Premature Atherosclerosis Research Articles

Genetic predisposition of metabolic syndrome independent of weight in premature atherosclerosis

Abstract Background Family history is a significant predictor of premature atherosclerotic cardiovascular events, which suggest that a genetic susceptibility underlies the development of premature atherosclerosis. Rather than the influence of single classic risk factors, such as hypertension, diabetes and dyslipidemia, these risk factors could be part of an underlying genetic insulin resistance or metabolic syndrome Methods Data on patients and their first degree family members visiting premature atherosclerosis clinic in a university medical centre, from 2007 until 2023 was analyzed. We divided them in controls (CACs=0 and Age >40 years), subclinical ASCVD (sASCVD) (CAC score ≥80th percentile) and premature ASCVD (PAS). We used principal component analysis (PCA) for clustering the predictor variables and generalized linear mixed model (GLMM) to analyze the mutual relationship between different clusters. The model performance was further validated in predicting the premature ASCVD. Result There were 1551 individuals divided across control (n=438), sASCVD (n=309) and PAS (804). We found 12 variables univariate significantly related to sASCVD. Using a principal component analysis (PCA) approach, these variables were loaded across 4 clusters which were defined as 1. Metabolic (elevated glucose or diabetes, elevated blood pressure or Hypertension, elevated Triglycerides, elevated waist circumference and elevated LDL-C); 2. Liver (elevated ALAT, elevated GGT, elevated triglycerides, decreased thrombocytes) 3. Inflammatory (decreased HDL-C, elevated Triglycerides and elevated leucocyte count) and 4. Lipid (elevated Lp(a) and elevated LDL-C). After mutual correction and model building, the metabolic (OR; 95% CI) (1.82; 1.48-2.27) and Liver clusters (1.20; 1.00-1.45) were only found to be significantly associated with risk of sASCVD. However, we did not find any association of inflammatory (1.19; 0.98-1.44) and lipid cluster (1.19; 0.99-1.41) with risk of sASCVD. Besides, association of these clusters with risk of sASCVD significantly varies among families suggested from variance of intercept when family was kept as a random effect in GLMM model and no interaction was noticed with BMI. We checked the performance of this model on premature atherosclerosis cohort and found model had a good discriminatory (AUC, 0.762; 0.735-0.790; P=0.001) ability for predicting PAS [Figure 1]. Conclusion In conclusion, our findings are suggestive of a significant association between metabolic syndrome factors and an increased risk of sASCVD in individuals with family history of premature atherosclerosis, regardless of weight. This association suggests the potential genetic predisposition towards premature atherosclerosis driving the observed metabolic parameters clustering in these individuals. Besides, the model demonstrated robust discriminatory power to predict premature atherosclerosis.ROC curve for premature atherosclerosis

Much ado about nothing: the impact of coronary angiography on kidney function in individuals with chronic kidney disease

Abstract Background and Objectives Chronic kidney disease (CKD) is associated with premature coronary artery disease and an increased risk of cardiovascular morbidity and mortality (1). Historically, there has been a tendency to delay or even avoid coronary angiography (CA) in those with CKD due to an increased risk of contrast-induced nephropathy or concern over precipitating the need for chronic dialysis. Such "renal nihilism" may account for the poorer outcomes observed in CKD patients who present with acute coronary syndromes (2). The role of this retrospective analysis was to evaluate the impact of CA on the temporal trend in kidney function in individuals with CKD over a 24-month period. Methods The clinical details of 120 individuals under long-term local follow-up by various Nephrology clinics (CKD clinic, low creatine clearance, polycystic kidney disease, transplant and immunosuppression clinics) was collected. All underwent CA locally. Kidney function was observed at set intervals of 12-, 9-, 6- and 3-months prior to CA, immediately post-CA, and at 3-, 6-, 9- and 12-months post-CA. Only results obtained after the desired time point but within 28 days were included. All CAs regardless of either their indication (elective or urgent) or whether percutaneous intervention (PCI) was performed, were included. Patients already on dialysis at the time of the CA were excluded. Statistical analysis was performed via one-way ANOVA. Results Patient characteristics are summarised in table 1. The average age of patients was 67, with a male preponderance (72%). 22% had CKD 3, 24% had CKD 4 and 12% had CKD 5. 9% were kidney transplant recipients. 37% underwent urgent CA whilst a total of 22% had PCI. 27% progressed to requiring renal replacement therapy (RRT). The mean length to RRT was 2.8 years. The rate of decline in kidney function in the last 12 months prior to CA was 7.7% and 6.3% in the year after CA (figure 1). There was no statistically significant difference in kidney function after CA (p = 0.395). This was replicated in analyses focussing on CKD classes 3, 4 and 5 individually, within stable kidney transplant recipients, and within analysis comparing PCI vs non-intervention CAs. Conclusion The results demonstrate CA does not accelerate the decline in kidney function in those with known CKD over a 12-month period, and suggests where appropriate, an invasive treatment strategy should be consider and utilised more often in this population.Table 1:Patient characteristicsFigure 1:Trend in eGFR relative to CA

