Primary Coronary Artery Disease Research Articles

Behavioral, Clinical, and Coronary Artery Calcium Screening for Prevention and Treatment of Subclinical Atherosclerosis: Implications for Health Education

ABSTRACT Background In the USA, heart disease is the leading cause of death for women and men. Coronary artery disease (CAD) is the most common type of heart disease. Purpose To investigate the association between behavioral and non-behavioral risk factors associated with subclinical atherosclerosis. Methods Patients referred for a CT angiography completed a demographic/behavioral questionnaire and medical history interview for CAD risk factors. Risk factor data were correlated with CAD subclinical atherosclerosis scores for 521 participants. Results Frequency among four levels of CAD revealed: no disease 38%, mild atherosclerotic 20%, moderate atherosclerotic 30%, and severe atherosclerosis 12%. Significant (p ≤ .05) demographic variables were as follows: age, race, marital status, and employment status. Significant predictive behavioral variables were as follows: tobacco use, daily water intake, sodium consumption, exercise days per week, and junk food consumption. Risk factors significantly associated with subclinical CAD included hypertension, diabetes, sleep apnea, and abnormal coronary calcium score. Discussion Multi-slice CT angiography allows early reliable evaluation of subclinical atherosclerosis and correlation with behavioral/non-behavioral risk factors with level of CAD, instrumental to primary and secondary CAD prevention, limiting tertiary CAD treatment. Translation to Health Education Practice Study results have implications for Health Educators with regard to intervention research planning, implementation, and evaluation.

Evaluation of Polygenic Risk Scores for Prediction of Coronary Artery Disease in a Greek Case-Control Study.

Coronary artery disease (CAD) stands as the most predominant type of cardiovascular disease (CVD). Polygenic risk scores (PRSs) have become essential tools for quantifying genetic susceptibility, and researchers endeavor to improve their predictive precision. The aim of the present work is to assess the performance and the relative contribution of PRSs developed for CVD or CAD within a Greek population. The sample under study comprised 924 Greek individuals (390 cases with CAD and 534 controls) from the THISEAS study. Nine PRSs drawn from the PGS catalog were replicated and tested for CAD risk prediction. PRSs computations were performed in the R language, and snpStats was used to process genotypic data. Descriptive characteristics of the study were analyzed using the statistical software IBM SPSS Statistics v21.0. The effectiveness of each PRS was assessed using the PRS R2 metric provided by PRSice2. Among nine PRSs, PGS000747 greatly increased the predictive value of primary CAD risk factors by 21.6% (p-value = 2.63 × 10-25). PGS000012 was associated with a modest increase in CAD risk by 2.2% (p-value = 9.58 × 10-4). The remarkable risk discrimination capability of PGS000747 stands out as the most noteworthy outcome of our study.

Cardiovascular and inflammatory biomarkers for non-invasive detection of coronary artery obstruction and prediction of long-term survival in patients with suspected chronic coronary syndrome

