Purpose: We investigated the associations of ten previously identified high risk molecular lipid species and three ceramide ratios with the occurrence of major adverse cardiac events (MACE) during a median follow-up of 4.7 years in patients with coronary artery disease (CAD). Methods: Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris (SAP) or acute coronary syndrome (ACS). Blood was drawn prior to the index procedure and lipid species were determined. The primary endpoint was the occurrence of MACE, comprising all-cause mortality, nonfatal ACS or unplanned coronary revascularization. The secondary endpoint comprised all-cause mortality or nonfatal ACS. Results: During a median follow-up of 4.7 [IQR: 4.2- 5.6] years, 155 patients (27%) had MACE. In multivariable analyses, Cer(d18:1/16:0) concentration was associated with MACE (HR 2.32; 95% CI [1.09-4.96] per ln(pmol/mL) p= 0.030) after adjustment for cardiac risk factors, clinical presentation, statin use at baseline and admission non-HDL cholesterol level. Furthermore, after multivariable adjustment, concentrations of Cer(d18:1/16:0), Cer(d18:1/20:0), Cer(d18:1/24:1) and their ratios to Cer(d18:1/24:0) were associated with the composite endpoint death or nonfatal ACS. Conclusion: Altogether, the circulating ceramide lipids we investigated here are associated with adverse cardiac outcome during long-term follow-up independent of clinical risk factors.

Antibodies to oxidized LDL (oxLDL) may be associated with improved outcomes in cardiovascular disease. However, analysis is restricted by heterogenous study design and endpoints. Our objective was to conduct a comprehensive systematic review assessing anti-oxLDL antibodies in relation to coronary artery disease (CAD). Through a systematic literature search, we identified all studies assessing the relationship of either, IgG or IgM ox-LDL/ copper-oxLDL/ malondialdehyde-LDL, with coronary atherosclerosis or cardiovascular events in populations with, and without, established CAD. Systematic review best practices were adhered to and study quality was assessed. An initial electronic database search identified 2059 records, which was subsequently followed by abstract and full-text review. Finally, we included 18 studies with over 1811 patients with CAD. The studies varied according to populations studied, conventional cardiovascular risk factors and interventional modalities used to assess CAD. IgM anti-oxLDL antibodies were found to indicate protection from more severe CAD and possibly cardiovascular events, whilst the relationship with IgG is more complex and difficult to elucidate, with studies reporting divergent results. In this systematic review, there is evidence that suggests a relationship between anti-oxLDL antibodies and CAD, especially for the IgM subclass. However, further studies, with well-characterized prospective cohorts, will be important to clarify these associations.

Background: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. Methods: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. Results: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78–2.57) unadjusted, 1.96 (1.49–2.53) after adjustment for clinical confounders and 1.44 (1.05–1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78–3.33) and 1.52 (1.15–2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). Conclusions: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice. Registration: URL: https://www.trialregister.nl/trial/1783 ; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893 .)

Background: Fractional flow reserve (FFR)-guided treatment has been demonstrated to improve percutaneous coronary intervention (PCI) results. However, little is known on the long-term impact of low post-PCI FFR. Methods: This is a large prospective all comers study evaluating the impact of post-PCI FFR on clinical outcomes. All patients undergoing successful PCI were eligible for enrollment. FFR measurements were performed immediately after PCI when the operator considered the angiographic result acceptable and final. No further action was undertaken based on the post-PCI result. Suboptimal post-PCI FFR was defined as FFR<0.90. The primary end point was major adverse cardiac events, a composite of cardiac death, any myocardial infarction, or any revascularization at 2-year follow-up. Secondary end points were target vessel revascularizations and stent thrombosis and the separate components of the primary end point. Results: A total of 1000 patients were enrolled. Post-PCI FFR was successfully measured in 1165 vessels from 959 patients. A poststenting FFR<0.90 was observed in 440 vessels (37.8%). A total of 399 patients had at least 1 vessel with FFR<0.90 post-PCI. At 2-year follow-up, a patient level analysis showed no association between post-PCI FFR and major adverse cardiac event (hazard ratio [HR], 1.08 [95% CI, 0.73–1.60], P =0.707), cardiac death (HR, 1.55 [95% CI, 0.72–3.36], P =0.261), any myocardial infarction (HR, 1.53 [95% CI, 0.78–3.02], P =0.217). A vessel level analysis showed a higher rate of target vessel revascularization (HR, 1.91 [95% CI, 1.06–3.44], P =0.030) and a tendency toward higher rate of stent thrombosis (HR, 2.89 [95% CI, 0.88–9.48], P =0.081) with final post-PCI FFR<0.90. Conclusions: Suboptimal post-PCI FFR has only a moderate impact on major adverse cardiac event but coronary arteries with a post-PCI FFR<0.90 have a higher rate of target vessel revascularization.