Family History Of Premature Coronary Artery Disease Research Articles

The prevalence of risk factors and pattern of obstructive coronary artery disease in young indians (< 45 years) undergoing percutaneous coronary intervention: a gender-based multi-center study

Abstract Funding Acknowledgements Type of funding sources: None. Background In a retrospective study, we aimed to explore the prevalence of risk factors and trends of obstructive coronary artery disease (CAD) in Indian females under 45 years old compared to males of the same age group who underwent percutaneous coronary intervention (PCI). Purpose With changing lifestyles, the onset of traditional risk factors at the early stages of life is the major culprit for developing CAD at an early age. For several years, the significance of CAD in young women was underestimated. There are some sex-related variations in CAD, and symptoms of CAD in women, regardless of age, have low specificity even in the absence of risk factors. Materials and Methods This was a retrospective, observational, multi-centre study of young Indian females and males (< 45 years) who underwent PCI as per the guidelines at three high-volume centres of India. The study evaluated the prevalence of risk factors, clinical and angiographic patterns of obstructive CAD in young Indian women compared to men. Results In a cohort of 3656 patients who underwent PCIs, 113 young females comprised 3.1% of those with obstructive CAD, while 254 young males constituted 6.9%. Traditional risk factors such as hypertension, diabetes, and family history of premature CAD were the most common in both genders, whereas dyslipidaemia, obesity, smoking, and alcoholism were more common in young males. The acute coronary syndrome was the most common clinical presentation. The single-vessel disease was common with the involvement of the left anterior descending artery as a most common angiographic feature. The prevalence of cardiogenic shock was 4.4% in females and 4.1% in males while the in-hospital mortality rate was 1.77% in young females and 2% in young males. Conclusion CAD in young Indians is on the rise, and frequent screening for obstructive CAD should be done, especially in those with symptoms and risk factors.

Abstract 017: Clinical Utility Of Genetic Testing For Familial Hypercholesterolemia In A Pediatric Dyslipidemia Clinic

Background: Familial hypercholesterolemia (FH) in children is diagnosed by identification of a known FH pathogenic variant or clinical criteria. We sought to determine the number of pediatric probands undergoing genetic testing for FH that met clinical criteria, and to evaluate differences between genotype positive and negative probands. Methods: All children ≤18 years old undergoing genetic testing for suspected FH were included. Clinical FH was defined as LDL ≥160 mg/dL and family history of premature CAD in 1 st /2 nd degree relatives. Screening of 1 st /appropriate 2 nd degree family members was recommended at all visits (lipid panel or genetic test) and was complete if obtained within 1 year of proband testing. Probands were stratified based on the presence or absence of known FH pathogenic variants. Wilcoxon rank sum or chi-squared tests compared lipid panel, LP(a), BMI percentile, number of screening tests performed, and family members diagnosed with FH. Results: Of 76 probands (age 12.5±2.9 years, 57% males) with suspected FH and genetic testing; 41 (54%) were genotype positive. Genotype positive probands were more likely to meet clinical criteria (44% vs. 17%, p=0.01), but only 19/41 (46%) had a positive family history. Genotype positive probands had higher total cholesterol (mg/dL) [median (IQR): 260 (242-297) vs. 226 (215-245), p<0.01] and LDL [199 mg/dL (174-229) vs. 153 mg/dL (144-171), p<0.01]. Sex, BMI percentile, family history, HDL, triglycerides, and LP(a) were similar between groups. Genotype positive probands (adopted probands excluded) had more screening tests performed [median (IQR): 4 (2-6) vs. 2 (1-3), p<0.01] and more new family members identified [3 (1-4) vs. 0 (0-1), p<0.01]. Conclusion: Clinical criteria alone underdiagnosed FH in children and a negative family history occurred in over half of pediatric FH patients. A positive genetic diagnosis increased the number of screening tests performed and improved identification of at-risk family members. Therefore, genetic testing should be performed in all suspected pediatric FH patients.

Significant Coronary Artery Disease in Patients Undergoing Valve Replacement Surgery

Objective: To determine the frequency of angiographically significant coronary artery disease (CAD) in patients undergoing valve replacement surgery and referred for Coronary angiography. Study Design: Cross Sectional Descriptive Study. Study Setting& duration: From 14th February 2016 to 14th August 2016 in the Department of Cardiology, Tabba Heart Institute, Karachi. Material and Methods: Total 127 patients of both genders with age 40-75 years undergone referred for coronary angiography and as a pre requisite of required valve replacement surgery were included and significant findings were noted. The history of comorbid, family history of premature CAD, smoking and basal metabolic index were noted. Results: There were 58.3% male and 41.7% female patients. Average age was 54.60±8.91 years. Mean BMI was 28.64±4.62 Kg/m2. 75.6% patients were obese. Angiographically significant CAD was observed positive in 27.6% patients. Significant association was found with hypertension and premature family history of CAD. The prevalence was high in patients with MVR followed in patients with AVR. Conclusion: The overall prevalence of angiographically significant coronary artery disease was 27.6%.in cases going through valve replacement is substantial. The prevalence was high in patients with MVR followed in patients with AVR. Keywords: CAD, Angiography, Significant Coronary Artery Disease, Valve Replacement Surgery

