Coronary Artery Risk Research Articles

Abstract P019: Compensatory Hyperinsulinemia Is An Independent Risk Factor For Atherosclerotic Cardiovascular Disease: CARDIA 30-year Follow Up

Introduction: Compensatory hyperinsulinemia (CH) is the heightened response of thepancreas and liver to early insulin resistance. Elevated blood insulin compensates for insulin resistance in tissues, maintainingfasting glucose, triglycerides and HDL-cholesterol within normal limits. Individuals with CH, as defined here, do notmeet the harmonized criteria for metabolic syndrome and elude screening for cardiovascularrisk. Previously, we reported that CH isprevalent in the U.S., especially in teenagers, young adults, Hispanic andBlack populations. However, it wasunclear whether CH increases the risk of future atherosclerotic cardiovasculardisease (ASCVD) or simply is a benign adaptation to energy imbalance. Hypothesis: Compensatory hyperinsulinemia is an independentrisk factor for ASCVD. Methods: We conducted a retrospectivecohort study of CARDIA: Coronary ArteryRisk Development in Young Adults. Theparent study enrolled 5,113 participants, ages 18-30 at baseline, with studyvisits every five years for a mean follow up of 30 years. In our study, the baseline exclusion criteriawere hyperglycemia, hypertriglyceridemia and low HDL-C (all using metabolicsyndrome cutpoints), as well as pregnancy, fasting <8 hours, baseline diabetesor cardiovascular disease. The resulting 3,292 participants wereanalyzed using Cox models that included CH, as well as the 2019 ACC/AHA riskfactors for ASCVD: hypertension, LDL ≥160mg/dL, family history of premature ASCVD, elevated waist circumference or BMI, fitness,race, nicotine use (serum cotinine) and estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m 2 . Theprimary outcome was time to incident ASCVD. The effect size was hazard ratio (HR) with 95% confidence intervals (CI). Results: In an adjusted Cox model that included CH, waistcircumference and the other ACC/AHA risk factors mentioned above, CH atbaseline was an independent risk factor for ASCVD: HR 1.86, 95% CI: 1.32, 2.61, p=0.0004. The other risk factors were significantexcept for race, eGFR, fitness and waist circumference. In an adjusted Cox model that substituted BMIcategory (≥25 vs. <25 kg/m 2 ) for elevated waist circumference, CHremained significant: HR 1.74, 95% CI:1.23, 2.46, p=0.0017. In that model, overweight/obesewas statistically significant as well (p=0.0289). To assess possible effect modificationbetween CH and BMI, a Cox model incorporating an interacting categorical variablerevealed that CH is a significant risk factor in overweight/obese participants (HR3.52, 95% CI: 1.76, 7.03, p=0.0004), but not those with BMI<25 (HR 1.23, 95%CI: 0.79, 1.94, p=0.3476). Thisobservation was confirmed using Cox models stratified by BMI category. Conclusion: After adjusting for canonical risk factors, compensatoryhyperinsulinemia is an independent risk factor for future ASCVD among CARDIA participantswho were overweight or obese at baseline.

Study to Evaluate Coronary Artery Disease Prevalence and Risk Factors in Heart Failure Patients with Reduced Ejection Fraction

Introduction: Even though heart failure (HF) is a major global health problem, studies on the prevalence and etiology of HF in Nepal are scant. The aim of this study was to assess the prevalence and risk factors of coronary artery disease (CAD) in HF with reduced ejection fraction (HFrEF) using invasive coronary angiography (CAG).
 Methods: This was a prospective, cross-sectional, descriptive observational study conducted from July 2020 to September 2021. All consecutive patients with HFrEF who met the inclusion criteria underwent CAG at Manipal Teaching Hospital were evaluated and analyzed using various statistical tools.
 Results: Total 108 patients with a male to female ratio of 2.02:1 were assessed. The mean age of patients was 63+6.08 years. The prevalence of CAD was 72% of which 42% were having significant CAD (stenosis >50%) with 45%, 32% and 23% having triple (TVD), double (DVD) and single vessel disease (SVD) respectively Smoking was the commonest risk factor (61%) followed by hypertension (52%), dyslipidemia (27%) and diabetes (22%). The prevalence of CAD increased with increase in the number of risk factors. There was significant association of smoking (OR: 11.5, P: 0.005), hypertension (OR: 8.5, P: 0.002) and diabetes (OR: 10, P: 0.001) for occurrence of significant CAD.
 Conclusion: In our study, otherwise unexplained HFrEF showed overall 72% of CAD with 42% having significant CAD (stenosis >50%). Conventional risk factors like smoking, hypertension and diabetes were significantly associated with development of CAD.

