Angiographic Coronary Disease Research Articles

Dietary Composition, Angiographic Coronary Disease, and Cardiovascular Outcomes in the WISE Study (Women's Ischemia Syndrome Evaluation).

Studies relating diet to angiographic coronary artery disease (CAD) and subsequent major adverse cardiac events (MACE) in women are limited. Information on diet was collected in the Women's Ischemia Syndrome Evaluation (WISE), a prospective cohort study of symptomatic women referred for coronary angiography to evaluate suspected ischemic heart disease. A consecutive subgroup (n = 201 of 936) of enrolled women completed the modified Block food frequency questionnaire (FFQ). Data on outcomes were collected and adjudicated after 8-year follow-up. A set of logistic regression models were fitted for non-obstructive versus obstructive coronary stenosis (<50% versus ≥50%). Cox proportional hazard regression models were fitted for outcomes, with each dietary composition variable adjusted for the degree of coronary stenosis. At baseline, the subgroup cohort was 58 ± 12 years old with a body mass index (BMI) of 30 ± 7 kg/m2. An increased proportion of calories consumed from protein was associated with higher levels of baseline obstructive coronary stenosis. Those individuals who ate a higher amount of protein, carotene, and servings of vegetables and meat, however, were each associated with lower subsequent adverse outcomes, respectively. Among women undergoing coronary angiography for suspected CAD, a higher percentage of protein intake was associated with higher baseline stenosis severity; however, the amount of protein intake, vegetable, meat, and carotene intake, was conversely associated with subsequent lower adverse cardiovascular outcome risk.

The value of calcium scoring in hypertensive patients as a referral criterion for the prediction of coronary artery disease detected on computed tomography coronary angiography

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The current national guidelines do not address the inequity between the increasing demand of Computed Tomography Coronary Angiography (CTCA) and the contrasting constrained imaging capacity. In a previous study we showed hypertension to be the strongest independent predictor of Coronary Artery Disease (CAD) detected on CTCA. In this study, the use of Coronary Calcium Scoring (CCS) for CTCA referrals is reviewed to identify the main parameters upon which CTCA referrals for the investigation of CAD, should be based. Methods After excluding TAVI and graft assessment patients, the individual electronic health records of 420 consecutive patients who underwent CTCA between July and November 2020, were reviewed with a mean age 59.1 years. Risk factors were recorded including smoking (23%), hyperlipidaemia (37%), positive family history (22%), systemic hypertension (51%), diabetes mellitus (30%) and male gender (50%). Referral criteria were also recorded for statistical analyses. Ethnicity, cardiac and past medical history were recorded. Patients were stratified into four groups according to CAD severity: absent, mild, moderate and severe disease, as seen on CTCA reports. The mean CCS for each CAD category was compared between hypertensive and non-hypertensive patients. Mean CCS were further compared in regard to the number of coronary arteries affected and the severity of CAD in each artery. Results Out of the total cohort, 247 (50.9%) patients were hypertensive. 249 (59.3%) CCS were interpreted in the very low risk category, 57 (13.6%) low risk, 58 (13.8%) moderate risk, 23 (5.48%) moderately high risk and 33 (7.86%) high risk. A significant difference in mean CCS and CAD severity was observed between mild, moderate and severe CAD (P = 0.015 and P &amp;lt; 0.001). Comparison of CCS between hypertensives and non-hypertensives, across the four CAD severity categories, revealed a significant difference in mean CCS in the severe CAD category (P = 0.013). Further comparison of CCS between hypertensives with chest pain and hypertensives without chest pain was non-significant. A higher number of affected coronary arteries was associated with a higher mean CCS and a significant difference in CCS was observed between hypertensives and non-hypertensives for the number of arteries affected. Similar results were observed when comparing mean CCS in moderate-severely affected coronary arteries. Conclusions Hypertensive patients with a high CCS were associated with higher incidence of severe CAD. Further, in those with hypertension, additional symptoms appear to have no effect on CCS. These results suggest that the incorporation of CCS in the investigation of CAD on CT angiography, may pose a powerful adjunct in proposing an alternative paradigm for the assessment of patients with hypertension and stable chest pain, in the progress of angiographic coronary disease.

Hypertensive patients are more likely to develop coronary artery disease on computed tomography coronary angiography

