Coronary Artery Tortuosity and Spontaneous Coronary Artery Dissection: Association With Echocardiography and Global Longitudinal Strain, Fibromuscular Dysplasia, and Outcomes.

BACKGROUND: The etiology and significance of coronary artery tortuosity (TCA) among patients with spontaneous coronary artery dissection (SCAD) are unknown. The aim of this prospective imaging cohort study was to report echocardiographic findings and evaluate whether TCA correlates with cardiac anatomy and function among patients with SCAD. Comorbidities including fibromuscular dysplasia (FMD) and outcomes were also assessed. METHODS: TCA was determined on coronary angiography performed during the diagnosis of SCAD, and cardiac structure and function were evaluated using prospective comprehensive echocardiography. RESULTS: Among 116 patients with SCAD, the mean age at echocardiography was 50.8 ± 8.8 years, a median of 10.9 months after SCAD. Sixty-two patients (53.4%) had FMD, 41 (35.3%) had histories of hypertension, and 17 (14.8%) were hypertensive during echocardiography. Most patients (n = 78 [69%]) had normal left ventricular geometry with normal median ejection fraction (61%; interquartile range, 56% to 64%) and normal global longitudinal strain (-22.2%; interquartile range, -24.0% to -19.9%). Fifteen patients (13.4%) had diastolic dysfunction that was associated with hypertension at the time of echocardiography. Patients with TCA (n = 96 [82.8%]) were older (mean age, 52.1 ± 8.0 vs 44.7 ± 9.9 years; P < .001) with a higher prevalence of FMD (59.4% vs 25%, P = .007) but a similar prevalence of hypertension (35% vs 35%, P > .99) compared with patients without TCA. Across the age range (31.5 to 66.9 years), each decade of age was associated with an approximately 0.89-unit increase in coronary tortuosity score (P < .0001). Echocardiographic parameters were not significantly different between the two groups. Median follow-up duration was 4.4 years (95% CI, 3.8 to 5.2 years). The Kaplan-Meier 3-year SCAD recurrence rate was 9.4% (95% CI, 3.7% to 14.8%). There were no deaths. CONCLUSIONS: The majority of patients with SCAD had normal or near normal echocardiographic results, including global longitudinal strain, with no differences according to TCA. However, patients with SCAD with TCA were older, with a higher prevalence of FMD.

Association of Pregnancy With Recurrence of Spontaneous Coronary Artery Dissection Among Women With Prior Coronary Artery Dissection.

Importance: Spontaneous coronary artery dissection (SCAD) is a notable cause of acute coronary syndrome in women of childbearing age. Objective: To test the hypothesis that pregnancy after SCAD is associated with recurrent SCAD. Design, Setting, and Participants: Three study designs were implemented: a case series of women with pregnancy after SCAD; a nested case-control study comparing patients with recurrent SCAD to matched controls without recurrent SCAD; and a cohort study. Women with SCAD who were of childbearing potential and enrolled into the Mayo Clinic SCAD Registry from August 30, 2011, to April 4, 2019, were included in the study. Patients with coronary dissections associated with iatrogenesis, trauma, or atherosclerosis were not enrolled. Exposures: Pregnancy after SCAD. Main Outcomes and Measures: The primary outcome was SCAD recurrence, defined as an acute coronary syndrome or cardiac arrest due to new SCAD. Other demographic measures collected included age, year of SCAD occurrence, and comorbidities. Results: The cohort included 636 women of childbearing potential. Twenty-three of those women had a total of 32 pregnancies after SCAD. The median (interquartile range) age of women with pregnancy after SCAD was 38 years (34-40 years), and 20 (87%) were White. In the nested case-control study, 92 cases of recurrent SCAD were matched to 158 controls. There was no significant difference in exposure to subsequent pregnancies in the women with recurrent SCAD as compared with matched controls (2 of 92 [2%] vs 13 of 158 [8%]; P = .06). In the overall cohort of 636 patients, recurrent SCAD was present in 122 patients with a Kaplan-Meier 5-year SCAD recurrence estimate of 14.8%. The Cox analysis showed no significant association between subsequent pregnancy and SCAD recurrence with a nonsignificant hazard ratio of 0.38 (95% CI, 0.09-1.6) when controlling for age at first SCAD, year of first SCAD, and fibromuscular dysplasia. Conclusions and Relevance: This study found that most women tolerated pregnancy and lactation after SCAD without evidence for increased risk of SCAD recurrence when compared with women with a history of SCAD who did not experience pregnancy. Although this study is reassuring and indicates complex contributors to SCAD recurrence, the results need to be interpreted prudently because of study selection bias and the small total number of women who became pregnant after SCAD. The notable hemodynamic changes that occur with pregnancy and severe presentation of pregnancy-associated SCAD are reasons for concern when considering pregnancy after SCAD.