Abstract 10363: Mitochondrial DNA Copy Number is Associated with Severe Coronary Artery Disease and Risk of Subsequent Long-Term Major Adverse Cardiovascular Events

Introduction: Mitochondrial DNA copy number (mtDNA-CN) is associated with cardiovascular disease (CVD) and mortality. Here we examine, in a high-risk CVD population, the association with prevalent coronary artery disease (CAD) and subsequent major adverse events (MACE) at 1-,5- and 10-year follow-up of mtDNA-CN. Methods: Consecutive subjects (n=2267) consenting to a blood sample drawn for the Intermountain INSPIRE biorepository at the time of a coronary angiogram from July 1994 to Sept 2003 were included. The mtDNA-CN was determined by multiplexed real-time polymerase chain reaction coamplifying a stable site of mt D- Loop and a region of a single copy genomic β-2-microglobulin gene(β2M). MtDNA-CN is given as the ratio of Mt to β2M DNA. The presence of severe CAD (>70% stenosis) was analyzed using multivariate logistic regression. The subsequent MACE (including all-cause mortality and non-fatal MI) outcomes were studied using multivariate Cox proportional hazard regression. Results: The average age of subjects was 62.3 ± 13.8, 35% were female, and 50% had prior CAD. Over half (55%) had severe CAD at the angiogram. As the mtDNA-CN increased, severe CAD decreased (58% for 1 st quartile vs. 51% for 4 th quartile). After adjustment for baseline differences, subjects with mtDNA-CN in the 1 st quartile were 1.31 times more likely to have severe CAD than subjects with mtDNA-CN in the 4 th quartile (95% CI: 1.01, 1.71; p=0.04). A total of 902(39.8%) had a subsequent MACE event within 10-years (193[8.5%] in 1-year and 548[24.2%] in 5-years). There was no association between mtDNA-CN and 1-year MACE. However, mtDNA-CN was associated with 5-year (p=0.006) and 10-year (p=0.003) MACE. After adjustment, subjects with mtDNA-CN in the 1 st quartile were at 1.29 increased risk of 10-year MACE than subjects with mtDNA-CN in the 4 th quartile (95% CI: 1.07, 1.56; p=0.008). Conclusions: In a coronary angiographic population, mtDNA-CN was associated with severe CAD and the risk of subsequent long-term MACE. These findings suggest that mtDNA-CN could be used as a clinical biomarker for risk. Moreover, understanding the factors impacting mtDNA-CN may also help in the prevention of secondary CVD outcomes.

Genetic and epigenetic associations of ANRIL with coronary artery disease and risk factors

