Conventional Coronary Risk Factors Research Articles

Genetics and Ischemic Heart Disease: Should We Opt for Genetic Testing for Primary Prevention?

Cardiovascular diseases (CVD) are a prevalent health concern within the general population of Pakistan, where the average lifespan is notably lower than the global average, with men typically living to 67 years and women to 69 years. According to the 2019 Global Burden of Disease study, Pakistan had an estimated age-standardized incidence rate of CVD at 918.18 per 100,000 (compared to the global rate of 684.33 per 100,000), along with an age-standardized death rate of 357.88 per 100,000 (globally, this rate is 239.85 per 100,000).1 Coronary heart disease (CHD), as revealed by the Framingham Heart Study focusing on individuals aged 40 to 94 without prior heart disease, displayed a lifetime risk of 49% for men and 32% for women when reaching the age of 40.2 There has been a declining trend in death rates in the United States attributed to CVD, CHD, and stroke since 1975. Data from 2000 to 2008 also indicate a decline in CHD mortality.3 Worryingly, the World Health Organization (WHO) reports a concerning rise in CHD-related fatalities in Pakistan. In 2020, 240,720 individuals died due to CHD, accounting for 16.49% of all deaths. This highlights an escalating trend of CHD-related mortality in Pakistan. It's important to note that most individuals presenting with cardiac events have one or more established or borderline risk factors aside from age and gender.4-6 While some essential risk factors are discernible, others may remain elusive. The screening of these risk factors and the evidence for targeted therapeutic interventions are still emerging and require further exploration.7 The starting point for assessing CVD risk factors is variables used to predict major cardiovascular events. These include age, sex, blood pressure, cholesterol levels, diabetes mellitus, and smoking status. Although risk assessment tools like the Pooled Cohort Equation in 2014 and Astro-CHARM have been developed, they have yet to provide satisfactory assessments for potential new CVD risk factors.8 CHD is recognized as a multifactorial disorder resulting from genetic and environmental factors interplay. Environmental risk factors have been identified in approximately 80% of CHD cases.9 Several risk scores, such as the Framingham Risk Score, PROCAM, Reynolds Risk Score, and QRISK 2, have been proposed to guide the use of statins in high-risk groups.10-14 Yet, these risk scores often lack precision and may either overestimate or underestimate future CHD events.15,16 The variation in disease susceptibility among individuals with similar environmental factors and conventional coronary artery disease risk factors (CRFs) may be attributed to genetic variations.17 Genetic analysis can potentially enhance risk discrimination beyond the consideration of CRFs alone. Family history of heart disease, accounting for more than 40% of risk estimation, has long been considered a part of CRFs.18 Candidate gene studies have been conducted to identify common variants in genes associated with disease pathways.19 Single-nucleotide polymorphisms (SNPs) have been employed as markers of genetic diversity. Among these SNPs, those located on the 9p21 locus have shown the strongest association with CHD risk to date.20,21 However, despite the clear link between these variants and incident CHD, 9p21 locus SNPs have not definitively improved the prediction or classification of CHD risk compared to traditional risk factors.22-24 It is important to note that most genetic studies on CHD have predominantly focused on European/Caucasian populations, and their applicability to the South Asian population, including Pakistan, requires further investigation.25,26 In this context, the Pakistani population, much like other Asian countries, is underrepresented in genetic research on CHD. Shahid SU et al. did some work in this respect,27 showing 21 SNPs risk score for genetic risk analysis in the Pakistani population. In conclusion, while different risk assessment tools have been developed for the Pakistani population aged 40 years and above, there is an urgent need to expand cardiac risk evaluation by identifying genetic markers related to CHD, particularly in the younger population. This will be crucial for advancing our understanding of CHD risk factors and developing more effective prevention and intervention strategies.

Vasospastic angina in women: Clinical backgrounds and prognoses of patients younger than and older than 60 years

We frequently encounter cases of women with vasospastic angina (VSA). Additionally, some women with VSA are younger than 60 years old. However, it is unknown whether the characteristics of VSA in women aged < 60 years are different from those in women aged ≥ 60 years. To investigate and compare the clinical characteristics and prognosis of VSA in women aged < 60 years from those in women aged ≥ 60 years. We enrolled 94 women with VSA who were diagnosed using the spasm provocation test. According to the age at diagnosis, the patients were divided into two groups: Group Y (age < 60 years, n = 17) and Group O (age ≥ 60 years, n = 77). Flow-mediated dilation (FMD) and nitroglycerin (NTG)-induced dilation (NID) of the brachial artery were performed and assessed using brachial ultrasonography. Moreover, conventional coronary risk factors, such as atherosclerotic lesions (stenosis > 20%) detected using coronary angiography and focal spasms (coronary spasm within one segment of one coronary artery), and major cardiovascular adverse events (MACE) were assessed in both groups. Smoking was more prevalent in Group Y than in Group O (P = 0.04). FMD was similar in both groups (Group O: 4.3% ± 3.2%, Group Y: 4.5% ± 3.3%; P = 0.75), whereas NID was higher in Group Y (20.5% ± 8.6%) than in Group O (13.6% ± 5.3%, P < 0.01). Atherosclerosis was not detected in Group Y but was detected in Group O (61%, P < 0.01). Focal spasms were less frequent in Group Y (12%) than in Group O (38%, P = 0.04). The incidence of major adverse cardiac events did not differ between the two groups (P = 0.40). Women aged < 60 years with VSA have less atherosclerotic lesions and focal spasms. These characteristics may be affected by smoking habits and vascular smooth muscle dysfunction.