Abstract Introduction and methods: The knowledge about diagnostic and prognostic value of cardiac and inflammatory biomarkers in patients with chronic coronary syndrome (CCS) is limited. To address this, we analyzed serum levels of selected biomarkers in 2536 patients with suspected CCS (35% female) from the Leipzig LIFE Heart Study who were admitted for coronary angiography. The median follow-up was 10 years. The following biomarkers were considered: high sensitive troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, high sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6). Patients were stratified according to the angiographic severity of coronary artery disease (CAD): CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis < 50%), CAD2 (≥ one stenosis ≥ 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2, GC2: CAD0 vs. CAD1 + 2. Using age-, sex and symptom-based pre-test probability (PTP) table for obstructive CAD (i.e. CAD 2) which was published in the current CCS guidelines, patients were further classified into the following three categories: PTP < 5% (n=559), PTP 5-15% (n=545) and PTP > 15% (n=1432). Results CAD0, CAD1, CAD2 were apparent in 999, 529, and 1008 patients, respectively. Upon adjustment for traditional risk factors (TRF) the levels of hsTNT, NT-proBNP and IL-6 showed significant difference in GC1 (hsTNT: p=2.0x10-10, NT-proBNP: p=0.049, IL6: p=0.030). In GC2 only elevated hsTNT remained significant (p=1.9x10-7). In the ROC analysis only hsTNT slightly improved the AUC for the GC1-comparison in addition to TRF (0.729 with vs 0.712 witt hsTNT, p=0.013). Within the PTP subcategories the following results were obtained: PTP < 5%: AUC 0.747 with vs 0.730 without hsTNT, p=0.017; PTP 5-15 %: AUC 0.636 with vs 0.670 without hsTNT, p<0.001; PTP > 15%: AUC 0.699 with vs 0.677 without hsTNT, p= 0.024). In PTP 5-15% subgroup TropT cut-off value < 3 pg/mL (N= 119 / 23.4%) showed sensitivity of 89.7% and specificity of 73.1% for CAD2 detection. Ten years survival in groups CAD0, CAD1, CAD2 were 88.3%, 77.3%, 72.4%, respectively. In the multivariate analysis elevated hsTNT, NT-proBNP, copeptin and IL-6 remained significant mortality predictors in CAD2 patients with hazard ratios of similar magnitude (i.e. 1.5, 1.3, 1.4 and 1.3 per unit on the log-scale of the parameters, respectively). hsCRP did not reach significance. In the model stratified into tertiles according to the effects of classical risk factors and the joint biomarker levels for except hsCRP, hazard rates were 3.13 (tertile 2 vs 1) and 11.2 (tertile 3 vs 1). Conclusions In the present study hsTNT substantially improved the detection of obstructive CAD particularly in patients with intermediate PTP 5-15%. Furthermore, the studied biomarkers enable fast and precise non-invasive prediction of mortality risk in patients with suspected CCS, allowing tailored primary and secondary CAD prevention in this high-risk group.

Biomarkers for Non-Invasive Stratification of Coronary Artery Disease and Prognostic Impact on Long-Term Survival in Patients with Stable Coronary Heart Disease.

Knowledge about cardiac and inflammatory biomarkers in patients with stable coronary artery disease (CAD) is limited. To address this, we analyzed 3072 patients (36% female) with a median follow-up of 10 years in the Leipzig LIFE Heart Study with suspected CAD with coronary angiography. Selected biomarkers included troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, C-reactive protein (hsCRP), and interleukin-6 (IL-6). Patients were stratified by CAD severity: CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis < 50%), and CAD2 (≥one stenosis ≥ 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2; GC2: CAD0 vs. CAD1 + 2. CAD0, CAD1, and CAD2 were apparent in 1271, 631, and 1170 patients, respectively. Adjusted for classical risk factors, hs-cTnT, NT-proBNP, and IL-6 differed significantly in both GC and hsCRP only in GC2. After multivariate analysis, hs-cTnT, NT-proBNP, and IL-6 remained significant in GC1. In GC2, hs-cTnT (p < 0.001) and copeptin (p = 0.014) reached significance. Ten-year survival in groups CAD0, CAD1, and CAD2 was 88.3%, 77.3%, and 72.4%. Incorporation of hs-cTnT, NT-proBNP, copeptin, and IL-6 improved risk prediction (p < 0.001). The studied cardiac and inflammatory biomarkers enable fast and precise non-invasive identification of mortality risk in CAD patients, allowing the tailoring of primary and secondary CAD prevention.

Classical risk factors for primary coronary artery disease from an aging perspective through Mendelian Randomization.