Risk Factors for Coronary Artery Disease in Patients Undergoing Coronary Angiogram at a Tertiary Level Hospital in Nepal

Background: Ischemic heart disease is the leading cause of CVD health loss globally, as well as in each world region, followed by stroke. In Nepal, CVD was found to be the second most common non-communicable disease among indoor patients of the non-specialist hospital. Age, gender, smoking, obesity, dyslipidemia, physical inactivity, hypertension, and diabetes mellitus (DM) are established risk factors for CVD. In Nepal, hypertension is found to be the most prevalent risk factor for CVD.
 Aims and Objectives: This study aimed to assess risk factors for coronary artery disease in patients undergoing coronary angiograms in Nepal. This study also investigated the socio-demographic characteristics of the participants and the nature of the involvement of coronary arteries.
 Materials and Methods: We examined in this cross-sectional study a total of 74 patients who underwent coronary angiography (CAG) at National Medical College between May 2020 and June 2021. Patients were grouped according to the number of major epicardial coronary arteries involved in SVD, DVD, and TVD. Patients were checked for risk factors like smoking, diabetes mellitus, hypertension, dyslipidemia, family history of coronary artery disease, and obesity. Microsoft Office Excel and SPSS version 21.0 were used for data analysis. The study was approved by the ethical committee.
 Results: Among 74 participants 53 were male. The mean age was 59.65±10.74 years. Premature coronary artery disease was present in six patients. SVD was the commonest CAD type. Hypertension was the commonest risk factor followed by Diabetes mellitus. Hypertension, Diabetes mellitus, Family history of premature CAD, and obesity were found to be statistically significant.
 Keywords: CAD, Risk factors for CAD, Premature CAD, Hypertension, Diabetes, obesity, family history of CAD, dyslipidemia, Smoking, SVD, DVD, TVD, Nepal

A Validated Model to Identify Patients With Low Likelihood of High-Risk Coronary Artery Disease Anatomy

In stable coronary artery disease (CAD), revascularization improves outcomes only for patients with high-risk coronary anatomy (HRCA). We sought to derive and validate a prediction model, incorporating clinical and exercise stress test characteristics, to identify patients with HRCA. We conducted a retrospective analysis of patients undergoing exercise stress testing at Cleveland Clinic (2005 to 2014), followed by invasive coronary angiography within 3 months. We excluded patients with acute coronary syndrome, known CAD or ejection fraction <50%. HRCA was defined as left main, 3-vessel, or 2-vessel disease involving the proximal left anterior descending artery. Clinical and stress test predictors of HRCA were identified in a multivariable logistic regression model, internally validated with 1,000-fold bootstrapping. The model was then externally validated at the University of Pittsburgh Medical Center (2017 to 2019). The model was derived from 2,758 patients with complete data. HRCA was identified in 418 patients (15.2%) in the derivation cohort. The model consisted of 10 variables: age, male gender, hypertension, hypercholesterolemia, diabetes mellitus, family history of premature CAD, high-density lipoprotein, chest pain, exercise time, and Duke Treadmill Score. Bias-corrected c-statistic was 0.79 (95% confidence interval 0.77 to 0.81) with excellent calibration. In all, 762 patients (27.6%) had a predicted probability and observed prevalence of HRCA <5%. In the validation cohort, the model had a c-statistic of 0.79 (95% confidence interval 0.74 to 0.85) and 210 patients had an observed prevalence of HRCA <5% (40%). In conclusion, an externally validated prediction model, based on clinical characteristics and exercise stress test variables, can identify stable patients with CAD who have HRCA.

Importance of myocardial perfusion scintigraphy for early detection of coronary artery disease in patients with positive family history of premature CAD -case study

Background: Acute coronary syndrome refers to a spectrum of clinical presentations ranging from those for ST-segment elevation myocardial infarction (STEMI) to presentations found in non-STEMI or unstable angina. Case presentation: We present a case of a 36-year-old female who visited cardiac outdoor patient department with continuous left arm pain. She was then referred to nuclear cardiology for screening of coronary artery disease (CAD). A pharmacological stress study was planned but the rest study was done instead due to the patient having persistent pain in the left arm. The rest study showed a large perfusion defect in left anterior descending artery (LAD) territory. As the patient was not having any previous history of CAD except for positive family history of premature CAD, she was immediately referred to an interventional cardiologist where her primary percutaneous coronary revascularization to LAD (3 × drug eluting stent) got done and she was saved from impending MI. Conclusion: Regular follow-up and monitoring should be fine in young adults with a positive family history of premature CAD. This may help in early detection leading to time management and acute coronary events in young adults may be avoided. This will eventually reduce mortality and morbidity.