Spontaneous Coronary Artery Dissection Associated With Pregnancy.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is the most common cause of pregnancy-associated myocardial infarction and remains poorly characterized. OBJECTIVES: This study sought to assess presentation, clinical factors, and outcomes of pregnancy-associated spontaneous coronary artery dissection (P-SCAD) compared with spontaneous coronary artery dissection not associated with pregnancy (NP-SCAD). METHODS: A Mayo Clinic registry was established in 2010 to include comprehensive retrospective and prospective SCAD data. Records were reviewed to identify women who were pregnant or ≤12 weeks postpartum at time of SCAD. Complete records were available for 323 women; 54 women met criteria for P-SCAD (4 during pregnancy) and they were compared with 269 women with NP-SCAD. RESULTS: Most events occurred within the first month postpartum (35 of 50). Compared with NP-SCAD, P-SCAD patients more frequently presented with ST-segment elevation myocardial infarction (57% vs. 36%; p = 0.009), left main or multivessel SCAD (24% vs. 5%; p < 0.0001; and 33% vs. 14%; p = 0.0027, respectively), and left ventricular function ≤35% (26% vs. 10%; p = 0.0071). Among women with imaging of other vascular territories, P-SCAD was less likely with a diagnosis of fibromuscular dysplasia and extracoronary vascular abnormalities (42% vs. 64%; p = 0.047; and 46% vs. 77%; p = 0.0032, respectively). Compared with U.S. birth data, women with P-SCAD were more often multiparous (p = 0.0167), had a history of infertility therapies (p = 0.0004), and had pre-eclampsia (p = 0.001). On long-term follow-up (median 2.3 years) recurrent SCAD occurred in 51 patients, with no difference in the Kaplan Meier 5-year recurrence rates (10% vs. 23%; p = 0.18). CONCLUSIONS: P-SCAD patients had more acute presentations and high-risk features than women with NP-SCAD did. The highest frequency of P-SCAD occurred during the first postpartum month and P-SCAD patients less often had extracoronary vascular abnormalities. Hormonal, hemodynamic variations, and yet-undefined mechanisms might be significant contributors to P-SCAD. (The "Virtual" Multicenter Spontaneous Coronary Artery Dissection [SCAD] Registry [SCAD]; NCT01429727; Genetic Investigations in Spontaneous Coronary Artery Dissection [SCAD]; NCT01427179).

Spontaneous coronary artery dissection: revascularization versus conservative therapy.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic acute coronary syndrome for which optimal management remains undefined. METHODS AND RESULTS: We performed a retrospective study of 189 patients presenting with a first SCAD episode. We evaluated outcomes according to initial management: (1) revascularization versus conservative therapy and (2) percutaneous coronary intervention (PCI) versus conservative therapy stratified by vessel flow at presentation. Demographics were similar in revascularization versus conservative (mean age, 44±9 years; women 92% both groups), but vessel occlusion was more frequent in revascularization (44/95 versus 18/94). There was 1 in-hospital death (revascularization) and 1 late death (conservative). Procedural failure rate was 53% in those managed with PCI. In the subgroup of patients presenting with preserved vessel flow, rates of PCI failure were similarly high (50%), and 6 (13%) required emergency coronary artery bypass grafting. In the conservative group, 85 of 94 (90%) had an uneventful in-hospital course, but 9 (10%) experienced early SCAD progression requiring revascularization. Kaplan-Meier estimated 5-year rates of target vessel revascularization and recurrent SCAD were no different in revascularization versus conservative therapy (30% versus 19%; P=0.06 and 23% versus 31%; P=0.7). CONCLUSIONS: PCI for SCAD is associated with high rates of technical failure even in those presenting with preserved vessel flow and does not protect against target vessel revascularization or recurrent SCAD. A strategy of conservative management with prolonged observation may be preferable.