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Systemic hypertension (HTN) is the strongest cause for morbidity and mortality all over the world for its association with target organ damage including coronary artery disease (CAD). It creates a great challenge in medical field because it is often asymptomatic. CT coronary angiography (CTCA) being a non-invasive tool can be used to assess the presence of CAD successfully. In this study we aimed to identify the association between HTN and CAD. Methods The individual electronic health records of 566 consecutive patients who underwent CTCA between July and November 2020, were retrospectively reviewed. TAVI studies and graft assessment studies were excluded. A total of 485 patient (mean age 60.4) reports were analysed. All risk factors were recorded including smoking (23%), hyperlipidaemia (37%), positive family history (22%), systemic hypertension (51%), diabetes mellitus (30%) and male gender (50%). Referral criteria were also recorded for statistical analyses. Ethnicity, cardiac and past medical history were also recorded. Results Of the 170 patients with moderate-severe CAD, 127 (74.7%) had hypertension, and of the 100 patients with severe CAD, 78 (78%) had hypertension. Univariate analysis for comparison of patients with none (n = 222), mild (n = 93), moderate (n = 70) and severe (n = 100) CAD revealed that hypertension (P &amp;lt; 0.001), diabetes (P = 0.007), gender (P &amp;lt; 0.001), dyslipidaemia (P &amp;lt; 0.001) and smoking (P = 0.005), were all significantly associated with the presence of CAD on CTCA. However, multivariate analysis using a multiple logistic regression model, confirmed a significant association between hypertension and CAD (OR = 1.26, P &amp;lt; 0.001). SHAP-values for model interpretation revealed that hypertension has the strongest impact on CAD presence on CTCA. Conclusions Hypertension is the strongest independent predictor for the presence of CAD detected on CTCA, amongst diabetes, gender, dyslipidaemia, positive family history and smoking. These results suggest that hypertension and the other risk factors associated with CAD, should form the main parameters on consideration for CTCA referral. Further studies relating our results to the CTCA reports of same patients after a longer period of aggressive hypertension treatment, would prove essential in establishing the role of blood pressure management in the progress of angiographic coronary disease.

Prediction of angiographic coronary disease and mortality with a cadmium-zinc-telluride camera: a comparison of upright and supine ejection fractions and left ventricular volumes

IntroductionPerfusion imaging strongly predicts coronary artery disease (CAD), whereas cardiac volumes and left ventricular ejection fraction (LVEF) strongly predict mortality. Compared to conventional Anger single photon emission computed tomography (SPECT) cameras, cadmium-zinc-telluride (CZT) cameras provide higher resolution, resulting in different left ventricular volumes. The cadmium-zinc-telluride D-SPECT camera is commonly used to image in the upright position, which introduces changes in left ventricular loading conditions and potentially alters left ventricular volumes. However, little or no data exist on the predictive value of left ventricular volumes and ejection fraction when acquired in the upright position. We investigated models for the prediction of CAD and mortality, comparing upright and supine imaging.MethodsA retrospective study of patients with upright/supine stress and rest imaging and coronary angiography within 3 months was performed. Univariate and multivariable analyses were performed to predict abnormal angiograms and all-cause mortality.ResultsOf the 392 patients, 210 (53.6%) had significant angiographic CAD; 78 (19.9%) patients died over 75 months. The best multivariable model for CAD included the supine summed stress score and supine stress LVEF, with an area under the receiver operating characteristic of 0.862, a sensitivity of 76.7%, and a specificity of 82.4%, but this model was not statistically superior to the best upright model. The best multivariable models for mortality included age, diabetes, history of cardiovascular disease, and end-systolic volume, with the upright and supine models being equivalent.DiscussionAngiographic CAD was best predicted by the supine summed stress score and LVEF but was not statistically superior to the next-best upright model. Mortality was best predicted by end-systolic volume in combination with age, diabetes status, and cardiovascular disease status, with equivalent results from the upright and supine images.

Cardiac troponins and growth-differentiation factor-15 (GDF-15) for prediction of angiographic coronary artery disease in chest pain patients without myocardial injury

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Grieg Foundation and Western Norway Regional Health Authority. Background There is a growing evidence that patients with angiographic signs of coronary artery disease should receive preventive therapy to reduce the risk of future adverse cardiac events. Purpose Evaluate whether cardiac troponin T and I (cTnT and cTnI) concentrations within the range from the limit of detection of the assay to the 99th percentile or GDF-15 may help identify patients with angiographic evidence of coronary artery disease (CAD). Methods A subgroup of 550 patients from the WESTCOR study with both cTnT and cTnI concentrations ≤99th percentile was evaluated with coronary computed tomography angiography (CCTA). CAD was defined as ≥10% narrowing of lumen of any coronary artery on CT angiogram or too high calcium score for anatomy to be evaluated. Overall diagnostic accuracy of cTnT, cTnI and GDF-15 and their combination were evaluated calculating the area under the receiver-operating characteristics curve (ROC-AUC). cTn analysis were performed using high-sensitivity assays from Roche Diagnostics (cTnT, limit of detection of 5 ng/L and gender-neutral 99th percentile of 14 ng/L) and Abbott Diagnostics (cTnI, limit of detection 1.6 ng/L and 99th percentile 16 ng/L for women and 34 ng/L for men). GDF-15 analyses were performed using the GDF-15 assay on Cobas e801 (Roche Diagnostics). Results A total of 53.5 percent (294 of 550 patients) had angiographic coronary disease. The risk of having CAD was significantly higher in patients with cTnT between 5 ng/ml and the gender-neutral 99th percentile compared to very low levels of cTnT &amp;lt;5 ng/ml, 65.7% (95% CI: 60-71%) vs 38.1% (95% CI: 32-44%, p-value for difference &amp;lt;0.001). Similar numbers for cTnI between 2 ng/ml and the gender-specific 99th percentile compared to very low levels &amp;lt;2 ng/ml was 62.9% (95% CI: 57-69%) vs 43.2% (95% CI: 37-49%, p-value for difference &amp;lt;0.001). The odds ratio for CAD if cTnT was ≥5 ng/ml or cTnI ≥2 compared to very low levels was 3.1 (2.1-4.4) for cTnT and 2.2 (1.6-3.1) for cTnI. For GDF-15, the risk of having CAD was lower in patients with low values &amp;lt;1200 ng/L (49.7%, 95% CI: 45-54%) compared to patients with higher concentrations &amp;gt;1200 ng/L (75.9%, 95% CI: 66-86%, p-value for difference &amp;lt;0.001). The accuracy of cTnT was significantly higher than for cTnI for identifying CAD (AUC 0.67, 95% CI 0.63-0.71 vs. 0.61, 95% CI 0.58-0.66, p-value for difference &amp;lt;0.01), and borderline higher than for GDF-15 (AUC 0.62, p-value for difference 0.067). Adding GDF-15 to cTn did not increase diagnostic performance of cTnT (AUC 0.67 vs. 0.68, p-value for difference 0.56) or cTnI (AUC 0.61 vs. 0.63, p-value for difference 0.23). Conclusion Overall diagnostic performance of cTnT is superior to cTnI in identifying patients without angiographic evidence of CAD. Adding GDF-15 does not increase overall diagnostic performance. Legend: Figure 1. Receiver-operating characteristics curve of cTnT, cTnI and GDF-15 for the identification of CAD (≥10% lumen reduction).

