Knowledge of the human genome has provided more information on the contribution of genetic factors to the emergence and development of ischemic heart disease. A study based on blood samples obtained in the WOSCOPS registry found an association between the Y chromosome and the risk of coronary artery disease in European men, through genes involved in inflammation and the immune response.1 In the same line, another study, which analyzed 25 000 patients enrolled in 12 studies, found associations between various polymorphisms and coronary events, involving risk factors other than the classically established ones.9 The association between the expression of 8 specific loci in the human genome and the activity and concentration of lipoprotein phospholipase A2, which is related to the development of coronary artery disease, has been demonstrated in a meta-analysis of 13 664 patients.10

With respect to cardiovascular risk factors, several American population studies have demonstrated reductions in the prevalence of smoking, hypertension, and hypercholesterolemia, increases in obesity and diabetes mellitus, and no change in physical activity levels.3,11 In an American registry of 50149 patients with acute myocardial infarction, extreme obesity (body mass index>40) was associated with higher in-hospital mortality despite presenting a favorable coronary anatomy and ventricular function and undergoing similar treatment patterns.12 In a meta-analysis of nearly 4 million individuals, smoking in men was associated with a 25% increase in the risk of coronary heart disease compared to women; however, the interference of other environmental factors could not be ruled out.13

A recent study has shown that measuring growth differentiation factor 15 (GDF-15) levels on admission improves the predictive value of the GRACE score, a validated scoring system that is recommended in the guidelines. In a study including 1122 patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), the use of this marker reclassified 31% of patients without events as low risk and 27% of patients with events as high risk.19 Similarly, measuring N-terminal pro-B-type natriuretic peptide levels enhances the predictive value of the GRACE score.

The role of high-sensitivity troponin T in identifying NSTEACS in individuals with normal conventional troponin was the focus of a study that included 446 patients with chest pain seen in the emergency department. Although elevated high-sensitivity troponin T levels reclassified 19% of the patients into the NSTEACS category, their additive prognostic value to classic clinical and electrocardiographic variables was marginal. However, it was found that levels≤3 ng/L provided high negative predictive value.20

An interesting translational study has shown that metabolic profiling can be very useful in the early management of patients with acute myocardial ischemia.21

In elderly patients, medication use and revascularization are still under-prescribed compared to what is recommended in the guidelines. In a study which included 213 patients with ischemic heart disease aged≥80 years, angiotensin-converting enzyme inhibitors, beta blockers, statins, and acetylsalicylic acid were prescribed to 43%, 56%, 56%, and 66% of patients, respectively, without the degree of comorbidity influencing medication use.22 A registry that included patients admitted with NSTEACS aged≥85 years suggested that an interventional approach was associated with increased survival and fewer ischemic events than conservative management, and that the benefits were maintained after minimizing selection bias using a propensity score.23 The reperfusion rate in a large sample of elderly individuals≥80 years admitted with STEMI in the United States in the period 2004-2008 was<50%, although the proportion of patients undergoing mechanical revascularization has increased in the last decade.24 A similar Spanish single-center study conducted between 2005 and 2011, which included 102 elderly patients aged≥85 years, demonstrated a reperfusion rate of 68%, although the proportion undergoing fibrinolysis was greater.25

Although greater long-term survival has been reported among patients aged>65 years with multivessel disease who had undergone coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI),26 in a sample of 476 octogenarians with 3-vessel disease complete revascularization was not significantly better than incomplete revascularization.27 Two randomized trials have demonstrated similar mortality rates (at 30 days and at 6 months) after CABG with or without cardiopulmonary bypass.28,29 A subanalysis of the CUSTOMIZE registry showed that CABG was superior to PCI with drug-eluting stents in younger patients with unprotected left main coronary artery disease; however, this advantage disappeared in patients aged≥75 years.30

Recent studies31,32 have concluded that, compared to men, young women with ACS have higher mortality rates. However, this difference disappears with age and long-term prognosis among the elderly is actually better for women. In stable coronary artery disease, sex does not appear to be an independent prognostic factor33; however, in both acute and chronic coronary artery disease, fewer women undergo revascularization than men, although absence of epicardial coronary disease is more common among women.31–33