Single nucleotide polymorphisms associated with abnormal coronary microvascular function.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most common source of genetic variation. Although microvascular pathology is associated with cardiovascular events, genetic phenotypes causing microvascular disease remain largely unknown. This study identifies sex-specific SNPs associated with coronary microvascular dysfunction. METHODS AND RESULTS: Six hundred and forty-three patients without significant obstructive coronary heart disease were enrolled, referred for cardiac catheterization, and underwent invasive coronary microcirculatory assessment. Patient data were collected from 1529 autosomal SNPs and seven X chromosome SNPs, which were selected to represent the variability from 76 candidate genes with published associations with coronary vasoreactivity, angiogenesis, inflammation, vascular calcification, atherosclerosis risk factors, female hormones, blood coagulation, or coronary heart disease. Coronary flow reserve (CFR) was assessed by an intracoronary injection of adenosine. Patients were categorized according to a CFR above or below 2.5 and were stratified by sex.After adjusting for age, sex, and BMI, this study shows that SNPs within VEGFA and CDKN2B-AS1 are associated with abnormal CFR (P<0.005). SNPs within MYH15, VEGFA, and NT5E are associated with abnormal CFR in men. No SNPs were associated with abnormal CFR in women. CONCLUSION: Genetic variations within defined regions of VEGFA and CDKN2B-AS1 genes are associated with coronary microvascular dysfunction. Furthermore, sex-specific allelic variants within MYH15, VEGFA, and NT5E are associated with an increased risk of coronary microvascular dysfunction in men.

Clinical features, management, and prognosis of spontaneous coronary artery dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an acute coronary event of uncertain origin. Clinical features and prognosis remain insufficiently characterized. METHODS AND RESULTS: A retrospective single-center cohort study identified 87 patients with angiographically confirmed SCAD. Incidence, clinical characteristics, treatment modalities, in-hospital outcomes, and long-term risk of SCAD recurrence or major adverse cardiac events were evaluated. Mean age was 42.6 years; 82% were female. Extreme exertion at SCAD onset was more frequent in men (7 of 16 versus 2 of 71; P<0.001), and postpartum status was observed in 13 of 71 women (18%). Presentation was ST-elevation myocardial infarction in 49%. Multivessel SCAD was found in 23%. Initial conservative management (31 of 87) and coronary artery bypass grafting (7 of 87) were associated with an uncomplicated in-hospital course, whereas percutaneous coronary intervention was complicated by technical failure in 15 of 43 patients (35%) and 1 death. During a median follow-up of 47 months (interquartile range, 18-106 months), SCAD recurred in 15 patients, all female. Estimated 10-year rate of major adverse cardiac events (death, heart failure, myocardial infarction, and SCAD recurrence) was 47%. Fibromuscular dysplasia of the iliac artery was identified incidentally in 8 of 16 femoral angiograms (50%) undertaken before closure device placement and in the carotid arteries of 2 others with carotid dissection. CONCLUSIONS: SCAD affects a young, predominantly female population, frequently presenting as ST-elevation myocardial infarction. Although in-hospital mortality is low regardless of initial treatment, percutaneous coronary intervention is associated with high rates of complication. Risks of SCAD recurrence and major adverse cardiac events in the long term emphasize the need for close follow-up. Fibromuscular dysplasia is a novel association and potentially causative factor.

SCAI consensus document on occupational radiation exposure to the pregnant cardiologist and technical personnel.

Concerns regarding radiation exposure and its effects during pregnancy are often quoted as an important barrier preventing many women from pursuing a career in Interventional Cardiology. Finding the true risk of radiation exposure from performing cardiac catheterisation procedures can be challenging and guidelines for pregnancy exposure have been inadequate. The Women in Innovations group of Cardiologists with endorsement of the Society for Cardiovascular Angiography and Interventions aim to provide guidance in this publication by describing the risk of radiation exposure to pregnant physicians and cardiac catheterisation personnel, to educate on appropriate radiation monitoring and to encourage mechanisms to reduce radiation exposure. Current data do not suggest a significant increased risk to the foetus of pregnant women in the cardiac catheterisation laboratory and thus do not justify precluding pregnant physicians from performing procedures in the cardiac catheterisation laboratory. However, radiation exposure amongst pregnant physicians should be properly monitored and adequate radiation safety measures are still warranted.

