Risk Of Premature Coronary Artery Disease Research Articles

LncRNA RP1-276N6.2 Expression and RP1-276N6.2 Gene Polymorphisms Contribute to the Risk of Coronary Artery Disease in Chinese Han Population.

Long noncoding RNAs (lncRNAs) have been implicated in coronary artery disease (CAD) processes. However, the relationship between the gene polymorphisms of lncRNA RP1-276N6.2 as a novel molecule and susceptibility to CAD remains unclear. In our case-control study, 949 CAD patients and 892 healthy controls were genotyped using the TaqMan genotyping assay. The quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay were performed to examine the expression levels of RP1-276N6.2 and SLC22A3(OCT3). We observed that CAD patients had significantly lower RP1-276N6.2 levels than those healthy participants (p < 0.05). Compared to the wild-type genotype, the rs611950 T allele and the rs10499313 AG genotype and G allele significantly increased the premature CAD risk (p = 0.02, p = 0.002, and p = 0.01, respectively), while the rs505000 G allele reduced this risk (p = 0.01); moreover, the rs505000 CG genotype significantly enhanced the delayed CAD risk (p = 0.03), and the rs505000 G allele reduced the expression levels of RP1-276N6.2 and SLC22A3 (p < 0.05 and p < 0.05, respectively). In addition, RP1-276N6.2 positively regulated the mRNA and secreted protein levels of SLC22A3 (p < 0.05). In conclusion, the RP1-276N6.2 gene polymorphisms were closely associated with CAD risk. LncRNA RP1-276N6.2 may be a potential genetic target for CAD early diagnosis and treatment.

The association between glycemic index, glycemic load and total carbohydrate intake and risk of premature coronary artery disease: Iran Premature Coronary Artery Disease Study (IPAD) - A Case-Control Study

Background and aimsThe association between glycemic index (GI), glycemic load (GL), total carbohydrate intake, and risk of cardiovascular diseases has been controversial. Premature coronary artery disease (PCAD) is characterized by the age of onset lower than 55 and 65 respectively in men and women. The aim of the current study is to investigate the relationship between GI, GL and carbohydrate levels and the risk of PCAD in Iran. Methods and resultsIn total, 419 healthy people and 553 patients struggling with PCAD have participated in this case-control study. Dietary GI and GL were calculated using a validated food frequency questionnaire at the baseline. Crude and multivariable logistic regression were used to assess the relationship between GI, GL, and total carbohydrate intake and risk of PCAD. The mean age of participants was 51.13 ± 6.90 and 46 % of them were women. A significant direct relationship was observed between higher carbohydrate intake (OR: 1.74, 95%CI: 1.27–2.38) and GL levels (OR: 1.56, 95 % CI:1.14–2.14) and risk of PCAD. These associations were not significant after adjusting for potential variables. No significant association has been observed between GI and odds of PCAD even after controlling for all covariates. ConclusionWe found no significant association between GI, GL, and total carbohydrate intake and risk of premature coronary heart disease. Further observational and clinical trials are required to assess this relationship.

Pregnancy Complications Are Associated with Premature Coronary Artery Disease: Linking Three Cohorts.

Background: There is increasing evidence that women who experience placenta-mediated pregnancy complications and gestational diabetes mellitus (GDM) are at higher risk for the development of coronary artery disease (CAD) later in life. We hypothesized that there is an association between placenta-mediated pregnancy complications, GDM, and risk of premature CAD (PCAD). Methods: This research project involved a data linkage approach merging three databases of South Australian cohorts by using a retrospective, age-matched case-control study design. Cases (n = 721) were ascertained from the Coronary Angiogram Database of South Australia (CADOSA). Women <60 years from CADOSA were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain their prior pregnancy outcomes. Controls (n = 194) were selected from North West Adelaide Health Study (NWAHS) and comprised women who were healthy or had other health conditions unrelated to CAD, age-matched to CADOSA (±5 years), and linked to SAPSC to determine their pregnancy outcomes. PCAD was defined as >50% stenosis in one or more coronary arteries at coronary angiography. Results: Compared with women without a history of PCAD, women who were diagnosed with PCAD were more likely to have experienced the placenta-mediated pregnancy complications of preterm birth (adjusted odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.21-5.00) or low-birth weight (adjusted OR = 2.44, 95% CI: 1.22-4.88), or have been diagnosed with active asthma during pregnancy (adjusted OR = 3.52, 95% CI: 1.05-11.76). Conclusion: Placenta-mediated pregnancy complications should be recognized as clear risk markers for future PCAD.

