Premature Atherosclerosis Research Articles

Disparity of gene expression in coronary artery disease: insights from MEIS1, HIRA, and Myocardin.

Coronary artery disease (CAD) in young adults can have devastating consequences. The cardiac developmental gene MEIS1 plays important roles in vascular networks and heart development. This gene effects on the regeneration capacity of the heart. Considering role of MEIS1 in cardiac tissue development and the progression of myocardial infarction this study investigated the expression levels of the MEIS1, HIRA, and Myocardin genes in premature CAD patients compared to healthy subjects and evaluated the relationships between these genes and possible inflammatory factors. The study conducted a case-control design involving 35 CAD patients and 35 healthy individuals. Peripheral blood mononuclear cells (PBMCs) were collected, and gene expression analysis was performed using real-time PCR. Compared with control group, the number of PBMCs in the CAD group exhibited greater MEIS1 and HIRA gene expression, with fold changes of 2.45 and 3.6. The expression of MEIS1 exhibited a negative correlation with IL-10 (r= -0.312) expression and positive correlation with Interleukin (IL)-6 (r = 0.415) and tumor necrosis factor (TNF)-α (r = 0.534) gene expression. Moreover, there was an inverse correlation between the gene expression of HIRA and that of IL-10 (r= -0.326), and a positive correlation was revealed between the expression of this gene and that of the IL-6 (r = 0.453) and TNF-α (r = 0.572) genes. This research demonstrated a disparity in expression levels of MEIS1, HIRA, and Myocardin, between CAD and healthy subjects. The results showed that, MEIS1 and HIRA play significant roles in regulating the synthesis of proinflammatory cytokines, namely, TNF-α and IL-6.

Associations of circulating adipokines and coronary artery disease in young adults

Aim. To evaluate the associations of abdominal obesity (AO), adipokines and premature coronary artery disease (CAD) in young people for a deeper understanding of the pathogenesis of atherosclerotic diseases.Material and methods. A total of 1457 people were examined, including 653 (44,8%) men. Mean age was 36,7±6,0 years. Premature CAD was detected in 46 people, while 4 following subgroups were formed (138 people in total): with CAD and AO; with CAD, without AO; control groups by age and sex: without CAD, with AO; without CAD, without AO.Results. Premature CAD in young people is associated with an increase in non-high-density lipoprotein cholesterol (non-HDL-C). Univariate analysis found that the probability of CAD increased by 1% with an increase in adiponectin level, and by 0,2% with an increase of 1 ng/ml in resistin level. Multivariate regression analysis, including sex, age, waist circumference, non-HD-C, adiponectin, and resistin, significant associations were obtained for non-HDL-C and adiponectin. With AO, the CAD probability increased by 0,6% with an increase in plasminogen activator inhibitor-1 level (PAI-1). However, when non-HDL-C was included in the model, significance for this biomarker was not achieved.Conclusion. In young people, CAD is associated with increased levels of non-HDL cholesterol, adiponectin, resistin and PAI-1. Independent associations with premature CAD were obtained only for adiponectin, which makes this marker promising for study in young people.

A Rare Symptomatic Case of Heterozygous Cerebro-Tendinous Xanthomatosis (CTX) Treated with Urso-Deoxycholic Acid (UDCA): With Mini Review

Cerebrotendinous Xanthamatosis (CTX) is a rare autosomal recessive disorder caused by a mutation in the CYP27A1 gene leading to impaired metabolism of cholesterol and accumulation of cholestenol and the cholesterol in various tissues such as the brain, eyes, lungs and bones and reduced formation of cheno-deoxycholic acid (CDCA). The clinical presentation is diverse, starting in the early neonatal period and progressing till adulthood unless treated early. A common neurological manifestation is a spino-cerebellar ataxia followed by spastic paraparesis. Tendon xanthoma is a classical finding that usually helps in clinching the diagnosis but may not be present in all cases. Brain MRI also reveals characteristic abnormalities with cerebellar atrophy and hyper-intensities in the dentate nucleus and surrounding cerebellar white matter on T1weighted images. It is a rare cause of treatable ataxia in young individuals. Treatment is by replacement by CDCA or Urso-deoxycholic acid (UDCA). Supplemented with statins these individuals also have premature atherosclerosis causing death due to athero-sclerotic coronary artery disease. Here a rare case of symptomatic heterologous CYP27A1 mutation is reported with syndrome of spino-cerebellar ataxia treated with UDCA.