SCAI consensus document on occupational radiation exposure to the pregnant cardiologist and technical personnel.

Concerns regarding radiation exposure and its effects during pregnancy are often quoted as an important barrier preventing many women from pursuing a career in Interventional Cardiology. Finding the true risk of radiation exposure from performing cardiac catheterisation procedures can be challenging and guidelines for pregnancy exposure have been inadequate. The Women in Innovations group of Cardiologists with endorsement of the Society for Cardiovascular Angiography and Interventions aim to provide guidance in this publication by describing the risk of radiation exposure to pregnant physicians and cardiac catheterisation personnel, to educate on appropriate radiation monitoring and to encourage mechanisms to reduce radiation exposure. Current data do not suggest a significant increased risk to the fetus of pregnant women in the cardiac catheterisation laboratory and thus do not justify precluding pregnant physicians from performing procedures in the cardiac catheterisation laboratory. However, radiation exposure among pregnant physicians should be properly monitored and adequate radiation safety measures are still warranted.

SCAI consensus document on occupational radiation exposure to the pregnant cardiologist and technical personnel.

Concerns regarding radiation exposure and its effects during pregnancy are often quoted as an important barrier preventing many women from pursuing a career in Interventional Cardiology. Finding the true risk of radiation exposure from performing cardiac catheterization procedures can be challenging and guidelines for pregnancy exposure have been inadequate. The Women in Innovations group of Cardiologists with endorsement of the Society for Cardiovascular Angiography and Interventions aim to provide guidance in this publication by describing the risk of radiation exposure to pregnant physicians and cardiac catheterization personnel, to educate on appropriate radiation monitoring and to encourage mechanisms to reduce radiation exposure. Current data do not suggest a significant increased risk to the fetus of pregnant women in the cardiac catheterization laboratory and thus do not justify precluding pregnant physicians from performing procedures in the cardiac catheterization laboratory. However, radiation exposure among pregnant physicians should be properly monitored and adequate radiation safety measures are still warranted.

Metastatic malignant melanoma manifesting as an intracardiac mass.

INTRODUCTION: Antemortem diagnoses of intracardiac metastases are uncommon. Metastatic melanoma shows a propensity for cardiac involvement, but cardiac involvement by melanoma is rarely identified clinically due to a paucity of cardiac symptoms. METHODS: The surgical pathology files of Mayo Clinic were searched for cases of metastatic melanoma presenting or manifesting as an intracardiac mass. The lesions were evaluated pathologically for diagnoses. Clinical information was obtained by chart review. RESULTS: Seven patients, four female and three male (age 31 to 79 years), were identified. No patient had a history of metastatic melanoma. All patients presented with dyspnea and symptoms of outflow obstruction. Echocardiography or CT revealed an intracardiac mass (four atrial, three ventricular). Six cases involved the right side of the heart and one involved the left ventricle. Five of the seven patients had a history of malignant melanoma, but none had a history of metastases when they presented with cardiac symptoms. In four cases, the history of primary melanoma was remote, occurring 7, 9, 13, and 28 years prior to the discovery of their cardiac mass. One patient had no history of melanoma, and no primary melanoma was ever identified. One patient had a history of a benign melanocytic lesion biopsied 2 years before, but retrospective review showed malignant melanoma. CONCLUSIONS: Melanoma is known to have an unpredictable and prolonged course. Neoplastic involvement of the heart should be considered in patients with cardiac symptoms when a documented malignancy exists, no matter how remote.

Cardiovascular disease in older women: a challenge in diagnosis and treatment.

Cardiovascular disease is the leading cause of death in women and more heart disease is present in elderly women than men. Risk factors for heart disease affect men and women differently, with a greater impact of diabetes, hyperlipidemia and smoking in women. Diagnosis of heart disease can be more challenging in women, especially when elderly, as symptoms may be vague. Understanding the appropriate use of diagnostic testing and appropriate treatment is essential, given the high burden of disease in elderly women. This article will discuss the current guidelines for diagnosis and therapy of heart disease in women and will discuss the appropriate role of prevention strategies.

