Resting Pd/Pa correlates with fractional flow reserve but not angiographic severity in calcified coronary arteries.

OBJECTIVE: Study the effect of coronary artery calcium (CAC) on resting coronary physiological indices. BACKGROUND: Prior studies found no correlation between angiographic stenosis and fractional flow reserve (FFR) in heavily calcified arteries. METHODS: Two hundred consecutive patients undergoing whole-cycle resting Pd/Pa and FFR evaluation of a single lesion of intermediate severity (40-80%) had CAC quantified based upon radiopacities at the site of the stenosis, where 0 = none or mild calcium, 1 = moderate calcium, and 2 = severe calcium. RESULTS: Mean age was 61 ± 11 years and 34% were female. The mean degree of stenosis, FFR, and resting Pd/Pa were 60 ± 12%, 0.83 ± 0.08, and 0.93 ± 0.05, respectively. Resting Pd/Pa correlated with degree of angiographic diameter stenosis (DS) as determined by quantitative coronary angiography (QCA) or visual estimation in arteries with calcium score of 0 or 1, but there was no correlation in severely calcified arteries. The diagnostic accuracy of DS ≥70% by QCA to predict hemodynamic significance was 68% with calcium scores of 0/1, but only 43% with calcium score = 2. Resting Pd/Pa was highly correlated with FFR irrespective of the degree of CAC (R2 = 0.68, p < .001) and the sensitivity of resting Pd/Pa ≤0.91 for predicting an FFR ≤0.80 was 0.67 in arteries with calcium scores of 0 or 1 and 0.69 in arteries with a calcium score of 2. CONCLUSIONS: There was no correlation between angiographic stenosis and either resting Pd/Pa or FFR in heavily calcified coronary artery lesions.

Ability of a novel shock index that incorporates invasive hemodynamics to predict mortality in patients with ST-elevation myocardial infarction.

OBJECTIVE: To determine whether the use of invasively measured hemodynamics improves the prognostic ability of a shock index (SI). BACKGROUND: SI such as Admission-SI, Age-SI, Modified SI (MSI), and Age-MSI predict short-term mortality in ST-elevation myocardial infarction (STEMI). METHODS: Single-center study of 510 patients who underwent primary percutaneous coronary intervention. STEMI SI was defined as age × heart rate (HR) divided by coronary perfusion pressure (CPP). RESULTS: The mean age was 62 ± 14 years, 66% were males with hypertension (69%), tobacco use (38%), diabetes (28%) and chronic kidney disease (6%). The mean HR, systolic blood pressure (SBP), and CPP were 81 ± 18 bpm, 124 ± 28 mmHg, and 52.8 ± 16.3 mmHg, respectively. Patients with STEMI SI ≥182 (n = 51) were more likely to experience a cardiac arrest in the catheterization laboratory (9.8% vs. 2.0%; p = .001), require mechanical circulatory support (47.1% vs. 8.5%; p < .0001) and be treated with vasopressors (56.9% vs. 10.7%; p < .0001) compared to STEMI SI < 182 (n = 459). After multivariate adjustment, patients with STEMI SI ≥182 were 10, 10.1 and 4.8 times more likely to die during hospitalization, at 30 days and at 5 years, respectively. The C statistic of STEMI SI was 0.870, similar to GRACE score (AUC = 0.902; p = .29) and TIMI STEMI score (AUC = 0.895; p = .36). CONCLUSION: STEMI SI is an easy to calculate risk score that identifies STEMI patients at high risk of in-hospital death.

Twenty Year Trends and Sex Differences in Young Adults Hospitalized With Acute Myocardial Infarction.

