Canadian Spontaneous Coronary Artery Dissection Cohort Study: 3-Year Outcomes.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI) in young to middle-aged women. OBJECTIVES: We aim to define the long-term natural history of SCAD. METHODS: We performed a multicenter, prospective, observational study of patients with nonatherosclerotic SCAD presenting acutely from 22 North American centers. We recorded baseline demographics, in-hospital characteristics, precipitating and predisposing conditions, angiographic features (adjudicated), in-hospital and 3-year major adverse cardiovascular events (MACE). Cox regression multivariable analysis was performed. RESULTS: We prospectively enrolled 750 consecutive patients with SCAD from June 2014 to June 2018. Mean age was 51.7 ± 10.5 years, 88.5% were women (55.0% postmenopausal); 31.3% presented with ST-segment elevation myocardial infarction, and 68.3% with non-ST-segment elevation myocardial infarction. Precipitating emotional stressor was reported in 50.3%, and physical stressor in 28.9%. Predisposing conditions included fibromuscular dysplasia in 42.9% (56.4% in those with complete screening), peripartum state 4.5%, and genetic disorders 1.6%. Most patients were treated conservatively (84.3%); 14.1% underwent percutaneous coronary intervention (PCI), 0.7% coronary artery bypass graft. At 3.0-year median follow-up, mortality was 0.8%, recurrent MI 9.9% (extension of previous SCAD 3.5%, de novo recurrent SCAD 2.4%, iatrogenic dissection 1.9%), with overall MACE 14.0%. Presence of genetic disorders, peripartum SCAD, and extracoronary fibromuscular dysplasia were independent predictors of 3-year MACE. Patients who underwent PCI at index hospitalization had similar postdischarge MACE compared with no PCI. At 3 years, 80.0% remained on aspirin and 73.5% on beta-blockade. CONCLUSIONS: Long-term mortality and de novo recurrent SCAD was low in our contemporary large SCAD cohort that included low revascularization rate and high use of beta-blockade and aspirin. Genetic disorders, extracoronary fibromuscular dysplasia, and peripartum SCAD were independent predictors of long-term MACE.

Canadian spontaneous coronary artery dissection cohort study: in-hospital and 30-day outcomes.

AIMS: Spontaneous coronary artery dissection (SCAD) was underdiagnosed and poorly understood for decades. It is increasingly recognized as an important cause of myocardial infarction (MI) in women. We aimed to assess the natural history of SCAD, which has not been adequately explored. METHODS AND RESULTS: We performed a multicentre, prospective, observational study of patients with non-atherosclerotic SCAD presenting acutely from 22 centres in North America. Institutional ethics approval and patient consents were obtained. We recorded baseline demographics, in-hospital characteristics, precipitating/predisposing conditions, angiographic features (assessed by core laboratory), in-hospital major adverse events (MAE), and 30-day major adverse cardiovascular events (MACE). We prospectively enrolled 750 SCAD patients from June 2014 to June 2018. Mean age was 51.8 ± 10.2 years, 88.5% were women (55.0% postmenopausal), 87.7% were Caucasian, and 33.9% had no cardiac risk factors. Emotional stress was reported in 50.3%, and physical stress in 28.9% (9.8% lifting >50 pounds). Predisposing conditions included fibromuscular dysplasia 31.1% (45.2% had no/incomplete screening), systemic inflammatory diseases 4.7%, peripartum 4.5%, and connective tissue disorders 3.6%. Most were treated conservatively (84.3%), but 14.1% underwent percutaneous coronary intervention and 0.7% coronary artery bypass surgery. In-hospital composite MAE was 8.8%; peripartum SCAD patients had higher in-hospital MAE (20.6% vs. 8.2%, P = 0.023). Overall 30-day MACE was 8.8%. Peripartum SCAD and connective tissue disease were independent predictors of 30-day MACE. CONCLUSION: Spontaneous coronary artery dissection predominantly affects women and presents with MI. Despite majority of patients being treated conservatively, survival was good. However, significant cardiovascular complications occurred within 30 days. Long-term follow-up and further investigations on management are warranted.

Soluble receptors for advanced glycation end products (sRAGE) as a predictor of restenosis following percutaneous coronary intervention.