Clinical Characteristics and Prognosis of Patients with Multi-Vessel Coronary Spasm in Comparison with Those in Patients with Single-Vessel Coronary Spasm.

(1) Background: We have sometimes experienced patients with vasospastic angina (VSA) who presented multi-vessel spasm (MVS) on coronary angiography and spasm provocation test (SPT). However, the clinical characteristics of VSA patients with MVS and the prognosis of such patients in the clinical setting have not been clarified. Therefore, we compared the clinical characteristics and prognosis in VSA patients with MVS with those in VSA patients with single-vessel spasm (SVS). (2) Methods: A total of 152 patients (mean age, 67 years, 74 men and 78 women) with VSA, in which the presence of coronary spasm was assessed in both left coronary artery (LCA) and right coronary artery (RCA) on SPT, were enrolled. We defined VSA as the presence of >90% narrowing of the epicardial coronary artery on angiograms, accompanied by usual chest symptoms and/or ischaemic ST-T changes on the electrocardiogram. On SPT, MVS was defined as the presence of spasms on ≥2 major coronary arteries. Based on the presence of MVS, patients were divided into the MVS group and the SVS group. The frequencies of conventional coronary risk factors, blood chemical parameters, average times of anginal attack, SPT findings such as spasm provocation induced by a low dose of acetylcholine (L-ACh) and total occlusion due to coronary spasm (TOC), number of coronary vasodilators at discharge and major cardiovascular events (MACE, including cardiac death and readmission due to any cause of cardiovascular diseases) were compared between the two groups. (3) Results: The MVS and SVS groups were comprised of 98 (64%) and 54 (36%) patients, respectively. The level of fasting blood glucose (FBS) was lower (p < 0.01), and the level of cystatin-C (n = 89) tended to be higher (p = 0.07) in the MVS group than in the SVS group. The frequencies of L-ACh-induced coronary spasm (33% in MVS and 17% in SVS, p = 0.04) and TOC (12% in MVS, 0% in SVS, p < 0.01) were higher in the MVS group than in the SVS group. The average number of coronary vasodilators at discharge was higher in the MVS group (1.2 ± 0.4) than in the SVS group (0.9 ± 0.5, p < 0.01). The frequency of MACE was not different between the two groups. (4) Conclusions: Patients with MVS may have higher VSA activity on SPT and have more aggressive medications, leading to a comparable prognosis in VSA patients with SVS. MVS is an important indicator of at least VSA activity, and cardiologists should confirm this in SPT whenever possible. Further studies should confirm whether lower FBS levels and higher cystatin-C levels are any markers of MVS.

RISK FACTOR PROFILING OF ACUTE CORONARY SYNDROME IN PREMENOPAUSAL WOMEN PRESENTING AT A TERTIARY CARE HOSPITAL IN URBAN INDIAN SETTING: AN OBSERVATIONAL STUDY

Objective: This study aimed to evaluate cardiovascular risk factors in premenopausal women presenting with acute coronary syndrome (ACS). Design and method: Premenopausal women presenting with ACS at the Deenanath Mangeshkar hospital &amp; research center, Pune between January 2012 and June 2019 were enrolled. Data concerning demographics, risk factors and medical history (self-reported) were collected. Results: Ninety premenopausal women (mean age: 40.8 ± 5.0 years) were included in the study. The most common presenting symptoms were chest pain (83.3%) and shortness of breath. ACS presentation included ST-elevation myocardial infarction (38.9%), unstable angina (34.4%) and non-ST-elevation myocardial infarction (25.6%). Mild-to-severe left ventricular dysfunction was seen in 52.2% women and triple or double vessel disease in 52.2% women. The most frequent conventional coronary risk factors were diabetes (of total 41%, 48. 6% were poorly controlled) and hypertension (38.9%); lifestyle-related risk factor were low levels of physical activity (51.1%); and obstetric and gynaecological factors were history of at least one miscarriage (26.7%) and hormonal contraceptive use (26.7%). No correlation was found between the risk factors and presentation of ACS or severity of coronary artery disease. Conclusions: The high prevalence of conventional risk factors need to be identified and addressed early. Novel gynaecological risk factors are often ignored and need fair attention in routine practice in premenopausal women presenting with ACS. To our knowledge, this is one of the largest data set that determined cardiovascular risk factors in premenopausal women with ACS.

