Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure. Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1-22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Results: ST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52-0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up. Conclusions: There are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes. Trial Registration: 4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.

Identification of acute myocardial infarction in elderly patients using optimized highly sensitive troponin I thresholds.

Purpose: Established diagnostic thresholds for high-sensitivity cardiac troponins (hs-cTn) might not apply for elderly patients as they are elevated irrespective of the presence of an acute myocardial infarction (AMI). Aim of the present study was to investigate hs-cTnI in elderly patients with suspected AMI and to calculate optimized diagnostic cutoffs. Material and methods: Data from a prospective multi-centre study and from a second independent prospective single-centre cohort study were analysed. A number of 2903 patients were eligible for further analysis. Patients > 70 years were classified as elderly. hs-cTnI was measured upon admission. Results: Around 34.7% of 2903 patients were classified as elderly. Around 22.5% of elderly patients were finally diagnosed with AMI. Elderly patients had higher hs-cTnI levels at admission irrespective of the final diagnosis (p < 0.001). According to the AUROC, hs-cTnI was a strong marker for detection of AMI in elderly patients. Application of the 99th percentile cutoffs showed a substantially lower specificity in elderly. By using optimized thresholds, specificity was improved to levels as in younger patients in both cohorts but accompanied with a decrease in sensitivity. Conclusions: hs-cTnI levels have a lower specificity for detecting AMI in elderly patients. This lower specificity can be improved by using hs-cTnI thresholds optimized for elderly patients.

Antiplatelet and anticoagulation agents in acute coronary syndromes: what is the current status and what does the future hold?

Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.

Effect of smoking relapse on outcome after acute coronary syndromes.

The aim of the present study was to evaluate the smoking relapse rate among smokers who had become abstinent during admission for acute coronary syndromes. The association between smoking relapse and mortality was also analyzed. A cohort of 1,294 consecutive active smokers who had interrupted smoking after admission for acute coronary syndromes (1,018 men and 276 women, mean age 59.7 ± 12.3 years) was followed up for 12 months after the index admission. All patients received a brief in-hospital smoking cessation intervention consisting of repeated counseling sessions. During follow-up, 813 patients (62.8%) resumed regular smoking (median interval to relapse 19 days, interquartile range 9 to 76). Increasing age (hazard ratio [HR] 1.034 per year, 95% confidence interval [CI] 1.028 to 1.039, p = 0.001) and female gender (HR 1.23, 95% CI 1.09 to 1.42, p = 0.03) were independent predictors of smoking relapse. Patients enrolled in a cardiac rehabilitation program (HR 0.74, 95% CI 0.51 to 0.91, p = 0.02) and those with diabetes (HR 0.79, 95% CI 0.68 to 0.94, p = 0.03) were more likely to remain abstinent. During follow-up, 97 patients died (1-year probability of death 0.075, 95% CI 0.061 to 0.090). Multivariate analysis with the Cox proportional hazard regression method, including smoking relapse as a time-dependent covariate, demonstrated that, after adjustment for patient demographics, the clinical history features and variables related to the index event, the resumption of smoking was an independent predictor of total mortality (HR 3.1, 95% CI 1.3 to 5.7, p = 0.004). In conclusion, smoking relapse after acute coronary syndromes is associated with increased mortality, and counseling interventions should be integrated into the postdischarge support to reduce the negative effects of smoking resumption.

[Secondary cardiovascular prevention after acute coronary syndrome in clinical practice]. / Prevenzione cardiovascolare secondaria dopo sindrome coronarica acuta nella pratica clinica.

Secondary prevention after acute coronary syndromes should be aimed at reducing the risk of further adverse cardiovascular events, thereby improving quality of life, and lengthening survival. Despite compelling evidence from large randomized controlled trials, secondary prevention is not fully implemented in most cases after hospitalization for acute coronary syndrome. The Lazio Region (Italy) has about 5.3 million inhabitants (9% of the entire Italian population). Every year about 11 000 patients are admitted for acute coronary syndrome in hospitals of the Lazio Region. Most of these patients receive state-of-the art acute medical and interventional care during hospitalization. However, observational data suggest that after discharge acute coronary syndrome patients are neither properly followed nor receive all evidence-based treatments. This consensus document has been developed by 11 Scientific Societies of Cardiovascular and Internal Medicine in order develop a sustainable and effective clinical approach for secondary cardiovascular prevention after acute coronary syndrome in the local scenario of the Lazio Region. An evidence-based simplified decalogue for secondary cardiovascular prevention is proposed as the cornerstone of clinical intervention, taking into account regional laws and relative shortage of resources. The following appropriate interventions should be consistently applied: smoking cessation, blood pressure control (blood pressure < 130/80 mmHg), optimal lipid management (LDL cholesterol < 80 mmHg), weight and diabetes management, promotion of physical activity and rehabilitation, correct use of antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system blockers.