Profiles of Hospitalized Patients with Angiographic Coronary Heart Disease in Taiwan during 2014-2016: Report of a Tertiary Hospital.

The Taiwan Society of Cardiology (TSOC) has established multicenter registries for coronary artery disease (CAD) to investigate clinical characteristics, management and risks for mortality. However, the impacts of newly-emerged evidence-based therapies, including the use of drug-eluting stents (DESs), on patients with CAD in Taiwan remain unclear. The Tri-Service General Hospital-Coronary Heart Disease (TSGH-CHD) registry is a single-center, prospective, longitudinal registry in Taiwan containing data from 2014-2016. Individuals who were admitted for coronary angiography were enrolled. Patient profiles, management and in-hospital outcome data were collected. We included 3352 patients: 2349 with stable angina and 1003 with acute coronary syndrome (ACS). In the stable angina group, both patients receiving stenting and those receiving medical treatment had a 0.7% mortality rate; DESs were used in 70.4% of the patients receiving stenting. In the ACS group, the patients receiving stenting and those receiving medical treatment had a 4.9% and 10.7% mortality rate, respectively; DESs were used in 63.1% of the patients receiving stenting. In the 2008-2010 Taiwan ACS registry, DESs were used in only 28% of all stenting procedures, and the estimated hospital mortality rate was 1.8%. Multivariate analysis indicated that older age, prior stroke, and cardiogenic shock on admission were associated with an increased risk of in-hospital mortality in the ACS group. Compared with the Taiwan ACS cohort, the TSGH-CHD registry revealed increased DES use and increased disease complexity and severity after 2010. Although unlikely to significantly improve survival, interventionists seemed to perform high-risk procedures for complex CAD more often in the new DES era.

P4575UA and NSTEMI in the era of high-sensitivity Troponin: impact on patient risk profile and management

Abstract Aim High-sensitivity troponin assays (HST) entered the clinical arena to facilitate exclusion of ACS in the emergency department (ER) in patients presenting with chest pain. Due to its higher sensitivity there is the potential for an overestimation of the diagnosis of NSTEMI, and possibly ACS overall. We assessed the impact of HST in the classification of ACS (NSTEMI vs UA) and its ability to predict obstructive coronary disease (CAD), in a population of pts referred to coronary angiography (ICA). Methods Retrospective analysis of 1844 pts with suspected NSTEMI or UA referred for ICA from a single ER between Feb 2013 and Nov 2018. Standard Troponin-I was used until Feb 2016 and HST thereafter. The characteristics of UA and NSTEMI pts before and after the introduction of HST were compared. Multivariate binary logistic regression models were used to access the association of different troponin assays with CAD (&gt;50% for LM and &gt;70% for the remaining). Sensitivity, specificity, NPV and PPV for angiographic CAD were also determined. Results The relative proportion of patients with UA and NSTEMI was similar between study periods: 31% vs 29% and 69% vs 71%, respectively (p=0.3). Clinical and angiographic characteristics did not differ in UA pts before and after the use of HST. NSTEMI patients in the HST era were less frequently women (39% vs 32%, p=0.026), had higher creatinine (0.93 IQR 0.75–1.3 vs 1.0 IQR 0.82–1.38), higher number of lesions (2 IQR 1–4 vs 3 IQR 1–4) and a lower rate of normal coronary arteries (10.5% vs 3.9%, p&lt;0.001). The prevalence of significant CAD in this population, before and after HST, was 65% and 73%, respectively (p=0.001). However, when clinically relevant characteristics and judgement were accounted for, both standard troponin (OR 0.99, 95% CI 0.99–1.01) and HST (1.0, 95% CI 1.0–1.0) were poor predictors of significant CAD. Sensitivity was 69% vs 72%, specificity 30% vs 30%, PPV 65% vs 73% and NNP 34% vs 28%, respectively. Finally, rates of percutaneous intervention did not differ between the two periods (30% vs 33.5%, p=0.157), nor between ACS types within each period. CAD/PCI in ACS within each period Conclusion The introduction of HST did not result in an increase of the diagnosis of NSTEM vs UA, suggesting that clinical judgment remains an important determinant of the diagnosis of ACS. Also there was no evidence of an increase in PCI rates, despite worse CAD severity in NSTEMI patients.