Identification of premature cardiovascular disease using a family-based strategy: a feasibility pilot study

Abstract Background Current guidelines fail to identify and effectively prevent cardiovascular disease (CVD) in young adults. Purpose To assess the feasibility of a systematic cardiovascular risk assessment in first-degree relatives of individuals with premature coronary artery disease (CAD). Method Index patients with obstructive CAD aged ≤ 45 years or ≤ 55 years without standard modifiable cardiovascular risk factor or ≤ 55 years with a 3-vessel coronary disease were prospectively identified among admissions. Pre-existing cases of CVD and prior cardiovascular check-ups were assessed among their first-degree relatives. Siblings and adult-children (≥25 years) without known CVD or active cardiology follow-up were eligible for a first cardiovascular evaluation. Index patients were encouraged to invite their eligible relatives to contact the Cardiology service for consultation. The primary endpoint was the relative’s eligibility for a cardiovascular prevention consultation. Result From September 2022 to June 2023, 137 patients with premature CAD, with 55.5% aged ≤ 45, were invited to initiate cardiovascular screening among their first-degree relatives. Of the 626 identified relatives, 153 (24.4%) had known atherosclerotic disease, primarily CAD (19.6%). Premature onset (before the age of 45) occurred in 5% of first-degree relatives. Among the 352 siblings and adult-children, 48 (13.6%) were already diagnosed with CVD, 68 (19.3%) were treated or followed for primary prevention, and 226 (64.2%) lacked active cardiovascular monitoring or treatment and were eligible for a first cardiovascular check-up (Figure 1). Within 10 months, 11.1% (25/226) of eligible relatives attended a first cardiovascular evaluation. Conclusion This family-based screening strategy for premature CVD demonstrated 1) a significant familial dimension, with 33% of siblings & adult-children already monitored for CVD prevention, and 2) an opportunity for cardiovascular prevention in two out of three young relatives.

Unveiling homozygous familial hypercholesterolemia in Greece: a comprehensive analysis of baseline traits and LDL goal achievement in adults from the HELLAS-FH Registry

Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a severe genetic disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to analyze demographic characteristics, lipid profile, and rate in achieving LDL-C targets in adult HoFH patients in Greece. Methods This is a cross-sectional analysis of the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Adults with genetically or clinically diagnosed HoFH were included. Median LDL-C levels were assessed during HoFH diagnosis and enrollment. Results Seventeen HoFH adults (mean age 41 years and mean age at diagnosis 31 years, men 58.8%). Genetic confirmation of HoFH was available in 10 patients, while the remaining were diagnosed based on clinical criteria. Family history of atherosclerotic cardiovascular disease was documented in 70.5% of patients. Clinical presentations varied, with 47.0% exhibiting tendon xanthomas, 17.6% xanthelasmas, 23.5% corneal arcus, and 52.9% premature coronary artery disease (CAD). Predominant treatment involved statins (88.2%), ezetimibe (58.8%),PCSK9i (23.5%), lomitapide (29.4%), while LDL apheresis was utilized in 23.5%. Median LDL-C levels were 407 mg/dL (10.53 mmol/L) at diagnosis and 226 mg/dL (5.84 mmol/L) at enrollment. None of the patients achieved the LDL-C target set by the 2019 EAS/ESC Guidelines. Conclusion The challenges of delayed diagnosis, undertreatment, and unattained LDL-C targets persist in HoFH management in Greece, emphasizing the critical need for effective lipid-lowering interventions to mitigate cardiovascular risk.