Risk factor profile and outcomes in young patients presenting with acute ST-segment elevation myocardial Infarction

Abstract Introduction ST-elevation myocardial infarction (STEMI) is more prevalent in the elderly population1, but is now becoming more common in the younger population. It has been of particular concern due to its potential for premature death and long-term morbidity. Early identification and timely modification of risk factors in this population is critical2,3. Secondary prevention issues in populations are well studied, and such data for young adults are lacking in the literature. Purpose The purpose of this study was to compare pattern of traditional CVD risk factors, hospital mortality and major adverse cardiac events at discharge in young versus old patients (≤45years and above 45 years age respectively) admitted with STEMI and undergoing primary PCI. Methods This retrospective cohort study was conducted on consecutive patients presenting with STEMI between June 2013 and June 2018 in a single centre cardiac only tertiary care setup. Institute’s registry is fashioned along and is affiliated with US NCDR. Patients with cardiac arrest or cardiogenic shock at arrival were excluded. MACE was defined as post PCI cardiac arrest or cardiogenic shock, heart failure, major bleed or hospital death. Results Total of 5343 patients were admitted with STEMI during study period, after exclusion data of 1642 patients were analyzed. Table 1 demonstrates demographic and historical characteristics of the study population. Among young patients, the frequency of the male gender,any tobacco use and family history of premature coronary artery disease were significantly higher (all p values < 0.001). While in older STEMI patients frequency of heart failure, hypertension, prior myocardial infarction, diabetes mellitus ,abnormal creatinine clearance (<90 mL/min/1.73 m²) , multi-vessel coronary disease, advanced Killip class and higher body mass index was more prevalent (all P<0.001). Table 2 demonstrates predictors of in hospital death and MACE. Among young patients advanced Killip class and femoral access site(all P values <0.001), diabetes mellitus (p=0.03), abnormal creatinine clearance(p=0.04),and left ventricular ejection fraction less than 40%(p=0.01), were more significant in-hospital mortality predictor where as advanced Killip class,Left ventricular ejection fraction less than 40% male gender(p=0.04), diabetes mellitus(p=0.001),femoral access site(p=0.001), and Left ventricular ejection fraction less than 40% were more significant MACE predictors (all P<0.001). Conclusion There were no significant difference in hospital mortality and MACE among young versus old STEMI patients when adjusted for diabetes mellitus, abnormal creatinine clearance (<90 mL/min/1.73 m²), multi-vessel coronary disease, advanced Killip class. Tobacco use is the main modifiable risk factors for young patients with STEMI. Surprisingly, being a woman and having a positive family history with premature coronary artery disease were protective.

Senescence-Induced Atherosclerosis: The Potency of Senolytic Therapy

The aging process is an inevitable occurrence that involves physiological changes at the cellular level. The presence of intrinsic and extrinsic stressors can cause cellular damage, leading to senescence and premature aging. Senescent cells undergo activation of the p53/p21 and p16INK4a pathways, induce cell cycle arrest, increased expression of senescence-associated beta-galactosidase (SA-β-Gal), and secretion of SASP (senescence-associated secretory phenotype), leading to "inflamm-aging" or chronic inflammation associated with senescence. These premature aging and “inflamm-aging” accelerates the occurrence of age-related diseases, one of which is atherosclerosis. The relationship between premature aging, senescence, and atherosclerosis has been a focus of research on pathogenesis, prevention, and therapy. Recent research has emphasized the crucial role of senolytics, compounds or agents capable of eliminating senescent cells, in inhibiting the progression of atherosclerosis and slowing down premature aging. Obtaining a more comprehensive understanding of the processes and effectiveness of senolytics in premature aging and atherosclerosis should facilitate the development of more potent medicines to mitigate side effects in the management of cardiovascular disease and extend longevity.