Clinical Outcome of Patients With Inducible Capillary Blood Flow Abnormalities During Demand Stress in the Presence or Absence of Angiographic Coronary Disease.

Our aim was to determine the cardiovascular outcome of patients with capillary blood flow (CBF) abnormalities detected during demand stress in the absence of obstructive coronary artery disease. We identified 380 consecutive patients referred for coronary angiography (CA) after dobutamine or exercise stress echocardiography (SE) between 2008 and 2013 performed with real-time perfusion imaging to examine myocardial CBF with a continuous ultrasound contrast infusion. Patients with left ventricular ejection fraction <40% were excluded. There were 3 groups based on results: positive SE/negative CA, patients who had abnormal regional CBF but no significant angiographic disease; positive SE/positive CA, those with abnormal CBF and significant disease on subsequent CA; and negative SE/negative CA, patients with normal CBF and negative CA. Event-free survival examining death and nonfatal myocardial infarction was compared. Median follow-up was 4 years. There were 91 positive SE/negative CA, 189 positive SE/positive CA, and 100 negative SE/negative CA patients over the study period. The positive SE/negative CA patients were more frequently women and had a lower prevalence of hypertension and hyperlipidemia (all P<0.001). Analysis of event-free survival with Cox regression demonstrated that death/nonfatal myocardial infarction rates were higher in the positive SE/positive CA (hazard ratio, 2.10; CI, 1.02-4.29) and positive SE/negative CA (hazard ratio, 2.02; CI, 0.99-4.31) groups when compared with negative SE/negative CA groups. Patients with inducible CBF abnormalities in the absence of significant obstructive disease at CA still have similar death/nonfatal myocardial infarction rates as those with significant disease at CA.

Caracterización de los pacientes con diagnóstico presuntivo de síndrome coronario agudo sin elevación del segmento ST que asisten a un servicio de urgencias

Chest pain is one of the main reasons for consulting the Emergency Department, and it is secondary to conditions, such as acute coronary syndrome. For its diagnosis, it not only requires a Troponin result, but also a full clinical evaluation, in which factors like cardiovascular risk have to be taken into account, as well as characteristics of the pain and the findings on the electrocardiogram. The poor interpretation of the ultrasensitive Troponins leads to the patient being subjected to unnecessary risks due to studies such as cardiac catheterisation. A cross-sectional study was conducted in a hospital in Bogota, in which chest pain was the main reason for consulting the Emergency Department, and acute coronary syndrome the first cause of admission to Cardiology. The study included a total of 411 patients on whom a coronary angiography was performed. The majority were males with risk factors such as arterial hypertension, smokers, and with a previous coronary event. Among the para-clinical studies, the mean ejection fraction was around 50%, and significant epicardial lesions were found in only 201 patients.Of the sample analysed, 13% had a creatinine greater than 1.5mg/dl as an alternative cause of the elevation of the biomarker, and 28% had some degree of left ventricular function. the majority of patients that did not have significant angiographic lesions in the cardiac catheterisation documented, the Troponin did not meet the criteria for being positive, based on an increase of 20% as regards the initial value if this was positive or 50% in the case where the first value was negative. Furthermore, of the patient group with significant angiographic coronary disease, the combination of three or more cardiovascular risk factors was the most frequent in the presence of a positive biomarker.

Sex differences in plaque characteristics by intravascular imaging in patients with coronary artery disease.

We aimed to study sex differences in coronary plaque burden and plaque composition in patients with coronary artery disease (CAD). Virtual histology intravascular ultrasound (VH-IVUS) and near-infrared spectroscopy (NIRS) imaging of a non-culprit coronary artery was performed in 178 (23.5%) women and 581 (76.5%) men who underwent invasive management of stable angina pectoris (SAP) or acute coronary syndrome (ACS). Women were older and had a worse cardiovascular risk profile than men, but less extended angiographic coronary disease. Irrespective of the presenting diagnosis, women had lower VH-IVUS-derived plaque burden than men (38.1% vs. 40.5% in SAP, and 35.9% vs. 38.8% in ACS). Standardised (mean 211 vs. 263 mm3 in SAP, and 199 vs. 245 mm3 in ACS) total plaque volume was lower in women. Volumes of fibrous tissue, fibro-fatty tissue, necrotic core and dense calcium were also lower in women. NIRS-derived lipid core burden index (LCBI) was lower in women, in particular in SAP (mean LCBI in the worst 4 mm 220 vs. 240). The observed differences remained significant after adjustment for clinical characteristics. Women had more favourable plaque characteristics than men, despite their worse risk profile. Long-term follow-up studies are required to evaluate the clinical consequences.

Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients

Reducing levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels. Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors produce incremental LDL-C lowering in statin-treated patients; however, the effects of these drugs on coronary atherosclerosis have not been evaluated. To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients. The GLAGOV multicenter, double-blind, placebo-controlled, randomized clinical trial (enrollment May 3, 2013, to January 12, 2015) conducted at 197 academic and community hospitals in North America, Europe, South America, Asia, Australia, and South Africa and enrolling 968 patients presenting for coronary angiography. Participants with angiographic coronary disease were randomized to receive monthly evolocumab (420 mg) (n = 484) or placebo (n = 484) via subcutaneous injection for 76 weeks, in addition to statins. The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to week 78, measured by serial intravascular ultrasonography (IVUS) imaging. Secondary efficacy measures were nominal change in normalized total atheroma volume (TAV) and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated. Among the 968 treated patients (mean age, 59.8 years [SD, 9.2]; 269 [27.8%] women; mean LDL-C level, 92.5 mg/dL [SD, 27.2]), 846 had evaluable imaging at follow-up. Compared with placebo, the evolocumab group achieved lower mean, time-weighted LDL-C levels (93.0 vs 36.6 mg/dL; difference, -56.5 mg/dL [95% CI, -59.7 to -53.4]; P < .001). The primary efficacy parameter, PAV, increased 0.05% with placebo and decreased 0.95% with evolocumab (difference, -1.0% [95% CI, -1.8% to -0.64%]; P < .001). The secondary efficacy parameter, normalized TAV, decreased 0.9 mm3 with placebo and 5.8 mm3 with evolocumab (difference, -4.9 mm3 [95% CI, -7.3 to -2.5]; P < .001). Evolocumab induced plaque regression in a greater percentage of patients than placebo (64.3% vs 47.3%; difference, 17.0% [95% CI, 10.4% to 23.6%]; P < .001 for PAV and 61.5% vs 48.9%; difference, 12.5% [95% CI, 5.9% to 19.2%]; P < .001 for TAV). Among patients with angiographic coronary disease treated with statins, addition of evolocumab, compared with placebo, resulted in a greater decrease in PAV after 76 weeks of treatment. Further studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes. clinicaltrials.gov Identifier: NCT01813422.

Comparing Coronary Atheroma Progression Rates and Coronary Events in the United States, Canada, Latin America, and Europe

We explored for geographic variations in coronary atheroma progression rates in the United States compared to other world regions (Canada, Latin America, Western Europe, and Central-Eastern Europe) and sought to ascertain if this associated with regional differences in major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, coronary revascularization). Across 7 randomized trials with a global recruitment pattern, 5,451 participants with angiographic coronary disease underwent serial coronary intravascular ultrasonography during 18 or 24months, with adjudicated MACE. Change in coronary percent atheroma volume (ΔPAV) and MACE in the United States versus other world regions were assessed. Despite similar baseline angiographic and plaque characteristics across participants and regions, following propensity-weighted and multivariate analysis, US (n= 3,706) versus non-US (n= 1,745) participants demonstrated marginal but significantly greater annualized ΔPAV (least-square means ± SE: 0.27 ± 0.14% vs 0.062 ± 0.14%, p= 0.005). However, MACE rates were disproportionately higher in US compared to non-US participants (23.5% vs 10.9%, p <0.001), driven by a doubling in crude rates of coronary revascularization procedures (16.1% vs 7.8%, p <0.001). The US participants hospitalized with unstable angina demonstrated more significant disease progression than their non-US counterparts (ΔPAV: 0.57 ± 0.19% vs-0.30 ± 0.36%, p= 0.033) and greater MACE (9.1% vs 4.8%, p <0.001). A US geographic disposition independently associated with MACE (hazard ratio 1.53, 95% confidence interval 1.22 to 1.92, p <0.001). In conclusion, in participants with stable coronary disease, coronary atheroma progression rates are modestly higher in US-based compared to non-US-based participants. Elective coronary revascularization rates however are disproportionately greater in US-based participants.

A Cross-sectional Study of KLKB1 and PRCP Polymorphisms in Patient Samples with Cardiovascular Disease.