BACKGROUND: Sex differences are known to exist in the management of older patients presenting with acute myocardial infarction (AMI). Few studies have examined the incidence and risk factors of AMI among young patients, or whether clinical management differs by sex. METHODS: The Atherosclerosis Risk in Communities (ARIC) Surveillance study conducts hospital surveillance of AMI in 4 US communities (MD, MN, MS, and NC). AMI was classified by physician review, using a validated algorithm. Medications and procedures were abstracted from the medical record. Our study population was limited to young patients aged 35 to 54 years. RESULTS: From 1995 to 2014, 28 732 weighted hospitalizations for AMI were sampled among patients aged 35 to 74 years. Of these, 8737 (30%) were young. The annual incidence of AMI hospitalizations increased for young women but decreased for young men. The overall proportion of AMI admissions attributable to young patients steadily increased, from 27% in 1995 to 1999 to 32% in 2010 to 2014 ( P for trend=0.002), with the largest increase observed in young women. History of hypertension (59% to 73%, P for trend<0.0001) and diabetes mellitus (25% to 35%, P for trend<0.0001) also increased among young AMI patients. Compared to young men, young women presenting with AMI were more often black and had a greater comorbidity burden. In adjusted analyses, young women had a lower probability of receiving lipid-lowering therapies (relative risk [RR]=0.87; 95% confidence interval [CI], 0.80-0.94), nonaspirin antiplatelets (RR=0.83; 95% CI, 0.75-0.91), beta blockers (RR=0.96; 95% CI, 0.91-0.99), coronary angiography (RR=0.93; 95% CI, 0.86-0.99) and coronary revascularization (RR = 0.79; 95% CI, 0.71-0.87). However, 1-year all-cause mortality was comparable for women versus men (HR=1.10; 95% CI, 0.83-1.45). CONCLUSIONS: The proportion of AMI hospitalizations attributable to young patients increased from 1995 to 2014 and was especially pronounced among women. History of hypertension and diabetes among young patients admitted with AMI increased over time as well. Compared with young men, young women presenting with AMI had a lower likelihood of receiving guideline-based AMI therapies. A better understanding of factors underlying these changes is needed to improve care of young patients with AMI.

Frequency and clinical outcomes of CYP2C19 genotype-guided escalation and de-escalation of antiplatelet therapy in a real-world clinical setting.

PURPOSE: To evaluate the frequency and clinical impact of switches in antiplatelet therapy following implementation of CYP2C19 genotyping after percutaneous coronary intervention (PCI). METHODS: The frequency of escalation (clopidogrel switched to prasugrel/ticagrelor) and de-escalation (prasugrel/ticagrelor switched to clopidogrel) was evaluated in 1063 PCI patients who underwent CYP2C19 genotyping. Risk of major adverse cardiovascular or cerebrovascular (MACCE) and bleeding events over one year was evaluated. RESULTS: Antiplatelet therapy switches were common (19%), with escalation (101/115: 88%) and de-escalation (77/84: 92%) occurring predominantly in patients with and without a CYP2C19 nonfunctional allele, respectively. Nonfunctional allele carriers initiated and continued on clopidogrel had a significantly higher risk of experiencing either a MACCE or bleeding event compared with those escalated to prasugrel/ticagrelor (52 vs. 19 events/100 patient-years; adjusted hazard ratio [HR] 2.89 [1.44-6.13], p = 0.003). Patients without a nonfunctional allele de-escalated to clopidogrel had no difference in risk compared with those initiated and continued on prasugrel/ticagrelor (21 vs. 19 events/100 patient-years; adjusted HR 1.13 [0.51-2.34], p = 0.751). CONCLUSION: CYP2C19-guided escalation and de-escalation is common in a real-world setting. Continuation of clopidogrel in nonfunctional allele carriers is associated with adverse outcomes. De-escalation to clopidogrel in patients without a nonfunctional allele appears safe and warrants prospective study.

Clinical Utility of CYP2C19 Genotyping to Guide Antiplatelet Therapy in Patients With an Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention.

Current guidelines recommend dual antiplatelet therapy-a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin-for patients undergoing percutaneous coronary intervention. Although clopidogrel is the most commonly prescribed P2Y12 inhibitor, it is associated with an increased risk of major adverse cardiovascular events in patients carrying loss-of-function CYP2C19 alleles. In contrast, CYP2C19 genotype does not impact clinical response to prasugrel or ticagrelor. Nevertheless, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial because of the lack of large randomized controlled trials evaluating this strategy. Emerging results from registry studies and small clinical trials of CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention offer new insight and contribute to a growing evidence base that supports the clinical utility of a genotyping strategy to personalize antiplatelet therapy selection.

Clinical Evidence Supports a Protective Role for CXCL5 in Coronary Artery Disease.

