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.

Combined Therapy with Anthracyclines and GnRH Analogues for Breast Cancer: Impact on Ischemic Heart Disease.

The combination of classic chemotherapy agents like anthracyclines with novel targeted medications has had a positive impact on women's survival from breast cancer. GnRH analogues are primarily employed to temporarily suppress ovarian function in premenopausal women with hormone-receptor-positive (HR+) breast cancer. Despite their benefits, the true degree of their collateral effects has been widely understudied, especially when it comes to ischemic heart disease. This review aims at summarizing the current state of the art on this issue, with particular focus on the risk for cardiotoxicity associated with the combined use of GnRH analogues and anthracyclines.

The Role of Vasospasm and Microcirculatory Dysfunction in Fluoropyrimidine-Induced Ischemic Heart Disease.

Cardiovascular diseases and cancer are the leading cause of morbidity and mortality globally. Cardiotoxicity from chemotherapeutic agents results in substantial morbidity and mortality in cancer survivors and patients with active cancer. Cardiotoxicity induced by 5-fluorouracil (5-FU) has been well established, yet its incidence, mechanisms, and manifestation remain poorly defined. Ischemia secondary to coronary artery vasospasm is thought to be the most frequent cardiotoxic effect of 5-FU. The available evidence of 5-FU-induced epicardial coronary artery spasm and coronary microvascular dysfunction suggests that endothelial dysfunction or primary vascular smooth muscle dysfunction (an endothelial-independent mechanism) are the possible contributing factors to this form of cardiotoxicity. In patients with 5-FU-related coronary artery vasospasm, termination of chemotherapy and administration of nitrates or calcium channel blockers may improve ischemic symptoms. However, there are variable results after administration of nitrates or calcium channel blockers in patients treated with 5-FU presumed to have myocardial ischemia, suggesting mechanisms other than impaired vasodilatory response. Clinicians should investigate whether chest pain and ECG changes can reasonably be attributed to 5-FU-induced cardiotoxicity. More prospective data and clinical randomized trials are required to understand and mitigate potentially adverse outcomes from 5-FU-induced cardiotoxicity.

Sex beyond cardiovascular risk factors and clinical biomarkers of cardiovascular disease.

In recent years, increasing attention has been reserved to the analysis of sex-related differences in pathophysiology and prognosis of ischemic heart disease (IHD). The traditional conventional cardiovascular risk factors (hypertension, hypercholesteremia, diabetes mellitus and cigarette smoking) are still considered the major risk factors for IHD in both sexes. Nevertheless, recent studies show that they may interact with male and female coronary anatomy in a different manner. The path to sex-specific risk stratification of IHD is also supported by differences in inflammation and necrosis biomarkers (such as C-reactive protein and troponins, respectively). Indeed, large cohort studies often show different mean values of these markers in men and women. The current review summarizes the state-of-art knowledge on sex-related differences in cardiovascular risk factors and cardiac biomarkers with a prognostic value.

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.

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.

Gender Differences in Residual Risk Factors for Major Adverse Cardiovascular Events Following ACS and How to Bridge the Gap.

PURPOSE OF REVIEW: The review aims to describe the differences between men and women in those factors that can influence a worse prognosis in women after an acute cardiovascular event. RECENT FINDINGS: Women adequately treated with current evidence-based medications for acute myocardial infarction and for conventional cardiovascular risk factors, such as hypertension, diabetes, smoking, and dyslipidemia, still have an extra risk of death compared with men. Additional factors that increase the risk of poor prognosis for the index event have been identified. The residual risk can be due to factors affecting the prognosis of the women from outside (they are external to the patient's body) and also to factors that, on the contrary, belong to the female body (female being/female sex). The review will give an update on those residual risk factors, including young age, vulnerability for de novo heart failure, time from symptom onset to treatment, heath care delivered during the weekend, and depression, which generally negatively influence the outcome of women with an acute myocardial infarction.

Post Cardiovascular Surgery Atrial Fibrillation. Biomarkers Determining Prognosis.

BACKGROUND: New onset of atrial fibrillation (AF) after cardiovascular surgery is associated with increased risk of complications and length of hospital stay. Identification of patients at high risk of post-operative AF (POAF) may help to act with preventive strategies having clinical and economic relevance. OBJECTIVE: The focus of this review is to summarize findings on biomarkers of myocardial fibrosis (PICP and PIIINP), profibrotic mediators (TGF-beta1), extracellular matrix remodeling (MMP-9), myocardial stretch (BNP and NTpro-BNP), inflammation (interleukins, C-reactive protein and sCD40L), and myocardial necrosis (high-sensitivity troponin T), biomarkers, that can be used in clinical practice to stratify patients at risk for POAF. METHOD: We searched English-language studies on MEDLINE and PubMed. Evidence synthesis was based on cohort studies, clinical trials and meta-analysis data. International clinical practice guidelines were reviewed, as well. RESULTS: Factors such as cardiac remodelling, atrial pressure, surgery trauma, inflammation, oxidative stress, and sympathetic/parasympathetic activation have been implicated in the development of POAF. On the basis of multifactorial mechanism underlying the onset of POAF, several studies have investigated the predictive value of some serum biomarkers. To date, there are promising preliminary data on the clinical utility of PICP, PIINP, TGF-ß1 and sCD40L, whereas data on NT-proBNP, BNP, CRP, IL- 6, and hs-cTnT are controversial. CONCLUSION: Although some studies have shown promising results, there is a need for future larger studies with longer follow-up, before applying biomarkers as tools for POAF risk-stratification into clinical practice.