The relationship between ultra processed food consumption and premature coronary artery disease: Iran premature coronary artery disease study (IPAD).

Ultra-processed foods (UPF) consumption may affect the risk of PCAD through affecting cardio metabolic risk factors. This study aimed to evaluate the association between UPFs consumption and premature coronary artery disease (PCAD). A case-control study was conducted on 2,354 Iranian adults (≥ 19 years). Dietary intake was assessed using a validated 110-item food frequency questionnaire (FFQ) and foods were classified based on the NOVA system, which groups all foods according to the nature, extent and purposes of the industrial processes they undergo. PCAD was defined as having an stenosis of at least single coronary artery equal and above 75% or left main coronary of equal or more than 50% in women less than 70 and men less than 60 years, determined by angiography. The odds of PCAD across the tertiles of UPFs consumption were assessed by binary logistic regression. After adjustment for potential confounders, participants in the top tertile of UPFs were twice as likely to have PCAD compared with those in the bottom tertile (OR: 2.52; 95% CI: 1.97-3.23). Moreover, those in the highest tertile of the UPFs consumption had more than two times higher risk for having severe PCAD than those in the first tertile (OR: 2.64; 95% CI: 2.16-3.22). In addition, there was a significant upward trend in PCAD risk and PCAD severity as tertiles increased (P-trend < 0.001 for all models). Higher consumption of UPFs was related to increased risk of PCAD and higher chance of having severe PCAD in Iranian adults. Although, future cohort studies are needed to confirm the results of this study, these findings indicated the necessity of reducing UPFs intake.

Ethnic differences in the lifestyle behaviors and premature coronary artery disease: a multi-center study

BackgroundDiverse ethnic groups that exist in Iran may differ regarding the risk factors such as hypertension, hyperlipidemia, dyslipidemia, diabetes mellitus, and family history of non-communicable disease. Premature Coronary Artery Disease (PCAD) is more endemic in Iran than before. This study sought to assess the association between ethnicity and lifestyle behaviors in eight major Iranian ethnic groups with PCAD.MethodsIn this study, 2863 patients aged ≤ 70 for women and ≤ 60 for men who underwent coronary angiography were recruited in a multi-center framework. All the patients’ demographic, laboratory, clinical, and risk factor data were retrieved. Eight large ethnicities in Iran, including the Farses, the Kurds, the Turks, the Gilaks, the Arabs, the Lors, the Qashqai, and the Bakhtiari were evaluated for PCAD. Different lifestyle components and having PCAD were compared among the ethnical groups using multivariable modeling.ResultsThe mean age of the 2863 patients participated was 55.66 ± 7.70 years. The Fars ethnicity with 1654 people, was the most subject in this study. Family history of more than three chronic diseases (1279 (44.7%) was the most common risk factor. The Turk ethnic group had the highest prevalence of ≥ 3 simultaneous lifestyle-related risk factors (24.3%), and the Bakhtiari ethnic group had the highest prevalence of no lifestyle-related risk factors (20.9%). Adjusted models showed that having all three abnormal lifestyle components increased the risk of PCAD (OR = 2.28, 95% CI: 1.04–1.06). The Arabs had the most chance of getting PCAD among other ethnicities (OR = 2.26, 95%CI: 1.40–3.65). While, the Kurds with a healthy lifestyle showed the lowest chance of getting PCAD (OR = 1.96, 95%CI: 1.05–3.67)).ConclusionsThis study found there was heterogeneity in having PACD and a diverse distribution in its well-known traditional lifestyle-related risk factors among major Iranian ethnic groups.