The significance of classical risk factors in coronary artery disease (CAD) remains unclear in older age due to possible changes in underlying disease pathologies. Therefore, we conducted Mendelian Randomization approaches to investigate the causal relationship between classical risk factors and primary CAD in different age groups. A Mendelian Randomization study was conducted in European-ethnicity individuals from the UK Biobank population. Analyses were performed using data of 22,313 CAD cases (71.6% men) and 407,920 controls (44.5% men). Using logistic regression analyses, we investigated the associations between standardized genetic risk score and primary CAD stratified by age of diagnosis. In addition, feature importance and model accuracy were assessed in different age groups to evaluate predictive power of the genetic risk scores with increasing age. We found age-dependent associations for all classical CAD risk factors. Notably, body mass index (OR 1.22 diagnosis < 50years; OR 1.02 diagnosis > 70years), blood pressure (OR 1.12 < 50years; OR 1.04 > 70years), LDL cholesterol (OR 1.16 < 50years; OR 1.02 > 70years), and triglyceride levels (OR 1.11 < 50years; 1.04 > 70years). In line with the Mendelian Randomization analyses, model accuracy and feature importance of the classical risk factors decreased with increasing age of diagnosis. Causal determinants for primary CAD are age dependent with classical CAD risk factors attenuating in relation with primary CAD with increasing age. These results question the need for (some) currently applied cardiovascular disease risk reducing interventions at older age.

Coronary Artery Disease in Patients Older than 35 and Eligible for Cardiovascular Secondary Prevention: An Italian Retrospective Observational Analysis of Healthcare Administrative Databases.

Background: This study describes patients with coronary artery disease (CAD) who are eligible for secondary prevention and assesses their healthcare consumption and costs from the perspective of the Italian National Health Service (INHS). Methods: From the Fondazione Ricerca e Salute’s database, which collects Italian healthcare administrative data, all patients aged ≥ 35, with ≥1 primary in-hospital CAD diagnosis and/or procedure on the coronary arteries, or with the specific disease exemption code, and who are suitable for long-term secondary prevention treatments, were identified in 2018 and analyzed. Demographics, comorbidities, one-year supplied drugs, hospitalizations, and costs were analyzed. Results: From >3 million inhabitants aged ≥ 35, 46,063 (1.3%) were identified (72.1% males, mean age 70 ± 12; approximately 50% with ≥3 comorbidities). During a one-year follow-up, 96.4% were treated with ≥1 drug for secondary prevention (mainly antiplatelets and lipid lowering agents), 69.4% with ≥1 concomitant cardiovascular drug, and 95.8% with ≥1 concomitant non-cardiovascular therapy. Within one year, 30.6% of patients were hospitalized at least once, mostly due to non-cardiovascular events. Calculated by mean, the INHS paid EUR 6078 per patient. Conclusions: This analysis confirms the relevant burden of CAD for patients with many comorbidities and who are frequently hospitalized, and the burden on the INHS. A multidisciplinary healthcare approach is encouraged to improve patients’ outcomes and reduce costs for the INHS.

Classical risk factors for primary coronary artery disease from an ageing perspective through Mendelian randomization

Background and Aims: The significance of classical risk factors in coronary artery disease (CAD) remain unclear in older age due to possible changes in underlying disease pathologies. Therefore, we conducted a combined Mendelian Randomization and Machine Learning approach to investigate the causal relationship between classical risk factors and primary CAD in different age groups.

Validation and comparison of 28 risk prediction models for coronary artery disease.

Risk prediction models (RPMs) for coronary artery disease (CAD), using variables to calculate CAD risk, are potentially valuable tools in prevention strategies. However, their use in the clinical practice is limited by a lack of poor model description, external validation, and head-to-head comparisons. CAD RPMs were identified through Tufts PACE CPM Registry and a systematic PubMed search. Every RPM was externally validated in the three cohorts (the UK Biobank, LifeLines, and PREVEND studies) for the primary endpoint myocardial infarction (MI) and secondary endpoint CAD, consisting of MI, percutaneous coronary intervention, and coronary artery bypass grafting. Model discrimination (C-index), calibration (intercept and regression slope), and accuracy (Brier score) were assessed and compared head-to-head between RPMs. Linear regression analysis was performed to evaluate predictive factors to estimate calibration ability of an RPM. Eleven articles containing 28 CAD RPMs were included. No single best-performing RPM could be identified across all cohorts and outcomes. Most RPMs yielded fair discrimination ability: mean C-index of RPMs was 0.706 ± 0.049, 0.778 ± 0.097, and 0.729 ± 0.074 (P < 0.01) for prediction of MI in UK Biobank, LifeLines, and PREVEND, respectively. Endpoint incidence in the original development cohorts was identified as a significant predictor for external validation performance. Performance of CAD RPMs was comparable upon validation in three large cohorts, based on which no specific RPM can be recommended for predicting CAD risk.