Distinct Population Characteristics Seen in Patients with Premature Atherosclerosis

Distinct Population Characteristics Seen in Patients with Premature Atherosclerosis

Management of Pregnancy in a Patient with Familial Hypercholesterolemia and Previous Myocardial Infarction—Treatment with LDL Apheresis: A Case Report

Familial hypercholesterolemia, a genetic disorder marked by elevated low-density lipoprotein cholesterol (LDL-C), poses significant risks for premature atherosclerosis and cardiovascular diseases, particularly during pregnancy. One of the safe methods of treating this condition in pregnancy is with the use of LDL apheresis. We present a 38-year-old primigravida with homozygous Familial Hypercholesterolemia (HoFH), ischemic cardiomyopathy, and angina pectoris. Two years before conception, extremely elevated lipid levels prompted statin therapy and lifestyle changes. Stent placements followed acute myocardial infarction. When planning pregnancy, statins were discontinued, but lipid levels elevated. LDL apheresis was initiated, achieving a 60% reduction. Throughout pregnancy, 16 LDL apheresis sessions were performed every 14 days, maintaining optimal lipid profiles. A cesarean section was performed in the 38th week of gestation, delivering a healthy infant. The patient resumed statin therapy after 8 months of breastfeeding. The patient maintained cardiovascular health, demonstrating the feasibility of controlled HoFH pregnancies. This case highlights the successful management of HoFH during pregnancy using LDL apheresis, ensuring maternal and fetal well-being. Future research on novel treatments and their safety during pregnancy is essential for refining therapeutic approaches in similar cases.

CLINICAL CHALLENGE: AORTITIS IN THE EMERGENCY DEPARTMENT

Abstract A 67 yo woman presented to the ED for a sustained episode of palpitations and acute chest pain. Past medical history: suspected psoriatic arthritis previously treated with steroids and hydroxychloroquine; previous suspicion of rheumatic polymyalgia and Horton arteritis, regressed with steroids; gastroesophageal reflux disease; mild hypercholesterolemia and a family history of premature coronary artery disease. In the ED the patient was hemodynamically stable. On physical examination: tachyarrhythmic heart sounds with no murmurs. The peripheral arterial pulses were preserved and symmetrical. The remaining physical examination was unremarkable. ECG: atrial fibrillation at 150 bpm. The D–dimer was increased, normal hs–troponin and normal haemoglobin. On echocardiography: normal biventricular structure and function; normal aortic root with dilatation of proximal ascending aorta (47 mm), without visible intimal flaps. The anterior wall of the proximal ascending aorta was thickened. A moderate circumferential pericardial effusion was present, without signs of hemodynamic impact. On suspicion of an acute aortic syndrome with possible intramural haematoma of an ascending aortic aneurism, an urgent CT scan was ordered. It showed a severe dilatation of ascending aorta (52 mm) involving of the proximal aortic arch. The anterior aortic wall was thickened (5 mm), without clear images of IMH, aortic dissection or penetrating ulcer. The pericardial effusion had a supra–fluid density without blood density. A repeated CT at 6 hours showed no changes. The case was suggestive of an inflammatory aetiology. The patient was admitted to the cardiac intensive care unit. A PET–CT scan showed signs of an inflammatory disease of the great vessels. A serological autoimmunity screening was negative. The patient was diagnosed with inflammatory aortitis (giant cell vs Takayasu arteritis) and started on high dose iv glucocorticoid therapy. Given the high risk of severe aortic complications, adjunctive therapy with tocilizumab was prescribed. The therapy was gradually tapered, with subsequent switch to oral steroids plus tocilizumab. At one and a half month of follow–up, a CT scan was repeated, documenting stable aortic diameters and the disappearance of the abnormal thickness and of the enhancement of the aortic wall. A follow–up PET–CT scan has been scheduled at 6 months time. An elective aortic intervention has been indicated after remission of the inflammatory phase.