BackgroundBoth DNA genotype and methylation of antisense non-coding RNA in the INK4 locus (ANRIL) have been robustly associated with coronary artery disease (CAD), but the interdependent mechanisms of genotype and methylation remain unclear.MethodsEighteen tag single nucleotide polymorphisms (SNPs) of ANRIL were genotyped in a matched case–control study (cases 503 and controls 503). DNA methylation of ANRIL and the INK4/ARF locus (p14ARF, p15INK4b and p16INK4a) was measured using pyrosequencing in the same set of samples (cases 100 and controls 100).ResultsPolymorphisms of ANRIL (rs1004638, rs1333048 and rs1333050) were significantly associated with CAD (p < 0.05). The incidence of CAD, multi-vessel disease, and modified Gensini scores demonstrated a strong, direct association with ANRIL gene dosage (p < 0.05). There was no significant association between ANRIL polymorphisms and myocardial infarction/acute coronary syndrome (MI/ACS) (p > 0.05). Methylation levels of ANRIL were similar between the two studied groups (p > 0.05), but were different in the rs1004638 genotype, with AA and AT genotype having a higher level of ANRIL methylation (pos4, p = 0.006; pos8, p = 0.019). Further Spearman analyses indicated that methylation levels of ANRIL were positively associated with systolic blood pressure (pos6, r = 0.248, p = 0.013), diastolic blood pressure (pos3, r = 0.213, p = 0.034; pos6, r = 0.220, p = 0.028), and triglyceride (pos4, r = 0.253, p = 0.013), and negatively associated with high-density lipoprotein cholesterol (pos2, r = − 0.243, p = 0.017). Additionally, we identified 12 transcription factor binding sites (TFBS) within the methylated ANRIL region, and functional annotation indicated these TFBS were associated with basal transcription. Methylation at the INK4/ARF locus was not associated with ANRIL genotype.ConclusionsThese results indicate that ANRIL genotype (tag SNPs rs1004638, rs1333048 and rs1333050) mainly affects coronary atherosclerosis, but not MI/ACS. There may be allele-related DNA methylation and allele-related binding of transcription factors within the ANRIL promoter.

Younger patients have an increased risk for dementia after coronary artery bypass grafting, a population-based cohort study from the SWEDEHEART registry

Abstract Background Previous studies investigating the association between coronary artery bypass grafting (CABG) and risk for dementia show conflicting results. Purpose To compare the long-term risk for dementia in CABG patients to matched individuals in the general population, and to identify independent predictors for developing dementia after CABG. Methods Data from the SWEDEHEART registry and three other mandatory national registries were merged to compare all patients who underwent isolated CABG in Sweden from 1992 to 2015 (n=111.335) with an age- and sex-matched control individuals from the general population (n=222.396). Cumulative incidence adjusted for the competing risk for death and Cox regression models with Hazard Ratio (HR) and 95% confidence interval (CI) adjusted for age, gender, co-morbidity and socioeconomic variables, were used to calculate the risk of dementia. Median follow-up was 10.1 years (IQR 2.5–14.7) among CABG patients and 10.7 years (5.6–15.7) among the controls. Identified interactions of the excess risk for dementia with sex and age categories (&amp;lt;65, 65-&amp;lt;75, ≥75 years) resulted in analyses being stratified on those sub-cohorts. Results The overall cumulative incidence at 20 years follow up of all-cause dementia was 9.6% (95% CI 9.4–9.9) among CABG patients and 9.0 (8.8–9.2) among individuals in the general population. The adjusted relative risk for all-cause dementia was increased among CABG patients &amp;lt;65 years and 65–75 years, (HR 1.29 (95% CI 1.17–1.41) and HR 1.06 (1.01–1.11), respectively (fig 1). The risk for all-cause dementia was higher in CABG women than in CABG men (HR 1.62 (1.30–2.03) vs HR 1.22 (1.10–1.35)). In the oldest age group (75 years and older) the risk for all cause dementia, vascular dementia and Alzheimer's disease was lower for CABG patients compared to controls (HR 0.73 (0.69–0.78). Female CABG patients &amp;lt;65 years had an increased risk for Alzheimer's disease (HR 1.83 (1.06–3.15). Hypertension, diabetes, preoperative stroke, renal failure, heart failure, atrial fibrillation, depression and low income were independent predictors for all-cause dementia in CABG patients. Conclusion CABG patients younger than 75 years at the time of surgery have an increased risk of all-cause dementia compared to an age- and sex-matched population. Women younger than 65 years that underwent CABG had also a markedly higher risk for Alzheimer disease. Increased awareness of the higher risk for dementia in younger CABG patients is warranted to avoid delay of diagnosis and treatment. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Swedish Heart and Lung Foundation, Swedish State