A critical review of chronic kidney disease as a risk factor for coronary artery disease.

Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD). In addition to common CVD risk factors, the presence of CKD is independently associated with an elevated cardiovascular (CV) risk. We examined the association between CKD and CVD, focusing on coronary artery disease (CAD) in both primary and secondary CVD. A total of 94 articles were included for this review using search strategies on Pubmed and Google scholar. The main findings of our review included that besides sharing common risk factors, CKD induces several physiological microscopic changes leading to increased CV risk. These microscopic changes manifest macroscopically with evidence of the development of primary CAD in CKD patients, in addition to accelerating CAD in those with pre-established CV pathology, with CKD consequently being a risk factor for both primary and secondary CAD progression. Current CV guideline recommendations do not discriminate between those patients with and without CKD. Future research is needed in this area, examining if there may be a role for tighter modifiable risk factor targets in this high-risk population.

Circulating MicroRNA-423-3p Improves the Prediction of Coronary Artery Disease in a General Population - Six-Year Follow-up Results From the China-Cardiovascular Disease Study.

Circulating microRNAs (miRNA) are potential prognostic biomarkers for cardiovascular disease. We aimed to identify serum miRNA as an effective predictor for coronary artery disease (CAD) events in a general population cohort. Serum miRNAs associated with CAD were determined by small RNA sequencing and quantitative RT-PCR. Further, the predictive ability of identified serum miRNAs was measured in a general population of 2,812 people. As a main outcome measure, CAD events were collected for 6 years and included acute myocardial infarction and subsequent myocardial infarction. Out of the 48 miRNA candidates, 5 miRNAs (miR-10a-5p, miR-126-3p, miR-210-3p, miR-423-3p and miR-92a-3p) showed better reliability and repeatability in serum. Then, the association of serum levels of the 5 miRNAs with CAD was validated. Furthermore, miR-10a-5p and miR-423-3p, which showed better performance, were tested in the large cohort, with a median follow up of 6.0 years. In multivariable Cox regression analysis, only miR-423-3p (P for trend<0.001) was able to precisely predict CAD events. Moreover, the addition of circulating miR-423-3p with the traditional risk factors together markedly improved the various model performance measures, including the area under the operating characteristics curve (0.782 vs. 0.806), Akaike Information Criterion (965.845 vs. 943.113) and net reclassification improvement (19.18%). Circulating miR-423-3p can improve the prediction of primary CAD outcomes on the basis of a traditional risk factor model in general population.

Canonical Correlation between Behavioral-Psychological Variables and Predictors of Coronary Artery Disease Prognosis.

Metabolic syndrome (MetS) and severity of coronary artery disease (CAD) are considered predictors of CAD prognosis. Unhealthy lifestyles and type-D personality are associated with MetS and are potential causes of primary and secondary CAD. In this cross-sectional descriptive study, we aimed to investigate the relationship between behavioral-psychological variables and predictors of CAD prognosis. The behavioral-psychological variable set contained six lifestyle categories and two type-D personality categories. Descriptive analyses, t-tests, analysis of variance, Pearson’s correlation, and canonical correlation were used. The behavioral-psychological variable set was related to the predictor set for CAD prognosis, with a significant canonical variate of 0.67 (45% overlapping variance). Significant pairs of canonical variates indicated that poor physical activity and weight control (−0.77), poor dietary habits (−0.78), alcohol consumption and cigarette smoking (−0.37), lack of sleep and rest (−0.40), stress (−0.64) in the lifestyle set, higher negative affectivity (0.52), and social inhibition (0.71) in the type-D personality set were associated with a high MetS score (0.59) and severity of CAD (0.91). A combination of behavioral and psychological variables was found to be important in predicting the prognosis of CAD; therefore, interventions aimed at preventing combinations of these variables may be effective in improving CAD prognosis.