Algorithm for detection and screening of familial hypercholesterolemia in Lithuanian population

BackgroundFamilial hypercholesterolemia (FH) is one of the most common autosomal dominant diseases. FH causes a lifelong increase in low-density lipoprotein cholesterol (LDL-C) levels, which in turn leads to atherosclerotic cardiovascular disease. The incidence of FH is widely underestimated and undertreated, despite the availability and effectiveness of lipid-lowering therapy. Patients with FH have an increased cardiovascular risk; therefore, early diagnosis and treatment are vital. To address the burden of FH, several countries have implemented national FH screening programmes. The currently used method for FH detection in Lithuania is mainly based on opportunistic testing with subsequent cascade screening of index cases’ first-degree relatives.MethodsA total of 428 patients were included in this study. Patients with suspected FH are referred to a lipidology center for thorough evaluation. Patients who met the criteria for probable or definite FH according to the Dutch Lipid Clinic Network (DLCN) scoring system and/or had LDL-C > = 6.5 mmol/l were subjected to genetic testing. Laboratory and instrumental tests, vascular marker data of early atherosclerosis, and consultations by other specialists, such as radiologists and ophthalmologists, were also recorded.ResultsA total of 127/428 (30%) patients were genetically tested. FH-related mutations were found in 38.6% (n = 49/127) of the patients. Coronary artery disease (CAD) was diagnosed in 13% (n = 57/428) of the included patients, whereas premature CAD was found in 47/428 (11%) patients. CAD was diagnosed in 19% (n = 9/49) of patients with FH-related mutations, and this diagnosis was premature for all of them.ConclusionsMost patients in this study were classified as probable or possible FH without difference of age and sex. The median age of FH diagnosis was 47 years with significantly older females than males, which refers to the strong interface of this study with the LitHir programme. CAD and premature CAD were more common among patients with probable and definite FH, as well as those with an FH-causing mutation. The algorithm described in this study is the first attempt in Lithuania to implement a specific tool which allows to maximise FH detection rates, establish an accurate diagnosis of FH, excluding secondary causes of dyslipidaemia, and to select patients for cascade screening initiation more precisely.

Abstract 3118: An Unusual Case Of Severe Multivessel Atherosclerotic Coronary Artery Disease In A Very Young Patient

Introduction: Premature coronary artery disease (CAD) is defined as CAD prior to the age of 55 for men and 65 for women, while CAD in young is defined as age <45 years. In the last decade, incidence of global premature CAD has increased by 25 %. Case presentation: A 20-year-old female with medical history of dyslipidemia, hypertension, type 1 diabetes mellitus and family history of premature coronary artery disease presented to the emergency room with chief complaint of chest pain and shortness of breath. EKG revealed sinus tachycardia and poor R-wave progression on anterior precordial leads. Serum troponin trend was unremarkable. Echocardiogram revealed severely reduced left ventricular (LV) ejection fraction of 20-25% with global LV hypokinesis, trace mitral and tricuspid regurgitation. Given new onset cardiomyopathy and family history of premature CAD, CT heart with coronary calcium scoring was performed which was concerning for severe LAD disease. Surprisingly, coronary angiogram revealed severe atherosclerotic disease in LAD, left circumflex and right coronary artery territories. Patient was started on guideline directed medical therapy for cardiomyopathy and has been referred to tertiary center for surgical revascularization. Discussion: To our best knowledge only one case has been reported before in the literature when a 21-year-old male patient had multivessel CAD requiring surgical revascularization. However, we report a case, which will be the youngest ever to have severe multivessel CAD needing surgical revascularization in the future. Cole et al, in a study of 800 young patients with CAD at long term follow up of 15 years, showed an overall mortality rate of 30 %, with 83% mortality rate in patients with EF< 30%, thus carrying a poor long-term prognosis.(2) Hence, an early initiation of treatment, including both medical therapy and revascularization should strongly be considered in these young patient population. Conclusion: With the increasing prevalence of premature CAD and associated risk factors, age alone should not be taken as a reliable indicator for risk stratifying patients. Emphasizing awareness among young adults with high risk of CAD that primary prevention and early lifestyle modification are of paramount importance.