Assessment of Reliability of Advanced Lipid Parameters for Premature Coronary Artery Disease in Young Indians: A Case-control Study

Introduction: Coronary Artery Disease (CAD) appears even in patients with normal level of conventional lipid parameters. But due to lack of specific guidelines on Indian population, involving detection of advanced lipid indices, has resulted in inadequate finding, management, and control of cardiovascular disease risks. This emphasises the need of advanced lipid indices for prediction of CAD at younger age. Aim: To evaluate the reliability of advanced lipid indices compared to conventional lipid parameters for diagnosis of CAD. Also, to determine the effectiveness of advanced lipid indices in screening young Indian for the risk of Premature CAD (PCAD). Materials and Methods: A case-control study was conducted at a tertiary care centre in Bengaluru, Karnataka, India, between January 2020 to January 2022. The study enrolled total 983 subjects which were divided into cases and controls. The estimation of usual lipid profile (Triglycerides (TG), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), and Total Cholesterol (TC)) and advanced lipid parameters, oxidized LDL, Apolipoprotein A1 (Apo A1), lipoprotein (a), small density LDL (Sd-LDL), and Apolipoprotein B-100 (Apo B) was studied for each enrolled individual. These lipid parameters were used to calculate various lipid indices like Lipid Pentad Index (LPI), Lipid Tetrad Index (LTI), Atherosclerotic Index (AI), and Advanced Atherosclerotic Index (AAI); and TC/HDL ratio. Statistical analysis was performed using Chi-square test, Fisher’s exact test, multivariate logistic regression, and Student’s t-test/ Analysis of Variance (ANOVA) test. Results: Mean age of patient in case group was 32.31±5.42 years and individuals in control group was 32.13±5.21 years. Among case group, 427 (88.04%) enrolled males had PCAD. In case group, total 45 (9.28%) had diabetes, 51 (10.51%) had family history of PCAD and 230 (47.42%) patients were smokers. The values of TC (p=0.009), LDL (p&lt;0.001), Apo A1 (p&lt;0.001), HDL (p&lt;0.001) were significantly lower among cases compared to controls, lipoprotein (a) (p=0.04), Sd-LDL (p&lt;0.001), TG (p&lt;0.001) were significantly higher among cases compared to controls. Among the calculated lipid indices, the values of AI (p&lt;0.001), LTI (p&lt;0.001), LPI (p=0.001) and AAI (p=0.01) were significantly higher among cases as compared to controls. Conclusion: Advanced lipid indices are statistically more reliable than conventional lipid parameters. Newer advanced lipid indices are effective in screening young Indian individuals for the risk of PCAD.

Clinical presentation, risk factors, and coronary angiographic profile of very young adults (≤30 years) presenting with first acute myocardial infarction at a tertiary care center in Rajasthan, India

Introduction: Acute coronary syndrome (ACS) in very young adults with age ≤30 years is rare. In India, the prevalence of acute myocardial infarction (AMI) in this population is &lt;2%. ACS leads to significant effects on patient's psychology, morbidity, and increased financial burden when it occurs at this young age. Young patients with ACS on coronary angiography (CAG) show a relatively increased incidence of single-vessel disease and nonobstructive stenosis. Materials and Methods: This retrospective observational study was conducted at the Department of Cardiology, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan. The medical records of very young adults (≤30 years of age) with first AMI between September 2019 to August 2021 were collected and analyzed. Results: Twenty-two very young adult patients aged ≤30 years were admitted with first AMI. Most of the patients were within the age group of 25–30 years. Mean patient age was 27.63 ± 2.03 years and 21 patients (95.4%) were men. Regarding the risk factors for coronary artery disease (CAD), smoking was the most common (54.5%) in young patients. Dyslipidemia and family history of premature CAD were present in 8 (36.3%) and 6 (27.2%) of patients. The most common symptom in patients was chest pain (90.9%). Obstructive CAD (vessel lumen stenosis ≥ 70%) was found in 18 (81.8%) patients. Conclusion: Very young adults presented with less extensive CAD as compared to elderly likely due to less atherosclerosis of the coronary arteries in them. The major modifiable risk factors in very young Indian population are smoking and dyslipidemia. Primary prevention by educating the public about the effects of smoking, unhealthy dietary habits, and sedentary lifestyle in early years of life may help to prevent the development of cardiac problems later in life.

Premature Coronary Artery Disease in Young Male Patient with Strong Family History

BACKGROUND: Coronary artery disease (CAD) occurring in less than 45 years of age is termed as premature CAD (PCAD). Recent studies showed a prevalence of 4-10 % of PCAD. PCAD is associated with unfavorable outcomes for the patients and had a greater impact on the quality of life. Family History is the best method to explained complex interaction between shared risk factor. CASE ILLUSTRATION: A 37-years old male admitted to Saiful Anwar Hospital for further evaluation of anginal pain. The patient complains of recurrent chest pain since 5 months ago but still relieved by rest. The electrocardiogram showed Wellens Type B which is specific for critical stenosis of the left anterior descending artery (LAD). Then the patient undergoing DCA Ad Hoc. The implantation of a 46 mm DES at proximal until distal LAD was performed. The patient discharged after a day observation. DISCUSSION: The challenging point, in this case, was it happen at a young age with strong family history. There was positive family history of PCAD in 1st degree relative on her brother and mother, despite several risk factors were identified in this case consist of smoking, and dyslipidemia, which make CAD risk higher. Despite adequate control of risk factors, family screening is important to reveal subclinical atherosclerosis. CONCLUSION: Approach to a patient with PCAD comprises of management of traditional risk factors and careful investigation of Family History. Individual with positive family history of PCAD should be treated more cautiously

