Prognostic performance of the IABP-SHOCK II Risk Score among cardiogenic shock subtypes in the critical care cardiology trials network registry.

BACKGROUND: Risk stratification has potential to guide triage and decision-making in cardiogenic shock (CS). We assessed the prognostic performance of the IABP-SHOCK II score, derived in Europe for acute myocardial infarct-related CS (AMI-CS), in a contemporary North American cohort, including different CS phenotypes. METHODS: The critical care cardiology trials network (CCCTN) coordinated by the TIMI study group is a multicenter network of cardiac intensive care units (CICU). Participating centers annually contribute ≥2 months of consecutive medical CICU admissions. The IABP-SHOCK II risk score includes age > 73 years, prior stroke, admission glucose > 191 mg/dl, creatinine > 1.5 mg/dl, lactate > 5 mmol/l, and post-PCI TIMI flow grade < 3. We assessed the risk score across various CS etiologies. RESULTS: Of 17,852 medical CICU admissions 5,340 patients across 35 sites were admitted with CS. In patients with AMI-CS (n = 912), the IABP-SHOCK II score predicted a >3-fold gradient in in-hospital mortality (low risk = 26.5%, intermediate risk = 52.2%, high risk = 77.5%, P < .0001; c-statistic = 0.67; Hosmer-Lemeshow P = .79). The score showed a similar gradient of in-hospital mortality in patients with non-AMI-related CS (n = 2,517, P < .0001) and mixed shock (n = 923, P < .001), as well as in left ventricular (<0.0001), right ventricular (P = .0163) or biventricular (<0.0001) CS. The correlation between the IABP-SHOCK II score and SOFA was moderate (r2 = 0.17) and the IABP-SHOCK II score revealed a significant risk gradient within each SCAI stage. CONCLUSIONS: In an unselected international multicenter registry of patients admitted with CS, the IABP- SHOCK II score only moderately predicted in-hospital mortality in a broad population of CS regardless of etiology or irrespective of right, left, or bi-ventricular involvement.

Initial electrocardiogram as determinant of hospital course in ST elevation myocardial infarction.

BACKGROUND: A proportion of patients with ST elevation myocardial infarction (STEMI) have an initial electrocardiogram (ECG) that is nondiagnostic and are definitively diagnosed on a subsequent ECG. Our aim was to assess whether patients with a nondiagnostic initial ECG are different than those with a diagnostic initial ECG. METHODS: We collected demographic, ECG, medication, angiographic, and in-hospital clinical outcome data in consecutive patients undergoing primary percutaneous coronary intervention for STEMI at our institution from June 2009 to June 2013. RESULTS: A total of 334 patients were included, 285 (85%) diagnosed on the initial ECG and 49 (15%) on a subsequent ECG. Patients with a nondiagnostic initial ECG had more comorbidities including prior congestive heart failure (14% vs. 3%, p < .001), coronary artery disease (47% vs. 24%, p = .001), diabetes (37% vs. 16%, p = .001), and hyperlipidemia (55% vs. 40%, p = .048); higher rates of chronic medication use including aspirin (47% vs. 27%, p = .005), beta-blocker (47% vs. 22%, p < .001), and statins (53% vs. 28%, p = .001); longer door-to-balloon times (106 min vs. 45 min, p < .001); lower peak troponin levels (25 ng/ml vs. 50 ng/ml, p = .004), longer diagnostic ECG to balloon times (84 min vs. 75 min, p = .006); and higher rates of a patent infarct-related artery on baseline angiography (41% vs. 24%, p = .018) which remained significant in a multivariable logistic regression model. CONCLUSIONS: Approximately one in seven STEMI patients had an initial ECG that was nondiagnostic for STEMI. These patients had more comorbidities, higher rates of medication use, and received delayed intervention (even after the diagnosis was definitive).

The presence of angiographic collaterals in non-ST elevation myocardial infarction is a predictor of long-term clinical outcomes.