Clinical results at a long-term follow-up of percutaneous coronary intervention in ostial left main coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Left main coronary ostial lesions are notable for being found more commonly among middle-aged women with fewer conventional coronary artery risk factors and for lower long-term patency of internal thoracic grafts. Isolated ostial left main coronary artery (LMCA) disease is involved in the 18% of lesions and have a management approach do well either with percutaneous coronary intervention (PCI) or cardiac surgery. Continuous improvement in the devices and the emergence of better drug-eluting stents (DES) has improved the results of PCI in these high-risk lesions. Purpose The main objective of this study was to evaluate the efficacy and safety of PCI in ostial LMCA disease at a 14-year follow-up. Methods We prospectively included 109 consecutive patients (72± 12 years, 72.5% male) with ostial LMCA disease treated with PCI between June 2006 and June 2020. We evaluated the presence of major adverse cardiovascular events (MACE) defined as cardiac death, non-fatal myocardial infarction, target lesion revascularization (TLR) and stent thrombosis after a 14-year clinical follow-up (median 63.6 months). Results 55.9% had stable coronary disease and 44.1% had acute coronary syndrome (35.9% Non-STEMI and 8.2% STEMI). 45% were diabetic patients and 36.6% presented moderate-severe left ventricular systolic dysfunction. The mean logistic EuroSCORE was 8.1 % and SYNTAX score was ≥ 23 in 72.5% of the patients. We implanted second-generation DES in the 83.5% of patients (76% zotarolimus-eluting stent) and post-dilatation was performed in the 68.8%. The angiographic success rate was 99%. Complication rate in the procedure was 5.5% without intra-procedure deaths. During follow-up, MACE rate at 14 years was 18.3% (13.7% of cardiac death, 4.6% of nonfatal myocardial infarction, 7.3% of TLR and thrombosis rate of 0.9%). 24.2% of patients had an angiographic follow-up. Conclusions In spite of high surgical risk, complex coronary anatomy and older aged patients, PCI in ostial LMCA disease is safe and effective with a low rate of major cardiovascular events at long-term follow-up.

Coronary Artery Disease in Very Young Patients: Analysis of Risk Factors and Long-Term Follow-Up

Coronary artery disease (CAD) is a common chronic condition in the elderly. However, the earlier CAD begins, the stronger its impact on lifestyle and costs of health and social care. The present study analyzes clinical and angiographic features and the outcome of very young patients undergoing coronary angiography due to suspected CAD, including a nested case-control study of ≤40-year-old patients referred for coronary angiography. Patients were divided into two groups: cases with significant angiographic stenosis, and controls with non-significant stenosis. Of the 19,321 coronary angiographies performed in our center in a period of 10 years, 504 (2.6%) were in patients ≤40 years. The most common cardiovascular risk factors for significant CAD were smoking (OR 2.96; 95% CI 1.65–5.37), dyslipidemia (OR 2.18; 95% CI 1.27–3.82), and family history of CAD (OR 1.95; 95% CI 1.05–3.75). The incidence of major adverse cardiovascular events (MACE) at follow-up was significantly higher in the cases compared to controls (HR 2.71; 95% CI 1.44–5.11). Three conventional coronary risk factors were directly related to the early signs of CAD. MACE in the long-term follow-up is associated to dyslipidaemia and hypertriglyceridemia. Focusing efforts for the adequate control of CAD in young patients is a priority given the high socio-medical cost that this disease entails to society.

Identification of Risk Factors for Coronary Artery Disease in Asymptomatic Patients with Type 2 Diabetes Mellitus

Background: Patients with diabetes mellitus (DM) are a high-risk group for coronary artery disease (CAD). In the present study, we investigated predictive factors to identify patients at high risk of CAD among asymptomatic patients with type 2 DM based on coronary computed tomographic angiography (CCTA) findings. Methods: A single-center prospective study was performed on 452 consecutive patients with type 2 DM who were provided with a weekly hospital-based diabetes education program between 3 October 2015, and 31 March 2020. A total of 161 consecutive asymptomatic patients (male/female: 111/50, age: 57.3 ± 9.3 years) with type 2 DM without any known CAD underwent CCTA. Based on conventional coronary risk factors and non-invasive examination, i.e., measurement of intima-media thickness, subcutaneous and visceral fat area, a stress electrocardiogram test, and the Agatston score, patients with obstructive CAD, CT-verified high-risk plaques (CT-HRP), and optimal revascularization within 90 days were evaluated. Results: Current smoking (OR, 4.069; 95% C.I., 1.578–10.493, p = 0.0037) and the Agatston score ≥100 (OR, 18.034; 95% C.I., 6.337–51.324, p = 0.0001) were independent predictive factors for obstructive CAD, while current smoking (OR, 5.013; 95% C.I., 1.683–14.931, p = 0.0038) was an independent predictive factor for CT-HRP. Furthermore, insulin treatment (OR, 5.677; 95% C.I., 1.223–26.349, p = 0.0266) was the only predictive factor that correlated with optimal revascularization within 90 days. Conclusions: In asymptomatic patients with type 2 DM, current smoking, an Agatston score ≥100, and insulin treatment were independent predictive factors of patients being at high-risk for CAD. However, non-invasive examinations except for Agatston score were not independent predictors of patients being at high risk of CAD.

Coronary microvascular function in patients with angina with no obstructive coronary artery disease-What factors affect it clinically or angiographically?