Coronary artery disease risk reduction in HIV-infected persons: a comparative analysis

ABSTRACTDespite an increased risk of coronary artery disease (CAD) in persons infected with human immunodeficiency virus (HIV), few data are available on primary prevention of CAD in this population. In this retrospective cohort study, HIV-infected patients treated in an academic medical center HIV Specialty Clinic between 1996 and 2010 were matched by age, gender, and ethnicity to a cohort of presumed uninfected persons followed in an academic medical center Internal Medicine primary care clinic. We compared CAD primary prevention care practices between the two clinics, including use of aspirin, HMG-CoA reductase inhibitors (“statins”), and anti-hypertensive drugs. CAD risk between the two groups was assessed with 10-year Framingham CAD risk scores. In the comparative analysis, 890 HIV-infected persons were compared to 807 controls. Ten-year Framingham CAD Risk Scores were similar in the two groups (median, 3; interquartile range [IQR], 0–5). After adjusting for relevant risk factors, HIV-infected persons were less likely to be prescribed aspirin (odds ratio [OR] 0.53; 95% confidence interval [CI], 0.40–0.71), statins (OR, 0.70; 95% CI, 0.53–0.92), and anti-hypertensive drugs (OR, 0.63; 95% CI, 0.50–0.79) than persons in the control group. In summary, when compared to demographically similar uninfected persons, HIV-infected persons treated in an HIV specialty clinic were less likely to be prescribed medications appropriate for CAD risk reduction. Improving primary preventative CAD care in HIV specialty clinic populations is an important step toward diminishing risk of heart disease in HIV-infected persons.

Urinary proteomic biomarkers to predict cardiovascular events.

We have previously demonstrated associations between the urinary proteome profile and coronary artery disease (CAD) in cross-sectional studies. Here, we evaluate the potential of a urinary proteomic panel as a predictor of CAD in the hypertensive atherosclerotic cardiovascular disease (HACVD) substudy population of the Anglo-Scandinavian Cardiac Outcomes Trial study. Thirty-seven cases with primary CAD endpoint were matched for sex and age to controls who had not reached a CAD endpoint during the study. Spot urine samples were analyzed using CE coupled to Micro-TOF MS. A previously developed 238-marker CE-MS model for diagnosis of CAD (CAD238 ) was assessed for its predictive potential. Sixty urine samples (32 cases; 28 controls; 88% male, mean age 64 ± 5 years) were analyzed. There was a trend toward healthier values in controls for the CAD model classifier (-0.432 ± 0.326 versus -0.587 ± 0.297, p = 0.170), and the CAD model showed statistical significance on Kaplan-Meier survival analysis p = 0.021. We found 190 individual markers out of 1501 urinary peptides that separated cases and controls (AUC >0.6). Of these, 25 peptides were also components of CAD238 . A urinary proteome panel originally developed in a cross-sectional study predicts CAD endpoints independent of age and sex in a well-controlled prospective study.

Late-outgrowth endothelial progenitors from patients with coronary artery disease: Endothelialization of confluent stromal cell layers

Patients with coronary artery disease (CAD) are the primary candidates to receive small-diameter tissue-engineered blood vessels (TEBVs). Peripheral blood derived endothelial progenitor cells (EPCs) from CAD patients (CAD EPCs) represent a minimally invasive source of autologous cells for TEBV endothelialization. We have previously shown that human CAD EPCs are highly proliferative and express many of the hallmarks of mature and healthy endothelial cells; however, their behavior on stromal cells that comprise the media of TEBVs has not yet been evaluated. Primary CAD EPCs or control human aortic endothelial cells (HAECs) were seeded over confluent, quiescent layers of human smooth muscle cells (SMCs) using a direct co-culture model. The percent coverage, adhesion strength, alignment under flow and generation of flow-induced nitric oxide of the seeded CAD EPCs were compared to that of HAECs. The integrin-binding profile of CAD EPCs was also evaluated over a layer of confluent, quiescent SMCs. Direct comparison of our CAD EPC results to analogous co-culture studies with cord blood EPCs show that both types of blood-derived EPCs are viable options for endothelialization of TEBVs.