OBJECTIVES: To determine whether the presence of angiographic coronary collaterals is a predictor of long-term clinical outcomes in patients with non-ST elevation myocardial infarction (NSTEMI). BACKGROUND: The presence of coronary collaterals on angiography provides prognostic information in patients with STEMI, but it is unknown whether they provide prognostic information in patients with NSTEMI. METHODS: This was a prospective cohort study of 931 consecutive patients undergoing coronary angiography of which 269 (29%) had a NSTEMI. Baseline characteristics, angiographic details, and long-term clinical outcomes including death, recurrent MI, coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), stroke, and congestive heart failure (CHF) were collected. Each clinical outcome as well as the combined endpoint of death, recurrent MI, CABG, PCI stroke and CHF was compared in subjects with and without collaterals. RESULTS: At one year, individuals with collaterals had significantly increased rates of the combined endpoint compared with those without (25% vs. 16%, P = 0.0001). On multivariate analysis, the presence of collaterals was a strong predictor of the combined endpoint of death, recurrent MI, CABG, PCI, stroke and CHF (HR 1.95, CI 95% 1.08-3.52; P = 0.027). Similarly, in the subset of 115 patients (43%) in whom the culprit artery was identified, the presence of collaterals was a strong negative predictor (HR 3.71, CI 1.31-10.57, P = 0.014), driven by a 13-fold increase in subsequent CABG. CONCLUSIONS: In patients with NSTEMI the presence of angiographic coronary collaterals is a predictor of long-term clinical outcomes primarily driven by increased rates of surgical revascularization.

Prevalence of obstructive coronary artery disease in patients undergoing lung transplantation: case series and review of the literature.

BACKGROUND: Coronary angiography is commonly performed prior to lung transplantation, but its utility is unproven. METHODS: We conducted a single-center retrospective analysis of consecutive patients referred for coronary angiography as part of a pre-operative evaluation for lung transplantation and reviewed the literature for prior series. RESULTS: A total of 89 patients, 48 men and 41 women were included. Obstructive (≥70% stenosis) CAD was present in 9 (10%), non-obstructive (<70% stenosis) CAD in 24 (27%), and no angiographic evidence of CAD in 56 (63%) patients. We found 13 previously published series in the literature, in which a total of 1998 patients underwent coronary angiography pre-lung transplant. Together with our 89 patients, obstructive CAD was found in 11%. CONCLUSIONS: In conclusion, given the low prevalence of obstructive CAD in patients referred for lung transplantation, the inherent risk of angiography, and unproven benefit of detection of obstructive CAD, the utility of routine coronary angiography in this population requires validation in prospective studies.

The association of angiographic collaterals with long-term clinical outcomes in patients with chronic stable angina.

OBJECTIVES: To determine the impact of coronary collaterals in stable angina. BACKGROUND: Whether spontaneously visible coronary collaterals are associated with long-term clinical outcomes in stable angina remains unclear. METHODS: We prospectively enrolled patients with stable angina referred for coronary angiography and followed them clinically for 1 year. RESULTS: A total of 1,134 consecutive patients were enrolled, and of these, 550 had at least single-vessel coronary artery disease (CAD) and were included. Patients with collaterals had more congestive heart failure (16% vs. 9%, P = 0.023), peripheral vascular disease (22% vs. 15%, P = 0.044), and 2-vessel (36% vs. 26%) and 3-vessel (28% vs. 10%) CAD compared to those without collaterals (P < 0.001). Patients with collaterals were less likely to undergo percutaneous intervention at the time of the index angiogram (32% vs. 61%, P < 0.001). At 1 year, there were no differences in angina (HR 0.74, 95% CI 0.50-1.10; P = 0.141), myocardial infarction (MI) (HR 1.22, 95% CI 0.46-3.21; P = 0.691), revascularization (HR 0.84, 95% CI 0.55-1.30; P = 0.431), death (HR 1.83, 95% CI 0.63-5.31; P = 0.269), or the combined end-point of death, MI, and revascularization (HR 0.87, 95% CI 0.61-1.24; P = 0.426) between patients with and without collaterals. When analyzed according to collateral grade, patients with Rentrop grade 1 had less angina (HR 0.48, 95% CI 0.26-0.89; P = 0.019). CONCLUSIONS: At 1 year, there was no difference in adverse events between patients with or without collaterals. The presence of Rentrop grade 1 collaterals, however, was associated with significantly less angina.

Omega-3 fatty acids in the treatment of heart failure.

Omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) have garnered increased attention as a therapeutic option in cardiovascular disease. Most of the research to date has focused on their lipid altering effects and clinical benefits in patients with coronary artery disease, however, there are data supporting their use in the treatment of heart failure. We review the mechanisms through which Ω-3 PUFAs exert their positive effects on the cardiovascular system and highlight the observational and treatment studies that assessed their effects in patients with heart failure.

A Rare Presentation of Lyme Disease in an Immunocompromised Patient.

Lyme disease is a progressive infectious disease caused by the Borrelia species that affects multiple organ systems, including the brain, heart, skin, and musculoskeletal systems. The cardiac manifestations of Lyme disease typically present with atrioventricular nodal conduction abnormalities and, more rarely, myocarditis. We report a case of an immunocompromised 57-year-old woman who presented with acute onset shortness of breath, hypervolemia, injective conjunctiva, and global vision loss of the left eye in the setting of a recent tick bite. Serologic testing confirmed borreliosis, and cardiac testing demonstrated acute isolated systolic heart failure without any cardiac conduction system abnormalities on the electrocardiogram. The diagnosis of Lyme carditis was made, and the patient was started on doxycycline with complete recovery of cardiac systolic function. This case demonstrates atypical cardiac manifestations of Lyme disease and highlights the difficulty in workup and understanding of Lyme carditis particularly in immunocompromised patients.

Single Nucleotide Polymorphisms in Coronary Microvascular Dysfunction.

Coronary microvascular dysfunction is an underdiagnosed pathologic process that is associated with adverse clinical outcomes. There are data to suggest that coronary microvascular dysfunction, in some cases, may be genetically determined. We present an updated review of single nucleotide polymorphisms in coronary microvascular dysfunction.

Cardiometabolic biomarker patterns associated with cardiac MRI defined fibrosis and microvascular dysfunction in patients with heart failure with preserved ejection fraction.

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a complex disease process influenced by metabolic disorders, systemic inflammation, myocardial fibrosis, and microvascular dysfunction. The goal of our study is to identify potential relationships between plasma biomarkers and cardiac magnetic resonance (CMR) imaging markers in patients with HFpEF. Methods: Nineteen subjects with HFpEF and 15 age-matched healthy controls were enrolled and underwent multiparametric CMR and plasma biomarker analysis using the Olink® Cardiometabolic Panel (Olink Proteomics, Uppsala, Sweden). Partial least squares discriminant analysis (PLS-DA) was used to characterize CMR and biomarker variables that differentiate the subject groups into two principal components. Orthogonal projection to latent structures by partial least squares (OPLS) analysis was used to identify biomarker patterns that correlate with myocardial perfusion reserve (MPR) and extracellular volume (ECV) mapping. Results: A PLS-DA could differentiate between HFpEF and normal controls with two significant components explaining 79% (Q2 = 0.47) of the differences. For OPLS, there were 7 biomarkers that significantly correlated with ECV (R2 = 0.85, Q = 0.53) and 6 biomarkers that significantly correlated with MPR (R2 = 0.92, Q2 = 0.32). Only 1 biomarker significantly correlated with both ECV and MPR. Discussion: Patients with HFpEF have unique imaging and biomarker patterns that suggest mechanisms associated with metabolic disease, inflammation, fibrosis and microvascular dysfunction.

Use of Electronic Health Records to Characterize Patients with Uncontrolled Hypertension in Two Large Health System Networks.

Background: Improving hypertension control is a public health priority. However, consistent identification of uncontrolled hypertension using computable definitions in electronic health records (EHR) across health systems remains uncertain. Methods: In this retrospective cohort study, we applied two computable definitions to the EHR data to identify patients with controlled and uncontrolled hypertension and to evaluate differences in characteristics, treatment, and clinical outcomes between these patient populations. We included adult patients (≥ 18 years) with hypertension receiving ambulatory care within Yale-New Haven Health System (YNHHS; a large US health system) and OneFlorida Clinical Research Consortium (OneFlorida; a Clinical Research Network comprised of 16 health systems) between October 2015 and December 2018. We identified patients with controlled and uncontrolled hypertension based on either a single blood pressure (BP) measurement from a randomly selected visit or all BP measurements recorded between hypertension identification and the randomly selected visit). Results: Overall, 253,207 and 182,827 adults at YNHHS and OneFlorida were identified as having hypertension. Of these patients, 83.1% at YNHHS and 76.8% at OneFlorida were identified using ICD-10-CM codes, whereas 16.9% and 23.2%, respectively, were identified using elevated BP measurements (≥ 140/90 mmHg). Uncontrolled hypertension was observed among 32.5% and 43.7% of patients at YNHHS and OneFlorida, respectively. Uncontrolled hypertension was disproportionately higher among Black patients when compared with White patients (38.9% versus 31.5% in YNHHS; p < 0.001; 49.7% versus 41.2% in OneFlorida; p < 0.001). Medication prescription for hypertension management was more common in patients with uncontrolled hypertension when compared with those with controlled hypertension (overall treatment rate: 39.3% versus 37.3% in YNHHS; p = 0.04; 42.2% versus 34.8% in OneFlorida; p < 0.001). Patients with controlled and uncontrolled hypertension had similar rates of short-term (at 3 and 6 months) and long-term (at 12 and 24 months) clinical outcomes. The two computable definitions generated consistent results. Conclusions: Our findings illustrate the potential of leveraging EHR data, employing computable definitions, to conduct effective digital population surveillance in the realm of hypertension management.