Abstract 11538: Impact of Family History of Premature Coronary Artery Disease on Non-Invasive Testing in Stable Chest Pain: A PROMISE Analysis

Introduction: Family history (FH) of premature CAD is a risk enhancer for adverse cardiovascular events. The preferred testing strategy to diagnose CAD in this high-risk population presenting with stable chest pain is unknown. Methods: This was a secondary analysis of the PROMISE trial, which randomized participants with stable chest pain to coronary computed tomographic angiography (CCTA) versus functional stress testing for the diagnosis of CAD and followed them for incident CV death or MI. Statistical analyses included logistic regression and Cox proportional hazard modeling. The effect of FH of premature CAD on the relationship between non-invasive testing modality and incident CV death or MI was assessed using interaction testing. Results: Patients with FH of premature CAD (n=3,098) were younger (58y vs 60y, p&lt;0.001) and more likely to be women (57% vs 51%, p&lt;0.001) than those without (n=6,584). They also had higher LDL-c levels (115 vs 112 mg/dL, p=0.01) and were more likely to be on aspirin (46% vs 44%, p=0.05) and a statin (48% vs 44%, p&lt;0.001) at baseline. Over a median follow-up of 2.1 years, 60 (1.9%) participants with and 148 (2.3%) participants without FH of premature CAD had a primary outcome event. FH of premature CAD was not associated with an increased risk of the primary composite outcome (HR 1.01; 95% CI 0.66, 1.57). There was no significant difference in CV death or MI whether patients underwent CCTA or functional stress testing, irrespective of FH of premature CAD (FIGURE; FH: 1.9% vs 2.0%, No FH: 2.2% vs 2.3%; interaction p-value=0.8). Conclusions: In patients with FH of premature CAD presenting with stable chest pain, an initial strategy of using CCTA to diagnose CAD is similar to functional testing for adverse cardiovascular outcomes.

Abstract 13449: Myocardial Infarction With Non-Obstructive vs Obstructive Coronary Arteries Among Patients With Acute Coronary Syndrome at a Large Safety-Net Hospital

Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) has been increasingly recognized. The differences between MINOCA and obstructive coronary artery disease (OCAD) patients have not been studied in lower socioeconomic status populations. Methods: The records of all patients undergoing angiography for ACS at a large Dallas County safety-net hospital from January 2018 to January 2020 were reviewed and categorized as MINOCA or OCAD. Results: During the study period, 592 cases of acute coronary syndrome (ACS) were identified; 10.8% (n=64) were MINOCA. OCAD patients had higher peak pre-angiography troponin compared with MINOCA patients (2498 vs 335 ng/L, p&lt;0.001). MINOCA patients were younger compared with OCAD patients (56 vs 60 y, p=0.01), while MINOCA men were younger than MINOCA women (53 vs 61 y, p=0.009). A higher proportion of MINOCA patients were Black, compared with OCAD (Figure 1). MINOCA patients had a lower prevalence of dyslipidemia and diabetes mellitus but there were no differences in the prevalence of smoking, hypertension, family history of premature CAD, current dialysis or heart failure between the groups. There were no differences in statin, aspirin, beta blocker or calcium channel blocker prescription at presentation between MINOCA and OCAD patients, regardless of sex. The majority of MINOCA patients (75%) did not have a definitive etiology of their ACS event by discharge. Conclusions: In this analysis of ACS patients presenting to a large safety-net hospital, MINOCA was common and MINOCA patients had many traditional risk factors. Men presented with MINOCA more commonly than has been seen in other studies. More Black patients presenting with ACS had MINOCA vs OCAD, likely reflecting the higher rates of left ventricular hypertrophy and diabetes in these patients. Lack of a definitive diagnosis for most MINOCA patients may reflect unfamiliarity with the diagnostic workup of MINOCA patients.

Abstract 11681: An Extremely Rare Case of Intercostal Artery Rupture After Percutaneous Coronary Intervention

Introduction: There are a few case reports of Intercostal artery injury after pleural tap and trauma but none after a PCI. Case: A 61-year-old Caucasian male with PMH of T2DM, Hypertension, Hyperlipidemia, former tobacco chewing, family history of premature CAD presented to ED with midsternal chest pressure of 2 hours and three weeks of dyspnea on exertion. He was seen earlier in the outpatient office where an ECHO showed an EF of 55%, and a Nuclear stress test showed moderate inferior ischemia. CT coronary Angiogram showed complex plaques in Mid RCA and mid LAD. Troponin and EKG were normal. A diagnosis of unstable angina was suspected, and he was loaded with clopidogrel and heparin drip. He underwent emergency cardiac catheterization via a trans-radial approach. The standard J wire was switched to an angled-tip stiff Terumo guidewire due to difficulty traversing the aortic arch. The guidewire briefly went down the descending thoracic aorta. There was complex, eccentric stenosis of 99% in mid LAD and mid-RCA, which were stented with DES. The patient developed right chest pain radiating to his back. He became hypotensive, and Hemoglobin dropped from 13 to 8g/dl. CT scan showed a large right-sided hemothorax, and a chest tube was placed. He was resuscitated, and Angiogram showed three pseudoaneurysms and rupture of the right 8 th intercostal artery with active contrast extravasation. The right 9 th intercostal artery had one pseudoaneurysm. Both the vessels were embolized by an interventional radiologist. Discussion: Intercostal arteries arise from descending thoracic aorta. It is likely the catheter advanced into the descending aorta and the intercostal artery resulting in injury. Proper guidewire advancement under fluoroscopy and confirming the position of guidewire before advancing the guiding catheter may prevent this complication. Prompt recognition and emergency treatment with a chest tube and IR-guided embolization should be done.