Cardiovascular risk factors among oil refinery workers: ecological study

Monitoring the health of workers is indispensable to develop indicators to identify potential risk factors and the workload impact on illness and characterize their morbidity profile. To identify modifiable and non-modifiable cardiovascular risk factors among employees of an oil refinery with fixed work schedule or allocated to shifts. Ecological, exploratory, descriptive and quantitative study with data retrieved from the company's record system. We performed time series analysis of the prevalence of risk factors in the period from 2008 through 2017. We found an increasing trend in the prevalence of hypertension and diabetes and a decreasing trend for high cholesterol, high LDL, low HDL, smoking and coronary artery risk. The prevalence of hypertension increased, while that of all other risk factors, except for diabetes, decreased in 2017 by comparison to 2008. The analyzed sample is at medium risk for cardiovascular disease despite their young age, high educational level and available resources. We call attention to the need to systematize workplace health promotion programs.

PREVALENCE AND ROLE OF DIFFERENT RISK FACTORS WITH EMPHASIS ON GENETICS IN DEVELOPMENT OF PATHOPHYSIOLOGY OF CORONARY ARTERY DISEASE (CAD)

To focus on the prevalence and role of different risk factors contributing inpathophysiology of coronary artery disease (CAD). Relevant articles publishedbetween 2006 and 2018 were studied with the help of various data basesincluding Google scholar, PubMed, Medline, Springer link, and Science direct.Articles published only in indexed journals were taken in account to ensure thecredibility of data. Coronary artery disease (CAD) is a silently progressivechronic disorder which generally establishes overtime to an advance stage till thesymptoms appear. In high income countries, the mortality rate has declined since1980 whereas, middle and low income countries bear three quarters of the globalCAD burden. South Asians are at a greater risk and the prevalence is 50% to 300%higher than the rest of the world. It is a multifactorial disorder and arises from aninteraction between environmental and genetic factors. The conventional CADrisk factors (CRFs) include age, gender, blood lipids, smoking, blood pressureand diabetes. Most of the CAD risk factors are modifiable by targeting lifestylechanges, drug intervention and prior identification of those who are at high risk ofdeveloping disease. The variability in disease susceptibility in individualsexposed to similar environmental factors and having almost same CRFs can beattributed to the genetic variations. Genetic testing may improve discriminationover and above the CRFs. Key Words: Coronary artery disease (CAD), Risk factors, genetic testing,Oxidative and inflammatory pathways, Diabetes, Hypertension, Obesity.

Racial differences in weathering and its associations with psychosocial stress: The CARDIA study

Biological age (BA) is a construct that captures accelerated biological aging attributable to “wear and tear” from various exposures; we measured BA and weathering, defined as the difference between BA and chronological age, and their associations with race and psychosocial factors in a middle-aged bi-racial cohort. We used data from the Coronary Artery Risk in Young Adults study (CARDIA), conducted in 4 U.S. cities from 1985–2016 to examine weathering for adults aged 48–60 years. We estimated BA via the Klemera and Doubal method using selected biomarkers. We assessed overall and race-specific associations between weathering and psychosocial measures. For the 2694 participants included, Blacks had a BA (SD) that was 2.6 (11.8) years older than their chronological age while the average BA among Whites was 3.5 (10.0) years younger than their chronological age (Blacks weathered 6.1 years faster than Whites). Belonging to more social groups was associated with less weathering in Blacks but not Whites, and after multivariable adjustment, lower SES and more depressive symptoms were associated with more weathering among Blacks than among Whites. We confirmed racial differences in weathering, and newly documented that similar psychosocial factors may take a greater toll on the biological health of Blacks than Whites.

0884 Sleep as a Mediator between Chronic Stress and Metabolic Syndrome, the Coronary Artery Risk and Development in Young Adults (CARDIA) Study

0884 Sleep as a Mediator between Chronic Stress and Metabolic Syndrome, the Coronary Artery Risk and Development in Young Adults (CARDIA) Study

Genome-wide association study of homocysteine in African Americans from the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Coronary Artery Risk in Young Adults study.