Full-dose atorvastatin versus conventional medical therapy after non-ST-elevation acute myocardial infarction in patients with advanced non-revascularisable coronary artery disease.

AIMS: This study tested the hypothesis that the addition of full-dose atorvastatin (80 mg/day) to conventional medical treatment could reduce ischaemic recurrences after non-ST-elevation acute myocardial infarction (NSTE-AMI) in patients with severe and diffuse coronary artery disease (CAD) not amenable to any form of mechanical revascularisation. METHODS AND RESULTS: The study was an open-label, randomised, controlled, blinded end-point classification trial, employing the PROBE (Prospective Open Treatment and Blinded End Point Evaluation) design. A total of 290 patients (mean age 74.6 +/- 9.6 years) with NSTE-AMI and angiographic evidence of severe and diffuse CAD, not amenable to revascularisation by either coronary surgery or angioplasty, were randomised to atorvastatin 80 mg/day (n = 144) or conventional medical treatment (n = 146). A primary end point event (combination of cardiovascular death, non-fatal acute myocardial reinfarction and disabling stroke within 12 months of randomisation) occurred in 16.0% of patients treated with atorvastatin 80 mg/day and in 26.7% of patients receiving conventional treatment (HR 0.56; 95% CI 0.33-0.93, p = 0.027). The study was not blinded. Consequently, a bias in the assessment of clinical outcome cannot be completely excluded. CONCLUSIONS: In conclusion, when compared with a conventional treatment strategy, full-dose therapy with atorvastatin 80 mg/day provides greater protection against ischaemic recurrences after NSTE-AMI in patients with severe, diffuse, non-revascularisable CAD.

Myocardial infarction in the young: a sex-based comparison.

A relative paucity of information concerns the natural history, clinical features and coronary anatomy in young patients with acute myocardial infarction. In particular, there is a dearth of data relating to sex differences in young patients. The objective was to evaluate whether or not there are correlations between the clinical characteristics and the extent and localization of coronary artery lesions in young men compared with young women. The study population consisted of 1646 young patients (87% men, 13% women; mean age 39+/-5 years) with a first acute myocardial infarction admitted to one of the 125 coronary care units of Italy in a period of 3 years. Clinical data were collected. All patients underwent coronary angiography during hospitalization. Smoking, hypercholesterolemia and obesity were significantly more prevalent in men than in women; physical inactivity was significantly more prevalent among women. Hemodynamically significant coronary stenosis occurred in 82% of patients and were more frequent in men than in women (P<0.05). Women more frequently had single-vessel disease and no coronary lesions at all (58 vs. 47% and 24 vs. 9% women vs. men respectively, both P<0.05). Men more frequently had multivessel disease (38 vs. 13%, P<0.05). Significant stenosis mainly affected the left anterior descending artery (52%) with no gender-related difference; men more likely had lesions of the left circumflex or right coronary artery (P<0.05). In conclusion, young patients with a first acute myocardial infarction risk factors profile and extent of coronary artery lesions were significantly different between sexes.

Autologous bone marrow mononuclear cell transplantation in patients undergoing coronary artery bypass grafting.

BACKGROUND: Recent studies have shown that autologous bone marrow mononuclear cell (aBM-MNC) transplantation can be effectively performed in human beings either by the coronary route or by endoventricular injections. However, scanty data are available for patients undergoing coronary artery bypass grafting (CABG). Accordingly, the aim of this study was to evaluate the feasibility and safety of aBM-MNC transplantation in patients with recent myocardial infarction undergoing CABG. METHODS AND RESULTS: The study population included 36 consecutive patients with recent myocardial infarction (< 6 months) undergoing CABG. Eighteen patients (17 men, mean age 64 years) underwent CABG plus aBM-MNC transplantation, whereas 18 subjects undergoing conventional CABG (17 men, mean age 67 years) served as control subjects. Cell transplantation was performed by direct injections in the border zone of the recently infarcted area. An average number of 292 +/- 232 x 10(6) aBM-MNCs was injected in each patient. When compared with control subjects, transplanted patients showed higher values of troponin I peak after CABG (median values of 1.65 ng/mL vs 0.64 ng/mL, P < .001). No major transplant-related adverse event could be detected. During follow-up, transplanted patients had an improvement in left ventricular ejection fraction (from 0.46 to 0.51, P < .05) and wall motion score index (from 1.71 to 1.42, P < .01). The incidence of arrhythmias immediately after CABG and during follow-up was similar in the 2 groups. CONCLUSIONS: Our data support the idea that direct injection of aBM-MNCs in the myocardium during CABG is feasible and safe. Larger studies are needed to assess the efficacy of such an approach in patients undergoing CABG.