Abstract Background In the clinical setting, we have often experienced patients with angina with no obstructive coronary artery disease (ANOCA), and it has been proposed that the presence of coronary microvascular dysfunction (CMD) play a pivotal role in the pathogenesis of ANOCA. Thus, it is important to assess coronary microvascular function (CMF). However, it has not been clarified what clinical factors or lesion characteristics on coronary angiography (CAG) affect CMF. Thus, we investigated the relationship between CMF and clinical factors or lesion characteristics on CAG in patients with ANOCA. Methods Thirty-four patients with chest pain, who underwent CAG, spasm provocation test (SPT) and CMF test, were enrolled. We excluded patients who had moderate coronary stenosis (% stenosis &amp;gt;30%). In the SPT with acetylcholine for left coronary artery and right coronary artery (RCA), the coronary spasm was defined as &amp;gt;90% narrowing of coronary artery on CAG accompanied with chest symptoms and/or ST-T changes on ECG during SPT, and coronary microvascular spasm (MVS) was defined as ≤90% narrowing of coronary artery on CAG with accompanied with chest pain and ST-T changes during SPT. In each coronary artery, the presences of atherosclerosis (20%≤%stenosis≤30%), focal spasm (spasm occurred within one segment of AHA classification), diffuse spasm (spasm occurred over two segments of AHA classification) and MVS, were checked. In the CMF test with a pressure-wire during adenosine triphosphate infusion, the index of microvascular resistance (IMR) was measured. IMR values were obtained in 34 of the left anterior descending coronary artery (LAD) and 12 in RCA. In each patient, conventional coronary risk factors, blood chemical parameters, peripheral endothelial function such as flow-mediated dilation (FMD) of brachial artery and left ventricular mass index (LVMI) were checked. Results In 34 patients, clinical factors including blood chemical parameters, FMD and LVMI, except for smoking status did not affect IMR values on LAD. Only the smoking status was associated with IMR values as follows: median IMR values were 44, 22 and 25 in current smokers (n=5), past smokers (n=8) and never smokers (n=21, p=0.03), respectively. In 46 coronary arteries, the presence of atherosclerosis, the type of the coronary spasm, such as focal and diffuse spasm and MVS, did not affect the IMR values, however, it was significantly higher in the RCA (median 38) than that in the LAD (median 26, p=0.02). Conclusion These results suggest that smoking status affected CMF in patients with ANOCA, suggesting the possibility of improvement of CMF by stop smoking in such patients. In addition, in the assessment of CMF, it may be important to take into account which coronary artery being evaluated. Funding Acknowledgement Type of funding sources: None.

Role of LA strain assessed by speckle tracking echocardiography in predicting patients who develop POAF after a coronary artery bypass surgery

Abstract Objectives To evaluate the correlation between left atrial dysfunction assessed by speckle tracking echocardiography and development of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass grafting. To determine the role of coronary risk factors in development of POAF. Method Patients undergoing CABG from January 2019 till June 2020 in Apollo institute, fulfilling the inclusion and exclusion criteria were included.Total of 200 patients were followed.They were subjected to LA strain and strain rate analysis by speckle tracking. Results The incidence of POAF in our study was 24% (n=48). The mean age of this study population was 59.13 years. The patients who developed POAF were older (68.5±9.048 vs 58.39±9.74 years, p value=0.05) than those with no POAF. POAF occurred in 2 phases. the highest proportion of POAF occurrence noticed on postoperative day 2. Among the total POAF cases 79.% occurred within the first 48 hours and 20.8% occurred later (p=0.001). Among the 48 patients who developed POAF, 5 of them developed recurrence during their hospital stay. They had reverted to sinus rhythm following anti-arrhythmic medication for a duration of &amp;gt;24 hours, but went on to develop recurrence of AF at a later. 4 among them reverted to sinus rhythm at discharge while 1 continued to remain in AF at discharge.The duration of hospital stay for patients with POAF group was 10.4 days compared with 10.04 days for those without POAF. Similarly the post-operative stay in the hospital was 7.4 days for the POAF group and 7.04 days for the NO POAF.There was no added economic impact secondary to AF.Comparing the values of left atrial volume index of both the groups it was derived that the mean LAVI value of the POAF group was 26.84+3.654 ml/m2 and that for the NO POAF group was 26.6+3.037ml/m2. Though the patients with POAF had larger LA volume, the chi square test analysis did not yield any clinically significant relationship between LAVI and POAF in our study (p=0.3). The mean LA global strain for the patients with POAF was 29.73+3.695%. And for the patients with no POAF was 36.3+4.854%. LA global strain was reduced in patients who developed POAF (P&amp;lt;0.001) which indicated a strong correlation between LA strain and POAF. Conclusion There is significant correlation between Global Left Atrial Strain and POAF in patients undergoing CABG (P&amp;lt;0.001).There is no significant correlation between patient factors like age, BMI, and the conventional coronary risk factors with POAFThere is no significant correlation between the conventional echocardiographic parameters like LA diameter, LAVI, LVDD, LVSD, LVEF and transmitral flow velocities with POAF. To conclude, preoperative speckle tracking assessment of LA has a strong predictive role in determining the occurrence of POAF in patients undergoing Coronary artery bypass grafting surgery. Funding Acknowledgement Type of funding sources: None.