Incidence, retrieval methods, and outcomes of stent loss during percutaneous coronary intervention: a large single-center experience.

Our goal was to examine the incidence and consequences of stent loss during percutaneous coronary intervention (PCI) and the retrieval techniques used. We retrospectively reviewed 11,773 consecutive PCI cases involving stents performed at our institution between January 1994 and March 2004 to identify cases of stent loss. Stent loss occurred in 38 of 11,773 PCI procedures involving stents (0.32%; 95% CI = 0.23-0.44%). Mean age of the patients was 67 +/- 11 years and 82% were men. Stent loss occurred more frequently in lesions with calcification and/or significant proximal angulation. In three patients, the stent was crushed and covered with another stent without attempting retrieval. Stent retrieval was attempted in 35 of 38 cases and was successful in 30 (86%). The following retrieval methods were used (more than one method was used in some cases): advancing a balloon through the stent, inflating the balloon, and withdrawing the stent (45%); twirling two wires around the stent (5%); loop snare (26%); biliary forceps (12%); Cook retained fragment retriever (10%); and basket retrieval device (2%). Patients in whom stent loss occurred had a higher incidence of bleeding requiring transfusion (24% vs. 7%; P < 0.001) and more often required emergency coronary artery bypass surgery (5% vs. 0.4%; P < 0.001). No patients in whom the stent was crushed or deployed in the coronary artery had any major cardiac complication. Stent loss during PCI occurs infrequently. Lost stents can be successfully retrieved in the majority of cases using a variety of retrieval techniques, yet stent loss is associated with an increased risk of complications. Stent deployment or crushing may be a good alternative to retrieval.

Endothelin type A receptor antagonism restores myocardial perfusion response to adenosine in experimental hypercholesterolemia.

Experimental hypercholesterolemia is characterized by increased endothelin-1 (ET-1) activity and is associated with an attenuated myocardial perfusion response and an inappropriate increase in coronary microvascular permeability during episodes of increased myocardial demand. This study was designed to determine the effect of chronic selective ET type A (ET(A)) receptor antagonism on coronary vascular response to simulated cardiac stress in experimental hypercholesterolemia. Twenty-one pigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC), and HC diet plus ABT-627, a selective ET(A) receptor antagonist, (HC+ABT-627). After 12 weeks, cardiac electron beam computed tomography (EBCT) was performed before and during intravenous infusion of adenosine, and myocardial perfusion (ml/min per g) and coronary microvascular permeability index (arbitrary units) were calculated. Basal myocardial perfusion was similar in all groups (N: 0.91+/-0.10; HC: 0.95+/-0.08; HC+ABT-627: 1.03+/-0.09; P=0.64). Adenosine infusion led to a significant increase in myocardial perfusion in the N (1.32+/-0.15; P<0.001) but not in the HC (0.95+/-0.07) group. However, in the HC+ABT-627 group, adenosine also significantly increased myocardial perfusion (1.33+/-0.12; P=0.001). Basal permeability index did not differ between the groups (N: 1.56+/-0.13; HC: 1.34+/-0.19; HC+ABT-627: 1.62+/-0.10; P=0.38). Adenosine infusion significantly increased permeability index in HC pigs (2.29+/-0.22; P<0.001) but not in N (1.71+/-0.21) and HC+ABT-627 (1.82+/-0.08) pigs. We conclude that chronic selective ET(A) receptor antagonism preserves myocardial perfusion response and coronary microvascular integrity during episodes of increased myocardial demand in experimental hypercholesterolemia, indicating an important role for the endogenous endothelin system in this disorder.

Dendroaspis natriuretic peptide relaxes isolated human arteries and veins.