Genetic and Lifestyle Risk Factors of Metabolic Dysfunction-Associated Fatty Liver Disease and Its Relationship with Premature Coronary Artery Disease: A Study on the Pars Cohort.

The main objective of this study is to identify the risk factors of metabolic dysfunction-associated fatty liver disease (MAFLD) in coronary artery disease (CAD) patients. The present retrospective cohort study is part of the Pars Cohort Study (PCS). The participants were categorized as having MAFLD or not. The pattern of independent variables in patients was compared with those who did not have MAFLD. All variables were retained in the multivariable logistic regression model. Totally, 1862 participants with CAD were enrolled in this study. MAFLD was diagnosed in 647 (40.1%) participants. Gender, diabetes, hypertension, tobacco, opium, alcohol, age, weight, waist circumference, cholesterol, HDL, triglyceride, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly different in MAFLD and non-MAFLD patients. Also, the results of multivariable logistic regression show male gender (OR=0.651, 95% CI: 0.470‒0.902, P value=0.01) and opium consumption (OR=0.563, 95% CI: 0.328‒0.968, P value<0.001) to be negative risk factors of MAFLD occurrence in CAD patients. Having diabetes (OR=2.414, 95% CI: 1.740-3.349, P value<0.001), high waist circumference (OR=1.078, 95% CI: 1.055‒1.102, P value<0.01), high triglyceride (OR=1.005, 95% CI: 1.001‒1.008, P value=0.006), and high ALT (OR=1.039, 95% CI: 1.026‒1.051, P value<0.01) were positive risk factors of MAFLD in CAD patients. Our study found that consuming opium decreases the likelihood of MAFLD in CAD patients, since these patients have decreased appetite and lower body mass index (BMI). On the other hand, female gender, having diabetes, high waist circumference, high triglyceride levels, and high ALT levels increase the probability of MAFLD in CAD patients.

Abstract 2065: Activation Of Cgas-sting Axis By DNA Double-strand Breaks In Atherosclerosis: A Possible Link From DNA Damage To Inflammation And Cell Senescence

Aim: Premature atherosclerosis in some progeroid syndromes suggests the involvement of DNA damage in the progression of atherosclerosis. However, causative links between DNA double-strand breaks (DSBs) and atherosclerosis have yet to be determined. The aim of this study was to elucidate the role of DSBs in atherosclerosis using mice and vascular smooth muscle cells (VSMCs) deficient in Ku80, a DSB repair protein. Methods and Results: The plaque size and DSBs were increased in the aorta of Ku80-deficient apolipoprotein E knockout mice (Ku80 +/- ApoE -/- ) compared to those of ApoE -/- control after 4 weeks of a high-fat diet. At the early stages of atherosclerosis (two-week high-fat diet), although the plaque size of Ku80 +/- ApoE -/- was similar to that of ApoE -/- control, the number of DSBs and mRNA levels of inflammatory cytokines such as IL-6 and MCP-1 were significantly increased in the Ku80 +/- ApoE -/- aortas. We further investigated molecular links between DSBs and inflammatory responses using VSMCs isolated from Ku80 +/- mice. In VSMCs from Ku80 +/- mice, IL-6 mRNA level was elevated along with increased cellular senescence markers, such as p16 mRNA and senescence-associated (SA) β-gal activity. Additionally, Ku80 +/- VSMCs showed accumulated cytosolic free DNA, an increased level of cGAMP, and activation of TBK1, interferon regulatory factor 3 (IRF3) and NF-κB, suggesting the activation of cGAS-STING axis, a cytosolic DNA sensing machinery. Activation of cGAS-STING axis was also shown in the aortae from Ku80 +/- ApoE -/- in comparison with those from ApoE -/- control. Silencing IRF3, but not NF-κB attenuated the IL-6 mRNA level in Ku80 +/- VSMCs, so did cGAS-silencing. Of interest, cGAS-silencing also attenuated DNA damage-induced SA β-gal activity in wild-type VSMCs. Furthermore, depletion of either p16 or p53 suppressed IRF3 activation by DNA damage. Conclusions: These results suggest that accumulation of cytosolic DNA induced by DNA damage accelerates atherosclerosis via the activation of cGAS-STING-IRF3 axis. cGAS-STING-IRF3 axis may play a pivotal role as a common signaling pathway that serve as a link from DNA damage to inflammatory and cell senescence response in arterial wall.