Homocysteine (Hcy) is a heritable biomarker for CVD, peripheral artery disease, stroke, and dementia. Little is known about genetic associations with Hcy in individuals of African ancestry. We performed a genome-wide association study for Hcy in 4,927 AAs from the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Coronary Artery Risk in Young Adults (CARDIA) study. Analyses were stratified by sex and results were meta-analyzed within and across sex. In the sex-combined meta-analysis, we observed genome-wide significant evidence (p<5.0×10−8) for the NOX4 locus (lead variant rs2289125, β= −0.15, p= 5.3 × 10−11). While the NOX4 locus was previously reported as associated with Hcy in European American populations, rs2289125 remained genome-wide significant when conditioned on the previously reported lead variants. Previously reported genome-wide significant associations at NOX4, MTR, CBS, and MMACHC were also nominally (p<0.050) replicated in AAs. Associations at the CPS1 locus, previously reported in females only, also was replicated specifically in females in this analysis, supporting sex-specific effects for this locus. These results suggest that there may be a combination of cross-population and population-specific genetic effects, as well as differences in genetic effects between males and females, in the regulation of Hcy levels.

TCTAP A-112 Novel Cardiac Biomarkers Copeptin, MR-proANP, and MR-proADM Are Associated with Clinical Phenotypes of Coronary Artery Disease and Risk of Type 2 Diabetes Mellitus in a Chinese Han Population

TCTAP A-112 Novel Cardiac Biomarkers Copeptin, MR-proANP, and MR-proADM Are Associated with Clinical Phenotypes of Coronary Artery Disease and Risk of Type 2 Diabetes Mellitus in a Chinese Han Population

Abstract MP076: Angiographic Coronary Artery Disease Severity and Risk of Mental and Conventional Stress Induced Myocardial Ischemia

Background: Mental stress induced myocardial ischemia (MSIMI) is linked to increased risk of adverse cardiovascular outcomes, but its mechanisms are thought to be different from those of conventional stress-induced ischemia (CSIMI). Specifically, whether MSIMI is associated with more severe underlying obstructive coronary artery disease (CAD) is unclear. We investigated the association between angiographically-defined CAD severity and both MSIMI and CSIMI with a hypothesis that, CAD severity will be linked to CSIMI, but not MSIMI. Methods: A total of 273 patients with stable CAD, aged 51±7 years, 49% female, who survived a myocardial infarction (MI) within the past 8 months (median 167±52 days) were enrolled in the Myocardial Infarction and Mental Stress 2 (MIMS-2) study. The coronary angiogram performed during the index MI hospitalization was used to assess CAD severity. Coronary artery obstruction was assessed by counting the number of diseased vessels with 70% stenosis (DV70%) and using the Gensini Score (GS) after correcting for revascularized vessels. Patients underwent 99mTc sestamibi myocardial perfusion imaging during mental stress, using a public speaking task, and during conventional stress test, using exercise or pharmacological stress. MSIMI and CSIMI were defined as a new or worsening impairment in myocardial perfusion using a 17-segment model. Results: A total of 68 (26%) patients developed CSIMI, while 46 (17%) developed MSIMI. Median DV70% and GS were 0 (0-1), and 3 (0-12), respectively. Using logistic regression models, and after adjustment for age, gender, hypertension, hyperlipidemia and diabetes, obstructive CAD was associated with increased risk of CSIMI [OR(95%CI) of 1.54 (1.02 - 2.31) for DV70% and 1.25 (1.03-1.53), for GS], but not MSIMI [OR(95%CI) of 0.93 (0.56 - 1.53) for DV70%, and 0.94 (0.75-1.18) for GS]. Conclusion: Although CSIMI is linked to underlying coronary obstruction, MSIMI is independent of CAD severity among post- MI patients. Other mechanisms are likely responsible for MSIMI post MI.