Abstract 9856: Associations of a Polygenic Risk Score (PGS) with High Risk Coronary Artery Disease (CAD) in PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain)

Introduction: PGSs summarize the polygenic risk for CAD and may have clinical utility. We tested whether a previously validated PGS for CAD is associated with coronary CT angiography (CTA) findings predictive of future cardiovascular events in the PROMISE trial, which randomized individuals with stable outpatient chest pain to standard of care vs. CTA. Methods: This nested case-control study compared genotyped PROMISE participants with no CAD (0% stenosis), obstructive CAD (oCAD, ≥50% stenosis) or high-risk CAD defined as either oCAD ≥70% stenosis, CAC &gt;400, Leaman Score &gt; 5 (measure of stenosis and plaque burden), or any high-risk plaque feature (positive remodeling, low attenuation, napkin ring sign) on CTA. The Illumina Global Screening Array with imputation from the 1000 Genomes reference panel was used with LDpred to calculate ancestry-adjusted PGS. We calculated adjusted odds ratios (aORs) of oCAD and high-risk CAD for PGS quintiles 2-5 with quintile 1 as the referent using logistic regression and age, sex, and European Society of Cardiology pre-test probability (PTP) for obstructive CAD as covariates. Results: Among the 518 participants, 414=no CAD, 86=oCAD, and 103=high risk CAD (overlap of oCAD and high-risk CAD=85), the median age (±S.D.) was 58 (±7) years, 58% were female, and 13% were of non-white race or Hispanic ethnicity. Baseline characteristics, family history of premature CAD, PTP risk score and medications were similar across PGRS quintiles (all P&gt;0.2). After multivariate adjustment, PGRS quintile 5 was associated with significantly increased odds of oCAD ≥50% (aOR 6.09) and high-risk CAD (aOR 6.13) as compared with quintile 1. Conclusions: In a population of stable symptomatic outpatients, higher PGS was associated with oCAD and high-risk CAD on CTA, even after adjustment for age, sex and pretest probability of CAD. The PGS may be useful for risk stratification of outpatients with suspected CAD.

Positive family history of premature coronary artery disease and long-term mortality in patients undergoing conventional coronary angiography. The ECAD registry

Abstract Background The clinical value of positive family history of premature coronary artery disease (CAD) in risk prediction of cardiovascular diseases is controversial. While an association with risk factors and disease manifestation has been described in observational studies, it is not implemented in clinically established risk algorithms. Purpose We evaluated the association of positive family history of premature CAD with cardiovascular risk factors, presence of obstructive CAD, and long-term mortality. Methods The present analysis is based on the ECAD registry of patients undergoing invasive coronary angiography at the Department of Cardiology and Vascular Medicine at the University Clinic Essen between 2004 and 2019. For this analysis, we excluded all patients with missing follow-up information. Self-reported family history of premature CAD was categorized as positive, negative, or unknown. Baseline characteristics and presence of obstructive CAD were compared between patient with and without positive family history. Cox regression analysis was used to determine the association of positive family history with morality. Results Overall, data from 33,865 patient admissions (mean age: 65.0±13.1 years, 69% male) were included. Positive family history was present in 4,995 (14.8%) patients, negative family history in 17,806 patients (52.6%), while family history of premature CAD was unknown in 11,064 (32.7%) patients. Patients with positive family history were significantly younger (63.6±12.4 vs. 65.9±13.3 years, p&amp;lt;0.0001), more frequently had diabetes (11.4 vs. 9.3%, p&amp;lt;0.0001), and more frequently were active smokers (23.5 vs. 13.8%, p&amp;lt;0.0001). Obstructive CAD with need for revascularization therapy was more frequently present in patients with positive family history (36.2 vs. 30.2%, p&amp;lt;0.0001), while highest rate of obstructive CAD was observed in patients without known status regarding family history (37.9%, p&amp;lt;0.0001). In multivariable Cox regression analysis, known positive family history as compared to no family history of premature CAD was associated with best long-term survival (hazard ratio [95% confidence interval]: 0.65 [0.59–0.70], p&amp;lt;0.0001), while slightly higher mortality was observed for patients with unknown status (1.14 [1.08–1.21], p&amp;lt;0.0001). Kaplan-Meier analysis revealed, that patients with unknown family status regarding premature disease had worst short to intermediate-term survival (figure 1). Conclusion Positive family history of premature CAD is associated with younger age, higher rates of smoking and diabetes, and higher frequency of obstructive coronary artery disease, while long-term survival was improved as compared to patients without family history of premature CAD. In contrast, patients with unknown status regarding family history of CAD seem to represent a heterogeneous cohort and may qualify for intensified workup, as they have highest rates of obstructive CAD and poorest short- to intermediate survival. Funding Acknowledgement Type of funding sources: None. Figure 1. Survival by status of family history