Predictors of coronary slow flow phenomenon in patients with angina and normal epicardial coronaries

Abstract Background Coronary slow flow phenomenon (CSFP), also called as syndrome Y is characterized by the delayed passage of contrast distally when injected into the epicardial coronaries. It accounts for upto 7% of patients undergoing coronary angiogram (CAG) for angina. Conventionally, it is determined by the coronary filling time. We aimed to determine whether coronary emptying time is a significant predictor of the coronary slow flow. Purpose To determine the coronary artery filling time and emptying time at prespecified vascular landmarks in patients with chest pain and normal epicardial coronaries. To determine the association of coronary arterial filling time and emptying time in patients with coronary slow flow phenomenon. To determine the association of various conventional coronary artery disease risk factors and various clinical parameters in patients with coronary slow flow phenomenon. Methods Patients with angina, having normal epicardial coronaries on CAG were selected consecutively between January 2019 and December 2020. Each angiogram was assessed for the coronary filling and emptying times at prespecified standard vascular landmarks on the basis of TIMI frame counts (TFC). Results A total of 37 patients with normal epicardial coronaries were analyzed, out of which 27 patients had slow flow in LAD and 17 patients had slow flow in RCA (10 had normal flow in LAD and 12 had normal flow in RCA). Eight had non dominant RCA, which were too small for analyzing TFC were excluded from the study. We observed positive correlation of coronary filling times and emptying times, both in LAD (R-Sq 0.24) and RCA (R-Sq 0.05) in slow flow patients unlike those with normal flow. We found the filling times and emptying times are significantly prolonged in slow flow patients [with mean CTFC values of 77.94 &amp; 92.85 in LAD and 36.91 &amp; 120.82 in RCA, respectively (P&amp;lt;0.05)]. The capillary and venous transit time is prolonged both in LAD and RCA slow flow groups, which was of statistical significance in the RCA slow flow group (P&amp;lt;0.05), but not in LAD slow flow group (P=0.43). We observed slow flow significantly more in male population (P=0.02) and associated with high LDL/HDL ratios and high triglycerides. Conclusion 1. In addition to coronary artery filling times, Coronary artery emptying time is an independent and significant predictor of coronary slow flow phenomenon. 2. Capillary and venous transit time is significantly prolonged in patients with slow flow in RCA whereas in patients with LAD slow flow there is non significant prolongation of capillary and venous transit time. 3. There is a positive correlation of coronary emptying time with coronary filling time in Coronary Slow Flow. This correlation is not seen in patients with normal coronary flow. 4. Coronary slow flow is observed significantly more in male population. 5. Coronary slow flow is significantly associated with high LDL/HDL ratios and triglyceride levels. Funding Acknowledgement Type of funding sources: None. Study designAngiographic landmarks for LAD and RCA – Pictorial representation

Clinical characteristics and prognosis in patients with multi-vessel coronary spasm – comparison with those in patients with single-vessel coronary spasm

Abstract Background We have sometimes experienced patients with vasospastic angina (VSA), who showed multi-vessel spasm (MVS) on coronary angiography (CAG) and spasm provocation test (SPT). However, it has not been clarified what clinical characteristics VSA patients with MVS have or whether such patients have poor prognosis. Therefore, we compared the clinical characteristics and prognosis in VSA patients with MVS with those in VSA patients with single-vessel spasm (SVS). Methods One hundred and fifty-two patients (mean age: 67 yrs, 74 men and 78 women) with VSA, in which presence of coronary spasm was assessed in both left coronary artery (LCA) and right coronary artery (RCA) on SPT, were subjected. We defined VSA as the presence of more than 90% narrowing of the epicardial coronary artery on angiograms, accompanied by the usual chest symptoms and/or ischemic ST-T changes on electrocardiogram. On SPT, MVS was defined as the presence of spasm on ≥ two major coronary arteries. Base on the presence of MVS, patients were divided into the following 2 groups: MVS group and SVS group. The frequencies of conventional coronary risk factors, the average times of anginal attack (per month), the findings of SPT such as spasm provocation induced by low dose of acetylcholine (LDA) and total occlusion due to coronary spasm (TOC), the number of coronary vasodilators at discharge, and the major cardiovascular events (MACE) including death of any cause and readmission due to heart failure, acute coronary syndrome and unstable angina, were compared in the two groups. Results There were 98 patients (64%) in the MVS group and 54 patients (36%) in the SVS groups. The frequencies of conventional coronary risk factors and the average times of anginal attacks (4/month in both groups) were not different in the two groups. The frequencies of LDA (33% in MVS and 17% in SVS, p&amp;lt;0.05) and TOC (12% in MVS, 0% in SVS, p&amp;lt;0.01) were higher in the MVS group than in the SVS group. The average numbers of coronary vasodilators was higher in the MVS group (1.1±0.4) than in the SVS group (0.9±0.4, p&amp;lt;0.01). The frequency of MACE did not differ in the two groups as follows (figure). Conclusions These findings suggest that there was no clinical characteristic, suggesting the presence of MVS in VSA patients. Such patients may have higher VSA activity on SPT and have more aggressive medications, leading to the similar prognosis in VSA patient with SVS. Funding Acknowledgement Type of funding sources: None.