Polygenic prediction of coronary artery disease among 130,000 Mexican adults

Abstract Background Coronary artery disease (CAD) is a leading cause of premature mortality globally. Polygenic risk scores (PRSs) have been reported to enhance CAD prediction in populations of European ancestry but evidence from other populations is limited. We assessed the transferability and relevance of eight different external PRSs to the odds of premature CAD in a Mexican population with high levels of relatedness and ancestry admixture. Methods 128,388 genotyped participants aged 35-74 years who were recruited between 1998 and 2004 into the Mexico City Prospective Study (MCPS) were included. We selected and recreated eight previously-reported CAD PRSs. The number of single nucleotide polymorphism variants included in the PRSs varied from 44 to 6,472,620. Premature CAD was defined as either self-reported history of heart attack or angina at recruitment or death before age 75 with CAD recorded on the death certificate. Age and sex-adjusted logistic regression was used to estimate the ability of each PRS to predict CAD, both overall and separately by age, sex and estimated proportion of Indigenous American ancestry. Analyses were repeated after further adjustment for conventional risk factors (blood pressure, adiposity, smoking, diabetes and highest education achieved). Risk discrimination was assessed using C-statistic. Results Of the 128,388 participants, 68% were women, mean (SD) age was 50.2±10.9 years and the average proportion of Indigenous American ancestry was 67%. CAD was identified for 3,871 (3.0%) participants; prior CAD was reported by 1,669 (1.3%) participants while 2,360 (1.8%) participants died before age 75 years with CAD mentioned on the death certificate. All eight PRSs were positively and approximately log-linearly associated with the odds of CAD, but the strength of association varied between the PRSs, ranging from a 7% increase per 1SD higher PRS (odds ratio [OR] 1.07, 95% CI 1.04-1.11) to a 33% increase (OR 1.33, 95% CI 1.29-1.37). Collectively, age, sex and (any) PRS resulted in a C-statistic of 0.70-0.71. C-statistics were slightly lower among those with a higher proportion of indigenous American ancestry. For four of the eight PRSs (including three of the four multi-ancestry PRSs) the increase in odds of CAD per 1SD higher PRS was significantly greater for men than women (eg, for the PRS with the strongest overall association with CAD the OR per 1SD higher PRS was 1.43 [95% CI 1.36-1.49] in men and 1.25 [1.20-1.31] in women). Further inclusion of conventional vascular risk factors reduced the strengths of associations of each PRS with CAD only slightly but increased the model C statistic to 0.74 in all cases. Conclusions In this population of admixed Mexican adults, existing PRSs predicted CAD reasonably well and independently of conventional vascular risk factors. Ancestry-specific instruments that more closely represent genetic variation in Mexico may further enhance polygenic prediction of CAD risk.Table 1.Baseline characteristicsFigure 1.Main analysis results

CT-perfusion quantitation of cardiac infarct size - a novel technique

Abstract Introduction Cardiac infarct size is associated with cardiac prognosis after AMI. Cardiac CT is able to delineate both coronary anatomy and myocardial pefusion. Thus far, CT identification of infarction has been qualitative. We describe a novel technique for quantitation of myocardial infarct size in CT-perfusion imaging. Methods Patient Population comprised 51 patients that were previously clinically diagnosed with myocardial infarction on the basis of clinical presentation, ECG findings and elevated cardiac enzymes. CTP Imaging All patients had undergone dynamic rest, vasodilator-stress, rest, delayed enhancement CT perfusion imaging performed on a dual-source, third generation scanner (FORCE, Siemens Healthcare). Image Analysis 2 trained investigators independently quantified the infarct volume in 51 patient studies using Siemens SmartSimulator software. Mean ± SD HU were taken from a 1cm² circular ROI of normal myocardium used in a thresholding method. The epicardium and endocardium of infarcted areas were manually contoured from apex to base. Volumetric measurements were obtained of the infarct and total myocardium. Interpolation of contours for segmentation objects was performed. Subtraction of left ventricle cavity from total left ventricle allowed volumetric measurements of total left ventricular myocardium. ROIs of the infarct were estimated using SDs above mean HU of normal myocardium (0.5, 1, 1.5 and 2 SDs) in delayed imaging. Selection of optimal threshold HU was based on visual assessment that best mapped the hyperenhanced infarct area. This allowed volumetric asessment of infarct and total myocardium. Inter-investigator variability was evaluated with Bland-Altman and Intra-Class Correlation Coefficient (ICC). Results Patient characteristics are follow: Age 60.20±11.35 years, 41(89%)male, BMI 25.41±4.17kg/m², Hypertension 23(50%), diabetes 10(22%), hyperlipidemia 40(87%), smoking 7(15%), family history of premature CAD 4(8.7%), previous PCI 45(97.8%). In 51 patients, 23(41%), 24 (46%) & 5(10%) of the infarctions were quantitated as being medium-sized (10%-20%), large (20% -30%) and very large (>30%). Thirty-seven (70%), 6 (11%) & 10(19%) involved the LAD, LCx and RCA territories respectively. 49 (94%) of infarctions were transmural. Identical thresholding was selected by both investigators for each SD above mean (mean 1.42; SD 0.46). 93% of the total cases were within a set threshold of 1 to 2 SDs above the mean HU for both. Interclass correlation coefficient was 0.95, CI range 0.90 – 0.97. Bland-Altman analysis did not demonstrate systemic variations or proportional bias from the plot. Conclusion The study suggests that a method of quantifying cardiac infarct size using a threshold technique and delayed hyperenhancement images with dynamic perfusion imaging is clinically feasible and consistent.Rest-Stress-Delayed Enhancement infarct

Is there a gender difference in the effects of cardiovascular risk factors on the anatomical localization and severity of obstruction on coronary arteries?