Association of growth differential factor-15, hs-cardiac troponin T and N-terminal pro-brain natriuretic peptide with coronary artery disease in patients undergoing elective coronary angiography

Abstract Background Although the importance of conventional risk factors is well established, a significant proportion of patients with coronary artery disease (CAD) lack any of these factors and many patients without CAD have one or more of them. Better tools are needed to improve risk stratification of patients. Purpose We aimed to investigate the association between plasma levels of growth differentiation factor 15 (GDF-15), a marker of stress and inflammation, high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) with the presence of CAD in stable patients referred for elective coronary angiography. Methods Plasma levels of the three biomarkers were measured in 252 consecutive patients. Patients with known CAD, acute coronary syndrome, or with chronic inflammatory conditions were excluded. CAD was defined by the presence of at least one lesion causing &amp;gt;50% stenosis. The outcome was defined as an ordinal variable with 3 levels: no CAD, 1- or 2-vessel CAD and 3-vessel or left main CAD. Results Median age was 63 years (56–71), and 35% of patients were females. Among conventional risk factors, hypertension was the most prevalent (70%), followed by hyperlipidemia (69%), smoking (42%), diabetes (33%) and family history of CAD (32%). Of the 252 patients enrolled, 153 (61%) had no CAD, 81 (32%) 1- or 2-vessel CAD, and 18 (7%) 3-vessel or left main CAD. Plasma levels of GDF-15, hs-cTnT and NT-proBNP in each of the 3 groups of CAD are summarized in table 1. In unadjusted ordinal logistic regression analysis, GDF-15 and hs-cTnT were statistically significantly associated with the presence and extent of CAD, while NT-proBNP was not (table 1). However, in a multivariable analysis including age, sex and traditional risk factors, the association of GDF-15 and hs-cTnT with angiographic CAD was attenuated and no longer statistically significant. Age, male sex, family history of premature CAD and the presence of hyperlipidemia, were independent predictors of the presence and extent of CAD (table 2). Conclusion In stable patients referred for coronary angiography, plasma levels of GDF-15 and hs-cTnT could predict the presence of CAD when evaluated separately. However, that association was attenuated by clinical characteristics. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Roche Diagnostics International LtdForrenstrasse 26343 RotkreuzSwitzerland Table 1Table 2

Increased classical monocyte subsets in South Asians compared to White Caucasians at risk for coronary atherosclerosis

Abstract Background South Asians (SA) have an increased prevalence of coronary artery disease (CAD) and myocardial infarction compared with age- and sex-adjusted White Caucasians (WC). The mechanism for this increased risk is poorly understood. While classical CD14++CD16- monocytes act as independent predictors of cardiovascular disease, differences in the distribution of monocyte subsets between SA and WC have not been established. Purpose We aimed to determine if differences exist in monocyte subsets between SA and WC at risk for CAD. Methods Our cohort consisted of 119 consecutively enrolled patients (59 SA, 60 WC) at intermediate or higher risk for CAD by the INTERHEART score using self-reported history and physical exam. A single blood sample was collected prospectively for the purpose of monocyte analysis. Flow cytometry using dual colour fluorescence (CD14, CD16) within the monocyte gate was used to identify monocyte subsets (classical, intermediate and non-classical) by staff blinded to the individuals' characteristics. Variables were compared using Mann-Whitney U test and Chi-squared test, as appropriate. Eta coefficient was calculated to analyze the relationship between ethnicity and proportion of monocyte subsets. Eta squared values were calculated to assess the impact of ethnicity on monocyte subset proportions. Results The SA group consisted of 64% males with a mean age of 54 (± 9), while the WC group consisted of 55% males with a mean age of 59 (± 7). Both groups had similar body mass index, rates of hypertension, dyslipidemia and family history of premature CAD. Compared to WC, SA had higher prevalence of diabetes (36% vs. 13%, p=0.005) and hemoglobin A1C levels (6.0±1.1% vs. 5.6±0.6%, p&amp;lt;0.001). SA patients had a higher proportion (85.3±10.7% vs. 81.4±11.0%, p=0.009) and total level (449.0±180.4 vs. 388±127.4, p=0.010) of classical CD14++CD16- monocytes compared to WC. There was no difference between the two groups in the proportion of intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes. There was no association between diabetes and the proportion of monocyte subsets. Ethnicity had a moderate association with the proportion of classical CD14++CD16- monocytes (Eta coefficient = 0.525) with a large effect size (Eta squared = 27.5%). The association of ethnicity with intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes was either weak or negligible with minimal to no effect size. Conclusion In patients with substantive risk for CAD, SA had a significantly higher proportion and level of classical CD14++CD16- monocytes compared to WC. Our findings provide a novel insight into the potential mechanism of increased CAD susceptibility amongst SA compared to WC. Future studies are needed to determine whether these ethnic differences in the distribution of monocyte subsets can predict susceptibility to developing CAD and suffering atherothrombotic events. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Cardiology Academic Practice Plan grant at the University of British Columbia