Abstract 516: Urinary Proteomic Biomarkers to Predict Cardiovascular Events

We have previously demonstrated associations between the urinary proteome profile and coronary artery disease (CAD) in cross-sectional studies. Here we evaluated the potential of urinary proteomics as a predictor of CAD in the Hypertension Associated Cardiovascular Disease (HACVD) sub-study population of the ASCOT study. Thirty-seven cases with the primary endpoint CAD (fatal CAD, non-fatal myocardial infarction and coronary revascularisation) but without established cardiovascular disease at baseline were selected and matched for sex and age within ±2 years to controls who had not reached a CAD endpoint during the study (median observation time, 5 years). A spot urine sample collected at 1 to 1.5 years post randomisation was analysed using capillary electrophoresis (CE) on-line coupled to Micro-TOF mass spectrometry (MS). A previously developed 238-marker CE-MS model for diagnosis of CAD (CAD 238 ) was assessed for its predictive potential. Sixty urine samples (32 cases; 28 controls; 88% male, mean age 64±5 years) passed quality control for proteomic analysis. There was a trend towards lower ("healthier") values in controls for the CAD model classifier (-0.432±0.326 vs -0.587±0.297, P =0.062), and the CAD model showed statistical significance on Kaplan-Meier survival analysis (Log Rank (Mantel-Cox) P =0.021). After unblinding we found 190 individual markers out of 1501 urinary peptides that separated cases and controls with an AUC&gt;0.6. Of these, 28 peptides including fragments of PGRC1, PTGDS, CO1A1, CO3A1, COGA1, PXDC2, B3GT6 and RET4 were also components of CAD 238 . A urinary proteome panel that was originally developed in a cross-sectional study predicts CAD endpoints independent of age and sex in a well controlled prospective study. Proteomic analysis may have the potential to detect subclinical cardiovascular damage that is associated with increased cardiovascular risk.

POTENTIAL ROLE OF CYTOTOXIC CD4+CD28null Т LYMPHOCYTES AND CIRCULATING ENDOTHELIAL CELLS IN CARDIOVASCULAR RISK ASSESSMENT

Aim. To analyze usability of circulating endothelial cells’ (CECs) and CD4 + CD28null Т cells’ blood levels along with classic factors for cardiovascular risk stratification in healthy individuals. Methods. 31 healthy adults aged 43.9±8.5 yrs. without the coronary artery disease (CAD) were scrutinized in order to assess a cardiovascular risk profile and measure the levels of systemic inflammation marker high sensitive C-reactive protein (hsCRP). Using flow cytometry, we measured CECs and CD4 + CD28null Т cells’ concentrations. Results. Excessive body mass/obesity occupied the 1 st place (54.8 %) among all the risk factors. 38.7 % of the individuals suffered from dyslipidemia. BP level correlated both with BMI (p sp. = 0.465; p = 0.008) and hsCRP concentration (p sp. = 0375, p = 0.031). The level of CD4+CD28null Т cells was higher in the persons with LDL-cholesterol concentration that exceeded Me (3.29 mmol/l): 2.48 ± 1.64 vs. 5.13 ± 3.78 % (p = 0.020). The frequency of CECs varied from 0 to 5 760 cells in 1 ml, BMI being higher in adults with CECs detection: 26.9 ± 0.5 vs. 24.5 ± 0.8 kg/m 2 (p = 0,048). Conclusions. Excessive body mass/obesity and dyslipidemia are associated with endothelial dysfunction markers CD4 + CD28null Т cells и CECs allowing to discuss their significance in primary CAD prevention.