Factor V Leiden but not the factor II 20210G>A mutation is a risk factor for premature coronary artery disease: a case-control study in Iran

BackgroundFactor V Leiden (FVL) and factor II c.∗97G>A (rs1799963) are genetic risk factors for venous thromboembolism. Their contribution to coronary artery disease (CAD) is less clear. ObjectivesThis study aimed to investigate the association between FVL, rs1799963, and premature CAD in Iranians. MethodsWe performed a genetic case-control study of 944 cases and 1081 controls from the premature CAD Milano-Iran study, including patients aged 18-55 (female) and 18-45 years (male) who underwent coronary angiography at the Tehran Heart Centre (Iran) in 2004-2011. Cases had luminal stenosis ≥50% in at least 1 main coronary artery or branch. Controls were age- and sex-matched with no CAD history. FVL and rs1799963 were genotyped using TaqMan SNP genotyping assays. Association was tested by logistic regression adjusted for matching factors and ethnicity. Effect modification by sex and cardiovascular risk factors (metabolic [obesity, hypertension, hyperlipidemia, and diabetes], and smoking) was assessed. ResultsThe risk of premature CAD was increased by 50% in FVL carriers (adjusted odds ratio [adjOR] 1.54 [95% CI, 0.95-2.48]) and slightly reduced in rs1799963 carriers (adjOR 0.71 [95% CI, 0.40-1.27]). These effects were more pronounced in women than men (FVL, adjOR 1.66 vs 1.25; rs1799963, adjOR 0.60 vs 1.07). The risk of premature CAD was substantially increased in carriers of FVL with at least 1 metabolic risk factor compared with noncarriers without metabolic risk factors (adjOR 25.14 [95% CI, 12.51-50.52]). ConclusionFVL but not FII rs1799963 was associated with an increased risk of CAD in young Iranians. This risk increased considerably when combined with metabolic cardiovascular risk factors.

Food Intake Pattern and Cardiovascular Risk Factors in Patients with Premature Coronary Artery Disease in Iran

Background: There is limited evidence regarding the risk factors and nutritional patterns in patients with premature coronary artery disease (PCAD). This study aims to investigate the relationship between different dietary patterns and risk factors in patients with PCAD.&#x0D; Methods: This cross-sectional study was conducted on PCAD patients, including men younger than 55 years and women younger than 65 years, who underwent coronary angiography in the Angiography Department of the Shahid Mohamadi Hospital, Bandar Abbas, Iran. Anthropometric and clinical examination, demographic questionnaires, and containing dietary intake and physical activity questionnaires were filled for all participants.&#x0D; Results: The most prevalent risk factors for obstructive PCAD in the 65 selected patients were family history of coronary artery disease (CAD) (73%), hypertension (52%), and overweight/obesity (50%). Daily consumption of hydrogenated fats (P = 0.008) and high-fat milk (P &lt; 0.001) were significantly higher in obstructive PCAD patients compared to non-obstructive and non-PCAD patients. Daily consumption of fruits was significantly higher in non-obstructive and non-PCAD patients compared to obstructive PCAD patients (P = 0.039).&#x0D; Conclusion: Family history of CAD, hypertension, and obesity were found to be the most common risk factors among obstructive PCAD patients. According to the findings, increased consumption of high-fat milk and hydrogenated fats may increase the risk of PCAD, whereas, daily consumption of fruits may reduce the risk of PCAD.

A Machine Learning Model Based on Genetic and Traditional Cardiovascular Risk Factors to Predict Premature Coronary Artery Disease.