The results of the TRACER study were published this year. The study included 12944 patients with NSTEACS treated with acetylsalicylic acid and clopidogrel who were randomized to receive vorapaxar or placebo.34 Vorapaxar is an oral protease-activated-receptor 1 antagonist which inhibits thrombin-induced platelet activation; in the preclinical study, it showed a good safety profile. The primary endpoint of the TRACER study was the incidence of cardiovascular death, myocardial infarction, stroke, recurrent ischemia, or urgent coronary revascularization at 2 years. This endpoint occurred in 18.5% of patients treated with vorapaxar and 19.9% of those treated with placebo (P=.07). Moderate or severe bleeding (7.2% vs 5.2%; P<.001) and intracranial hemorrhage (1.1% vs 0.2%; P<.001) were more common in the vorapaxar group. To summarize, in patients with NSTEACS the addition of a third oral antiplatelet agent, vorapaxar, to standard therapy provided no added benefit.

The TRILOGY ACS study investigated the efficacy of prolonged treatment with prasugrel versus clopidogrel in 7243 patients with NSTEACS receiving conservative treatment (without coronary angiography or planned revascularization).35 The primary endpoint was the incidence of cardiovascular death, myocardial infarction or stroke at a mean follow-up of 17 months. The endpoint occurred in 13.9% of patients treated with prasugrel and in 16% of those treated with clopidogrel (P=.21). The prasugrel dose (5 mg daily) was adjusted for patients aged>75 years and for those weighing<60 kg. The incidence of major and intracranial bleeding was similar in both groups, although mild and moderate bleeding were more frequent with prasugrel. The authors concluded that the long-term use of prasugrel in patients with NSTEACS treated conservatively was not superior to clopidogrel for reducing the primary endpoint, although the risk of major bleeding remained low.

The ISAR-REACT 4 study included 1721 patients with high-risk NSTEACS undergoing PCI who were randomized to receive bivalirudin or abciximab plus heparin before PCI,36 after receiving treatment with acetylsalicylic acid (250 mg to 500 mg) and clopidogrel (600-mg loading dose). The primary endpoint was the 30-day incidence of death, infarction, new revascularization or major bleeding. The endpoint occurred in 10.9% of the patients treated with abciximab plus heparin and in 11.0% of those treated with bivalirudin (P=.94). A secondary endpoint was major bleeding at 30 days, which was lower in the bivalirudin group (2.6% vs 4.6%; P=.02). These results were consistent and confirmed the safety of bivalirudin in patients with NSTEACS undergoing PCI, in the same way that the HORIZONS-AMI study demonstrated its safety in patients with ST-segment elevation acute coronary syndrome (STEACS) undergoing primary PCI (PPCI). On the other hand, it should be noted that the ISAR-REACT 4 study did not include high-risk patients and that the results are difficult to extrapolate to patients treated via radial access or with new antiplatelet agents.

The ATLAS ACS 2-TIMI 51 was a major study published this year.37 The study assessed rivaroxaban, an oral factor Xa inhibitor, at doses of 2.5 mg or 5 mg every 12h, initiated in the week following the ACS. A total of 15 526 patients were randomized to receive rivaroxab or placebo with a mean follow-up of 13 months (maximum follow-up, 31 months), during which period the primary endpoint was the incidence of cardiovascular death, myocardial infarction, or stroke. This endpoint occurred in 8.9% of the patients treated with rivaroxaban versus 10.7% in those treated with placebo (hazard ratio=0.84; P=.008). The 2.5-mg dose of rivaroxaban also reduced cardiovascular mortality during follow-up (2.7% vs 4.1%; P=.002). On the other hand, the patients treated with rivaroxaban had increased rates of major bleeding (2.1% vs 0.6%; P<.001) and intracranial hemorrhage (0.6% vs 0.2%; P=.009), but without a significant increase in fatal bleeding (0.3% vs 0.2%; P=.66). This study marks a new stage in anticoagulant therapy as secondary prevention in ischemic heart disease, especially for patients with a low risk of bleeding.

A recent meta-analysis supported the guidelines that recommend an invasive strategy for diabetic patients with NSTEACS.38 Nine trials that compared an invasive and a conservative strategy were analyzed. They included 9904 patients with NSTEACS, of whom 1789 (18.1%) had diabetes mellitus. At 12 months, the absolute risk reduction in nonfatal myocardial infarction with an invasive strategy was greater in diabetic patients than in nondiabetic patients (3.7% vs 0.1%; P interaction=0.02), with no difference in mortality or stroke between the 2 groups (P interactions 0.68 and 0.20, respectively).