Coexistent coronary artery disease in Indian patients undergoing permanent pacemaker implantation (PPI) for symptomatic bradyarrhythmia

BackgroundThe cause-effect of conduction disturbance in chronic lesion of coronary arteries is complicated. This study was designed to evaluate coexistent CAD in patients with symptomatic bradyarrhythmia to find common anatomic basis for conduction disturbances and its relationship to conventional coronary risk factors. MethodsIn this prospective observational study, 929 patients who admitted for symptomatic bradyarrhythmia requiring permanent pacemaker implantation were included. All included patients underwent coronary angiography and were divided into groups based on angiographic findings. Association between conduction disturbances and these groups were analyzed. ResultsA total of 929 patients with mean age of 63.1 years were included in our study. We found age ≥50 years, male sex, presence of diabetes and hypertension as statistically significant predictors of abnormal coronary angiography. Obstructive CAD (≥50% stenosis) was found in 34.4% patients. Prevalence of single vessel disease, double vessel disease and triple vessel disease was 15.3%, 10.2% and 8.9% respectively. Severe coronary obstruction (≥90% obstruction) was found in 16.25% patients. Revascularization was advised in three fourth of cases of obstructive CAD. Approximately two third of patients didn’t have significant obstruction in coronaries supplying the conduction system. Type 4 was the commonest anatomy in obstructive CAD. SA Nodal artery was found more diseased in patients of SSS with p value of 0.01. ConclusionObstructive CAD was found in one third of patients undergoing PPI. Age ≥50 years, male sex, diabetes and hypertension were found significantly correlated with presence of CAD and may act as important markers for the judgment of further coronary evaluation.

Ceramide Scores Predict Cardiovascular Risk in the Community

[Figure: see text].

Abstract 14995: Family History of Coronary Artery Disease in Patients With Vasospastic Angina: What Does it Mean Clinically?

Introduction: It has been reported that a family history of coronary artery disease (FH-CAD) is one of the coronary risk factors for CAD with organic coronary stenosis (o-CAD). Hypothesis: However, the indication for FH-CAD in patients with vasospastic angina (VSA) is yet to be fully elucidated. Therefore, we investigated the frequency of FH-CAD in patients with VSA and examined the clinical characteristics of patients with VSA with FH-CAD. Methods: A total of 78 patients with VSA diagnosed by coronary angiography and spasm provocation test (SPT) were included. Patients with cardiomyopathies, long QT syndrome, or Brugada syndrome, were excluded. On SPT, VSA was defined as &gt;90% narrowing of coronary artery in response to acetylcholine accompanied with chest symptoms and/or ST- T changes on ECG. Each patient was interviewed about their FH-CAD, and its presence was defined as having known CAD and sudden cardiac death affecting first-degree relatives. According to the presence of FH-CAD, patients with VSA were classified into the two groups: Group I, with FH-CAD; and Group II, without FH-CAD. Conventional risk factors, blood chemical parameters, vascular function, including flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID), duration of angina, were checked. Furthermore, the frequency of FH-CAD was checked in 161 patients with o-CAD (≥50% coronary stenosis) and 69 patients without o-CAD or VSA (non-CAD) . Results: Group I and Group II comprised 17 (21%) and 61 patients (79%), respectively. The frequency of FH-CAD in patients with VSA was not significantly different between o-CAD and non-CAD groups (17% vs. 16%). The conventional coronary risk factors, blood chemical parameters, and FMD (3.2 ± 3.1%, vs. 3.4 ± 3.8%) were not significantly different between Group I and Group II. In contrast, NID and duration of angina were significantly higher in Group I than in Group II, (18.2 ± 9.1% vs. 14.0 ± 5.2%; 52 ± 15 months vs. 16 ± 7 months, respectively; both p &lt; 0.05). Conclusions: These findings suggest that the FH-CAD is associated with the duration of angina and abnormal vascular smooth muscle function. Thus, FH-CAD may provide clinically important information regarding the activity and the possible mechanism, even in patients with VSA.

Effect of eicosapentaenoic acid/docosahexaenoic acid on coronary high-intensity plaques detected with non-contrast T1-weighted imaging: subgroup analysis of the AQUAMARINE EPA/DHA study

Abstract Background In the recent the Reduction of Cardiovascular Events with EPA-Intervention Trial (REDUCE-IT), statin therapy plus high-dose eicosapentaenoic acid (EPA) significantly reduced the risk of cardiovascular death in patients with coronary artery disease (CAD) with elevated triglyceride (TG) levels. An epidemiologic study has shown that increasing the intake of long-chain n-3 polyunsaturated fatty acids, especially EPA and docosahexaenoic acid (DHA), are associated with a lower risk of fatal CAD. However, the anti-atherosclerotic effect of high-dose EPA/DHA has not be clarified. We reported that coronary high-intensity plaques (HIPs) detected with non-contrast T1-weighted imaging (T1WI) on cardiac magnetic resonance (CMR), which can be uniquely quantitative assessed using the plaque-to-myocardium signal intensity ratio (PMR) of ≥1.4, are significantly associated with future coronary events. Moreover, we demonstrated that intensive statin therapy reduces the PMR of coronary HIPs by 19% but is unlikely to completely resolve HIP (PMR&amp;lt;1.0). In the AQUAMARINE EPA/DHA study, our goal was to assess the anti-atherogenic effect of EPA/DHA in an exploratory manner by examining the change in PMR of coronary HIPs after 12 months of EPA/DHA therapy in patients with CAD on statin therapy. Methods This study was designed as a single-center, triple-arm, parallel-group, randomized controlled, open-label, superiority trial examining the effect of 12 months of additional EPA/DHA therapy on coronary HIPs in patients with CAD who receiving statin therapy. Eligible subjects are randomly assigned to the 2 g/day EPA/DHA group (n=26), the 4 g/day group (n=23), or the no EPA/DHA (statin-only) group (n=24) between May 2014 and December 2017. The PMR was defined as the signal intensity of the coronary plaque divided by that of nearby left ventricular myocardium. The primary endpoint is the change in PMR after EPA/DHA treatment. Results These 3 groups were well matched at baseline, with no statistically significant differences in age, male sex, conventional coronary risk factors, TG level, medications, and PMR. Figure 1 shows subgroup analysis of patients with high triglyceride levels (&amp;gt;150mg/dl). In the patient-based analysis (A), 12 months of EPA/DHA therapy significantly reduced the PMR of primary lesions. In the segment-based analysis (B), additional reduction of PMR was observed in the high-dose EPA/DHA group compared with the no EPA/DHA treatment group. Discussion The present study of patients with high triglyceride levels demonstrated that EPA/DHA had a dose-dependent anti-atherosclerotic effect. This finding may provide additional information of EPA/DHA for lowering the residual risk in patients with CAD on statin therapy. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Takeda Pharmaceutical Co., Ltd.

