Conventional Coronary Artery Disease Risk 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.

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 & 92.85 in LAD and 36.91 & 120.82 in RCA, respectively (P<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<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

Ceramide Scores Predict Cardiovascular Risk in the Community

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Investigation of LPA sequence variants rs6415084, rs3798220 with conventional coronary artery disease in Iranian CAD patients.

Conventional coronary artery disease (CAD) is the leading cause of morbidity and mortality in the general population. In recent years, multiple CAD promising risk factors have been reported and used for risk stratification. Lipoprotein(a) [LPA] concentration in plasma was shown associated with CAD risk and LPA genetic variants in different ethnic groups remains less clear. We obtained data from 100 affected patients with established CAD and 100 healthy controls. We tested Body mass index (BMI), total cholesterol level (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), fasting blood sugar (FBS) and two LPA (rs10455872 and rs3798220 SNPs) between cases and healthy controls. TaqMan SNP genotyping assays were performed to detect variants. Obtained data for BMI, TC, SBP, DBP, and LDL have significantly difference between two groups. Individually, the single SNPs were not associated with CAD in different analysis models. Also there was no significant difference in the incidence of CAD among cases carrying different genotypes of the two variants in LPA with p> 0.05. In this study patients with CAD, lipoprotein(a) concentrations and genetic variants showed no associations and we conclude that these variables are not useful risk factors to predict progression to disease is Iranian population. However, the prevalence and association of LPA SNPs with size of LPA and isoforms are highly variable and genetic background-specific. Our data did not indicate a relationship between genomic LPA variants (rs10455872 and rs3798220) and subsequent cardiovascular events in Iranian CAD patients. We did not confirm the association of the theses SNPs with CAD in our samples of Iranian patients. For the studied variants, our finding is consistent with reports which showed the lack of this genetic association in other populations.

Impact of Sex on Long-term Clinical Outcomes After Percutaneous Coronary Intervention.

To evaluate the impact of sex on long-term clinical outcomes after percutaneous coronary intervention (PCI). In a large prospective cohort, 5664 patients (1716 women and 3948 men) who underwent PCI in a tertiary cardiac center between March 2007 and March 2010 were enrolled. Patients were followed up for median of 74.3 months. We compared the occurrence of long-term mortality, myocardial infarction (MI), and repeated revascularization between 2 sexes. Major adverse cardiac events were defined as a composite end point consisting of occurrence of all-cause mortality, nonfatal MI, or target vessel revascularization during follow-up period. Women were older and had more conventional coronary artery disease risk factors, had smaller vessel diameter, and received drug-eluting stents more frequently than men. On the contrary, men were much more smokers and had higher frequency of acute coronary syndrome, multivessel disease, total coronary occlusion, and lower ejection fraction. After >6 years of follow-up, the all-cause mortality, nonfatal MI, target vessel revascularization, major adverse cardiac events, patient-oriented composite end point, and total repeat PCI were similar between 2 sexes. After adjusting for potential confounders, the total repeat PCI was the only observed difference that was significantly lower in women [11.2% in women vs. 12.4% in men, adjusted subdistributional hazard ratio=0.73 (95% confidence interval, 0.6-0.88); P = 0.001). During >6 years of follow-up, no significant difference was observed in major clinical outcomes between 2 sexes.

Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study

Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1-100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.

Long-Term Follow Up of Percutaneous Coronary Intervention of Coronary Artery Disease in Women ≤45 Years of Age