Our goal was to measure the association of CXCL5 and molecular phenotypes associated with coronary atherosclerosis severity in patients at least 65 years old. CXCL5 is classically defined as a proinflammatory chemokine, but its role in chronic inflammatory diseases, such as coronary atherosclerosis, is not well defined. We enrolled individuals who were at least 65 years old and undergoing diagnostic cardiac catheterization. Coronary artery disease (CAD) severity was quantified in each subject via coronary angiography by calculating a CAD score. Circulating CXCL5 levels were measured from plasma, and both DNA genotyping and mRNA expression levels in peripheral blood mononuclear cells were quantified via microarray gene chips. We observed a negative association of CXCL5 levels with CAD at an odds ratio (OR) of 0.46 (95% CI, 0.27-0.75). Controlling for covariates, including sex, statin use, hypertension, hyperlipidemia, obesity, self-reported race, smoking, and diabetes, the OR was not significantly affected [OR, 0.54 (95% CI, 0.31-0.96)], consistent with a protective role for CXCL5 in coronary atherosclerosis. We also identified 18 genomic regions with expression quantitative trait loci of genes correlated with both CAD severity and circulating CXCL5 levels. Our clinical findings are consistent with the emerging link between chemokines and atherosclerosis and suggest new therapeutic targets for CAD.

Causes and hemodynamic findings in chronic severe pulmonary regurgitation.

Severe pulmonary regurgitation (PR) most commonly occurs as a sequelae of treatment of pulmonic stenosis or Tetralogy of Fallot with fewer cases of primary pulmonic valvular regurgitation. The amount of PR is influenced by valvular integrity, right ventricular (RV) size, and RV diastolic pressures. In chronic severe PR, the RV remodels to accommodate the regurgitant flow and RV stroke volume increases to maintain effective forward blood flow. Hemodynamic changes include a widened pulmonary artery (PA) pulse pressure and low PA diastolic pressures. As the amount of regurgitation increases, RV end diastolic pressure becomes elevated and systemic cardiac output is reduced, especially with exercise. "Ventricularization" of the PA pressure tracing, in which the contour of the PA pressure is similar to the contour of the RV pressure, is a specific but not sensitive finding in severe PR. © 2015 Wiley Periodicals, Inc.

Correlation of infarct size with invasive hemodynamics in patients with ST-elevation myocardial infarction.

OBJECTIVES: To identify invasive hemodynamic parameters that correlate with infarction size in patients with ST-elevation myocardial infarction (STEMI). BACKGROUND: Invasive hemodynamics obtained during primary percutaneous coronary intervention (PPCI) are predictive of mortality in STEMI, but which parameters correlate best with the size of the infarction are unknown. METHODS: This is a single-center study of 405 adult patients with STEMI who had left ventricular end-diastolic pressure (LVEDP) measured during PPCI. Size of infarction was estimated by peak troponin I level and ejection fraction (LVEF) determined by echocardiography. RESULTS: The average (±SD) age was 61 ± 14 years, TIMI STEMI risk score was 3.5 ± 2.7 and Grace score was 157 ± 42. Hemodynamic parameters that correlated best with EF were LVEDP (r = -0.40), PP (r = 0.24), and SBP/LVEDP ratio (r = 0.22) and with peak troponin were SBP/LVEDP ratio (r = -0.41), LVEDP (r = 0.31), and PP (r = -0.29). SBP/LVEDP (AUC = 0.76) and SBP (AUC = 0.77) had a stronger association with in-hospital mortality than did LVEDP (AUC = 0.66) or PP (AUC = 0.64). Door-to-balloon time did not affect the correlations between hemodynamic parameters and infarct size. CONCLUSIONS: In this sample of 405 patients undergoing PPCI, SBP/LVEDP ratio had the strongest correlation with peak troponin levels and LVEDP with EF, whereas SBP/LVEDP and SBP had a strong association with in-hospital mortality. These results suggest that measurement of LVEDP as well as SBP may help risk stratify patients during PPCI.

Urinary 11-dehydro-thromboxane B2 levels are associated with vascular inflammation and prognosis in atherosclerotic cardiovascular disease.

Cyclooxygenase-derived thromboxane (TxA2) and prostacyclin (PGI2) regulate atherogenesis in preclinical models. However, the relationship between TxA2 and PGI2 biosynthesis, vascular inflammation, and atherosclerotic cardiovascular disease (ASCVD) progression in humans remains unclear. The association between stable urine metabolites of thromboxane (TxA2-M) and prostacyclin (PGI2-M), circulating levels of cellular adhesion molecules (CAMs: E-selectin, P-selectin), chemokines and C-reactive protein, and the incidence of major adverse cardiovascular events (MACE) were evaluated in 120 patients with stable ASCVD on aspirin therapy. Urinary TxA2-M levels were significantly correlated with circulating P-selectin (r=0.319, p<0.001) and E-selectin (r=0.245, p=0.007) levels, and associated with higher risk of MACE (p=0.043). In contrast, PGI2-M levels were not significantly associated with CAM levels or MACE. These results provide insight into the contribution of TxA2 biosynthesis to ASCVD progression in humans, and suggest that patients with elevated TxA2-M levels may be predisposed to advanced platelet and endothelial activation and higher risk of adverse cardiovascular outcomes.