Perfusion-metabolic mismatch in myocardial scintigraphy in patients with vasospastic angina: what does it mean clinically?

Abstract Background It has been reported that perfusion-metabolic mismatch (PMM) in thallium-201 (Tl) and 123I-βmethyl-p-iodophenyl-pentadecanoic acid (BMIPP) shows important information regarding myocardial ischemia in the clinical setting. Such findings have been frequently obtained, even in patients with vasospastic angina (VSA). However, it has not been fully clarified what such findings mean clinically in patients with VSA. There, we investigated the frequency of PMM in patients with VSA as well as clinical characteristics of patients with VSA who have PMM. Methods Seventy-eight patients (mean age: 70 yrs, 29 men and 49 women) were diagnosed with VSA by coronary angiography and spasm-provocation test (SPT). We defined VSA as the presence of more than 90% narrowing of the epicardial coronary artery on angiograms, accompanied by the usual chest symptoms and/or ischemic ST-T changes on electrocardiogram. On SPT, multi-vessel spasm was defined as the presence of spasm on ≥ two major coronary arteries. Dual myocardial scintigraphy with Tl and BMIPP was performed, and the presence of PMM was defined as the summed rest score (SRS) in BMIPP scintigraphy ≥4 and difference in SRS in BMIPP and Tl-201 ≥4. Patients were divided into two groups according to the presence of PMM: Group I (+PMM, n=30) and Group II (−PMM, n=48). Each patient with VSA was assessed for conventional coronary risk factors, numbers of angina attacks per month, and taking vasodilators. Results Age, gender distribution, and conventional risk factors were not different between the groups. The median number of angina attacks was higher in the Group I than in the Group II (Group I: 4.5 vs. Group II: 0.1, p&amp;lt;0.01), and fewer patients were taking vasodilators in Group I (Group I: 1.1±1.0 vs. Group II: 1.5±1.1, p&amp;lt;0.05). On SPT, the presence of multi-vessels spasm was significantly higher in Group I (76%) than Group II (44%, p&amp;lt;0.05). Logistic regression analysis showed that the presence of multi-vessels spasm (p&amp;lt;0.05) and taking a smaller amount of vasodilators (p&amp;lt;0.05) were associated with PMM. Conclusions These findings suggest that PMM in Tl and BMIPP scintigraphy are associated with multi-vessels spasm and a smaller amount of vasodilator medication. This imaging data may provide important information regarding activity of VSA and sufficient medication. Funding Acknowledgement Type of funding source: None

Relationship between the Severity of Coronary Artery Disease and Cardiovascular Risk Factors in Acute Coronary Syndrome: Based on Tehran Heart Center's Data Registry.

Background: Acute coronary syndrome (ACS) is one of the main causes of mortality worldwide. We sought to evaluate the correlation between the severity of coronary artery disease (CAD) and conventional coronary artery risk factors in a large cohort of patients with ACS. Methods: This study included all patients admitted to the coronary care unit with a diagnosis of ACS between 2003 and 2017. The patients were divided into 2 groups: 1) unstable angina and 2) myocardial infarction. The aims of this study were to evaluate the effects of the risk factors and extension of coronary artery stenosis in patients with ACS according to the Gensini score.Results: Of a total 40 319 patients who presented with ACS, 18 862 patients (mean age =60.4±11.14 y, male: 67.2%) underwent conventional coronary angiography and met our criteria to enter the final analysis. The median of the Gensini score was 50 (25–88) in the study population. The multivariable analysis showed that age, sex, diabetes mellitus, hypertension, dyslipidemia, family history, cigarette smoking, opium consumption, and myocardial infarction increased the risk of positive Gensini scores. All the aforementioned risk factors, except cigarette smoking and opium consumption, increased the severity of stenosis in those with positive Gensini scores. The strongest relationship was seen vis-à-vis myocardial infarction, sex, and diabetes mellitus.Conclusion: Our findings suggest that age, sex, diabetes mellitus, dyslipidemia, hypertension, family history, and myocardial infarction have significant effects on the severity of CAD. The obesity paradox in relation to CAD should be taken into consideration and needs further investigation in patients with ACS.

Epicardial fat attenuation, not volume, predicts obstructive coronary artery disease and high risk plaque features in patients with atypical chest pain.