The aim of the present study was to report the short- and long-term clinical outcomes of percutaneous coronary intervention in young women with premature coronary artery disease. From February 2003 to December 2011, 168 consecutive women aged ≤45 years who underwent percutaneous coronary intervention with stent implantation were retrospectively analyzed. The primary end point was the incidence of major adverse cardiac events (MACEs) at short- and long-term follow-up. The mean age was 40.3 ± 2.0 years. Conventional coronary artery disease risk factors were common. Autoimmune or connective tissue diseases were present in 6.5% of the population, 4% had gynecologic diseases, 4were postpartum, and 9 were taking contraceptives. The left anterior descending coronary artery was the most commonly affected vessel (83.3%) and the most common target vessel for stenting (76.8%). A total of 268 stents were implanted, 95.3% of which were drug-eluting stents. During the hospital stay, 1 patient died, and the incidence of MACEs was 1.2%. No additional events had occurred at 30-day follow-up. After a median follow-up duration of 36 months (interquartile range 12 to 60), cumulate MACE-free survival was 80.5%, the rate of target vessel revascularization was 16.5%, and the rate of stent thrombosis was 3.6%. Cox regression showed that hypertension, smoking, a left ventricular ejection fraction <50%, anterior myocardial infarction, and autoimmune disease were independent predictors of MACEs. In conclusion, percutaneous coronary intervention in young women tends to result in an increased rate of target vessel revascularization during long-term follow-up, which may be influenced by conventional and nonconventional risk factors.

SAT0243 Endothelial dysfunction reflected by high S-ICAM-1 and VWF levels accelerates coronary atherosclerosis in systemic lupus erythematosus patients

BackgroundConventional risk factors of coronary artery disease fail to explain accelerated atherosclerosis in systemic lupus erythematosus (SLE) patients. Clinical and experimental studies shows that soluble intercellular adhesion molecule 1 (sICAM-1)...

Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy (CAV) is the most important cause of morbidity and mortality following cardiac transplantation. CAV is largely mediated by immunologic damage and infiltration of the endothelium, resulting in proliferation of vascular smooth muscle cells and subsequent luminal narrowing. There are various risk factors for the development and progression of CAV. Coronary angiography is the gold standard for the diagnosis of CAV; intravascular ultrasound also plays an important role. The management of CAV includes immunosuppression, drugs that modify conventional coronary artery disease risk factors, and percutaneous coronary intervention (PCI) or surgical revascularization for severe obstructive lesions. Although revascularization with PCI has a high immediate success rate, rates of in-stent restenosis are higher as compared with PCI of native coronary arteries, although the advent of drug-eluting stents has somewhat improved in-stent restenosis rates. Thus, the only definitive treatment of CAV is repeat transplantation. Randomized trials are needed to determine the optimal immunosuppressive and conventional risk factor-modifying agents and revascularization strategies for patients who develop CAV.

Influence of chronic inflammation and autoimmunity on coronary calcifications and myocardial perfusion defects in systemic lupus erythematosus patients

ObjectiveConventional risk factors for coronary artery disease fail to explain the increased frequency or cardiovascular morbidity in systemic lupus erythematosus (SLE) patients. This study was conducted to determine the possible influence of autoimmune and inflammatory phenomena markers on coronary artery calcifications and myocardial perfusion abnormalities in SLE patients.Materials and methodsMulti-detector computed tomography (MDCT)-based coronary calcium scoring and single photon emission computerized tomography (SPECT) studies (Tc-99m sestamibi) were performed in 60 SLE patients in stable clinical condition, without a prior history of coronary artery disease. Laboratory evaluation included serum C-reactive protein (CRP), complement C3c and C4 components and antiphospholipid antibodies (aPL). The latter included anticardiolipin (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibodies, of both IgG and IgM classes, and lupus anticoagulant (LA) in plasma.ResultsSPECT revealed persistent perfusion defects in 22 (36.7%) patients and exercise-induced defects in eight (13.3%), while MDCT revealed coronary calcifications in 15 (25%). Calcium scores ranged from 1 to 843.2 (mean 113.5 ± 259.7). No association was found between conventional coronary artery disease risk factors (obesity, hypertension, tobacco use, hyperlipidaemia, diabetes) nor CRP, C3c or C4 levels and coronary calcifications or myocardial perfusion defects. On the contrary, in patients with these pathologies, augmented autoimmunization was found, reflected by increased aCL IgG and antiβ2GPI IgG levels. In patients with aCL IgG >20 RU/ml or antiβ2GPI IgG >3 RU/ml, the relative risk of coronary calcification formation was 4.1 compared to patients with normal values. Accordingly, in LA-positive patients the relative risk of coronary calcification formation was 4.4 compared to LA-negative patients.ConclusionsConventional risk factors for coronary artery disease as well as markers of an ongoing inflammation did not show any association with perfusion defects and/or coronary artery calcifications in SLE patients. On the contrary, calcified atherosclerotic plaques and myocardial perfusion defects were observed mainly in patients with elevated levels of anticardiolipin and aβ2GPI antibodies of the IgG class. It might be speculated that coronary artery calcifications and perfusion defects are a result of antiphospholipid antibodies-induced coronary artery microthrombosis.