CYP2C19 Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. METHODS AND RESULTS: Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P<0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], P=0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups. CONCLUSIONS: Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.

Effectiveness of Clopidogrel vs Alternative P2Y12 Inhibitors Based on the ABCD-GENE Score.

BACKGROUND: An ABCD-GENE (age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score ≥10 predicts reduced clopidogrel effectiveness, but its association with response to alternative therapy remains unclear. OBJECTIVES: The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y12 inhibitor (prasugrel or ticagrelor) therapy after percutaneous coronary intervention (PCI). METHODS: A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y12 inhibitor treatment were included. The primary outcome was major atherothrombotic events (MAE) within 1 year after PCI. Cox regression was performed to assess event risk in clopidogrel-treated (reference) vs alternatively treated patients, with stabilized inverse probability weights derived from exposure propensity scores after stratifying by ABCD-GENE score and further by CYP2C19 loss-of-function (LOF) genotype. RESULTS: Among patients with scores <10 (n = 3,200), MAE was not different with alternative therapy vs clopidogrel (weighted HR: 0.89; 95% CI: 0.65-1.22; P = 0.475). The risk for MAE also did not significantly differ by treatment among patients with scores ≥10 (n = 1,135; weighted HR: 0.75; 95% CI: 0.51-1.11; P = 0.155). Among CYP2C19 LOF allele carriers, MAE risk appeared lower with alternative therapy in both the group with scores <10 (weighted HR: 0.50; 95% CI: 0.25-1.01; P = 0.052) and the group with scores ≥10 (weighted HR: 0.48; 95% CI: 0.29-0.80; P = 0.004), while there was no difference in the group with scores <10 and no LOF alleles (weighted HR: 1.03; 95% CI: 0.70-1.51; P = 0.885). CONCLUSIONS: These data support the use of alternative therapy over clopidogrel in CYP2C19 LOF allele carriers after PCI, regardless of ABCD-GENE score, while clopidogrel is as effective as alternative therapy in non-LOF patients with scores <10.

Circulating Biomarkers in Coronary Microvascular Dysfunction.

Coronary microvascular dysfunction is an underdiagnosed pathologic process that is associated with adverse clinical outcomes. Biomarkers, molecules measurable in the blood, could inform the clinician by aiding in the diagnosis and management of coronary microvascular dysfunction. We present an updated review of circulating biomarkers in coronary microvascular dysfunction representing key pathologic processes, including inflammation, endothelial dysfunction, oxidative stress, coagulation, and other mechanisms.

Use of Electronic Health Records to Characterize Patients with Uncontrolled Hypertension in Two Large Health System Networks.