BACKGROUND: Dendroaspis natriuretic peptide (DNP) is the newest member of the natriuretic peptide family and is a circulating peptide in humans. The effects of DNP on the human vasculature are unknown. Since other natriuretic peptides are known to cause vasorelaxation, we determined the response to DNP on human blood vessels in vitro. We also investigated the mechanism of DNP mediated vasorelaxation. METHODS: Rings of human internal mammary artery and saphenous vein were suspended in an organ bath. The response to cumulative concentrations of DNP was obtained. Inhibiting agents were used to determine the mechanism of this vasorelaxation. RESULTS: DNP caused dose-dependent relaxation, with a greater effect on the internal mammary arteries (relaxation from 10(-7) mol/l DNP: 80.6+/-4.1%) than the saphenous veins (33.4+/-4.1%). At 10(-7) mol/l, DNP resulted in less arterial relaxation compared with atrial and C-type natriuretic peptides and similar relaxation to brain natriuretic peptide. In veins, DNP caused the greatest relaxation of the natriuretic peptides. DNP increased tissue cyclic guanosine monophosphate (cGMP) determined by radioimmunoassay by over 7-fold. Barium chloride and indomethacin attenuated DNP mediated vasorelaxation. However, glibenclamide, charydotoxin, apamin, tetraethyl-ammonium chloride and diisothiocyanato-stilbene-2,2'-disulfonic acid did not. DNP mediated vasorelaxation was mildly attenuated with removal of the endothelium. DNP immunoreactivity was identified in both arteries and veins. CONCLUSIONS: The current study demonstrates that DNP is an endogenous human natriuretic peptide that relaxes human arteries more than veins. Furthermore, DNP mediated vasorelaxation involves the inward rectifying potassium channels, prostaglandins, and cGMP. This newest member of the natriuretic peptide family may have an important physiologic role in the human vasculature.

The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions.

OBJECTIVES: We sought to determine the effect of varying degrees of renal insufficiency on death and cardiac events during and after a percutaneous coronary intervention (PCI). BACKGROUND: Patients with end-stage renal disease have a high mortality from coronary artery disease. Little is known about the impact of mild and moderate renal insufficiency on clinical outcomes after PCI. METHODS: Cardiac mortality and all-cause mortality were determined for 5,327 patients undergoing PCI from January 1, 1994, to August 31, 1999, at the Mayo Clinic, based on the estimated creatinine clearance or whether the patient was on dialysis. RESULTS: In-hospital mortality was significantly associated with renal insufficiency (p = 0.001). Even after successful PCI, one-year mortality was 1.5% when the creatinine clearance was > or =70 ml/min (n = 2,558), 3.6% when it was 50 to 69 ml/min (n = 1,458), 7.8% when it was 30 to 49 ml/min (n = 828) and 18.3% when it was < 30 ml/min (n = 141). The 18.3% mortality rate for the group with < 30 ml/min creatinine clearance was similar to the 19.9% mortality rate in patients on dialysis (n = 46). The mortality risk was largely independent of all other factors. CONCLUSIONS: Renal insufficiency is a strong predictor of death and subsequent cardiac events in a dose-dependent fashion during and after PCI. Patients with renal insufficiency have more baseline cardiovascular risk factors, but renal insufficiency is associated with an increased risk of death and other adverse cardiovascular events, independent of all other measured variables.

Nuclear factor-kappaB immunoreactivity is present in human coronary plaque and enhanced in patients with unstable angina pectoris.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a transcription factor which plays a coordinating role in inflammation and cellular proliferation and is thought to be involved in the pathogenesis of atherosclerosis. Its role in unstable coronary plaque in humans is unknown. METHODS AND RESULTS: Coronary atherectomy plaque was obtained via directional coronary atherectomy from 32 patients [16 with unstable angina pectoris (UAP) and 16 with stable angina pectoris (SAP)]. The predominant pathology in UAP consisted of richly cellular areas with atheromatous gruel or loose intimal proliferative tissue within a myxoid matrix (P<0.05 compared with SAP). By contrast, SAP plaques showed more dense fibrosis (P<0.01 compared with UAP). Sections were then stained with a monoclonal antibody to the activated p65 subunit of NF-kappaB and this staining was present in 31/32 specimens, localized to smooth muscle cells, macrophages and foam cells. Staining was then graded semiquantitatively by three independent observers. Immunostaining grades for activated NF-kappaB were significantly higher in UAP compared with SAP (2.60+/-0.1 vs. 1.98+/-0.18; P<0.01). CONCLUSIONS: NF-kappaB immunoreactivity is present in coronary atherosclerotic plaque and is increased among patients with unstable coronary syndromes. These data support a role for NF-kappaB in the pathogenesis of acute coronary syndromes in humans.