Identification of Noncalcified Plaque in Young Persons with Diabetes: An Opportunity for Early Primary Prevention of Coronary Artery Disease Identified with Low-dose Coronary Computed Tomographic Angiography

Coronary computed tomographic angiography (CTA) is a valuable tool for assessing coronary artery disease (CAD). Although statin use is widely recommended for persons with diabetes older than age 40, little is known about the presence and severity of CAD in younger patients with diabetes mellitus (DM). We evaluated coronary artery calcium (CAC) and coronary CTA in young persons with both DM1 and DM2 in an attempt to detect the earliest objective evidence of arteriosclerosis eligible for primary prevention. We prospectively enrolled 40 persons with DM (25 type 1 and 15 type 2) between the ages of 19 and 35 presenting with diabetes for 5 years or longer. All patients underwent coronary CTA and CAC scans to evaluate for early atherosclerotic disease. Each plaque in the coronary artery was classified as noncalcified or calcified-mixed. We also evaluated all segments with stenosis, dividing them into mild (<50%), moderate (50-70%), and severe (>70%). The average age of the DM1 subjects were 26 ± 4 (SD) years and 30 ± 4 years for DM2 patients (P < .01), with duration of diabetes of 8 ± 5 years and average HbA1c% of 8.7 ± 1.6 (norm = 4.6-6.2). Abnormal scans were present in 57.5%, noncalcified in 35% and calcified-mixed plaque in 22.5%. Persons with DM2 had a higher prevalence of positive coronary CTA scans than DM1: 80% versus 44% (P<.03) and more positive CAC scores 53% versus 4%, (P < .01). The total segment score of 2.1 ± 3.4 (P < .01) and total plaque score 1.9 ± 2.8 (P < .01) were highly correlated to each other. Plaque was almost uniformly absent below age 25, and became increasingly common in individuals over the age of 25 years for both groups. The average radiation exposure was 2.5 ± 1.3 mSv. Our study verifies that early CAD can be diagnosed with coronary CTA and minimal radiation exposure in young adults with DM. A negative CAC score was not sufficient to exclude early CAD as we observed a preponderance of noncalcified plaque in this cohort. Coronary CTA in young DM patients older than age 25 may provide earlier identification of disease than does a CAC because only noncalcified plaque is frequently present. Coronary CTA provides an opportunity to consider initiation of earlier primary CAD prevention rather than waiting for the age of 40 as currently recommended by the American Diabetes Association guidelines.

Abstract P334: Gender Disparities in Cholesterol Control Among Patients with Diabetes

Background: It has been reported that women often receive less aggressive primary and secondary prevention for cardiovascular disease. Diabetes decreases the cardiovascular protection that women experience, and is considered a coronary heart disease equivalent. National diabetes guidelines thus recommend similar LDL-cholesterol (LDL-c), blood pressure, and hemoglobin A1c (HbA1c) goals for men and women. Methods: We conducted a retrospective, longitudinal study in a cohort of 6,573 patients with incident type 2 diabetes at Kaiser Permanente Colorado (2000-2008). We examined LDL-c, blood pressure, and HbA1c at the time of diagnosis (baseline) and after one year follow-up. We identified baseline coronary artery disease (CAD) via diagnosis codes. Results: Women and men had similar age and race distributions. Women were more likely to be never smokers and had higher BMI (34.0 vs. 31.9 kg/m 2 ), while men were more likely to be former smokers and have CAD (20.9% vs. 9.8%). Men had slightly higher baseline HbA1c, but the difference disappeared at follow-up. No gender differences were seen for blood pressure. Women had higher baseline LDL-c ( Table , p-value &lt;0.0001), with 79% of the initial difference persisting after one year (p-value &lt;0.0001). Women were less likely to have LDL-c &lt; 100 mg/dL at one year follow-up (50.7% vs. 57.2%). In both genders, LDL-c was lower among individuals with CAD than those without CAD. Baseline CAD accounted for 35% of the follow-up LDL-c gender difference. At follow-up, women were slightly less likely to be taking a statin (40% vs. 38%). Conclusions: Even with population-based case-management programs aimed at cholesterol management, fewer women than men met the recommended LDL-c goal of &lt; 100 mg/dL one year after diabetes diagnosis. Some of the difference can be attributed to differences in CAD prevalence. These findings suggest that diabetes is often not treated as a CAD equivalent in clinical care, and greater emphasis should be placed on primary CAD prevention among both men and women with diabetes. Table LDL-c (mg/dL) by gender and baseline CAD status Women Men Mean difference Mean (SD) Median Mean (SD) Median Baseline No CAD 121.5 (37.0) 119.0 117.4 (36.4) 115.0 4.1 CAD 94.0 (35.0) 88.0 89.1 (29.1) 86.0 4.9 Total 118.8 (37.7) 116.0 111.5 (36.8) 109.0 7.3 Follow-up No CAD 106.0 (33.7) 102.0 102.2 (31.1) 100.0 3.8 CAD 86.5 (32.8) 82.0 82.9 (26.5) 79.0 3.6 Total 104.0 (34.1) 100.0 98.2 (31.2) 95.0 5.8