Background: Improving hypertension control is a public health priority. However, uncertainty remains regarding the optimal way to identify patients with uncontrolled hypertension using electronic health records (EHR) data. Methods: In this retrospective cohort study, we applied computable definitions to the EHR data to identify patients with controlled and uncontrolled hypertension and to evaluate differences in characteristics, treatment, and clinical outcomes between these patient populations. We included adult patients (≥18 years) with hypertension receiving ambulatory care within Yale-New Haven Health System (YNHHS; a large US health system) and OneFlorida Clinical Research Consortium (OneFlorida; a Clinical Research Network comprised of 16 health systems) between October 2015 and December 2018. We identified patients with controlled and uncontrolled hypertension based on either a single blood pressure (BP) measurement from a randomly selected visit or all BP measurements recorded between hypertension identification and the randomly selected visit). Results: Overall, 253,207 and 182,827 adults at YNHHS and OneFlorida were identified as having hypertension. Of these patients, 83.1% at YNHHS and 76.8% at OneFlorida were identified using ICD-10-CM codes, whereas 16.9% and 23.2%, respectively, were identified using elevated BP measurements (≥ 140/90 mmHg). Uncontrolled hypertension was observed among 32.5% and 43.7% of patients at YNHHS and OneFlorida, respectively. Uncontrolled hypertension was disproportionately higher among Black patients when compared with White patients (38.9% versus 31.5% in YNHHS; p<0.001; 49.7% versus 41.2% in OneFlorida; p<0.001). Medication prescription for hypertension management was more common in patients with uncontrolled hypertension when compared with those with controlled hypertension (overall treatment rate: 39.3% versus 37.3% in YNHHS; p=0.04; 42.2% versus 34.8% in OneFlorida; p<0.001). Patients with controlled and uncontrolled hypertension had similar rates of short-term (at 3 and 6 months) and long-term (at 12 and 24 months) clinical outcomes. The two computable definitions generated consistent results. Conclusions: Computable definitions can be successfully applied to health system EHR data to conduct population surveillance for hypertension and identify patients with uncontrolled hypertension who may benefit from additional treatment.

Presentation and Outcomes of Patients With Preoperative Critical Illness Undergoing Cardiac Surgery.

BACKGROUND: Little is known about the prevalence and post-surgical outcomes associated with cardiac intensive care unit (CICU) therapeutics among CICU patients referred for cardiac surgery. OBJECTIVES: The purpose of this study was to investigate the clinical characteristics and outcomes of CICU patients referred for cardiac surgery from the intensive care unit. METHODS: We analyzed characteristics and outcomes of CICU admissions referred from the CICU for cardiac surgery during 2017 to 2020 across 29 centers. The primary outcome was in-hospital mortality. RESULTS: Among 10,321 CICU admissions, 887 (8.6%) underwent cardiac surgery, including 406 (46%) coronary artery bypass graftings, 201 (23%) transplants or ventricular assist devices, 171 (19%) valve surgeries, and 109 (12%) other procedures. Common indications for CICU admission included shock (33.5%) and respiratory insufficiency (24.9%). Preoperative CICU therapies included vasoactive therapy in 52.2%, mechanical circulatory support in 35.9%, renal replacement in 8.2%, mechanical ventilation in 35.7%, and 17.5% with high-flow nasal cannula or noninvasive positive pressure ventilation. In-hospital mortality was 11.7% among all CICU admissions and 9.1% among patients treated with cardiac surgery. After multivariable adjustment, pre-op mechanical circulatory support and renal replacement therapy were associated with mortality, while respiratory support and vasoactive therapy were not. CONCLUSIONS: Nearly 1 in 12 contemporary CICU patients receive cardiac surgery. Despite high preoperative disease severity, CICU admissions undergoing cardiac surgery had a comparable mortality rate to CICU patients overall; highlighting the ability of clinicians to select higher acuity patients with a reasonable perioperative risk.

Pulmonary Artery Catheter Use and Mortality in the Cardiac Intensive Care Unit.

BACKGROUND: The appropriate use of pulmonary artery catheters (PACs) in critically ill cardiac patients remains debated. OBJECTIVES: The authors aimed to characterize the current use of PACs in cardiac intensive care units (CICUs) with attention to patient-level and institutional factors influencing their application and explore the association with in-hospital mortality. METHODS: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Between 2017 and 2021, participating centers contributed annual 2-month snapshots of consecutive CICU admissions. Admission diagnoses, clinical and demographic data, use of PACs, and in-hospital mortality were captured. RESULTS: Among 13,618 admissions at 34 sites, 3,827 were diagnosed with shock, with 2,583 of cardiogenic etiology. The use of mechanical circulatory support and heart failure were the patient-level factors most strongly associated with a greater likelihood of the use of a PAC (OR: 5.99 [95% CI: 5.15-6.98]; P < 0.001 and OR: 3.33 [95% CI: 2.91-3.81]; P < 0.001, respectively). The proportion of shock admissions with a PAC varied significantly by study center ranging from 8% to 73%. In analyses adjusted for factors associated with their placement, PAC use was associated with lower mortality in all shock patients admitted to a CICU (OR: 0.79 [95% CI: 0.66-0.96]; P = 0.017). CONCLUSIONS: There is wide variation in the use of PACs that is not fully explained by patient level-factors and appears driven in part by institutional tendency. PAC use was associated with higher survival in cardiac patients with shock presenting to CICUs. Randomized trials are needed to guide the appropriate use of PACs in cardiac critical care.