MONOCYTE SUBSETS HETEROGENEITY AND CORONARY ATHEROSCLEROSIS IN SOUTH ASIANS COMPARED TO WHITE CAUCASIANS

BACKGROUND South Asians (SAs) have an increased prevalence of coronary artery disease (CAD) and myocardial infarction compared with age- and sex-adjusted White Caucasians (WCs). The mechanism for this increased risk is poorly understood. While classical CD14++CD16- monocytes act as independent predictors of cardiovascular disease, differences in the distribution of monocyte subsets between SA and WC have not been established. We aimed to determine if differences exist in monocyte subsets between SAs and WCs at risk for CAD. METHODS AND RESULTS 119 consecutive patients (59 SA, 60 WC) of at least intermediate CAD risk by the INTERHEART score were prospectively enrolled. Patients with history of malignancy, age > 70, GFR < 30 or on dialysis were excluded. A single blood sample was collected for monocyte analysis. Flow cytometry using dual colour fluorescence (CD14, CD16) within the monocyte gate was used to identify monocyte subsets (classical, intermediate, and non-classical) by staff blinded to the individuals’ characteristics. The SA group consisted of 64% males with a mean age of 54 (+/- 9), while the WC group consisted of 55% males with a mean age of 59 (+/- 7). Both groups had similar body mass index, rates of hypertension, dyslipidemia and family history of premature CAD. Compared to WCs, SAs had higher prevalence of diabetes (36% vs. 13%, p = 0.005) and hemoglobin A1C levels (6.0 +/- 1.1% vs. 5.6 +/- 0.6%, p < 0.001). SA patients had a higher proportion (85.3 +/- 10.7% vs. 81.4 +/- 11.0%, p = 0.009) and total level (449.0 +/- 180.4 vs. 388 +/- 127.4, p = 0.010) of classical CD14++CD16- monocytes compared to WCs. There was no difference between the two groups in the proportion of intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes (see Figure 1). There was no association between diabetes and the proportion of monocyte subsets. Ethnicity had a moderate association with the proportion of classical CD14++CD16- monocytes (Eta coefficient = 0.525) with a large effect size (Eta squared = 27.5%). The association of ethnicity with intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes was either weak or negligible with minimal to no effect size (see Table 1). CONCLUSION In patients with substantive risk for CAD, SAs had a significantly higher proportion and level of classical CD14++CD16- monocytes compared to WCs. Our findings provide a novel insight into the potential mechanism of increased CAD susceptibility amongst SAs compared to WCs. South Asians (SAs) have an increased prevalence of coronary artery disease (CAD) and myocardial infarction compared with age- and sex-adjusted White Caucasians (WCs). The mechanism for this increased risk is poorly understood. While classical CD14++CD16- monocytes act as independent predictors of cardiovascular disease, differences in the distribution of monocyte subsets between SA and WC have not been established. We aimed to determine if differences exist in monocyte subsets between SAs and WCs at risk for CAD. 119 consecutive patients (59 SA, 60 WC) of at least intermediate CAD risk by the INTERHEART score were prospectively enrolled. Patients with history of malignancy, age > 70, GFR < 30 or on dialysis were excluded. A single blood sample was collected for monocyte analysis. Flow cytometry using dual colour fluorescence (CD14, CD16) within the monocyte gate was used to identify monocyte subsets (classical, intermediate, and non-classical) by staff blinded to the individuals’ characteristics. The SA group consisted of 64% males with a mean age of 54 (+/- 9), while the WC group consisted of 55% males with a mean age of 59 (+/- 7). Both groups had similar body mass index, rates of hypertension, dyslipidemia and family history of premature CAD. Compared to WCs, SAs had higher prevalence of diabetes (36% vs. 13%, p = 0.005) and hemoglobin A1C levels (6.0 +/- 1.1% vs. 5.6 +/- 0.6%, p < 0.001). SA patients had a higher proportion (85.3 +/- 10.7% vs. 81.4 +/- 11.0%, p = 0.009) and total level (449.0 +/- 180.4 vs. 388 +/- 127.4, p = 0.010) of classical CD14++CD16- monocytes compared to WCs. There was no difference between the two groups in the proportion of intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes (see Figure 1). There was no association between diabetes and the proportion of monocyte subsets. Ethnicity had a moderate association with the proportion of classical CD14++CD16- monocytes (Eta coefficient = 0.525) with a large effect size (Eta squared = 27.5%). The association of ethnicity with intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes was either weak or negligible with minimal to no effect size (see Table 1). In patients with substantive risk for CAD, SAs had a significantly higher proportion and level of classical CD14++CD16- monocytes compared to WCs. Our findings provide a novel insight into the potential mechanism of increased CAD susceptibility amongst SAs compared to WCs.