Association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography.

Many previous studies reported the relationship between lipoprotein(a) and cardiovascular disease, but the conclusions were controversial. The aim of our study was to retrospectively investigate the association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography. We collected and compared clinical information of patients hospitalized for coronary angiography. Multivariable hierarchical logistic regression was used to evaluate the association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography. There were no significant differences in gender, hypertension, APOA1, smoking, hyperuricemia, obesity, acute myocardial infarction (AMI), cardiac insufficiency, family history of diabetes, or family history of hyperlipidemia among the four groups of lipoprotein(a). Elevated lipoprotein(a) does not increase the risk of hypertriglyceridemia, while elevated lipoprotein(a) increases the risk of high total cholesterol and high low-density lipoprotein cholesterol (LDL-c). Elevated lipoprotein(a) increases the risk of diabetes and premature coronary artery disease (CAD). Elevated lipoprotein(a) increases the incidence of CAD, multivessel lesions, and percutaneous coronary intervention (PCI). Multivariate logistic regression analysis further showed that elevated lipoprotein(a) increases the incidence of high total cholesterol, high LDL‑c, diabetes, CAD, premature CAD, multivessel lesions, and PCI. The findings indicated that elevated lipoprotein(a)had no obvious relationship with hypertension and obesity. Elevated lipoprotein(a)increases the risk of high total cholesterol, high LDL‑c, and premature CAD, and increases the occurrence and severity of coronary heart disease.

Enhanced identification of familial hypercholesterolemia using central laboratory algorithms

Background and aimsFamilial hypercholesterolemia (FH) is a highly prevalent genetic disorder resulting in markedly elevated LDL cholesterol levels and premature coronary artery disease. FH underdiagnosis and undertreatment require novel detection methods. This study evaluated the effectiveness of using an LDL cholesterol cut-off ≥99.5th percentile (sex- and age-adjusted) to identify clinical and genetic FH, and investigated underutilization of genetic testing and undertreatment in FH patients. MethodsIndividuals with at least one prior LDL cholesterol level ≥99.5th percentile were selected from a laboratory database containing lipid profiles of 590,067 individuals. The study comprised three phases: biochemical validation of hypercholesterolemia, clinical identification of FH, and genetic determination of FH. ResultsOf 5614 selected subjects, 2088 underwent lipid profile reassessment, of whom 1103 completed the questionnaire (mean age 64.2 ± 12.7 years, 48% male). In these 1103 subjects, mean LDL cholesterol was 4.0 ± 1.4 mmol/l and 722 (65%) received lipid-lowering therapy. FH clinical diagnostic criteria were met by 282 (26%) individuals, of whom 85% had not received guideline-recommended genetic testing and 97% failed to attain LDL cholesterol targets. Of 459 individuals consenting to genetic validation, 13% carried an FH-causing variant, which increased to 19% in clinically diagnosed FH patients. ConclusionsThe identification of a substantial number of previously undiagnosed and un(der)treated clinical and genetic FH patients within a central laboratory database highlights the feasibility and clinical potential of this targeted screening strategy; both in identifying new FH patients and in improving treatment in this high-risk population.

What Causes Premature Coronary Artery Disease?