Premature coronary artery disease (PCAD) has a poor prognosis and a high mortality and disability rate. Accurate prediction of the risk of PCAD is very important for the prevention and early diagnosis of this disease. Machine learning (ML) has been proven a reliable method used for disease diagnosis and for building risk prediction models based on complex factors. The aim of the present study was to develop an accurate prediction model of PCAD risk that allows early intervention. We performed retrospective analysis of single nucleotide polymorphisms (SNPs) and traditional cardiovascular risk factors (TCRFs) for 131 PCAD patients and 187 controls. The data was used to construct classifiers for the prediction of PCAD risk with the machine learning (ML) algorithms LogisticRegression (LRC), RandomForestClassifier (RFC) and GradientBoostingClassifier (GBC) in scikit-learn. Three quarters of the participants were randomly grouped into a training dataset and the rest into a test dataset. The performance of classifiers was evaluated using area under the receiver operating characteristic curve (AUC), sensitivity and concordance index. R packages were used to construct nomograms. Three optimized feature combinations (FCs) were identified: RS-DT-FC1 (rs2259816, rs1378577, rs10757274, rs4961, smoking, hyperlipidemia, glucose, triglycerides), RS-DT-FC2 (rs1378577, rs10757274, smoking, diabetes, hyperlipidemia, glucose, triglycerides) and RS-DT-FC3 (rs1169313, rs5082, rs9340799, rs10757274, rs1152002, smoking, hyperlipidemia, high-density lipoprotein cholesterol). These were able to build the classifiers with an AUC >0.90 and sensitivity >0.90. The nomograms built with RS-DT-FC1, RS-DT-FC2 and RS-DT-FC3 had a concordance index of 0.94, 0.94 and 0.90, respectively, when validated with the test dataset, and 0.79, 0.82 and 0.79 when validated with the training dataset. Manual prediction of the test data with the three nomograms resulted in an AUC of 0.89, 0.92 and 0.83, respectively, and a sensitivity of 0.92, 0.96 and 0.86, respectively. The selection of suitable features determines the performance of ML models. RS-DT-FC2 may be a suitable FC for building a high-performance prediction model of PCAD with good sensitivity and accuracy. The nomograms allow practical scoring and interpretation of each predictor and may be useful for clinicians in determining the risk of PCAD.

Contribution of Genome-Wide Polygenic Score to Risk of Coronary Artery Disease in Childhood Cancer Survivors

BackgroundAdverse cardiovascular outcomes such as coronary artery disease (CAD) are the leading noncancer causes of morbidity and mortality among childhood cancer survivors. ObjectivesThe aim of this study was to assess the role of a genome-wide polygenic score (GPS) for CAD, well validated in the general population, and its interplay with cancer-related risk factors among childhood cancer survivors. MethodsIn a cohort study of 2,472 5-year childhood cancer survivors from the St. Jude Lifetime Cohort, the association between the GPS and the risk of CAD was performed using Cox regression models adjusted for age at cancer diagnosis, sex, cumulative dose of anthracyclines, and mean heart radiation dose. ResultsAmong survivors of European ancestry, the GPS was significantly associated with the risk of CAD (HR per 1 SD of the GPS: 1.25; 95% CI: 1.04-1.49; P = 0.014). Compared with the first tertile, survivors in the upper tertile had a greater risk of CAD (1.51-fold higher HR of CAD [95% CI: 0.96-2.37; P = 0.074]), although the difference was not statistically significant. The GPS-CAD association was stronger among survivors diagnosed with cancer at age <10 years exposed to >25 Gy heart radiation (HR top vs. bottom tertile of GPS: 15.49; 95% CI: 5.24-45.52; Ptrend = 0.005) but not among those diagnosed at age ≥10 years (Ptrend ≥ 0.77) and not among those diagnosed at age <10 years exposed to ≤25 Gy heart radiation (Ptrend = 0.23). Among high-risk survivors, defined by an estimated relative hazard ≥3.0 from fitted Cox models including clinical risk factors alone, the cumulative incidence of CAD at 40 years from diagnosis was 29% (95% CI: 13%-45%). After incorporating the GPS into the model, the cumulative incidence increased to 48% (95% CI: 26%-69%). ConclusionsChildhood cancer survivors are at risk for premature CAD. A GPS may help identify those who may benefit from targeted screening and personalized preventive interventions.