Abstract Background Whether there is a gender difference in the effects of traditional cardiovascular risk factors(CVRF) on the anatomical localization(AL) and severity(AS) of obstruction on coronary arteries(CA) remains unclear. Purpose In our study, we investigated whether there is a gender difference in the relationship between CVRF and obstruction on CA . Methods We included 978 patients(49.9% women, mean age: 61+10.3) with stable chest pain undergoing invasive coronary angiography between 2019-2021 who were recruited from the database of our clinic. We examined the gender difference in hypertension(HT), diabetes mellitus(DM), smoking, hyperlipidemia, previous history of CAD(H.CAD) and family history of premature CAD(F.CAD) and their correlation with the AL and AS of obstruction on CA in both gender. Results Women were older(p<0.001) with higher rates of HT (p=0.001) and DM(p=0.026) and higher TC, LDLC and HDLC levels respectively (rs) as (p=0.001, p=0.001, p=0.001). Whereas H.CAD and smoking rates were higher in men rs as (p=0.001, p=0.009). The incidence of critical stenosis (≥70 obstruction) & intermediate lesions (50-69%) on all CA and Syntax scores were higher in men(p<0,01). In patients with HT, severe CAD was more prominent on circumflex (Cx)(p=0.029) and right coronary artery(RCA)(p=0.002) in women and on the proximal ( p=0.024) and mid portion of left anterior descending artery(LAD) (p=0.045) in men. In patients with DM a statistically significant(ss) correlation was found between the presence of DM and AS in all vessels except for left main coronary artery (LMCA) in women (LAD prox:p=0.001; LAD mid:p=0.001; diagonal artery(Dg):p=0.003; Cx:p=0.001; RCA:p=0.001 ;LMCA:p>0.05). However no such correlation was observed in men(p>0.05). In patients with H.CAD moderate/severe lesions were more common on proximal(p=0.013) and mid portions of LAD(p=0.021), on CX( p=0.006) and on RCA(p=0.016) in men and more common on the proximal portion of LAD(p=0.047), CX(p=0.014) and RCA(p=0.009) in women. For either smoking and F.CAD there was no such correlation in either gender (p>0,05). As for blood lipid levels no correlation was observed between LDLC, HDLC and triglyceride levels and AL&AS in men(p>0,05). However there was a negative, weak correlation between the HDLC levels and obstruction on LAD mid portion(r=-0.140; p=0.003); on Dg(r=-0.100; p=0.034) on CX (r=-0.154; p=0.001) and on RCA (r=-0.151; p=0.001) in women. Conclusion Major traditional CVRFs have a sex specific impact on AL and AS of obstruction on CA. In the era of precisıon medicine we need gender specific risk scoring systems taking these gender differences into account.

The contemporary management and coronary angioplasty outcomes in young patients with ST-Elevation myocardial infarction (STEMI) age < 40 years old: the insight from nationwide Thai PCI registry

BackgroundCardiovascular disease (CVD) remains one of the major causes of death around the world in which ST elevation MI (STEMI) is in the lead. Although the mortality rate from STEMI seems to decline, this result might not be demonstrated in young adults who basically have different baseline characteristics and outcomes compared with older patients.MethodsData of the STEMI patients aged 18 years or older who underwent PCI during May 2018 to August 2019 from Thai PCI Registry, a prospective, multi-center, nationwide study, was included and aimed to investigate the predisposing factors and short-term outcomes of patients aged < 40 years compared with age 41–60, and > 61 years.ResultsData of 5,479 STEMI patients were collected. The patients’ mean age was 62.6 (SD = 12.6) years, and 73.6% were males. There were 204, 2,154, and 3,121 patients in the youngest, middle, and oldest groups. The young patients were mainly male gender (89.2% vs. 82.4% and 66.6%; p < 0.001), were current smokers (70.6%, 57.7%, 34.1%; p < 0.001), had BMI ≥ 25 kg/m2 more frequently (60.8%, 44.1%, 26.1%; p < 0.001), and had greater family history of premature CAD (6.9%, 7.2%, 2.9%; p < 0.001). The diseased vessel in the young STEMI patients was more often single vessel disease with the highest percentage of proximal LAD stenosis involvement. Interestingly, there were trends of higher events of procedural failure (2.9%, 2.1%, 3.3%; p = 0.028) and procedural complications (8.8%, 5.8%, 9.4%; p < 0.001) in both youngest and oldest groups compared to the middle-aged group. In-hospital death was found in 3.4% in the youngest group compared to 3.3% in the middle-aged patients and 9.2% in the older patients (p < 0.001).ConclusionsDespite experiencing higher rates of procedural failure and complications during treatment compared to middle-aged and older patients, young STEMI individuals demonstrate a significantly lower risk of death during hospitalization and within one year of the event. Younger patients might have a more robust physiological reserve or benefit from more aggressive post-procedure management. However, the higher prevalence of modifiable risk factors like smoking and obesity in younger individuals underscores the need for preventative measures. Encouraging smoking cessation and weight control in this demographic is crucial not only to prevent STEMI but also to potentially improve their long-term survival prospects.