Plasma kallikrein formed from prekallikrein (PK) produces bradykinin from kininogens and activates factor XII. Plasma PK is activated by factors αXIIa, βXIIa, or prolylcarboxypeptidase (PRCP). A cross-sectional investigation determined if there is an association of PRCP and KLKB1 polymorphisms with cardiovascular disease (CVD). DNA was obtained from 2243 individuals from the Prevention of Events with Angiotensin Converting Enzyme trial. Two PRCP SNPs, rs7104980 and rs2298668, and two KLKB1 SNPs, rs3733402 and rs3087505, were genotyped. Logistic regression models were performed for history of diabetes, myocardial infarction, stroke, angina, angiographic coronary disease, CABG, intermittent claudication, percutaneous transluminal coronary angioplasty (PTCA), and transient ischemic attack. The PRCP SNP rs7104980 increased the odds of having a history of PTCA by 21% [odds ratio (OR) = 1.211; 95% confidence intervals (CI) = (1.008, 1.454)]; P = 0.041, but was non-significant after Bonferroni correction. Alternatively, having the G allele for rs3733402 (KLKB1 gene) decreased the odds of having a history of angiographic coronary disease by 24% [OR = 0.759; 95% CI = (0.622, 0.927)]; P = 0.007 that was statistically significant (P < 0.01) after Bonferroni correction for multiple hypothesis testing. When the best-fit model based on the Akaike information criterion controlled for age, weight, gender, hypertension, and history of angina, the G allele of KLKB1 rs3733402 that is associated with less plasma kallikrein activity correlated with reduced history of CVD.

The association between triglyceride/high-density lipoprotein cholesterol ratio and all-cause mortality in acute coronary syndrome after coronary revascularization.

AimsHigh triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) are cardiovascular risk factors. A positive correlation between elevated TG/HDL-C ratio and all-cause mortality and cardiovascular events exists in women. However, utility of TG to HDL-C ratio for prediction is unknown among acute coronary syndrome (ACS).MethodsFasting lipid profiles, detailed demographic data, and clinical data were obtained at baseline from 416 patients with ACS after coronary revascularization. Subjects were stratified into three levels of TG/HDL-C. We constructed multivariate Cox-proportional hazard models for all-cause mortality over a median follow-up of 3 years using log TG to HDL-C ratio as a predictor variable and analyzing traditional cardiovascular risk factors. We constructed a logistic regression model for major adverse cardiovascular events (MACEs) to prove that the TG/HDL-C ratio is a risk factor.ResultsThe subject’s mean age was 64 ± 11 years; 54.5% were hypertensive, 21.8% diabetic, and 61.0% current or prior smokers. TG/HDL-C ratio ranged from 0.27 to 14.33. During the follow-up period, there were 43 deaths. In multivariate Cox models after adjusting for age, smoking, hypertension, diabetes, and severity of angiographic coronary disease, patients in the highest tertile of ACS had a 5.32-fold increased risk of mortality compared with the lowest tertile. After adjusting for conventional coronary heart disease risk factors by the logistic regression model, the TG/HDL-C ratio was associated with MACEs.ConclusionThe TG to HDL-C ratio is a powerful independent predictor of all-cause mortality and is a risk factor of cardiovascular events.

Coronary artery wall shear stress is associated with endothelial dysfunction and expansive arterial remodelling in patients with coronary artery disease

To investigate in vivo relationships between segmental wall shear stress (WSS), endothelium-dependent vasoreactivity and arterial remodelling. Twenty-four patients with minor angiographic coronary arterial disease (≤30% stenosis severity) underwent intracoronary (IC) salbutamol provocation during intravascular ultrasound (IVUS)-upon-Doppler guidewire imaging. Macrovascular response (change in segmental lumen volume [SLV] at baseline and following IC salbutamol), plaque burden (percent atheroma volume [PAV]), remodelling indices (RI), eccentricity indices (EI) and WSS were evaluated in 179 consecutive 5 mm coronary segments. Baseline WSS was directly related to endothelium-dependent epicardial coronary vasomotion (% change SLV, coefficient 17.2, p=0.004), and inversely related to RI (coefficient -0.23, p=0.02) and EI (coefficient -10.0, p=0.001). Baseline WSS was lower in segments displaying endothelial dysfunction (defined as any change in SLV ≤0) compared with preserved function (0.66±0.33 vs. 0.71±0.22 N/m2, p=0.046). Independent of plaque burden, segments with the lowest tertile of WSS displayed less vasodilatation, or vasoconstriction, than segments with the highest tertile of WSS. Higher plaque burden segments harbouring the lowest tertiles of WSS displayed vasoconstriction, expansive arterial remodelling and greater plaque eccentricity. In patients with stable coronary syndromes and minor angiographic coronary disease, coronary segments with lower in vivo WSS values display functional and morphological features of plaque vulnerability.