Association of various lipid parameters with premature coronary artery disease in men

Aim. To assess the relationship between premature coronary artery disease (CAD) and various lipid parameters.Material and methods. This retrospective longitudinal study included 166 men aged 57±9 years with coronary CAD with onset before age of 55. The control group consisted of 62 men (60±8 years old) who did not have CAD and peripheral arterial disease. In all patients, data on following lipid profile parameters were collected: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and lipoprotein(a) (Lp(a)) at the time of CAD onset, while in control group patients — at the first visit to the A.L. Myasnikov Institute of Clinical Cardiology. These indicators were measured in blood plasma at the time of enrollment in all patients. In addition, the concentration of LDL-C corrected for Lp(a)-cholesterol (LDL-Ccorr) was calculated. Hypercholesterolemia was diagnosed with an initial level of TC &gt;5 mmol/l, or LDL-C ≥3,0 mmol/l, or non-HDL-C ≥3,8 mmol/l, while hyperlipoproteinemia(a) (HLP(a)) — at the level of Lp(a) ≥30 mg/dl.Results. Lipid metabolism disorders were significantly more common in patients with premature CAD compared to the control group. Lp(a) concentration ≥30 mg/dl, along with elevated levels of non-HDL-C or LDL-Ccorr, were associated with premature CAD, regardless of heredity and smoking, in the general cohort of examined men. Kaplan-Meier survival analysis showed that any type of lipid metabolism disorder was associated with an increased risk of premature CAD. In addition, patients with isolated elevated Lp(a) concentrations lived to the CAD onset 8 years earlier — 47 vs 55 years, p&lt;0,02. The probability of premature CAD was maximum when the elevated level of non-HDL-C and HLP(a) was combined (hazard ratio, 2,91 (95% CI 1,96-4,33), p&lt;0,0001).Conclusion. HLP(a) is an independent factor of premature CAD, even with normolipidemia, which confirms the need for routine measurement of Lp(a) in clinical practice.

Lipoprotein(a) concentration and the blood content of INFγ-producing T-helpers 17 (Th17/1) in males with premature coronary artery disease

Aim. To analyze the relationship of blood lipid profile parameters, including the level of lipoprotein(a) (Lp(a)), and the content of circulating CD4+ T-lymphocytes with premature coronary artery disease (CAD).Material and methods. This retrospective cross-sectional study included 76 men aged 40 to 79 years. Patients were divided into following groups: main group — patients with CAD (58 [54;64] years, n=56) onset before the age of 55; control group — patients (62 [57;66] years, n=20) without CAD and obstructive CAD and peripheral arterial disease. Statins were taken by 51 (91%) and 9 (45%) patients in the main and control groups, respectively. In serum and plasma samples, lipid spectrum parameters and Lp(a) concentration were determined. Cellular phenotyping was performed by direct immunofluorescence in a culture of mononuclear leukocytes isolated from blood. To determine cytokines, cells were in vitro activated with inhibitor of intracellular transport of secretory proteins. Cell fluorescence was determined using flow cytometry.Results. Patients of both groups were comparable in age, body mass index, prevalence of hypertension and diabetes. Blood Lp(a) concentrations were higher in the CAD group than in the control group (49 [10;102] mg/dL vs 12 [4,3;32] mg/ dL, p&lt;0,05). The content of INFγ-producing T-helpers 17 (Th17/1) was also higher in the CAD group (19 [15;24] vs 13 [11;22], % of Th17, p=0,05). Logistic regression revealed that elevated Lp(a) levels (≥30 mg/dL) and relative amounts of Th17/1 (&gt;14% of Th17) independently of each other, atherogenic lipoprotein cholesterol levels, classical risk factors, and statin use were associated with premature CAD in the general group of patients with odds ratio (OR) of 4,6 (95% confidence interval (CI), 1,1-20,2) and 10,9 (2,1-56,7), p&lt;0,05, respectively. The combination of Lp(a) &gt;30 mg/dl and Th17/1 over 14% significantly increased the risk of premature CAD (OR, 28,0, 95% CI, 4,31-181,75, p=0,0005).Conclusion. We have shown for the first time that an increased Lp(a) concentration with an increased Th17/1 content is associated with the premature CAD in men.

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

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

Premature coronary artery disease in patients with immune-mediated inflammatory disease: a population-based study

BackgroundThe associations between premature atherosclerosis and immune-mediated inflammatory diseases (IMIDs) are not fully investigated. To determine whether IMIDs are associated with premature atherosclerosis, we examined the risk of incident coronary...