Electrocardiogram QRS duration and associations with telomere length: A cross-sectional analysis in Australian rural diabetic and non-diabetic population

Prolonged electrocardiogram QRS durations are often present in aging populations. Shorter telomere length is considered a biomarker of cellular aging. Decreased telomere length has been associated with coronary artery risk, and ventricular remodeling. However, the association between telomeres and cardiac conduction abnormalities, such as increased QRS duration are not well understood. A retrospective cross-sectional population was obtained from the CSU Diabetes Screening Research Initiative database where 273 participants had both ECG-derived QRS duration and DNA to permit leukocyte telomere length (LTL) determination. Telomere length was determined using the monochrome multiplex quantitative PCR method to measure mean relative LTL. Resting 12-lead electrocardiograms were obtained from each subject using a Welch Allyn PC-Based ECG system. Relative LTL was moderately negatively associated with QRS duration in type 2 diabetes mellitus (T2DM) patients (R2=0.055), compared to controls (R2=0.010). In general linear models with no adjustments a significant interaction between QRS duration and LTL is observed for a combined population of T2DM and non-diabetics. When we compared T2DM to non-diabetics, we found that T2DM increased the effect size for relative LTL on QRS duration in comparison to controls. Hence, for each 0.1 unit of relative LTL attrition, QRS duration in T2DM patients increased by 3.24ms (95% CI, −63.00 to −1.84), compared to 1.65ms in controls (95% CI, −40.44 to 7.40). In summary we have observed an association between LTL in a rural aging mixed population of T2DM and non-diabetes. We have observed an unadjusted association between QRS duration and LTL in T2DM. We noted that the control group demonstrated no such association. This highlights the complexity of T2DM when exploring disease phenotype–telomere interactions.

Relationship between glycated albumin and extent of coronary lesions, GRACE score in patients with acute non-ST segmentelevation myocardial infarction

Objective To investigate the relationship between glycated albumin(GA) and extent of coronary lesions, GRACE score in patients with acute non-ST segmentelevation myocardial infarction(NSTEMI). Methods A total of 226 NSTEMI patients who successfully underwent coronary angiography(CAG) were enrolled in the study.Groups: (1)According to GA level, the patients were divided into 3 groups: GA 17.0% group.(2)According to the extent of coronary lesions, the patients were divided into 2 groups: single or double branch lesion group, three and/or left main lesion group.(3)According to the GRACE score, the patients were divided into 3 groups: Low-risk GRACE score≤108 points group, Medium-risk 108 points 140 points group.The extent of coronary lesions was evaluated by Gensini score.The clinical characteristics and Gensini score, GRACE score of each group were compared.Pearson/Spearman correlation analysis and logistic regression were used to analyze the association of GA with the severity of coronary artery disease and GRACE score. Results With glycated albumin increasing, the Gensini score(56.51±38.57, 68.30±35.57, 77.38±36.52), GRACE score(139.43±29.96, 149.77±38.33, 170.75±27.52) increased significantly, and significant differences were found between groups(F=5.587, 16.006, P=0.004, 0.000). The ejection fraction(EF) of 3 groups were significantly decrease((58.30±13.95)%, (56.45±10.79)%, (53.06±12.51)%; F=3.126, P=0.046). Proportion of severe coronary lesions of 3 groups were increase significantly(59.5%(44/74), 68.2%(60/88), 87.5%(56/64), χ2=13.528, P=0.001). The level of GA in three and/or left main lesion group was higher than that in single or double branch lesion group((13.92±3.14)% vs.(16.80±3.58)%, t=-5.693, P=0.000). The level of GA in High-risk group was higher than that in Low-risk group((14.70±1.54)% vs.(16.63±4.02)%, t=6.512, P=0.002). Correlation analysis showed that the level of GA had significant positive correlation with Gensini score and GRACE score(r=0.309, 0.265; P=0.000, 0.000), while had a negative correlation with LVEF(r=-0.149, P=0.034). Logistic regression analysis indicated that GA was independent risk factors for severity of coronary artery disease in patients with NSTEMI who successfully underwent CAG(OR=1.441, 95% CI: 1.160-1.790, P=0.001). Conclusion GA level is increase in NSTEMI patients with severe coronary artery disease and risk stratification high.GA is the independent risk factors for severity of coronary artery disease in patients with NSTEMI; GA has significant correlation with dangerous degree in patients with NSTEMI. Key words: Acute myocardial infarction; Glycated albumin; Coronary lesions; GRACE score