Plasma CXCL12 levels as a predictor of future stroke.

BACKGROUND AND PURPOSE: The chemokine ligand CXCL12 is constitutively expressed in the bone marrow and other tissues including the brain endothelium and is responsible for regulating the trafficking of bone marrow progenitor cells. CXCL12 has been shown to play a significant role in animal models of ischemic stroke but its role in human stroke is unclear. The aim of this study was to test the hypothesis that elevated circulating baseline CXCL12 levels are associated with subsequent stroke. METHODS: We prospectively collected demographic and angiographic data from consecutive patients referred for elective coronary angiography. Before coronary angiography a peripheral blood sample was collected for subsequent measurement of CXCL12. One-year stroke risk was calculated using the Framingham Risk Profile. Clinical follow-up was performed at 6 months and 1 year. RESULTS: Of 206 subjects enrolled, 10 (4.9%) sustained an ischemic stroke over the 1 year follow-up. There were no significant differences in baseline clinical characteristics or angiographic findings. However, median CXCL12 levels were significantly higher in those who sustained an ischemic stroke compared with those who did not (10 856 pg/mL versus 2241 pg/mL, P=0.007). The time to stroke distribution between subjects with baseline CXCL12 levels≥10 421 pg/mL and those with baseline CXCL12 levels<10 421 pg/mL was significantly different (log rank P<0.001). The weighted Cox proportional hazard model demonstrated that baseline CXCL12 levels≥10 421 pg/mL were significantly associated with ischemic stroke at follow-up (hazard ratio, 15.29; 95% CI, 3.05-76.71). CONCLUSIONS: Plasma CXCL12 levels may represent a novel biomarker of future ischemic stroke.

Chemokines as mediators of tumor angiogenesis and neovascularization.

Chemokines are a superfamily of structurally homologous heparin-binding proteins that influence tumor growth and metastasis. Several members of the CXC and CC chemokine families are potent inducers of neovascularization, whereas a subset of the CXC chemokines are potent inhibitors. In this paper, we review the current literature regarding the role of chemokines as mediators of tumor angiogenesis and neovascularization.

Concomitant coronary microvascular dysfunction and spontaneous coronary artery dissection resulting in ST-segment elevation myocardial infarction.

We report a patient with angina and no flow-limiting epicardial coronary artery disease who presented with recurrent spontaneous coronary artery dissection resulting in an acute ST-elevation myocardial infarction and evidence of coronary microvascular dysfunction on coronary angiography. We review each condition's pathophysiology and provide a review of the literature for reported associations between these disease processes. .

CXCL5 gene polymorphisms and coronary collateralization.

Background: The presence of coronary collateralization is heterogenous, even amongst those with similar degrees of epicardial coronary artery stenoses. We hypothesized that genetic variation of CXCL5, a chemokine that mediates angiogenesis, is associated with coronary collateralization. Methods: We genotyped subjects undergoing coronary angiography for single nucleotide polymorphisms of CXCL5 and determined the presence of spontaneously visible coronary collaterals. Results: Subjects with collaterals had less angina (46 % vs 59 %, p = 0.006), and prior percutaneous coronary intervention (34 % vs 47 %, p = 0.010), and more hyperlipidemia (90 % vs 82 %, p = 0.018), peripheral arterial disease (25 % vs 17 %, p = 0.041), congestive heart failure (16 % vs 8 %, p = 0.007), and multi-vessel coronary artery disease (41 % vs 24 %, p = 0.0001) compared to those without collaterals. Multi-vessel disease and hyperlipidemia were positive predictors of angiographically visible collaterals while being a carrier of the CXCL5 polymorphism was a negative predictor. Conclusions: Coronary collateralization may, at least in part, be genetically determined.