Convergent experimental and clinical evidence have established the pathophysiological importance of pro-inflammatory pathways in coronary artery disease. Notably, the interest in treating inflammation in patients suffering acute myocardial infarction (AMI) is now expanding from its chronic aspects to the acute setting. Few large outcome trials have proven the benefits of anti-inflammatory therapies on cardiovascular outcomes by targeting the residual inflammatory risk (RIR), i.e. the smouldering ember of low-grade inflammation persisting in the late phase after AMI. However, these studies have also taught us about potential risks of anti-inflammatory therapy after AMI, particularly related to impaired host defence. Recently, numerous smaller-scale trials have addressed the concept of targeting a deleterious flare of excessive inflammation in the early phase after AMI. Targeting different pathways and implementing various treatment regimens, those trials have met with varied degrees of success. Promising results have come from those studies intervening early on the interleukin-1 and -6 pathways. Taking lessons from such past research may inform an optimized approach to target post-AMI inflammation, tailored to spare ‘The Good’ (repair and defence) while treating ‘The Bad’ (smouldering RIR) and capturing ‘The Ugly’ (flaming early burst of excess inflammation in the acute phase). Key constituents of such a strategy may read as follows: select patients with large pro-inflammatory burden (i.e. large AMI); initiate treatment early (e.g. ≤12 h post-AMI); implement a precisely targeted anti-inflammatory agent; follow through with a tapering treatment regimen. This approach warrants testing in rigorous clinical trials.

Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of angiotensin II which disturbs peripheral blood pressure regulation and compromises left ventricular function. This study examined the relationship of circulating DPP3 (cDPP3) with cardiogenic shock (CS) and mortality in patients presenting with acute coronary syndromes (ACS). Plasma cDPP3 levels were assessed at baseline and 12–24 h after presentation in patients with ACS prospectively enrolled into the multi-centre SPUM-ACS study (n = 4787). Circulating DPP3 levels were associated with in-hospital CS when accounting for established risk factors including the ORBI risk score [per log-2 increase, hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.05–1.82, P = .021]. High cDPP3 was an independent predictor of mortality at 30 days (HR 1.87, 95% CI 1.36–2.58, P < .001) and at one year (HR 1.61, 95% CI 1.28–2.02, P < .001) after adjustment for established risk factors and the GRACE 2.0 score. Compared to values within the normal range, persistently elevated cDPP3 levels at 12–24 h were associated with 13.4-fold increased 30-day mortality risk (HR 13.42, 95% CI 4.86–37.09, P < .001) and 5.8-fold increased 1-year mortality risk (HR 5.79, 95% CI 2.70–12.42, P < .001). Results were consistent across various patient subgroups. This study identifies cDPP3 as a novel marker of CS and increased mortality in patients with ACS. Circulating DPP3 offers prognostic information beyond established risk factors and improves early risk assessment. Circulating dipeptidyl peptidase 3 (cDPP3) was identified as a novel marker of cardiogenic shock (CS) and increased mortality risk in patients with acute coronary syndromes (ACS). Upon ischaemic cell death, the intracellular aminopeptidase DPP3 is released in the circulation where it cleaves angiotensin II (ATII) and exerts negative inotropic effects on the left ventricle. Circulating DPP3 levels were measured at presentation and after 12–24 h in patients enrolled into the multi-centre prospective SPUM-ACS study. High baseline levels of cDPP3 were independently associated with in-hospital CS, mortality risk at 30 days, and mortality risk at 1 year beyond established risk factors. Patients with persistently high cDPP3 levels at 12–24 h displayed substantially increased 30-day and 1-year mortality risk, whereas normalization of initially high cDDP3 levels was associated with a decrease in mortality risk. In a subcohort of patients undergoing cardiac magnetic resonance imaging (MRI), cDPP3 trajectories were associated with infarct size at 30 days of follow-up. Circulating DPP3 provides prognostic information beyond established risk factors in patients with ACS.

Background: The heart is subject to structural and functional changes with advancing age. However, the magnitude of cardiac age-dependent transformation has not been conclusively elucidated. Methods: This retrospective cardiac magnetic resonance (CMR) study included 183 subjects with normal structural and functional ventricular values. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were obtained from the left and the right ventricle in breath-hold cine CMR. Patients were classified into four age groups (20–29, 30–49, 50–69, and ≥70 years) and cardiac measurements were compared using Pearson’s rank correlation over the four different groups. Results: With advanced age a slight but significant decrease in ESV (r=−0.41 for both ventricles, P<0.001) and EDV (r=−0.39 for left ventricle, r=−0.35 for right ventricle, P<0.001) were observed associated with a significant increase in left (r=0.28, P<0.001) and right (r=0.27, P<0.01) ventricular EF reaching a maximal increase in EF of +8.4% (P<0.001) for the left and +6.1% (P<0.01) for the right ventricle in the oldest compared to the youngest patient group. Left ventricular myocardial mass significantly decreased over the four different age groups (P<0.05). Conclusions: The aging process is associated with significant changes in left and right ventricular EF, ESV and EDV in subjects with no cardiac functional and structural abnormalities. These findings underline the importance of using age adapted values as standard of reference when evaluating CMR studies.

OBJECTIVE In observational cohorts, adiponectin is inversely associated and free fatty acids (FFAs) are directly associated with incident coronary heart disease (CHD). Adiponectin tends to be reduced and FFAs elevated in type 2 diabetes. We investigated relationships of adiponectin and FFA and major adverse cardiovascular events (MACEs) and death in patients with acute coronary syndrome (ACS) and type 2 diabetes using data from the AleCardio (Effect of Aleglitazar on Cardiovascular Outcomes After Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus) trial, which compared the PPAR-α/γ agonist aleglitazar with placebo. RESEARCH DESIGN AND METHODS Using Cox regression adjusted for demographic, laboratory, and treatment variables, we determined associations of baseline adiponectin and FFAs, or the change in adiponectin and FFAs from baseline, with MACEs (cardiovascular death, myocardial infarction, or stroke) and death. RESULTS A twofold higher baseline adiponectin (n = 6,998) was directly associated with risk of MACEs (hazard ratio [HR] 1.17 [95% CI 1.08–1.27]) and death (HR 1.53 [95% CI 1.35–1.73]). A doubling of adiponectin from baseline to month 3 (n = 6,325) was also associated with risk of death (HR 1.20 [95% CI 1.03–1.41]). Baseline FFAs (n = 7,038), but not change in FFAs from baseline (n = 6,365), were directly associated with greater risk of MACEs and death. There were no interactions with study treatment. CONCLUSIONS In contrast to prior observational data for incident CHD, adiponectin is prospectively associated with MACEs and death in patients with type 2 diabetes and ACS, and an increase in adiponectin from baseline is directly related to death. These findings raise the possibility that adiponectin has different effects in patients with type 2 diabetes and ACS than in populations without prevalent cardiovascular disease. Consistent with prior data, FFAs are directly associated with adverse outcomes.