Ultrafine particulate matter exposure impairs vasorelaxant response in superoxide dismutase 2-deficient murine aortic rings.

Studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism underlying observed adverse vascular effects. Advanced age is one factor known to decrease antioxidant defenses and confer susceptibility to the detrimental vascular effects seen following PM exposure. The present study was designed to investigate the vasomotor responses following ultrafine PM exposure in wild type (WT) and superoxide dismutase 2-deficient (SOD2+/-) mice that possess decreased antioxidant defense. Thoracic aortic rings isolated from young and aged WT and SOD2+/- mice were exposed to ultrafine PM in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with rising amounts of nitroglycerin (NTG). Data demonstrated that ultrafine PM decreased the relaxation response in both young WT and young SOD2+/- mouse aortas, and relaxation was significantly reduced in young SOD2+/- compared to WT mice. Ultrafine PM significantly diminished the NTG-induced relaxation response in aged compared to young mouse aortas. After ultrafine PM exposure, the relaxation response did not differ markedly between aged WT and aged SOD2+/- mice. Data demonstrated that the greater vascular effect in aortic rings in aged mice ex vivo after ultrafine PM exposure may be attributed to ultrafine PM-induced oxidative stress and loss of antioxidant defenses in aged vascular tissue. Consistent with this conclusion is the attenuation of NTG-induced relaxation response in young SOD2+/- mice. ABBREVIATIONS: H2O2: hydrogen peroxide; NTG: nitroglycerin; PAH: polycyclic aromatic hydrocarbons; PE: l-phenylephrine; PM: particulate matter; ROS: reactive oxygen species; SOD2: superoxide dismutase 2 deficient; WT: wild type.

Angiographic severity does not correlate with fractional flow reserve in heavily calcified coronary arteries.

OBJECTIVES: To determine the relationship between severity of stenosis and hemodynamic significance in calcified coronary arteries. BACKGROUND: Severity of stenosis is widely used to determine the need for revascularization but the effect of lesion calcification on hemodynamic significance is not well understood. METHODS: Two hundred consecutive patients undergoing fractional flow reserve (FFR) testing of an intermediate coronary lesion with a pressure wire and intravenous infusion of adenosine were studied. Coronary calcium was quantified based upon radiopacities at the site of the stenosis on cineangiography using the method of Mintz et al. (0 = none or mild calcium, 1 = moderate calcium, 2 = severe calcium). RESULTS: Mean age was 61 ± 11 years, 66% were males, 87.5% had hypertension, 44.5% had diabetes, and 20.5% were current smokers. The mean coronary stenosis by quantitative coronary angiography was 60 ± 12% and the mean FFR was 0.83 ± 0.08. There were 109, 45, and 46 patients classified as Calcium Score of 0, 1, or 2, respectively. Compared to those with no/mild or moderate calcification, patients with severe coronary calcium were older and more likely to have chronic kidney disease and pulmonary disease. The correlation between angiographic severity and FFR decreased as lesion calcification increased [calcium score = 0 (R2 = 0.25, P < 0.005); calcium score = 1 (R2 = 0.11, P < 0.005); calcium score = 2 (R2 = 0.02, P = 0.35)]. CONCLUSIONS: In patients with heavily calcified coronary lesions, there was no association between angiographic stenosis and hemodynamic significance and FFR is needed to determine hemodynamic significance of intermediate lesions. © 2016 Wiley Periodicals, Inc.

Ratio of systolic blood pressure to left ventricular end-diastolic pressure at the time of primary percutaneous coronary intervention predicts in-hospital mortality in patients with ST-elevation myocardial infarction.