BACKGROUND: Interaction of advanced glycation end products (AGEs) with their receptor (RAGE) increases expression of inflammatory mediators (tumor necrosis factor alpha [TNF-α] and soluble vascular cell adhesion molecule-1 [sVCAM-1]) and induces oxygen radicals that are implicated in atherosclerosis. Balloon-injury-induced atherosclerosis is associated with increased expression of AGEs and RAGE. The soluble receptor for AGE (sRAGE), which acts as a decoy for RAGE ligands (AGEs), prevents atherosclerosis in this model. HYPOTHESIS: We evaluated: 1) whether post-percutaneous coronary intervention (PCI) restenosis is associated with low pre-PCI serum sRAGE, high serum AGEs, TNF-α, and sVCAM-1, and high AGE/sRAGE ratio; 2) whether pre-PCI and post-PCI levels of these markers are similar in patients with or without restenosis; and 3) whether sRAGE and AGE/sRAGE ratio have predictive value for post-PCI restenosis. METHODS: Angiography was performed in 46 patients with non-ST-segment elevation myocardial infarction for assessment of restenosis. Serum sRAGE, AGEs, TNF-α, and sVCAM-1 were measured in these patients and 20 control subjects. RESULTS: : Nineteen of the 46 patients developed post-PCI restenosis, which was associated with lower sRAGE and higher TNF-α and sVCAM-1 levels, and higher AGE/sRAGE ratio compared with patients without restenosis. Pre-PCI and post-PCI levels of these biomarkers were similar in both groups, except in patients with restenosis, in whom the post-PCI level of sRAGE was lower and TNF-α was higher than the pre-PCI levels. The sensitivity and negative predictive value of sRAGE were 100%, and were higher than those of AGE/sRAGE ratio in identifying post-PCI restenosis. CONCLUSIONS: Both low serum sRAGE levels and high AGE/sRAGE ratio have predictive value for post-PCI restenosis.

Modulation of high sensitivity C-reactive protein by soluble receptor for advanced glycation end products.

High sensitivity C-reactive protein (hs-CRP) is synthesized mainly by hepatocytes in response to tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6). The interaction of advanced glycation end products (AGEs) with the receptor for advanced glycation end products (RAGE) increases the expression of the cytokines TNF-alpha, IL-1, and IL-6. Soluble receptor for advanced glycation end products (sRAGE) competes with RAGE for binding with AGEs. Hence, low sRAGE levels may increase interaction of AGEs with RAGE resulting in the increased production of cytokines. It is hypothesized that serum levels of sRAGE modulate serum levels of hs-CRP. The objectives are to determine if (i) serum levels of sRAGE are lower and those of TNF-alpha and hs-CRP are higher in non-ST-segment elevation myocardial infarction (NSTEMI) patients compared to control subjects; (ii) serum levels of TNF-alpha and hs-CRP are positively correlated; and (iii) sRAGE is negatively correlated with hs-CRP and TNF-alpha. The study consisted of 36 patients with NSTEMI and 30 age-matched healthy male subjects. Serum levels of sRAGE and TNF-alpha were determined by enzyme-linked immunoassay and hs-CRP was measured using near infrared immunoassay. Serum levels of sRAGE were lower, while those of TNF-alpha and hs-CRP were higher in patients with NSTEMI compared to controls. The levels of sRAGE were negatively correlated with those of TNF-alpha and hs-CRP, while TNF-alpha was positively correlated with hs-CRP in both the control subjects and NSTEMI patients. The data suggest that sRAGE modulates the synthesis of hs-CRP through TNF-alpha.

Low levels of soluble receptor for advanced glycation end products in non-ST elevation myocardial infarction patients.

BACKGROUND: Interaction of the receptors for advanced glycation end products (RAGEs) with advanced glycation end products (AGEs) results in expression of inflammatory mediators (tumor necrosis factor-alpha [TNF-α] and soluble vascular cell adhesion molecule-1 [sVCAM-1]), activation of nuclear factor-kappa B and induction of oxidative stress - all of which have been implicated in atherosclerosis. Soluble RAGE (sRAGE) acts as a decoy for the RAGE ligand and is protective against atherosclerosis. OBJECTIVES: To determine whether levels of serum sRAGE are lower, and whether levels of serum AGEs, TNF-α and sVCAM-1 are higher in non-ST elevation myocardial infarction (NSTEMI) patients than in healthy control subjects; and whether sRAGE or the ratio of AGEs to sRAGE (AGEs/sRAGE) is a predictor/biomarker of NSTEMI. METHODS: Serum levels of sRAGE, AGEs, TNF-α and sVCAM-1 were measured in 46 men with NSTEMI and 28 age- and sex-matched control subjects. Angiography was performed in the NSTEMI patients. RESULTS: sRAGE levels were lower, and levels of AGEs, TNF-α, sVCAM-1 and AGEs/sRAGE were higher in NSTEMI patients than in control subjects. sRAGE levels were negatively correlated with the number of diseased coronary vessels, serum AGEs, AGEs/sRAGE, TNF-α and sVCAM-1. The sensitivity of the AGEs/sRAGE test is greater than that of the sRAGE test, while the specificity and predictive values of the sRAGE test are greater than those of the AGEs/sRAGE test for identifying NSTEMI patients. CONCLUSIONS: Serum levels of sRAGE were low in NSTEMI patients, and were negatively correlated with extent of lesion, inflammatory mediators, AGEs and AGEs/sRAGE. Both sRAGE and AGEs/sRAGE may serve as biomarkers/predictors for identifying NSTEMI patients.