AB0081 ENDOTHELIAL MARKERS WITH DYSREGULATION IN SYSTEMIC LUPUS ERYTHEMATOSUS: A SYSTEMATIC LITERATURE REVIEW

Background:Systemic lupus erythematosus (SLE) is a severe, lifelong autoimmune disease known for its multisystem organ involvement. SLE patients are known to be at risk for premature atherosclerosis at a relatively young age (1). Endothelial dysregulation is one of the pathophysiologic mechanisms that can lead to the higher risk for cardiovascular disease in SLE (2). Multiple endothelial markers with dysregulation in SLE have been described so far, of which some are associated with disease activity.Objectives:To report a systematic literature review regarding endothelial markers that are dysregulated in SLE and search for associations with disease activity.Methods:The search was performed according to the Preferred Reporting Items for Systematic review and Meta-analysis Protocols (PRISMA-P) 2015 (3). In July 2020, the search terms were used in Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) published studies after the year 2000 that reported measurements of endothelial cell markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles and 3) disease activity measurement (i.e. SLEDAI, BILAG, SLAM, ECLAM or PGA). Exclusion criteria were 1) case reports or editorials, 2) studies performed in animals and 3) studies with microRNA/cytokine biomarkers. There was no minimum count for study population. The screening process is shown in figure 1.Results:From 1892 hits, we identified 110 eligible articles. Table 1 shows an overview of the most frequently studied endothelial markers. These identified endothelial markers are involved in endothelial cell (EC) activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. In most studies, dysregulation of the endothelial marker was associated with disease activity. The majority of the studies had a cross-sectional design, longitudinal data on endothelial markers in SLE are scarce.Conclusion:We identified multiple endothelial markers that are dysregulated in SLE and this dysregulation was often associated with disease activity in cross-sectional studies. Our future plan is to test the identified endothelial markers in (longitudinally collected) samples of (childhood onset) SLE patients, disease- and healthy controls. This will be a next step in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE-patients in young adulthood.Figure 1.

VDR Gene Polymorphisms in Healthy Individuals with Family History of Premature Coronary Artery Disease.

Aim The gene encoding the vitamin D receptor (VDR) is considered in many studies to be a good candidate responsible for susceptibility to several diseases such as coronary artery disease (CAD). Epidemiological data show that cardiovascular disease is one of the major health problems in Polish society. Basic studies show that genetic factors play a significant role in the pathogenesis of CAD. We conducted this clinical study to determine if the VDR gene polymorphisms TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570) could predispose healthy individuals to an increased risk of premature CAD (P-CAD) incidents. Methods We genotyped 845 subjects in a cohort consisting of 386 healthy volunteers with a documented P-CAD incident in their first-degree relatives and 459 healthy volunteers without family history (FH) of P-CAD. TaqI, ApaI, and FokI polymorphisms in VDR were genotyped using TaqMan assays and the endpoint genotyping method (qPCR). Statistical analyses were performed using the Power Analysis Software STATISTICA v.13.3. Results Although no statistical significance was found for TaqI and ApaI genotype frequencies, the AA genotype of FokI polymorphism was significantly more frequent in the study group compared to the control group (24.61% vs. 16.99%). The results of logistic regression analysis suggested a significant association between FokI polymorphism and FH of P-CAD in heathy people under the recessive model (OR: 1.26 (1.07-1.49, p = 0.007)); however, the frequency of VDR haplotypes did not differ significantly between the control and study populations. Conclusions FokI polymorphism is may be associated with FH of P-CAD. FokI polymorphism may predispose to the development of P-CAD among healthy people over the next years.