On the other hand, the 5-year prognostic impact of revascularization procedure-related myocardial infarction in patients with NSTEACS was recently investigated using the FRISC II, ICTUS, and RITA-3 data set.39 Long-term mortality rate was similar in patients who experienced procedure-related myocardial infarction and those who did not, whereas the rate was significantly higher in patients who had a spontaneous infarction within 6 months after revascularization.

The analysis of coronary thrombi underlying STEMI, based on material aspirated during PPCI, has provided information on some of the characteristics associated with an increased risk of distal embolization and impaired reperfusion. A study that included 178 patients showed that erythrocyte-rich thrombi lead to impaired myocardial reperfusion and late remodeling.40 The presence of thrombus is not always evident on angiography, especially in women. A study that included 51 women with STEMI without significant angiographic lesions detected plaque disruption on intravascular ultrasound in 38% of the patients and signs of necrosis on cardiac magnetic resonance imaging in 59%41; this indicates the possible involvement of embolization or vasospasm in the pathogenesis of STEMI in women without severe coronary lesions.

New cell groups that are relevant in the acute and subacute phases of STEMI continue to be studied. In the acute phase, a significant increase in the number of endothelial progenitor cells has been observed. In a group of 32 patients this increase was particularly common in patients with single-vessel disease.42 Although monocytes/macrophages play a key role in myocardial healing, an experimental study has demonstrated that regulatory CD4+ T-cells are also important and that their absence or inhibition hinders this process.43

An ECG is a fundamental tool in the diagnosis and management of STEMI. Classic, easily detectable signs indicate an unfavorable prognosis. Thus, right bundle branch block was detected in 6% of cases in a registry that included 6742 patients. Both in-hospital mortality (14%) and cardiogenic shock (16%) were identical in patients with left bundle branch block.44 The prognostic impact was concentrated in patients with new onset right bundle branch block, which had the highest mortality rate (19%) compared to patients with new left bundle branch block (13%), old left bundle branch block (10%), and old right bundle branch block (6%). The presence of acute ST-segment elevation in lead aVR increases the risk of death, which at 1 month was >22% for both anterior and lower infarction.45

A randomized study compared 300-mg and 600-mg clopidogrel loading doses in 201 patients undergoing PPCI for STEMI. Pretreatment with 600mg was associated with smaller infarct size, better angiographic results, better preservation of systolic function, and fewer events at 30 days.46

A randomized study of 452 patients with anterior STEMI analyzed the effect of manual aspiration thrombectomy and intracoronary abciximab in reducing infarct size in patients undergoing PPCI with bivalirudin anticoagulation. As assessed by cardiac magnetic resonance imaging, intracoronary abciximab, but not aspiration thrombectomy, reduced infarct size at 30 days.47 Drug-eluting stents continue to be a good choice in the invasive treatment of STEMI compared to bare-metal stents and to drug-eluting balloons plus bare-metal stents.48

Cardiac magnetic resonance imaging has become a technique of choice for assessing myocardium salvaged by various reperfusion strategies in patients with STEMI (Fig. 3). In a group of 118 patients it was observed that the determining factor in salvaging a significant amount of myocardium (>30%) was delay to revascularization, rather than the type of strategy, whether PPCI or pharmacoinvasive.49 The Achilles heel of a pharmacoinvasive strategy is the need for rescue angioplasty: in a series of 50 patients treated with rescue angioplasty, only 3% of the myocardium was salvaged.50

Figure 3.

Cardiac magnetic resonance imaging provides excellent quantification of the myocardium salvaged by reperfusion, due to the possibility of comparing the areas of risk and the areas of necrosis. A and B: Areas of hyperintensity representative of the area at risk (upper) and the area of necrosis (late gadolinium enhancement images, lower) in short-axis view; patient A was reperfused 340 min after the onset of pain and had a myocardial salvage index of 16; patient B was reperfused 115 min after the onset of pain and had a myocardial salvage index of 82%. Reproduced from Monmeneu et al.49 with permission.

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There is continuing effort to limit reperfusion injury. In a randomized trial that included 871 patients, out-of-hospital treatment with glucose-insulin-potassium versus placebo did not reduce infarct progression or short-term events.51 Data on ischemic postconditioning after PPCI are contradictory; whereas a randomized study of 79 patients found no reduction in infarct size and even a trend toward greater injury,52 a different series that included 50 patients found less edema and infarction in the treated group.53 Thus, more clinical and experimental information is needed to develop new therapies to add to the great advances achieved in the prognosis of STEMI during recent decades.