This study sought to investigate the association between volume and attenuation of epicardial fat and presence of obstructive coronary artery disease (CAD) and high-risk plaque features (HRPF) on CT angiography (CTA) in patients with atypical chest pain and whether the association, if any, is independent of conventional cardiovascular risk factors and coronary artery calcium score (CACS). Patients referred for coronary CTA with atypical chest pain and clinical suspicion of CAD were included in the study. Quantification of CACS, epicardial fat volume (EFV) and epicardial fat attenuation (EFat) was performed on non-contrast images. CTA was evaluated for presence of obstructive CAD and presence of HRPF. 255 patients (median age [interquartile range; IQR]: 51[41-60] years, 51.8% males) were included. On CTA, CAD, obstructive CAD (≥50% stenosis) and CTA-derived HRPFs was present in 133 (52.2%), 37 (14.5%) and 82 (32.2%) patients respectively. A significantly lower EFat was seen in patients with obstructive CAD than in those without (-86HU [IQR:-88 to -82 HU] vs -84 [IQR:-87 HU to -82 HU]; p = 0.0486) and in patients with HRPF compared to those without (-86 HU [IQR:-88 to -83 HU] vs -83 HU [-86 HU to -81.750 HU]; p < 0.0001). EFat showed significant association with obstructive CAD (unadjusted Odd's ratio (OR) [95% CI]: 0.90 [0.81-0.99];p = 0.0248) and HRPF (unadjusted OR [95% CI]: 0.83 [0.76-0.90];p < 0.0001) in univariate analysis, which remained significant in multivariate analysis. However, EFV did not show any significant association with neither obstructive CAD nor HRPF in multivariate analysis. Adding EFat to conventional coronary risk factors and CACS in the pre-test probability models increased the area-under curve (AUC) for prediction of both obstructive CAD (AUC[95% CI]: 0.76 [0.70-0.81] vs 0.71 [0.65-0.77)) and HRPF (AUC [95% CI]: 0.92 [0.88-0.95] vs 0.89 [0.85-0.93]), although not reaching statistical significance. EFat, but not EFV, is an independent predictor of obstructive CAD and HRPF. Addition of EFat to traditional cardiovascular risk factors and CACS improves estimation for pretest probability of obstructive CAD and HRPF. EFat is an important attribute of epicardial fat as it reflects the "quality" of fat, taking into account the effects of brown-white fat transformation and fibrosis, as opposed to mere evaluation of "quantity" of fat by EFV. Our study shows that EFat is a better predictor of obstructive CAD and HRPF than EFV and can thus explain the inconsistent association of increased EFV alone with CAD.

Association of coronary microvascular endothelial dysfunction with vulnerable plaque characteristics in early coronary atherosclerosis.

The aim of this study was to test the hypothesis that coronary microvascular endothelial dysfunction (CMED) is associated with epicardial coronary atherosclerosis. We performed a cross-sectional analysis of a comprehensive invasive assessment of coronary physiology with a focus on endothelium-dependent coronary microvascular function and virtual-histology intravascular ultrasound (VH-IVUS) in a total of 148 consecutive patients with chest pain and angiographically normal coronary arteries or non-obstructive coronary artery disease (CAD). Endothelium-dependent coronary vascular reactivity was evaluated by graded doses of intracoronary acetylcholine (ACh). CMED was defined as a percent increase in coronary blood flow of ≤50% in response to ACh. Patients with CMED (n=87) showed more vulnerable plaque characteristics as compared to those without (n=61); they showed higher plaque burden in association with larger necrotic core volume and higher frequency of imaged arteries containing at least one VH-IVUS-derived thin-capped fibroatheroma (TCFA) (n=22 [25.3%] vs 5 [8.2%], p=0.008). Multivariate logistic regression analysis revealed that CMED was an independent predictor of VH-IVUS-derived TCFA (adjusted odds ratio 2.28 [95% confidence interval: 1.30-4.02], p=0.004). Independently of conventional coronary risk factors, CMED was associated with vulnerable plaque characteristics in patients with non-obstructive CAD.

Impact of the triglyceride level on coronary plaque components in female patients with coronary artery disease treated with statins.

Several studies have reported that elevated triglyceride (TG) levels may be more strongly associated with an increased risk of coronary artery disease (CAD) in females than in males. We examined gender differences in the relationship between TG levels and coronary atherosclerosis using integrated backscatter intravascular ultrasound (IB IVUS) in CAD patients treated with statins. Three hundred seventy-eight CAD patients (105 females and 273 males) who underwent percutaneous coronary intervention using IB IVUS, and who were already receiving statin treatment, were included. Gray-scale and IB IVUS examinations were performed for the non-culprit segment of a coronary artery and fasting serum TG concentrations were measured. We found that TG levels were significantly correlated with increased lipid (r = 0.40, p < 0.001) and decreased fibrous (r = -0.37, p < 0.001) plaque components in females, but not in males. Low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were not related to either the gray-scale or IB IVUS parameters in both genders. After adjustment for conventional coronary risk factors by a multivariate stepwise regression analysis, higher TG levels in females were independently associated with increased lipid (β = 0.31, p<0.001) contents in coronary plaques. In conclusion, among CAD patients treated with statins, TG levels were associated with lipid-rich coronary plaques in females, but not in males. TG levels may be more important indicators of residual risk after statin treatment in females than in males.