Serum glutamate and glutamine-to-glutamate ratio are associated with coronary angiography defined coronary artery disease

Background and aimsSerum concentrations of glutamate (Glu), Glutamine (Gln) and Gln/Glu ratio have consistently been reported to be associated with metabolic disorders and diabetes. The aim of this study was to examine the relationship between these metabolites with the presence of coronary artery disease (CAD) and CAD severity in Chinese patients. Methods and results2970 Chinese patients undergoing coronary angiography (CAG) in Beijing Hospital were enrolled. Baseline demographics and medical history data was recorded by questionnaires. Serum Glu and Gln concentrations were analyzed by isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Statistical analysis showed that CAD patients had significantly higher levels of Glu and lower Gln/Glu ratios compared with non-CAD control group. Glu was significantly positively associated with body mass index (BMI), fasting blood glucose (FBG), triglycerides (TG), creatinine (Crea), and uric acid (UA), and negatively associated with high-density lipoprotein cholesterol (HDL-C), while inverse associations between Gln/Glu ratio and these risk factors were observed. Glu levels increased and Gln/Glu decreased with the increase of CAD severity as represented by either the number of stenosed vessels or the Gensini scores. Logistic regression analysis demonstrated that, after adjusting for smoking status, obesity or overweight, hypertension, dyslipidemia, diabetes, stroke and family history of premature CAD, high Glu level and low Gln/Glu ratio were positively associated with CAG defined CAD as well as CAD severity expressed by Gensini score. ConclusionsWe identified Glu and Gln/Glu ratio independently associated with CAG defined CAD as well as CAD severity in Chinese patients undergoing CAG.

Cardiac CT findings in patients with family history of premature CAD: an observational study

Introduction A family history of premature CAD may promote enhanced development of coronary atherosclerosis in a sibling population. Baseline CV algorithms may underestimate the risk of coronary incidents in individuals at familial risk. Cardiac CT provides high diagnostic performance for the detection of coronary plaques. There is little data on the use of this technology in the initial diagnostic approach of these patients. The prognostic value of early detection of coronary plaques by cardiac CT remains unknown in this population. Objectives The study aimed to estimate the global CV risk and the pre-test probability of CAD in patients with a family history of premature CAD. We investigated the potential role of cardiac CT imaging in the assessment of coronary risk in patients from high-risk families. We sought to remind the 2019 ESC guidelines for screening for CAD in asymptomatic subjects. Methods Fifty siblings of patients with premature CAD were investigated. The pre-test probability of CAD was determined with the Clinical Model of the CAD consortium. The risk of CV disease was calculated and compared with three different risk algorithms (SCORE, FRS, PROCAM). All patients underwent cardiac CT with both non-contrast and contrast imaging. Coronary artery calcium (CAC) scoring was calculated and CT angiograms were analyzed. Patients with suspected CT obstructive CAD underwent coronary angiography. Clinical outcomes in terms of treatment were analyzed. Results The pre-test probability of CAD was low: CAD consortium <10% in 60%, SCORE <5% in 100%, FRS <10% in 88%, CAC scoring <100% in 68%. However, PROCAM was <10% in 16 cases (32%). Only 12 patients (24%) presented normal CCTA findings. In patients with abnormal CCTA findings (n = 38), PROCAM was higher than FRS in 20 patients (53%). Coronary angiography was performed in 31 cases (62%) for suspected CT obstructive CAD. Most patients presented no significant lesions (55%). Revascularization was performed in 8 patients (16%), 6 of them (75%) presented CAC scoring <100, 4 of them (50%) presented CAC scoring <400. After investigation, lipid-lowering therapy was enhanced by 66%. Conclusion Coronary atherosclerotic-phenotyping using cardiac CT may provide discriminatory information allowing earlier identification of patients at familial risk of premature CAD. This diagnostic workup strategy may help to guide and improve the management of these patients. However, there is a paucity of data concerning the prognostic significance of this technology in relatives at familial risk of premature CAD. Therefore, further randomized controlled trials are needed to assess the incremental risk-predictive value of this approach in this population.

Impact of a coronary artery calcium-guided statin treatment protocol on cardiovascular risk at 12 months: Results from a pragmatic, randomised controlled trial

Background and aimsCoronary artery calcium (CAC) may encourage patients to adhere to primary prevention recommendations. This study sought to evaluate the benefit of a CAC-guided risk-management protocol in those with a family history of premature coronary artery disease (FHCAD). MethodsIn this Australian multi-centre, randomized controlled trial (Coronary Artery Calcium score: Use to Guide management of Hereditary Coronary Artery Disease, CAUGHT-CAD), asymptomatic, statin-native participants at low-intermediate cardiovascular risk with FHCAD underwent CAC assessment. Those with CAC between 1 and 400 were randomized (1:1) to disclosing the CAC result to both patient and physician and commencing atorvastatin (intervention) or blinding the CAC result with risk factor education only (control). The primary endpoint of this sub-study was change in Pooled Cohort Equation (PCE) at 12 months. ResultsOf 1088 participants who were scanned, 450 were randomised and 214 in both groups completed 1-year follow-up. At 1 year, PCE-risk decreased by 1.0% (95% CI 0.13 to 1.81) in the CAC-disclosed group and increased by 0.43% (95%CI 0.11–0.75) in the CAC-blinded group. LDL-C decreased in the CAC-disclosed group in both those who continued (1.5 mmol/L; 95% CI 1.36 to 1.74) and discontinued statins (0.62 mmol/L; 95% CI 0.32 to 0.92) but was unchanged in the CAC-blinded group. ConclusionParticipants unblinded to their CAC showed reductions in LDL irrespective of statin continuation when compared to controls at 12 months. Improvements in individual risk factors and PCE risk were also noted. CAC assessment may positively influence patients and physicians to improve risk factor control.