Correlation Between Severity of Coronary Artery Lesions and Risk Factors of Coronary Heart Disease

Correlation Between Severity of Coronary Artery Lesions and Risk Factors of Coronary Heart Disease

Abstract 41: SH2B3 Is a Genetic Determinant of Cardiac Inflammation and Fibrosis

Background: Genome wide association studies (GWAS) are powerful tools for nominating pathogenic variants, but offer little insight as to how candidate genes impact disease outcome. Such is the case for SH2B adaptor protein 3 (SH2B3), which is associated with coronary artery disease (CAD), atherosclerosis, and risk of myocardial infarction (MI), but its role in post-MI response is completely unknown. Methods: Using an experimental model of MI (left anterior descending artery [LAD] occlusion) in wild-type (WT) and Sh2b3 knockout (KO) rats, we assessed the role of Sh2b3 in post-MI fibrosis, leukocyte infiltration, angiogenesis, left ventricle (LV) contractility, and inflammatory gene expression. We also confirmed our findings in LV samples from end-stage heart failure patients with or without the MI-associated SH2B3 risk allele. Results: Compared with WT, Sh2b3 KO rats had significantly increased fibrosis (2.2-fold; P2-fold; P&lt;0.001), which coincided with decreased LV fractional shortening (FS) (-Δ11%; P&lt;0.05) at 7 days post-LAD occlusion. Despite an increased angiogenic potential in Sh2b3 KO rats (1.7-fold; P&lt;0.05), we observed no significant differences in LV capillary density between WT and Sh2b3 KO rats. Of the 903 genes examined, 19 were significantly elevated in the post-LAD occluded hearts of Sh2b3 KO rats relative to WT, of which three (NLRP12, CCR2, and IFNγ) were also significantly elevated in the LV of heart failure (HF) patients carrying the MI-associated rs3184504 [T] SH2B3 risk allele. Conclusions: These data suggest for the first time that SH2B3 is a master risk factor for MI by impacting both MI incidence and post-MI response.

Abstract P273: Enhancing Documentation and Control of Lipids in a University-Based Cardiology Clinic

Background: Non-compliance with laboratory appointments, separate from clinic visit appointments, for measuring fasting cholesterol may hinder documentation and control of patients’ lipids. Methods: A university-based cardiologist’s clinic notes, from a single year (yr 1), when patients were asked to have a fasting cholesterol a week prior to the clinic visit, were analyzed (100 patients). The poor compliance prompted a same day as the clinic visit measurement (fasting or non-fasting) of lipids, for patients who could not comply with their laboratory appointment, during the following year (yr 2; 130 patients). Lipid values were managed by a subsequent call to the patient. All patients had coronary artery disease or risk equivalent mandating LDL levels &lt; 100 mg/dL. Results: In yr 1, 62% (62/100) of patients had documented lipid profiles compared to 83% (108/130) of patients in yr 2. The average LDL in yr 1 was 115 +/- 36 mg/dL compared with 96 +/- 31 mg/dL in yr 2 (P &lt; 0.01). Only 22% of the patients in yr 1 reached goal of &lt; 100 mg/dL, compared with 65% in yr 2. There were no significant differences in the HDL, TG levels or blood pressures documented during the concurrent visits. Conclusion: Better documentation and control of lipids may be obtained when lipid profiles are done on clinic visit day, with fewer burdens on the patients who cannot comply with a separate laboratory appointment. Although there were many non-fasting levels as a result, the triglyceride levels where not significantly different among the two groups, probably reflecting an overall more intensive lipid management in yr 2, commensurate with the better documentation. Therefore, as has been shown by others, a lipid profile does not necessarily have to be fasting, especially in patients being treated for stricter targets such as our cohort, which may decrease the burden on patients unable to comply with a fasting state or added clinic visits.