Prolylcarboxypeptidase Is a Risk Factor for Cardiovascular Events

BACKGROUND: Prolylcarboxypeptidase (PRCP) is a membrane-associated serine protease that regulates biologic peptides bradykinin, angiotensin II, α-melanocyte stimulating hormone, and activates prekallikein. PRCP and its variants have been associated with metabolic syndrome in males, hypertension in preeclampsia, resistance to ACE inhibitors, and embryonic angiogenesis. Recent studies on PRCPgt/gt mice that have 25% normal PRCP levels show that these animals are hypertensive, have higher risk for arterial thrombosis, increased vascular inflammation, and reduced angiogenic repair after ischemia and injury (Blood 117:3929, 2011; Blood 122:1522, 2013). The hypothesis of this investigation is that polymorphisms in PRCP are associated with cardiovascular disease (CVD).METHODS: DNA from 2,243 subjects from the PEACE Trial (NEJM 351:2058, 2004) were genotyped at 2 PRCP SNPs (rs7104980, rs2298668) and 3 KLKB1 (prekallikrein) SNPs (rs4253252, rs3733402, rs3087505). These subjects were 82% female and had a history of (in decreasing frequency) angina (71%), angiographic coronary disease (66%), heart attack (58%), PTCA (44%), hypertension (42%), CABG (36%), diabetes (15%), stroke (4%), and TIA (3%). The association between single SNP alleles and different cardiovascular related phenotypes was assessed using logistic regression models. These models were adjusted for age, weight, gender, history of hypertension, and history of diabetes.RESULTS: When the logistic regression model was adjusted for age, weight, and gender, SNP rs710980 in PRCP had a 21% increased odds [odds ratio=1.211; 95% CI=(1.008, 1.454)] of having a history of PTCA if carrying the G allele (frequency of 66%) as compared to not having the G allele (frequency 34%). Additionally, adjusting the logistic regression model for history of hypertension and diabetes did not alter the odds ratio for PTCA history. However when the logistic regression model included history of hypertension and diabetes, the odds of having a history of a MI if carrying the same allele also is increased by 21% [odds ratio=1.21; 95% CI=(1.001, 1.455)]. In summary, the rs710980 intronic PRCP SNP conferred risk for CVD, while the PRCP exonic SNP rs2298668 showed no relationship in this population. Alternatively, the exonic KLKB1 SNP rs3733402 of Apple Domain 2 where high molecular weight kininogen binds conferred reduced odds of 24% [odds ratio=0.76; 95% CI=(0.622, 0.928)] of having a history of angiographic coronary disease if carrying the G allele (frequency 67%) as compared to not having the G allele (frequency of 33%). The other two KLKB1 SNPs showed no associations.DISCUSSION: These combined data on PRCP suggest that it is a risk factor for CVD. The present genetic data are consistent with biochemical, cell culture, and in vivo investigations showing that PRCP levels influence vascular biology, renal function, and metabolism. The extent of the genetic associations of PRCP polymorphisms with CVD may be resultant of the database interrogated. The PEACE trial consisted of individuals not severely ill with CVD. Its hypothesis to show that administration of ACE inhibitors leads to increased protection from mild CVD was not met. However, the present investigation showing several positive odds ratios with a certain PRCP SNP for CVD suggests that PRCP is a stronger risk factor for CVD than can be demonstrated in the PEACE subject population. PRCP should be interrogated in additional populations of subjects with CVD.Funding Support: NIH HL052779-17, HL112666-2 DisclosuresNo relevant conflicts of interest to declare.

Fragmented QRS on surface electrocardiogram is not a reliable predictor of myocardial scar, angiographic coronary disease or long term adverse outcomes.

Conflicting evidence remains regarding the value of fragmented QRS (fQRS) on surface electrocardiogram (EKG). We present the 5-year outcome of patients with fQRS on EKG and its correlation to SPECT and coronary angiography (CA). We retrospectively studied EKG's in 248 consecutive patients undergoing SPECT and CA with known or suspected coronary artery disease (CAD). The presence of fQRS or Q waves in two contiguous EKG leads was correlated with major coronary artery distributions on SPECT and cath. Patients with bundle-branch block, paced-rhythm or absence of EKG within one month of SPECT were excluded. The final EKG data for 238 patients were analyzed and compared with myocardial scar on SPECT and the presence of significant (>50%) coronary stenosis on CA. Predictors of MACE (death, MI, heart failure) were evaluated. Freedom from all-cause mortality was assessed by Kaplan-Meier analysis. Of 238 patients, no significant difference was noted in the presence of scar on SPECT in fQRS (3/77; 3.8%) versus no fQRS (11/161; 6.8%) (P=0.56); or CA based CAD (55/77; 71% fQRS) and no fQRS (99/161, 61.4%) (P=0.20). EKG Q wave presence was similar in both groups: (12/77; 15.5% fQRS), (17/161; 10.5% no fQRS) (P=0.3). Patients with CA based significant LAD disease were 3.680 times more likely to have fQRS (P=0.04), however, fQRS was not significantly associated with MACE (P=0.92) or all-cause mortality (P=0.93). This study does not support routine assessment of fQRS on surface EKG as a reliable predictor of SPECT myocardial scar, MACE or all-cause mortality over a long period of follow-up.