Cardiovascular risk knowledge in patients of South Asian origin living with rheumatoid arthritis: data from India and the UK

BackgroundSouth Asians have a higher risk of cardiovascular disease (CVD). Rheumatoid arthritis (RA) increases the risk of premature atherosclerosis. We investigated whether there was a substantial difference in the level of CVD risk knowledge among patients of South Asian origin with RA in India and in the UK.MethodsIn this cross-sectional survey, patients of South Asian origin with RA from India and the UK were recruited from secondary care settings. Data were collected via Heart Disease Fact Questionnaire-Rheumatoid Arthritis (HDFQ-RA), a validated self-completion questionnaire. The HDFQ-RA was translated into Hindi and piloted among patients from South Asian background before use. Additionally, clinical and demographic data was collected.ResultsAmong 118 patients from each country, 84% were female and they had similar age, education level, employment status and co-morbidities. Patients from India had longer disease duration (5.5 years versus 4.1 years (p = 0.012) whereas those from the UK had higher disease activity score (4.0 + 0.8 versus 3.1 + 0.7, p < 0.01). Regarding modifiable risk factors for CVD only 51.2% from India and 51.3% in the UK were aware of them. However, awareness of the link between RA and increased risk of CVD was even more limited (32.8% in India and 34.4% in UK).ConclusionPatients of South Asians origin with RA from both countries had limited knowledge about CVD risk. There is a need to educate them about CVD risk during consultation, as this will result in better outcomes.

Scavenger Receptor Class B Type 1 Gene rs5888 Single Nucleotide Polymorphism: Association with Risk and Severity of Premature Coronary Artery Disease

Background: Many different genetic associations with premature coronary artery disease (PCAD) have been identified. One exonic single nucleotide polymorphism (SNP) rs5888 of Scavenger receptor class B type1 (SCARB 1) gene has been linked to lipid traits as well as subclinical atherosclerosis. Objective: To investigate the association between SNP rs5888 of SCARB 1 gene and PCAD risk and severity. Patients and Methods: This study was conducted on 50 Egyptian patients diagnosed as PCAD by coronary angiograph (PCAD group) and (50) age- and sex-matched non-CAD subjects who showed no luminal stenosis in coronary angiographic served as a control group (non-CAD group). Gensini score was calculated as an indication for atherosclerosis severity for patients only. Detection of rs5888 polymorphism of SCARB 1 gene was done by realtime polymerase chain reaction (PCR) and high resolution melting analysis (HRM). Results: The mutant TT and CT genotypes were more frequently distributed in PCAD group compared to nonPCAD group (34 % and 48 % vs. 26 % and 18 %, respectively). The (CT) genotype conferred a positive risk for PCAD in males (OR: 6.117, 95% CI (1.744-21.452); p < 0.01). T allele conferred a positive risk for PCAD (OR: 2.564, 95% CI (1.440-4.543); p < 0.05). Highest Gensini score was found in PCAD patients with (TT) genotype (p < 0.01). Conclusion: The mutant (CT) genotype and the T allele of SCARB 1 SNP rs5888 were associated with increased risk of PCAD and the mutant (TT) genotype was associated with disease severity calculated by Gensini score.

Scavenger Receptor Class B Type 1 Gene rs5888 Single Nucleotide Polymorphism: Association with Risk and Severity of Premature Coronary Artery Disease

Background: Many different genetic associations with premature coronary artery disease (PCAD) have been identified. One exonic single nucleotide polymorphism (SNP) rs5888 of Scavenger receptor class B type1 (SCARB 1) gene has been linked to lipid traits as well as subclinical atherosclerosis. Objective: To investigate the association between SNP rs5888 of SCARB 1 gene and PCAD risk and severity. Patients and Methods: This study was conducted on 50 Egyptian patients diagnosed as PCAD by coronary angiograph (PCAD group) and (50) age- and sex-matched non-CAD subjects who showed no luminal stenosis in coronary angiographic served as a control group (non-CAD group). Gensini score was calculated as an indication for atherosclerosis severity for patients only. Detection of rs5888 polymorphism of SCARB 1 gene was done by realtime polymerase chain reaction (PCR) and high resolution melting analysis (HRM). Results: The mutant TT and CT genotypes were more frequently distributed in PCAD group compared to nonPCAD group (34 % and 48 % vs. 26 % and 18 %, respectively). The (CT) genotype conferred a positive risk for PCAD in males (OR: 6.117, 95% CI (1.744-21.452); p < 0.01). T allele conferred a positive risk for PCAD (OR: 2.564, 95% CI (1.440-4.543); p < 0.05). Highest Gensini score was found in PCAD patients with (TT) genotype (p < 0.01). Conclusion: The mutant (CT) genotype and the T allele of SCARB 1 SNP rs5888 were associated with increased risk of PCAD and the mutant (TT) genotype was associated with disease severity calculated by Gensini score.