This review provides an overview of genetic and non-genetic causes of premature coronary artery disease (pCAD). pCAD refers to coronary artery disease (CAD) occurring before the age of 65years in women and 55years in men. Both genetic and non-genetic risk factors may contribute to the onset of pCAD. Recent advances in the genetic epidemiology of pCAD have revealed the importance of both monogenic and polygenic contributions to pCAD. Familial hypercholesterolemia (FH) is the most common monogenic disorder associated with atherosclerotic pCAD. However, clinical overreliance on monogenic genes can result in overlooked genetic causes of pCAD, especially polygenic contributions. Non-genetic factors, notably smoking and drug use, are also important contributors to pCAD. Cigarette smoking has been observed in 25.5% of pCAD patients relative to 12.2% of non-pCAD patients. Finally, myocardial infarction (MI) associated with spontaneous coronary artery dissection (SCAD) may result in similar clinical presentations as atherosclerotic pCAD. Recognizing the genetic and non-genetic causes underlying pCAD is important for appropriate prevention and treatment. Despite recent progress, pCAD remains incompletely understood, highlighting the need for both awareness and research.

A predictive model for premature atherosclerosis in systemic lupus erythematosus based on clinical characteristics.

Systemic lupus erythematosus (SLE) is associated with a significant risk of atherosclerotic cardiovascular disease, especially in the development of premature atherosclerosis. Specific prediction models for premature atherosclerosis in SLE patients are still limited. The objective of this study was to establish a predictive model for premature atherosclerosis in SLE. The study collected clinical and laboratory data from 148 SLE patients under the age of 55, between January 2021 and June 2023. The least absolute shrinkage and selection operator logistic regression model was utilized to identify potentially relevant features. Subsequently, a nomogram was developed using multivariable logistic analysis. The performance of the nomogram was evaluated through a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA). A total of 148 SLE patients who fulfilled the inclusion criteria were enrolled in the study, of whom 53 patients (35.81%) met the definition of premature atherosclerosis. Hypertension, antiphospholipid syndrome, azathioprine use, duration of glucocorticoid, and age of patients were included in the multivariable regression. The nomogram, based on the non-overfitting multivariable model, was internally validated and demonstrated sufficient clinical utility for assessing the risk of premature atherosclerosis (area under curve: 0.867). The comprehensive nomogram constructed in this study serves as a useful and convenient tool for evaluating the risk of premature atherosclerosis in SLE patients. It is helpful for clinicians to early identify SLE patients with premature atherosclerosis and facilitates the implementation of more effective preventive measures. Key Points • SLE patients are at a significantly higher risk of developing premature atherosclerosis compared to the general population, and this risk persists even in cases with low disease activity. Traditional models used to evaluate and predict premature atherosclerosis in SLE patients often underestimate the risk. • This study establishes a comprehensive and visually orientated predictive model of premature atherosclerosis in SLE patients, based on clinical characteristics. • The scoring system allows for convenient and effective prediction of individual incidence of premature atherosclerosis, and could provide valuable information for identification and making further intervention decision.

Women and familial hypercholesterolemia

Cardiovascular diseases (CVD) are the leading cause of death worldwide. One of the risk factors of CVDs is dyslipidemia, defined as the imbalance of lipids in the blood. Early diagnosis and treatment of the disease is important. However, there appears to be a gender disparity, with women less likely to be diagnosed and start lipid-lowering therapy. In addition, it is difficult for them to continue treatment without interruptions, such as for reasons of childbearing, and as a result they do not achieve the target Low Density Lipoproteins (LDL) levels. Heterozygous Familial Hypercholesterolaemia (FH) is thought to occur in 1 in 500 people in most ethnicities in the world. However, in most cases, these figures are derived from limited numbers of data from selected populations or specific subgroups in the general population and therefore may lack the precision of more modern estimates. About 1 in 200 people have familial hypercholesterolemia, but the vast majority are undiagnosed. Women with untreated FH are at very high risk for early-onset atherosclerotic cardiovascular disease. In untreated women with FH, 30% will develop Atherosclerotic Cardiovascular Disease (ASCVD) by age 60. The onset of ASCVD occurs 20 years earlier in life for women with FH than for women without FH. Regarding women with FH during menopause, they had similar LDL values to premenopausal women and higher levels compared to men in the same age group. Postmenopausal women with FH may suffer the consequences of high LDL either from delayed diagnosis or because of interruptions in management they may have experienced during childbearing. The last 2 decades have seen the development of new therapies to lower LDL-cholesterol levels and delay premature atherosclerosis, especially in combination with lifestyle modifications. Management of patients with familial hypercholesterolemia requires a multiprofessional approach, including primary care providers, cardiologists, endocrinologists, dietitians, pharmacists, and nurses, to improve outcomes. Treatment strategies should be discussed extensively at diagnosis. Close follow-up to monitor treatment response and development of side effects from lipid-lowering agents is essential to optimize care. The representation of women in studies concerning the diagnosis and treatment of familial hypercholesterolemia must be improved, so that there is a more effective treatment of this disease.