OBJECTIVE: To determine the ability of simple hemodynamic parameters obtained at the time of cardiac catheterization to predict in-hospital mortality following ST-elevation myocardial infarction (STEMI). BACKGROUND: Hemodynamic parameters measured at the time of primary percutaneous coronary intervention (PPCI) could potentially identify high-risk patients who would benefit from aggressive hemodynamic support in the Cardiac Catheterization laboratory. METHODS: This is a retrospective single-center study of 219 consecutive patients with STEMI. Left ventricular end-diastolic pressure (LVEDP), systolic blood pressure (SBP), and aortic diastolic blood pressure were obtained after successful revascularization. The prognostic ability of LVEDP, pulse pressure, and SBP/LVEDP ratio were compared to major mortality risk scores. RESULTS: Patients had a mean age of 60 ±14 years, were predominantly white (73%), male (64%), with anterior wall infarcts in 39%. Comorbidities included diabetes mellitus (27%), heart failure (9%), and chronic kidney disease (7%). In-hospital mortality was 9%. Patients with SBP/LVEDP ≤ 4 had increased risk of in-hospital death (32% vs. 5.3%, P < 0.0001), intra-aortic balloon pump (IABP) usage (51.6% vs. 9.6%, P < 0.0001) and combined endpoint of death or IABP usage (58.1% vs. 13.3%, P < 0.0001) compared to patients with SBP/LVEDP > 4. The area under curve (AUC) for SBP/LVEDP ratio for in-hospital mortality (0.69) was more predictive than LVEDP (0.61, P = 0.04) or pulse pressure (0.55, P = 0.02) but similar to Shock Index (ratio of heart rate to SBP) and Modified Shock Index (ratio of HR to mean arterial pressure). CONCLUSION: An SBP/LVEDP ratio ≤ 4 identified a group of STEMI patients at high risk of in-hospital death. © 2017 Wiley Periodicals, Inc.

Cytochrome P450-derived epoxyeicosatrienoic acids and coronary artery disease in humans: a targeted metabolomics study.

Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) exhibit potent cardiovascular protective effects in preclinical models, and promoting the effects of EETs has emerged as a potential therapeutic strategy for coronary artery disease (CAD). The relationship between circulating EET levels and CAD extent in humans, however, remains unknown. A panel of free (unesterified) plasma eicosanoid metabolites was quantified in 162 patients referred for coronary angiography, and associations with extent of CAD [no apparent CAD (N = 39), nonobstructive CAD (N = 51), and obstructive CAD (N = 72)] were evaluated. A significant relationship between free EET levels and CAD extent was observed (P = 0.003) such that the presence of obstructive CAD was associated with lower circulating EET levels. This relationship was confirmed in multiple regression analysis where CAD extent was inversely and significantly associated with EET levels (P = 0.013), and with a biomarker of EET biosynthesis (P < 0.001), independent of clinical and demographic factors. Furthermore, quantitative enrichment analysis revealed that these associations were the most pronounced compared with other eicosanoid metabolism pathways. Collectively, these findings suggest that the presence of obstructive CAD is associated with lower EET metabolite levels secondary to suppressed EET biosynthesis. Novel strategies that promote the effects of EETs may have therapeutic promise for patients with obstructive CAD.

Factors Associated With Ineligibility for PCI Differ Between Inpatient and Outpatient ST-Elevation Myocardial Infarction.

OBJECTIVES: Without early revascularization, both inpatient and outpatient STEMIs have poor outcomes. Reasons for denying PCI for STEMI, however, remain uncertain. This single-center retrospective cohort study compares factors and outcomes associated with ineligibility for PCI between inpatients and outpatients following ST-elevation myocardial infarction (STEMI). METHODS: A total of 1,759 STEMI patients between June 2009 and January 2015 were assessed. Individual medical records were reviewed to obtain reasons for PCI ineligibility for STEMI patients who did not receive reperfusion therapy. RESULTS: Compared to outpatients with STEMI (n = 1,688), inpatients (n = 71) were less likely to receive coronary angiography (60.6% vs 95.9%; P < 0.001) or PCI (50.7% vs 80.9%; P < 0.001), with longer ECG/door to first device activation times (97 [78, 131] vs 63 [49, 78] minutes; P < 0.001). When coronary angiography was performed, however, similar rates of PCI and procedural success were seen in both groups. Principal contraindication for PCI was risk of bleeding within the inpatient population and complex coronary artery disease within the outpatient population. Total in-hospital mortality was higher in inpatient STEMIs compared to outpatients (42.2% vs 10.0%; P < 0.001), but lower for patients eligible for PCI in both groups. CONCLUSIONS: Reasons for PCI ineligibility differ between inpatient and outpatient STEMIs. Inpatients have increased risks of bleeding, lower coronary angiography and PCI use, and higher in-hospital mortality. Especially for inpatients, specific PCI STEMI protocols that anticipate and overcome types of ineligibility and delay for cardiac catheterization may improve outcomes.