Risk Factors Associated With Exaggerated Blood Pressure Response At The Time Of Exercise Treadmill Stress Test.

Exaggerated blood pressure response (EBPR) to exercise stress testing (EST) may be a marker of future hypertension and carry valuable information for the prediction of cardiovascular events. We sought to evaluate the clinical and resting EST parameters associated with increased likelihood to EBPR. The records of 14073 patients (mean age: 55±11 years) without known cardiovascular disease who underwent a treadmill EST were analysed. The overall prevalence of arterial hypertension was 44%. A considerable proportion (24%) of patients exhibited EBPR. Multivariate analysis of the entire study population showed that middle-aged individuals (40-60 years old), resting systolic BP>130mmHg and/or diastolic BP>80 mmHg, known arterial hypertension, current cigarette smoking and family history of premature coronary artery disease are all independent risk factors for EBPR (all P<0.001). Although the presence of arterial hypertension increased the likelihood of EBPR in the analysis of the entire population, the relevant association in subjects above 60 years old is statistically non-significant (P=0.120). Notably, the pre-test systolic BP>130mmHg and/or diastolic BP>80 mmHg level increased significantly the likelihood to manifest EBPR in all age categories (<40, 40-60 and >60 years old) independent of hypertension presence and in all hypertensive patients independently of antihypertension treatment intake (all P<0.001). Considering the diagnostic and prognostic utility of EBPR during treadmill EST the clinical and resting haemodynamic parameters that increase the likelihood to EBPR are targets for interventions and preventive measures to modify lifestyle risk behaviours and reduce hypertension and cardiovascular risk factors in the early stages.

Early-onset familial hypercholesterolemia: A case of extensive xanthomas and premature coronary artery disease.

Early recognition and management of familial hypercholesterolemia (FH) are crucial, especially in patients with extensive xanthomas and premature coronary artery disease. Prompt diagnosis and aggressive lipid-lowering therapy can significantly reduce morbidity and mortality rates. Careful clinical assessment in resource-limited settings is essential for optimal outcomes. Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder that causes chronically elevated levels of low-density lipoprotein (LDL) cholesterol. Based on LDL levels, FH can be heterozygous or homozygous, further established through clinical features, laboratory findings, and genetic analysis. Elevated cholesterol levels cause atherosclerosis, coronary artery disease, myocardial infarction, and sudden death. Xanthomas are a clinical manifestation of FH that reveal the underlying systemic genetic disease. We present the case of a 47-year-old male with triple vessel coronary artery disease and widespread xanthomas, diagnosed with homozygous FH based on "The Dutch Lipid Clinic Network Diagnostic Criteria for Familial Hypercholesterolemia." Lifelong therapy with lipid-lowering medications and lifestyle changes is necessary in such cases.

Does Adopting Western Low-density Lipoprotein Cholesterol Targets Expose Indians to a Higher Risk of Cardiovascular Events? Expert Opinion From the Lipid Association of India.

Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India.

Clinical Profiles and Risk Factors of Acute Myocardial Infarction in Young Adults: A Cross-Sectional Study in Myanmar.

Introduction Coronary artery disease (CAD) remains a leading cause of morbidity and mortality globally, with an increasing prevalence of acute myocardial infarction (AMI) among younger populations. Despite this rising trend, there are limited data from Myanmar on the clinical profile and associated risk factors for premature CAD in young adults. This study aims to investigate the clinical characteristics and predisposing risk factors for AMI in individuals aged 40 years and below, contributing to a better understanding of disease patterns in this population. Methods A cross-sectional descriptive study was conducted at the coronary care unit of Yangon General Hospital over a 12-month period from January 1, 2019, to December 31, 2019. A total of 59 young adults, diagnosed with AMI based on the Fourth Universal Definition of Myocardial Infarction, were included. Clinical data, laboratory investigations, and demographic characteristics were collected and analyzed. Results Among the 59 participants, 46 (78%) were male, and smoking was prevalent in 45 (76.3%) cases. Dyslipidemia was common, with 46 (77.9%) exhibiting low high-density lipoprotein (HDL) cholesterol levels and 27 (45.8%) having elevated total cholesterol. Hypertension was observed in 31 (52.5%) patients, and 32 (54.2%) reported a family history of premature atherosclerotic cardiovascular disease. Furthermore, 28 (47.5%) of the cohort were classified as overweight, and 26 (44.1%) demonstrated low levels of physical activity. Chest pain was universally reported by all 59 (100%) patients as the presenting symptom. ST-segment elevation myocardial infarction (STEMI) was the predominant type, affecting 47 (79.6%) patients, with anterior wall involvement in 36 (61%) cases. Conclusion The findings of this study reveal that AMI in young adults is more prevalent among males, with smoking and dyslipidemia being the most significant risk factors. The high prevalence of low physical activity, hypertension, and overweight status further underscores the need for early lifestyle interventions. These results can be directly applied to clinical practice and public health policy in Myanmar by prioritizing smoking cessation programs, improving dyslipidemia management, and promoting physical activity in young populations. Additionally, this study provides a foundation for further research to explore more specific risk factors and paves the way for broader studies focusing on young AMI cases in Myanmar.