Accelerated smooth muscle cell apoptosis in occluded aorto-coronary saphenous vein grafts

It has been suggested that apoptosis contributes to the pathogenesis of atherosclerosis and to the instable plaque syndrome. The role of apoptosis in aorto-coronary venous graft occlusion is unknown. Therefore, we compared the occurrence of smooth muscle cell (SMC) apoptosis and apoptosis-related molecular markers in occluded vein grafts (CABG) with native coronary artery disease. Neointimal SMC of occluded CABG (n=30) and desobliterates from occluded native coronary arteries (n=65) were immunohistochemically stained in situ for the detection of p53, bax, bcl-2 and TUNEL (TdT-mediated dUTP-biotin nick endlabeling). The occurrence of apoptosis-promoting molecular markers and concomitant SMC apoptosis (% positive stained SMC ± SE) was significantly increased in occluded CABG compared to coronary artery desobliterates (p53: 6.8±2.3 versus 0 p<0.005; bax: 5.4±1.5 versus 3.6±0.9 p<0.05; TUNEL: 3.8±1.7 versus 1.1±0.4 p<0.05). SMC apoptosis is significantly increased in occluded venous grafts compared to primary coronary artery disease, and may play a role in the pathogenesis of vein graft disease. The documented increase in apoptosis-promoting molecular markers could be the basis for new therapeutic strategies for the prevention of venous graft occlusion.

Diagnostic performance of magnetic resonance first pass perfusion imaging is equally potent in female compared to male patients with coronary artery disease

Noninvasive diagnosis of coronary artery disease (CAD) in women is crucial because of a lower prevalence of CAD in premenopausal women, different cardiac risk profile and pattern of CAD, lower exercise tolerance and more atypical symptoms compared to men. Therefore, we tested the diagnostic power of cardiac magnetic resonance first pass perfusion imaging (CMR-FPPI) for the diagnosis of significant coronary stenoses in females versus males. 256 consecutive patients, 77 females and 179 males with atypical or typical chest pain and intermediate risk of CAD were studied by coronary angiography and CMR-FPPI (1.5T Intera CV). A three-slice, short-axis perfusion scan with a saturation prepulse was performed during infusion of adenosine and at rest followed by late enhancement imaging for myocardial scar. Gadolinium-DTPA was administered at 0.1 mmol/kg body weight. Perfusion images were visually analysed, coronary stenoses by quantitative coronary angiography. Sensitivity, specificity and accuracy of CMR-FPPI for detection of a significant coronary artery stenosis (> or = 50% luminal narrowing) in the entire group were 91.3, 81.7 and 88.6%, the corresponding values for females were 90.9, 90.6 and 90.8% and for males 91.4, 74.4 and 87.7%, and in the subgroup of females with suspected primary CAD 83.3, 96.0 and 93.6%, and for suspected progression 92.1, 71.4 and 88.9%. Diagnostic accuracy of CMR-FPPI is very high in women with intermediate risk of CAD and comparable or in part superior to results in males. With the advantage of the absence of radiation exposure and high spatial and temporal resolution, CMR-FPPI has the potential to become the preferred imaging test to select women for coronary angiography.