Relation of asymmetric dimethylarginine levels with conventional risk score systems in the healthy subjects with positive family history for coronary artery disease

Coronary artery disease is the most common cause of death in Turkey and the world. Asymmetric dimethylarginine is the major inhibitor of nitric oxide synthesis in humans. It has been shown that increased levels of asymmetric dimethylarginine is associated with endothelial dysfunction and increased atherogenesis. In this study, we aimed to investigate whether asymmetric dimethylarginine level is related with conventional risk score systems in subjects who had family history of coronary artery disease. Fifty two subjects within 20-40 years old of whom first degree relatives had myocardial infarction at young ages and 26 age and sex matched control subjects were included in this cross-sectional observational study. Frequency of diabetes, hyperlipidemia, smoking and serum levels of homocysteine, high-sensitive C-reactive protein (hsCRP) and asymmetric dimethylarginine were compared between risk group and control subjects. Relation of asymmetric dimethylarginine level with Framingham and TEKHARF risk scores was also compared. Chi-square and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Fasting serum glucose, triglyceride, high-density lipoprotein, diastolic blood pressure, waist circumference and TEKHARF scores were increased in the subjects who had family history of myocardial infarction. Total cholesterol, low-density lipoprotein, hsCRP, homocysteine, creatinine and Framingham risk score were similar in studied groups . Asymmetric dimethylarginine levels were 0.1 µmol/L higher in the risk group; however this difference could not reach significance (0.7±0.1 µmol/l vs 0.8±0.1 µmol/l; p=0.061). Measurement of serum asymmetric dimethylarginine levels did not reveal utility in defining conventional coronary artery disease risk score systems in cases that had positive family history. Larger studies including patients with different risk tertiles are needed.

Relation of anthropometric variables to coronary artery disease risk factors.

Background and Objectives:Anthropometric variables and their relation to conventional coronary artery disease (CAD) risk factors in railway employees have been inadequately studied in India. This cross-sectional survey was carried out in the Solapur division of the Central railway in the year 2004, to assess the anthropometric variables in railway employees and their relation to conventional CAD risk factors.Materials and Methods:A total of 995 railway employees, with 872 males and 123 females participated in this cross-sectional study. All subjects underwent anthropometric measurements, fasting lipid profile, and blood sugar level. Various anthropometric indices were calculated for body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and abdominal volume index (AVI). Statistical analysis was done by EPI Info 6 statistical software.Results:Compared to all other obesity indices, WHtR was most prevalent in both genders. High WHtR was present in 699 (80.16%) males and 103 (83.73%) females. Age ≥45 years, high systolic BP, high diastolic BP, low HDL, high triglyceride, and diabetes mellitus were positively correlated with high BMI, high WC, high WHR, high WHtR, and high AVI. High BMI, high WC, high WHR, high WHtR, and high AVI were negatively associated with physical inactivity.Conclusions:Over all, anthropometric variables in both genders were significantly deranged in subjects with coronary risk factors. Compared to all other anthropometric variables, WHtR was statistically significantly associated with a majority of coronary artery risk factors. Hence we recommend inclusion of WHtR as a parameter of obesity to predict coronary artery disease risk factor along with WC, WHR, and BMI in epidemiologic studies.

Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults.

Conventional coronary artery disease (CAD) risk factors fail to explain nearly 50% of CAD events. This study examines the association between electron-beam tomography (EBT) coronary artery calcium (CAC) and cardiac events in initially asymptomatic low- to intermediate-risk individuals, with adjustment for the presence of hypercholesterolemia, hypertension, diabetes, and a history of cigarette smoking. The study was performed in 8855 initially asymptomatic adults 30 to 76 years old (26% women) who self-referred for EBT CAC screening. Conventional CAD risk factors were elicited by use of a questionnaire. After 37+/-12 months, information on the occurrence of cardiac events was collected and confirmed by use of medical records and death certificates. In men, events (n=192) were associated with the presence of CAC (RR=10.5, P<0.001), diabetes (RR=1.98, P=0.008), and smoking (RR=1.4, P=0.025), whereas in women, events (n=32) were linked to the presence of CAC (RR=2.6, P=0.037) and not risk factors. The presence of CAC provided incremental prognostic information in addition to age and other risk factors. The association between EBT CAC and cardiac events observed in this study of initially asymptomatic, middle-aged, low to intermediate-risk individuals presenting for screening suggests that in this group, knowledge of the presence of EBT CAC provides incremental information in addition to that defined by conventional CAD risk assessment.

Conventional coronary artery disease risk factors and coronary artery calcium detected by electron beam tomography in 30,908 healthy individuals.

Electron beam tomography (EBT) is a noninvasive measure of coronary artery calcium (CAC), a marker for atherosclerosis. In this study we examined the association between conventional risk factors for coronary artery disease (CAD) and CAC. EBT CAC screening was performed on 30,908 asymptomatic individuals aged 30 to 90 years. Prior to EBT screening, individuals provided demographic and CAD risk factor information. EBT utilized a C-100 EBT scanner, and the amount of CAC was determined using the Agatston scoring method. The results of this study demonstrate that for both men and women, all conventional risk factors were significantly associated with the presence of any detectable CAC, and the mean CAC score increased in proportion to the number of CAD risk factors. In age-adjusted (multivariable) logistic regression analysis, cigarette use, histories of hypercholesterolemia, diabetes, and hypertension were each significantly associated with mild to extensive CAC scores (> or =10.0). CAD risk factors are associated with higher atherosclerotic plaque burden in both men and women. The odds ratios associated with each risk factor relative to the extent of CAC are similar to those reported for the development of clinical CAD, suggesting the existence of an association between CAC (subclinical disease) and CAD (clinical disease).

Elevated fibrinogen in the healthy male relatives of patients with severe, premature coronary artery disease.

To assess the possible role of certain coagulation factors and associated genetic polymorphisms in families in which coronary disease has occurred prematurely. One hundred and eighty-five healthy male relatives aged 65 or less were recruited following the identification of 125 patients with confirmed, premature coronary artery disease and compared to a control group of 185 healthy, age-matched volunteers. None of the control subjects had a personal or family history of coronary artery disease. The relatives and controls were similar in terms of conventional coronary artery disease risk factors. Fibrinogen levels were elevated in relatives compared with controls and remained higher after adjustment for significant correlates, 3.0 g.l(-1) (2.9-3.1) vs 2.8 g.l(-1) (2.8-2.9),P =0.004. Factor VII coagulant activity and von Willebrand factor antigen did not differ between the groups nor were there any differences in genotype frequency for the fibrinogen beta-455 G/A polymorphism or the factor VII promoter deletion/insertion and Arg-Gln coding polymorphisms. A significant increase in fibrinogen levels was demonstrated in the healthy, male, first-degree relatives of patients with severe coronary artery disease. Fibrinogen may be of particular importance in subjects who, other than their family history, appear to be at low risk in terms of conventional coronary artery disease risk factors.