Prevalence of genetically diagnosed familial hypercholesterolemia in Vietnamese patients with premature acute myocardial infarction.

Familial hypercholesterolemia (FH) is a genetic disorder that results in elevated low-density lipoprotein cholesterol (LDL-C) levels, which manifest early in the first decades of life. It is a major cause of premature coronary artery disease worldwide, leading to significant public health challenges. The prevalence of genetically determined FH in patients with premature coronary artery disease remains underestimated, particularly in developing countries. This study aimed to assess the prevalence of genetically defined FH in Vietnamese patients with premature acute myocardial infarction (AMI) in the Vietnamese population. This cross-sectional study enrolled 218 consecutive patients diagnosed with premature AMI who underwent coronary angiography. The low-density lipoprotein receptor (LDLR), apolipoprotein B, and proprotein convertase subtilisin-kexin type 9 genes were analyzed by next-generation sequencing. FH was diagnosed according to Dutch Lipid Clinic Network criteria. Among the patients with premature AMI who underwent coronary angiography, the mean age was 46.9 ± 6.1 years, with a predominance of males (83.9%). The prevalence of potential FH diagnosed using Dutch Lipid Clinic Network criteria was 14.7% (definite FH, 6.0%; probable FH, 8.7%). Pathogenic or likely pathogenic variants in LDLR, apolipoprotein B, and proprotein convertase subtilisin-kexin type 9 were found in 9 of 218 patients (4.1%), all of which were causative mutations in LDLR. Patients with premature AMI and FH had significantly greater LDL-C levels (217.6 vs 125.7 mg/dL) and more severe coronary artery lesions, as assessed by the Gensini score (100.3 vs 60.5), than did those in the No FH group. The prevalence of genetically determined FH among Vietnamese patients with premature AMI is relatively high. Screening and diagnosis of hereditary conditions in patients with premature AMI are essential to improve early detection and management and reduce the burden of coronary artery disease in this population.

Clinical Expression of Familial Hypercholesterolemia in Patients from France and French Canada Carrying Identical-by-Descent Pathogenic LDLR Gene Variants: A Proof-of-Concept Study.

Background: Studying patients carrying identical-by-descent (IBD) pathogenic gene variants allows us to control for the disease-causing genetic background and to more accurately document the impact of modifiers. Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels and premature atherosclerosis and is often caused by defects in the LDLR gene. There is a high prevalence of FH in French Canada as a result of a founder effect from France in the 17th century. Several FH patients currently living in French Canada (founder population) and in France (colonizing population) carry IBD FH-causing variants. The expression of FH is affected by environmental and genetic modifiers, and patients with IBD variants may present different characteristics. Methods: In this study, we compared FH clinical expression patients carrying IBD LDLR pathogenic variants living in France or Canada. Four IBD variants, namely c.259T>G p.(Trp87Gly), c.2000G>A p.(Cys667Tyr), c.682G>A p.(Glu228Lys), and c.1048C>T p.(Arg350*), were selected. Untreated plasma lipid profiles, the apolipoprotein E (APOE) genotype, cardiovascular risk factors, and the occurrence of symptomatic ASCVD were compared in 105 adult carriers (30 from France and 75 from French Canada). Results: All parameters were similar between the two populations, except for untreated total cholesterol (10.14 ± 1.89 mmol/L vs. 8.65 ± 1.84 mmol/L, p = 0.0006) and LDL-c concentrations (7.94 ± 1.86 mmol/L vs. 6.93 ± 1.78 mmol/L, p = 0.016), which were significantly higher in FH patients living in France, an observation that was revealed across all studied LDLR variants. Conclusions: This study illustrates that FH patients sharing IBD pathogenic LDLR variants that have evolved in different geographic, cultural, and socio-economic environments for hundreds of years differ in terms of cholesterol levels, highlighting the importance of better understanding the interplay between genetic and environmental modulators of FH expression.