Association of inpatient vs outpatient onset of ST-elevation myocardial infarction with treatment and clinical outcomes.

IMPORTANCE: Reperfusion times for ST-elevation myocardial infarction (STEMI) occurring in outpatients have improved significantly, but quality improvement efforts have largely ignored STEMI occurring in hospitalized patients (inpatient-onset STEMI). OBJECTIVE: To define the incidence and variables associated with treatment and outcomes of patients who develop STEMI during hospitalization for conditions other than acute coronary syndromes (ACS). DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational analysis of STEMIs occurring between 2008 and 2011 as identified in the California State Inpatient Database. EXPOSURES: STEMIs were classified as inpatient onset or outpatient onset based on present-on-admission codes. Patients who had a STEMI after being hospitalized for ACS were excluded from the analysis. MAIN OUTCOMES AND MEASURES: Regression models were used to evaluate associations among location of onset of STEMI, resource utilization, and outcomes. Adjustments were made for patient age, sex, comorbidities, and hospital characteristics. The analysis allowed for the location of inpatient STEMI to have a multiplicative rather than an additive effect for resource utilization since these measures were highly skewed. RESULTS: A total of 62,021 STEMIs were identified in 303 hospitals, of which 3068 (4.9%) occurred in patients hospitalized for non-ACS indications. Patients with inpatient-onset STEMI were older (mean, 71.5 [SD, 13.5] years vs 64.9 [SD, 14.1] years; P < .001) and more frequently female (47.4% vs 32%; P < .001) than those with outpatient-onset STEMI. Patients with inpatient-onset STEMI had higher in-hospital mortality (33.6% vs 9.2%; adjusted odds ratio (AOR), 3.05; 95% CI, 2.76-3.38; P < .001), were less likely to be discharged home (33.7% vs 69.4%; AOR, 0.38; 95% CI, 0.34-0.42; P < .001), and were less likely to undergo cardiac catheterization (33.8% vs 77.8%; AOR, 0.19; 95% CI, 0.16-0.21; P < .001) or percutaneous coronary intervention (21.6% vs 65%; AOR, 0.23; 95% CI, 0.21-0.26; P < .001). Length of stay and inpatient charges were higher for inpatient-onset STEMI (mean length of stay, 13.4 days [95% CI, 12.8-14.0 days] vs 4.7 days [95% CI, 4.6-4.8 days]; adjusted multiplicative effect, 2.51; 95% CI, 2.35-2.69; P < .001; mean inpatient charges, $245,000 [95% CI, $235,300-$254,800] vs $129,000 [95% CI, $127,900-$130,100]; adjusted multiplicative effect, 2.09; 95% CI, 1.93-2.28; P < .001). CONCLUSIONS AND RELEVANCE: Patients who had a STEMI while hospitalized for a non-ACS condition, compared with those with onset of STEMI as an outpatient, were less likely to undergo invasive testing or intervention and had a higher in-hospital mortality rate.

Differential responses to thrombospondin-1 and PDGF-BB in smooth muscle cells from atherosclerotic coronary arteries and internal thoracic arteries.

Atherosclerosis is rare in internal thoracic arteries (ITA) even in patients with severe atherosclerotic coronary artery (ACA) disease. To explore cellular differences, ITA SMC from 3 distinct donors and ACA SMC from 3 distinct donors were grown to sub-confluence and growth arrested for 48 h. Proliferation and thrombospondin-1 (TSP1) production were determined using standard techniques. ITA SMC were larger, grew more slowly and survived more passages than ACA SMC. ACA SMC had a more pronounced proliferative response to 10% serum than ITA SMC. Both ACA SMC and ITA SMC proliferated in response to exogenous TSP1 (12.5 µg/ml and 25 µg/ml) and platelet derived growth factor-BB (PDGF-BB; 20 ng/ml) but TSP1- and PDGF-BB-induced proliferation were partially inhibited by anti-TSP1 antibody A4.1, microRNA-21(miR-21)-3p inhibitors and miR-21-5p inhibitors in each of the 3 ACA SMC lines, but not in any of the ITA SMC lines. PDGF-BB stimulated TSP1 production in ACA SMC but not in ITA SMC but there was no increase in TSP1 levels in conditioned media in either SMC type. In summary, there are significant differences in morphology, proliferative capacity and in responses to TSP1 and PDGF-BB in SMC derived from ITA compared to SMC derived from ACA.