Lipid-lowering therapy for primary prevention of premature atherosclerotic coronary artery disease: Eligibility, utilization, target achievement, and predictors of initiation

ObjectivesDespite advances in screening and prevention, rates of premature coronary artery disease (CAD) have been stagnant. The goals of this study were to investigate the barriers to early risk detection and preventive treatment in patients with premature CAD. In particular, we: 1) assessed the performance of the latest versions of major international guidelines in detection of risk of premature CAD and eligibility for preventive treatment; and, 2) investigated real-life utilization of primary prevention with lipid-lowering therapies in these patients. MethodsWe included patients in the Study to Avoid cardioVascular Events in British Columbia (SAVE BC), an observational study of patients with premature (males ​≤ ​50 years, females ​≤ ​55 years) angiographically confirmed CAD. Eligibility for primary prevention and treatment received were assessed retrospectively based on information recorded prior to or at the index presentation with CAD. ResultsOf 417 patients (28.1% females) who met the criteria, 94.3% had at least one major cardiovascular risk factor. In the retrospective risk assessment, 41.7%, 61.4%, and 34.3% (p ​< ​0.001) of patients met criteria for initiation of statin therapy, and an additional 13.9%, 8.4%, and 46.8% may be considered for treatment using the American College of Cardiology/American Heart Association, Canadian Cardiovascular Society, and European Society of Cardiology guidelines, respectively. Only 17.1% of patients received statins and 11.0% achieved guideline-recommended lipid goals before presentation. Diabetes and elevated plasma lipid levels were positively associated with treatment initiation, while smoking was associated with non-treatment. ConclusionsThe current versions of major guidelines fail to recognize many patients who develop premature CAD as being at risk. The vast majority of these patients, including patients who have guideline-directed indications, do not receive lipid-lowering therapy before presenting with CAD. Our findings highlight the need for more effective screening and prevention strategies for premature CAD.

Assessment of traditional and non-traditional risk factors for premature atherosclerosis in children with juvenile dermatomyositis and pediatric controls

BackgroundChildren with juvenile dermatomyositis (JDM), the most common inflammatory myopathy of childhood, may be at increased risk of premature atherosclerosis given a host of traditional and non-traditional risk factors. The primary aim of this study was to determine the underlying frequency of premature atherosclerosis in children with JDM compared to pediatric controls using flow-mediated dilation as a measure of endothelial function.MethodsChildren and adolescents with and without JDM were evaluated for traditional atherosclerotic risk factors and assessment of endothelial function, using Endothelial Pulse Amplitude Testing (Endo-PAT).ResultsIn this study, 75% of pediatric controls were of Black or Hispanic descent (compared to 55% in the JDM group) and 70% were found to live in a household with a medium income less than $50,000/year (compared to 45% in the JDM group). Among traditional atherogenic risk factors, lipoprotein A appeared to be different between controls and JDM patients (66 nmol/L and 16.5 nmol/L, respectively). Using a reactive hyperemia index (RHI) < 1.67 as evidence of endothelial dysfunction, 75% of controls were defined as having endothelial dysfunction compared to 50% in JDM group. When controlled for lipoprotein A as an atherogenic confounder, JDM patients were found to have a 41% increase in RHI, thus indicating less endothelial dysfunction compared to controls.ConclusionsIn this study, we have shown that atherogenic risk factors are present in the pediatric population and may be associated with endothelial dysfunction, even at very young ages. Despite increasing concerns that children with rheumatologic disorders may be at increased risk of developing premature atherosclerosis, traditional and sociodemographic features may play a greater role in the ultimate development of cardiovascular disease.