The predictive value of coronary artery calcium score combined with traditional risk factors for obstructive coronary heart disease in young people

ObjectivesThis study attempts to compare the predictive effects of several prediction models on obstructive coronary artery disease (OCAD) in young patients (30–50 years old), with a view to providing a new evaluation tool for the prediction of premature coronary artery disease (PCAD).MethodsA total of 532 hospitalized patients aged 30–50 were included in the study.All of them underwent coronary computed tomography angiography (CCTA) for suspected symptoms of coronary heart disease.Coronary artery calcium score (CACS) combined with traditional risk factors and pre-test probability models are the prediction models to be compared in this study.The PTP model was selected from the upgraded Diamond-Forrester model (UDFM) and the Duke clinical score (DCS).ResultsAll patients included in the study were aged 30–50 years. Among them, women accounted for 24.4%, and 355 patients (66.7%) had a CACS of 0. OCAD was diagnosed in 43 patients (8.1%). The CACS combined with traditional risk factors to predict the OCAD area under the curve of receiver operating characteristic (ROC) (AUC = 0.794,p < 0.001) was greater than the PTP models (AUCUDFM=0.6977,p < 0.001;AUCDCS=0.6214,p < 0.001). By calculating the net reclassification index (NRI) and the integrated discrimination index (IDI), the ability to predict the risk of OCAD using the CACS combined with traditional risk factors was improved compared with the PTP models (NRI&IDI > 0,p < 0.05).ConclusionThe predictive value of CACS combined with traditional risk factors for OCAD in young patients is better than the PTP models.

Association of hsCRP and Serum Kalirin Levels with the Development and Severity of Premature Coronary Artery Disease in Iraqi Patients

Background: Coronary artery disease (CAD) is a major contributor to morbidity and mortality worldwide. Early-onset CAD, also known as PCAD, is a severe form of CAD associated with high mortality and a poor prognosis. Early diagnosis is crucial to reducing complications. While hsCRP is an established biomarker for CAD, kalirin is a potential novel biomarker due to its role in promoting smooth muscle proliferation and endothelial dysfunction. Objective: To evaluate the relationship between serum kalirin and hsCRP levels with the presence and severity of PCAD and to compare the diagnostic value of both biomarkers. Method: The study recruited 92 participants into two groups: the PCAD group (46) included patients with confirmed CAD by angiographic findings and the second group was the non-CAD group (46) with negative findings by coronary angiography. The levels of serum kalirin and hsCRP were measured for both groups using enzyme-linked immunosorbent assay (ELISA) kits. Results: Serum levels of kalirin and hsCRP were strongly associated with the presence of PCAD (p&lt;0.001), and both biomarkers were associated with disease severity (p=0.002, &lt;0.001, respectively). ROC analysis showed that hsCRP possesses a slight advantage (AUC=0.796) over kalirin (ROC=0.717) as a diagnostic marker for PCAD. Conclusions: Serum kalirin and hsCRP levels are associated with PCAD and with the severity of the disease, both markers possess moderate diagnostic capabilities for PCAD with a slight advantage for hsCRP.

Importance of Dyslipidemias in Very Premature Coronary Artery Disease in India: A Registry-based Study.

Premature coronary artery disease (CAD) is an important cause of death in India. To identify risk factors in patients with premature CAD, we performed a registry-based study. Consecutive patients admitted for percutaneous coronary intervention (PCI) from October 2020 to June 2021 were recruited. The patients were classified into three groups-group I (very premature CAD < 40 years), group II (premature CAD 40-59 years), and group III (nonpremature CAD > 60 years). Major risk factors were determined, and intergroup comparison was performed. A total of 627 patients were enrolled (men 541, women 86). Group I had 79 (12.4%), group II had 420 (66.9%), and group III had 128 (20.4%) patients. The prevalence of risk factors in groups I, II, and III, respectively, were-CAD family history in 45.1, 41.1, and 26.6% (p = 0.005), current smoking/tobacco use in 29.1, 21.0, and 10.2% (p = 0.002), hypertension in 31.6, 43.6, and 59.4% (p < 0.001), and diabetes in 22.8, 34.3, and 46.1% (p < 0.001). High total cholesterol (>170 mg/dL) was present in 50.0, 38.0, and 29.9% (p = 0.005), nonhigh-density lipoprotein (HDL) cholesterol (>100 mg/dL) in 76.9, 64.4, and 54.5% (p = 0.001), low-density lipoprotein (LDL) cholesterol (>70 mg/dL) in 85.9, 76.8, and 76.4% (p = 0.167), triglycerides (>150 mg/dL) in 56.4, 45.3, and 33.1% (p = 0.001), and very low density lipoprotein (VLDL) cholesterol (>30 mg/dL) in 24.4, 10.4, and 9.4% (p = 0.005). Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) for smoking/tobacco use in groups I and II compared to group III, respectively, were 3.17 (1.60-6.27) and 2.59 (1.51-4.46); high total cholesterol 2.39 (1.29-4.13) and 1.42 (0.92-2.17); high non-HDL cholesterol 2.70 (1.45-5.03) and 1.48 (0.99-2.20); and high triglycerides 2.57 (1.44-4.58) and 1.64 (1.08-2.49). Important coronary risk factors in very premature and premature CAD in India are a family history of CAD, any tobacco use, and dyslipidemias (raised total, LDL, non-HDL, and VLDL cholesterol and triglycerides).