Metabolic score for insulin resistance predicts major adverse cardiovascular event in premature coronary artery disease.

The Metabolic Score for Insulin Resistance (METS-IR) index serves as a simple surrogate marker for insulin resistance (IR) and is associated with the presence and severity of coronary artery disease (CAD). However, the prognostic significance of METS-IR in patients with premature CAD remains unclear. This study aims to investigate the prognostic value of METS-IR in premature CAD. This retrospective study included 582 patients diagnosed with premature CAD between December 2012 and July 2019. The median follow-up duration was 63 months (interquartile range, 44-81 months). The primary endpoint was Major Adverse Cardiovascular Events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction (MI), repeat coronary artery revascularization, and non-fatal stroke. Patients with MACE had significantly higher METS-IR levels than those without MACE (44.88±8.11 vs. 41.68±6.87, p<0.001). Kaplan-Meier survival curves based on METS-IR tertiles demonstrated a statistically significant difference (log-rank test, p<0.001). In the fully adjusted model, the Hazard Ratio (95% CI) for MACE was 1.41 (1.16-1.72) per SD increase in METS-IR, and the P for trend based on METS-IR tertiles was 0.001 for MACE. Time-dependent Receiver Operator Characteristic (ROC) analysis of METS-IR yielded an Area Under the Curve (AUC) of 0.74 at 2 years, 0.69 at 4 years, and 0.63 at 6 years. METS-IR serves as a reliable prognostic predictor of MACE in patients with premature CAD. Therefore, METS-IR may be considered a novel, cost-effective, and dependable indicator for risk stratification and early intervention in premature CAD.

Impacts of pro-inflammatory cytokines variant on cardiometabolic profile and premature coronary artery disease: A systematic review and meta-analysis.

Interleukin-6 (IL-6), a pivotal pro-inflammatory cytokine, is closely linked to vascular wall thickening and atherosclerotic lesion. Since serum IL-6 levels are largely determined by the genetic variant in IL-6, this study was conducted to investigate whether the IL-6 variant impacts cardiometabolic profile and the risk of premature coronary artery disease (PCAD). PubMed, Cochrane Library, Central, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ClinicalTrials.gov were searched from May 13, 2022 to June 28, 2023. In total, 40 studies (26,543 individuals) were included for the analysis. The rs1800795 (a function variant in the IL-6 gene) C allele was linked to higher levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), fasting plasma glucose (FPG), body mass index (BMI), and waist circumference (WC), and a lower levels of high-density lipoprotein cholesterol (HDL-C). However, no significant association was observed of rs1800795 with triglycerides (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Interestingly, a significant association was detected between rs1800795 and PCAD. Subgroup analyses indicted that the impacts of rs1800795 on cardiometabolic risk factors were significant in Caucasians but stronger in obese patients. In contrast, the impact of rs1800795 on PCAD was significant in brown race population. In summary, rs1800795 had a slight but significant impact on cardiometabolic risk factors and PCAD. IL-6 inhibition with ziltivekimab or canakinumab may benefit high-risk populations (e.g. brown race population, Caucasians, obese patients, etc.) with rs1800795 to prevent PCAD.

Frequency of the R202Q mutation of MEFV gene in Iranian patients with premature coronary artery disease: a report from West Azerbaijan province of Iran

Frequency of the R202Q mutation of MEFV gene in Iranian patients with premature coronary artery disease: a report from West Azerbaijan province of Iran