 to 2016. Primary outcome was the occurrence of 30-day mortality. Key secondary outcome was the rate of suboptimal post- PCI Thrombolysis in Myocardial Infarction ( TIMI ; flow grade 0-2). Multivariate logistic regression and inverse probability of treatment weighted models were adjusted for baseline clinical covariates. We characterized patient outcomes associated with a delay from symptom onset to hospital presentation of ≤120 minutes. In multivariable regression models, female sex was associated with postprocedural TIMI flow grade 0 to 2 (odds ratio [ OR ], 1.68; 95% CI , 1.15-2.44) and higher mortality ( OR, 1.72; 95% CI , 1.02-2.90). Using inverse probability of treatment weighting, 30-day mortality was higher in women compared with men (4.8% versus 2.5%; OR , 2.00; 95% CI , 1.27-3.15). Likewise, we found a significant sex difference in post- PCI TIMI flow grade 0 to 2 (8.8% versus 5.0%; OR , 1.83; 95% CI , 1.31-2.56). The sex gap in mortality was no longer significant for patients having hospital presentation of ≤120 minutes ( OR , 1.28; 95% CI , 0.35-4.69). Sex difference in post- PCI TIMI flow grade was consistent regardless of time to hospital presentation. Conclusions Delay to hospital presentation and suboptimal post- PCI TIMI flow grade are variables independently associated with excess mortality in women, suggesting complementary mechanisms of reduced survival. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01218776.

Coronary Microcirculation in Heart Failure with Preserved Systolic Function.

BACKGROUND: The Heart Failure with Preserved Ejection Fraction (HFpEF) is defined as the preserved left ventricular ejection fraction (LVEF) with the signs of heart failure, elevated natriuretic peptides, and either the evidence of the structural heart disease or diastolic dysfunction. The importance of this form of heart failure was increased after studies where the mortality rates and readmission to the hospital were founded similar as in patients with HF and reduced EF (HFrEF). Coronary microvascular ischemia, cardiomyocyte injury and stiffness could be important factors in the pathophysiology of HFpEF. METHODS: The goal of this work is to analyse the relationship of HFpEF and coronary microcirculation in previous studies. RESULTS: The useful diagnostic marker of coronary microcirculation in HFpEF may be the parameters measured by transthoracic echocardiography (TTE), the coronary flow reserve (CFR), as well as fractional flow reserve (FFR) and quantitative myocardial contrast echocardiography (MCE). Cardiac magnetic resonance (CMR) imaging represents the diagnostic gold standard in HFpEF. Coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD) is poorly understood and may be more prevalent amongst women than men. Troponin level may be important in risk stratification of HEpEF patients. CONCLUSION: There are no precise answers with respect to the pathophysiological mechanism, nor are there any precise practical clinical assessment of and diagnostic method for coronary microvascular dysfunction and diastolic dysfunction. In accordance with that, there is no well-established treatment for HFpEF.

Sex Differences in Outcomes After STEMI: Effect Modification by Treatment Strategy and Age.

Importance: Previous works have shown that women hospitalized with ST-segment elevation myocardial infarction (STEMI) have higher short-term mortality rates than men. However, it is unclear if these differences persist among patients undergoing contemporary primary percutaneous coronary intervention (PCI). Objective: To investigate whether the risk of 30-day mortality after STEMI is higher in women than men and, if so, to assess the role of age, medications, and primary PCI in this excess of risk. Design, Setting, and Participants: From January 2010 to January 2016, a total of 8834 patients were hospitalized and received medical treatment for STEMI in 41 hospitals referring data to the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) registry (NCT01218776). Exposures: Demographics, baseline characteristics, clinical profile, and pharmacological treatment within 24 hours and primary PCI. Main Outcomes and Measures: Adjusted 30-day mortality rates estimated using inverse probability of treatment weighted (IPTW) logistic regression models. Results: There were 2657 women with a mean (SD) age of 66.1 (11.6) years and 6177 men with a mean (SD) age of 59.9 (11.7) years included in the study. Thirty-day mortality was significantly higher for women than for men (11.6% vs 6.0%, P < .001). The gap in sex-specific mortality narrowed if restricting the analysis to men and women undergoing primary PCI (7.1% vs 3.3%, P < .001). After multivariable adjustment for comorbidities and treatment covariates, women under 60 had higher early mortality risk than men of the same age category (OR, 1.88; 95% CI, 1.04-3.26; P = .02). The risk in the subgroups aged 60 to 74 years and over 75 years was not significantly different between sexes (OR, 1.28; 95% CI, 0.88-1.88; P = .19 and OR, 1.17; 95% CI, 0.80-1.73; P = .40; respectively). After IPTW adjustment for baseline clinical covariates, the relationship among sex, age category, and 30-day mortality was similar (OR, 1.56 [95% CI, 1.05-2.3]; OR, 1.49 [95% CI, 1.15-1.92]; and OR, 1.21 [95% CI, 0.93-1.57]; respectively). Conclusions and Relevance: Younger age was associated with higher 30-day mortality rates in women with STEMI even after adjustment for medications, primary PCI, and other coexisting comorbidities. This difference declines after age 60 and is no longer observed in oldest women.

Oxidative stress markers predict early left ventricular systolic dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Despite successful primary percutaneous coronary intervention (PCI) after ST-segment elevation myocardial infarction (STEMI), some patients develop left ventricular systolic dysfunction (LVSD) and acute heart failure (HF). Identifying patients with an increased risk of developing LVSD by means of biomarkers may help select patients requiring more aggressive therapy. OBJECTIVES: The aim of this study was to evaluate the relationship between the levels of oxidative stress markers and development of LVSD and acute HF early after STEMI. MATERIAL AND METHODS: The study enrolled 148 patients with the first STEMI, who were treated by primary PCI < 12 h from the onset of symptoms. We assessed the impact of different biomarkers for developing LVSD and acute HF (Killip ≥ 2) including: markers of necrosis - peak creatine kinase (CK), markers of myocardial stretch - B-type natriuretic peptide (BNP), inflammatory markers - C-reactive protein (CRP), leucocyte and neutrophil count, as well as oxidative stress markers - total thiol groups, catalase, superoxide dismutase (SOD) and glutathione reductase (GR). RESULTS: In multivariate analysis, thiol groups, peak CK, anterior wall infarction, and age were predictors of LVEF ≤ 40%. Out of 16 variables significantly associated with the Killip ≥ 2 in univariate logistic regression analysis, 5 appeared to be independently associated with acute HF in multivariate analysis: catalase, BNP, leucocytes, neutrophil count, and size of left atrium. CONCLUSIONS: In this study, we have shown for the first time that thiol groups and catalase are independent predictors of STEMI complication - LVSD and acute HF, respectively. Beside routine used biomarkers of necrosis and myocardial stretch, thiol groups and catalase may provide additional information regarding the risk stratification.