Coronary No-Reflow Phenomenon in Clinical Practice.

Timely delivered coronary revascularization with no residual anatomical stenosis does not always lead to prompt restoration of anterograde coronary flow and complete myocardial reperfusion. This condition is known as coronary no-reflow and is associated with major clinical adverse events and poor prognosis. The pathophysiology of no-reflow phenomenon is still poorly understood. Proposed mechanisms include distal microembolization of thrombus and plaque debris, ischemic injury, endothelial dysfunction and individual susceptibility to microvascular dysfunction/obstruction. Older age, diabetes, hypercholesterolemia, prolonged ischemic time, hemodynamic instability, high thrombus burden, complex angiographic lesions and multivessel disease are frequently reported to be associated with the no-reflow phenomenon. There is no general consensus on the correct prevention and management of no-reflow. Non-pharmacological measures such as distal embolic protection devices and manual thrombus aspiration did not result in improved flow or reduction of infarct size. Current preventive measures include reduction of time from symptoms onset to reperfusion therapy, and intracoronary administration of vasodilators such as adenosine, verapamil or nitroprusside.

Primary percutaneous coronary intervention in octogenarians.

BACKGROUND: Limited data are available on the outcome of primary percutaneous coronary intervention (PCI) in octogenarian patients, as the elderly are under-represented in randomized trials. This study aims to provide insights on clinical characteristics, management and outcome of the elderly and very elderly presenting with STEMI. METHODS: 2225 STEMI patients ≥70years old (mean age 76.8±5.1years and 53.8% men) were admitted into the network of the ISACS-TC registry. Of these patients, 72.8% were ≥70 to 79years old (elderly) and 27.2% were ≥80years old (very-elderly). The primary end-point was 30-day mortality. RESULTS: Thirty-day mortality rates were 13.4% in the elderly and 23.9% in the very-elderly. Primary PCI decreased the unadjusted risk of death both in the elderly (OR: 0.32, 95% CI: 0.24-0.43) and very-elderly patients (OR: 0.45, 95% CI 0.30-0.68), without significant difference between groups. In the very-elderly hypertension and Killip class ≥2 were the only independent factors associated with mortality; whereas in the elderly female gender, prior stroke, chronic kidney disease and Killip class ≥2 were all factors independently associated with mortality. Factors associated with the lack of use of reperfusion were female gender and atypical chest pain in the very-elderly and in the elderly; in the elderly, however, there were some more factors, namely: history of diabetes, current smoking, prior stroke, Killip class ≥2 and history chronic kidney disease. CONCLUSIONS: Age is relevant in the prognosis of STEMI, but its importance should not be considered secondary to other major clinical factors. Primary PCI appears to have beneficial effects in the octogenarian STEMI patients.

Invasive versus conservative strategy in acute coronary syndromes: The paradox in women's outcomes.

BACKGROUND: We explored benefits and risks of an early invasive compared with a conservative strategy in women versus men after non-ST elevation acute coronary syndromes (NSTE-ACS) using the ISACS-TC database. METHODS: From October 2010 to May 2014, 4145 patients were diagnosed as having a NSTE-ACS. We excluded 258 patients managed with coronary bypass surgery. Of the remaining 3887 patients, 1737 underwent PCI (26% women). The primary endpoint was the composite of 30-day mortality and severe left ventricular dysfunction defined as an ejection fraction <40% at discharge. RESULTS: Women were older and more likely to exhibit more risk factors and Killip Class ≥2 at admission as compared with men. In patients who underwent PCI, peri-procedural myocardial injury was not different among sexes (3.1% vs. 3.2%). Women undergoing PCI experienced higher rates of the composite endpoint (8.9% vs. 4.9%, p=0.002) and 30-day mortality (4.4% vs. 2.0%, p=0.008) compared with men, whereas those who managed with only routine medical therapy (RMT) did not show any sex difference in outcomes. In multivariable analysis, female sex was associated with favorable outcomes (adjusted HR for the composite endpoint: 0.72, 95% CI: 0.58-0.91) in patients managed with RMT, but not in those undergoing PCI (adjusted HR: 0.96, 95% CI: 0.61-1.52). CONCLUSIONS: We observed a more favorable outcome in women than men when patients were managed with RMT. Women and men undergoing PCI have similar outcomes. These data suggest caution in extrapolating the results from men to women in an overall population of patients in the context of different therapeutic strategies.