Familial Hypercholesterolaemia Patients with LDLR Mutation Among Asian Population in Southeast Asian Countries: Systematic Review

Familial hypercholesterolaemia (FH) is a genetic disorder associated with premature cardiovascular diseases; however, the majority of patients remain undertreated. This systematic review aimed to determine the prevalence of FH patients with low-density lipoprotein receptor (LDLR) gene pathogenic variants (PV) among the Asian population in Southeast Asian countries. Our search yielded 1,120 citations, with 28 deemed possibly suitable based on title and abstract screening. However, only six studies that utilised the Dutch Lipid Clinic Network (DLCN) or Simon Broome (SB) criteria were eligible to be included. These studies provided prevalence figures for clinically diagnosed FH patients, with a total of 17.1% (n=1,005/5,874); this rate was represented by three Malaysian studies, which estimated that 36–76% of clinically diagnosed FH patients had LDLR PV. Most patients reported having pre-existing cardiovascular disease, a family history of premature coronary artery disease and tendon xanthomata. This study found that the prevalence of LDLR PV among genetically confirmed FH patients in Southeast Asia is 20.5% (n=286/5,874). Genetically confirmed FH patients are at a higher risk of developing premature coronary artery disease, requiring more aggressive lipid-lowering treatment. Therefore, identifying LDLR PV among the population is essential for early FH diagnosis and treatment. KEYWORDS Arterial disease, autosomal dominant, LDL receptor, LDLR prevalence, pathogenic variants, premature CAD, Undertreated

Preliminary Results of Iran Premature Coronary Artery Disease (IPAD study) and Implementation of IPAD Biobank: A Case-Control Study.

Iran Premature Coronary Artery Disease (IPAD) is one of the first and largest studies of its kind in Asia that investigates different aspects of premature coronary artery disease (PCAD) in different ethnic groups in multiple cities. In this paper, we aim to describe the IPAD biobank establishment and present some preliminary results of the IPAD study. This case-control study was conducted on patients with documented angiography from different ethnicities in more than ten cities of Iran (males aged 60 years and below and females aged 70 years and below). Patients with coronary artery stenosis of more than 75% in at least one vessel (or left-main stenosis of more than 50%) were defined as the case group and patients with normal coronary angiography were considered as the control group. In addition to completing questionnaires and performing physical measurements, samples of serum, buffy coat, plasma, whole blood, saliva, urine, and feces were stored in the freezer at -80 °C. The mean age of patients was 51.1±8.2, of which 43% were women. There were 1221 people in the control group and 1702 in the case group. Our enrollment is completed and data entry and transferring biosamples from different cities is still ongoing. About 30000 biosamples of different ethnicities are saved in the IPAD biobank. This study aims to develop a high-quality biobank and facilitate research on different aspects of PCAD, especially gene-environment interaction regarding ethnicity.

Polygenic Risk Scores: The Next Step for Improved Risk Stratification in Coronary Artery Disease?

Despite significant advances in the management of coronary artery disease (CAD) and reductions in annual mortality rates in recent decades, this disease remains the leading cause of death worldwide. Consequently, there is an ongoing need for efforts to address this situation. Current clinical algorithms to identify at-risk patients are particularly inaccurate in moderate-risk individuals. For this reason, the need for ancillary tests has been suggested, including predictive genetic screening. As genetic studies rapidly expand and genomic data becomes more accessible, numerous genetic risk scores have been proposed to identify and evaluate an individual's susceptibility to developing diseases, including CAD. The field of genetics has indeed made substantial contributions to risk prediction, particularly in cases where children have parents with premature CAD, resulting in an increased risk of up to 75%. The polygenic risk scores (PRSs) have emerged as a potentially valuable tool for understanding and stratifying an individual's genetic risk. The PRS is calculated as a weighted sum of single-nucleotide variants present throughout the human genome, identifiable through genome-wide association studies, and associated with various cardiometabolic diseases. The use of PRSs holds promise, as it enables the development of personalized strategies for preventing or diagnosing specific pathologies early. Furthermore, it can complement existing clinical scores, increasing the accuracy of individual risk prediction. Consequently, the application of PRSs has the potential to impact the costs and adverse outcomes associated with CAD positively. This narrative review provides an overview of the role of PRSs in the context of CAD.