Abstract 18129: Sex-Based Comparison of Angina Severity, Extent of Inducible Ischemia, and Burden of Angiographic Coronary Disease: A Post Hoc Analysis of the COURAGE Trial

Background: While sex-based differences in anginal symptoms are well-described, it is unclear whether similar differences exist in the extent of inducible ischemia and angiographic findings between men and women with stable ischemic heart disease. We examined the interrelationship of angina severity, objective measures of ischemia (by myocardial perfusion imaging [MPI]), and the burden of angiographic coronary artery disease (CAD) in both men and women participants in the COURAGE trial. Methods: At baseline, 2,279 patients underwent coronary angiography and were divided into subgroups based on the number of diseased vessels and a myocardial jeopardy score to assess the extent/magnitude of inducible ischemia. Men and women were further stratified by Canadian Cardiology Society (CCS) angina class and were compared across measures of ischemia and anatomy. The 625 patients who underwent baseline stress MPI were also stratified by both angina severity and extent of angiographic CAD. Odds ratios for angina were calculated and compared by sex, after adjusting for potential confounders. Results: In the unadjusted analysis, as compared with men, women had a similar overall prevalence of angina (86.4% vs. 87.8%, p = 0.47) and mean percent ischemic myocardium (7.9% vs. 7.7%, P = 0.84), but a lower prevalence of 3-vessel CAD (14.5% vs. 24.5%, P= 0.001) and mean jeopardy score (2.3% vs. 2.5%, P = 0.08), despite exhibiting a greater proportion of CCS II-III angina (64.5% vs. 56.5%, P = 0.006); see Figure 1. After multivariable adjustment, the significantly higher prevalence of CCS Class II-III angina in women persisted. Conclusion: For any given severity of angiographic CAD or extent of myocardial ischemia, women had more moderate-severe (CCS Class II-III) angina than did men. However, this difference was more pronounced in subgroups of patients with more extensive angiographic CAD or severe ischemia by MPI, which likely reflects a greater atherosclerotic burden.

Pentraxin-3 a novel biomarker for predicting coronary artery disease

Aim: Atherosclerotic cardiovascular disease (CVD) is a chronic progressing disorder leading to the most common cause of death. Risk estimation helps health professionals to find who will take the advantage most. Pentraxin-3 (PTX-) is a member of pentraxin family which is more spesific to vascular inflammation than hs-CRP, another member of pentraxin family. In this study, we aimed to find the relationship between serum PTX-3 and hs-CRP levels and the presence of atherosclerotic heart disease. Methods: Between December 2010 and June 2011, 88 patients with stable angina pectoris referred to catheter lab were enrolled. Patients were divided into 2 groups according to the presence of angiographic coronary disease (ACD). Group 1 consisted of patients without ACD (N:33), group 2 consisted of patients with ACD (N:54) Serum PTX-3 and hs-CRP levels were obtained prior to catheterization. Results: Baseline characteristics are given at Table 1. PTX-3 levels in group 2 were significantly higher than group 1 (median 2,50 vs 1,20 ng/mL, p <0,001). However hs-CRP levels were non-significant between 2 groups (p=0,065). On multivariate analyses, PTX-3 levels (OR: 1,6 p=0,015) and male gender (OR:0,34 p=0,032) were found to be independent predictors for ACD. Cut-off value for PTX-3 level to show the presence of ACD was found to be 1,52 ng/mL (specificity %69,7, sensitivity %79,6). View this table: Table 1 Conclusion: Pentraxin 3, a novel inflammatory biomarker, is a better predictor for the presence of ACD than hs-CRP and can add more valuable information for primary prevention risk estimation.

Relation of Admission High-Density Lipoprotein Cholesterol Level and In-Hospital Mortality in Patients With Acute Non-ST Segment Elevation Myocardial Infarction (from the National Cardiovascular Data Registry)

Despite recent therapeutic advances, significant residual risk for in-hospital mortality persists among patients admitted with acute myocardial infarction (MI). Low levels of high-density lipoprotein cholesterol (HDL-C), a known independent predictor of increased cardiovascular events, may be an important modulator of heightened risk after acute MI. We evaluated admission HDL-C levels among 98,276 patients with non-ST elevation myocardial infarction with acute MI from the Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines (ACTION Registry-GWTG) program who were enrolled from 490 United States hospitals from January 2007 to December 2010. Clinical characteristics, treatments, atherosclerotic burden, and in-hospital outcomes were analyzed by quartiles of admission HDL-C (Q1: 10 to 30 mg/dl; Q2: 30.1 to 36.9 mg/dl; Q3: 37 to 45 mg/dl; and Q4: 45.1 to 100 mg/dl). Logistic regression was used to explore the relation among HDL-C quartiles, coronary artery disease severity, and in-hospital mortality. Almost half of the patients with acute MI had low admission levels of HDL-C (less than the median 36.9 mg/dl). Such patients were younger, more often men, white, obese, diabetic, smokers, and had higher rates of previous cardiovascular events. After multivariate adjustment, patients with low HDL-C levels had greater extent of severe angiographic multivessel coronary narrowings and higher mortality. Among the 26% of patients in the lowest HDL-C quartile (≤30 mg/dl), there was a 16% greater risk of in-hospital mortality compared with patients in the highest HDL-C quartile (p= 0.012). In conclusion, low levels of HDL-C were common in patients admitted with acute MI and were associated with more extensive angiographic coronary disease. Very low levels of admission HDL-C were observed in one-quarter of patients and associated with significantly higher in-hospital mortality.