320-slice CT-based finding of aortic wall tissue invasion into left-main coronary artery does not have relationship with coronary risk factors and coronary arteriosclerosis and stenosis

320-slice CT Aortic wall tissue invasion Left-main coronary artery Coronary risk factors Coronary arteriosclerosis Aortic wall tissue invasion into the ostium of the left main coronary artery (LMA) is frequently observed on computed tomography scan (CT) (Fig. 1) which sometimes might be diagnosed as a non-calcified plaque of the LMA and is ignored as its significance is unclear. To evaluate the significance of aortic wall tissue invasion into the ostium of LMA observed on CT, we examined the relationship between the presence of aortic wall tissue invasion on CT and coronary artery risk factors, coronary arteriosclerosis and stenosis confirmed on CT and invasive coronary angiogram (ICA) findings.

Coronary artery disease extent, severity and risk among active smokers, past smokers and non-smokers: a prospective study of 13,372 patients undergoing coronary CT angiography

Objective: Although smoking is an established risk factor for major cardiac adverse events (MACE), the relative risk of current versus past smoking is poorly understood. We evaluated coronary artery disease (CAD) extent, severity and risk of MACE for active smokers and past smokers undergoing coronary CT angiography (CCTA). Methods: From a prospective multicenter international study, we enrolled patients without known CAD who underwent CCTA [2853 current smokers (21%); 3175 past smokers who quit >3 months prior to CCTA (24%); and 7344 non-smokers (55%)]. By risk-adjusted Cox proportional hazards models, adjusting for age, gender, risk-factors, segment involvement score, ≥50% stenosis, we related smoking status to incident risk of MACE, as defined by death, myocardial infarction or unstable angina. We further performed 1:1:1 propensity matching for 1000 current smokers, past smokers and non-smokers each to evaluate MACE risk amongst individuals who were of similar age, gender, CAD risk factors and symptom presentation. Results: 13372 patients (56.2±12.8 years, 51% male) were followed for 2.0±0.9 years follow-up, with 279 (2.1%) MACE occurring. Compared to non-smokers, current and past smokers had higher prevalence of obstructive CAD (≥50%) [1-vessel disease (VD); 11.2% vs. 16.6% vs. 16.2%, p<0.001, 2VD; 4.8% vs. 7.3% vs. 7.8%, p<0.001, 3VD; 2.3% vs. 5.1% vs. 5.0%, p<0.001]. Current smokers experienced higher risk of MACE compared to non-smokers (HR 1.9, 95% CI 1.4-2.5, p<0.001), while past smokers did not (HR 1.2, 95% CI 0.9-1.6, p=0.29). Even amongst matched individuals, current smoking was associated with MACE risk (HR 2.3, 95% CI 1.2-4.4, p=0.01), while past smoking was not (HR1.0, 95% CI 0.5-2.1, p=0.98). Conclusion: While both current and past smokers possess a greater prevalence, extent and severity of CAD compared to non-smokers, current smokers experience higher risk of MACE than past smokers and non-smokers.

Association of Carotid Intima Media Thickness and Periscope Markers with Coronary Artery Disease, Risk factors and Biomarkers in Asian Indians

Association of Carotid Intima Media Thickness and Periscope Markers with Coronary Artery Disease, Risk factors and Biomarkers in Asian Indians Surrogate sub clinical markers provide an important dimension to cardiovascular risk stratification. We studied the association of carotid intima media thickness (CIMT) and Periscope markers with CAD, classical risk factors and cardiac biomarkers in a cohort of 125 CAD patients with strong family history of cardiovascular disease and 585 unaffected family members selected from the Indian Atherosclerosis Research Study.