Elevated Coronary Artery Disease Risk Research Articles

Cluster analysis of adult individuals with type 1 diabetes: Treatment pathways and complications over a five-year follow-up period

AimsTo identify subgroups of adults with type 1 diabetes and analyse their treatment pathways and risk of diabetes-related complications over a 5-year follow-up. MethodsWe performed a k-means cluster analysis using the T1DExchange Registry (n = 6,302) to identify subgroups based on demographic and clinical characteristics. Annual reassessments linked treatment trajectories with these clusters, considering drug and technology use. Complication risks were analysed using Cox regression. ResultsFive clusters were identified: 1) A favourable combination of all variables (31.67 %); 2) Longer diabetes duration (22.63 %); 3) Higher HbA1c levels (13.28 %); 4) Higher BMI (15.25 %); 5) Older age at diagnosis (17.17 %). Two-thirds of patients remained in their initial cluster annually. Technology adoption showed improved glycaemic control over time. Cox proportional hazards showed different risk patterns: Cluster 1 had low complication risk; Cluster 2 had the highest risk for retinopathy, coronary artery disease and autonomic neuropathy; Cluster 3 had the highest risk for albuminuria, depression and diabetic ketoacidosis; Cluster 4 had increased risk for multiple complications; Cluster 5 had the highest risk for hypertension and severe hypoglycaemia, with elevated coronary artery disease risk. ConclusionsClinical characteristics can identify subgroups of patients with T1DM showing differences in treatment and complications during follow-up.

Relationship between Parkinson’s disease and cardio-cerebrovascular diseases: a Mendelian randomized study

Parkinson’s disease (PD) and cardio-cerebrovascular diseases are related, according to earlier studies, but these studies have some controversy. Our aim was to assess the impact of PD on cardiocerebrovascular diseases using a Mendelian randomization (MR) method. The data for PD were single nucleotide polymorphisms (SNPs) from a publicly available genome-wide association study (GWAS) dataset containing data on 482,730 individuals. And the outcome SNPs data is were derived from five different GWAS datasets. The basic method for MR analysis was the inverse variance weighted (IVW) approach. We use the weighted median method and the MR-Egger method to supplement the MR analysis conclusion. Finally, We used Cochran’s Q test to test heterogeneity, MR-PRESSO method and leave-one-out analysis method to perform sensitivity analysis. We used ratio ratios (OR) to assess the strength of the association between exposure and outcome, and 95% confidence intervals (CI) to show the reliability of the results. Our findings imply that PD is linked to a higher occurrence of coronary artery disease (CAD) (OR = 1.055, 95% CI 1.020–1.091, P = 0.001), stroke (OR = 1.039, 95% CI 1.007–1.072, P = 0.014). IVW analyses for stroke’s subgroups of ischemic stroke (IS) and 95% CI 1.007–1.072, P = 0.014). IVW analyses for stroke’s subgroups of ischemic stroke (IS) and cardioembolic stroke (CES) also yielded positive results, respectively (OR = 1.043, 95% CI 1.008–1.079, P = 0.013), (OR = 1.076, 95% CI 1.008–1.149, P = 0.026). There is no evidence of a relationship between PD and other cardio-cerebrovascular diseases. Additionally, sensitivity analysis revealed reliable outcomes. Our MR study analysis that PD is related with an elevated risk of CAD, stroke, IS, and CES.

CDKN2B-AS (rs2891168), SOD2 (rs4880), and PON1 (rs662) polymorphisms and susceptibility to coronary artery disease and type 2 diabetes mellitus in Iranian patients: A case-control study.

Coronary artery disease (CAD) is a devastating illness and primary cause of death worldwide that arises from a combination of genetic and environmental factors. Several large-scale studies found that 9p21.3, superoxide dismutase 2 (SOD2), and paraoxonase 1 (PON1) polymorphisms increase type 2 diabetes mellitus (T2DM) and/or coronary artery disease (CAD) risk. Our research aimed to investigate whether the SNPs of the 9p21.3 locus (rs28911698), SOD2 (rs4880), and PON1 (rs662) genes were associated with the risk of T2DM and/or CAD in the Iranian population. In this case-control study four group subjects including patients with CAD non-T2DM, with CAD and T2DM, non-CAD with T2DM, and non-CAD non-T2DM were recruited to the study from 2019 to 2020. Molecular analysis was carried out by allele specific-polymerase chain reaction (AS-PCR) technique for rs4880, Taqman genotyping assay for rs2891168, and PCR followed by restriction fragment length polymorphism (PCR-RFLP) technique for rs662. The rs2891168 polymorphism presented an elevated risk of CAD in non-T2DM with CAD and with T2DM CAD groups compared to the non-T2DM non-CAD group with GG genotype and dominant model after adjustment (p < 0.05). G-allele in PON1 rs662 polymorphism associated with increased risk of T2DM in T2DM non-CAD, and T2DM CAD groups compared to non-T2DM non-CAD group with dominant model, GG and AG genotypes (p < 0.05). However, SOD2 rs4880 polymorphism presented no significant association with the development of diabetes or CAD. These results provide a prime witness that rs2891168 and rs662 gene variants might have a possible increased risk of CAD and T2DM occurrence, respectively. To obtain more definitive and accurate results in this area, further research is required.

Genetic Predisposition, Sedentary Behavior and Incident Coronary Artery Disease: A Prospective Chinese Cohort Study.

Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST), and further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups. This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models. During a median follow-up of 11.60 years, 1156 CAD events were documented.Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95%CI: 0.27-1.28). Compared with participants with low genetic risk and low ST (<6 h/day), those with high genetic risk and high ST (≥10 h/day) had the highest CAD risk, with the hazard ratio (HR) and 95% confidence interval (95%CI) of 4.22 (2.65-6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with the HR (95%CI) of 1.21 (0.61-2.40), 1.57 (1.14-2.16), and 2.15 (1.40-3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST (Ptrend = 0.024). Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk.

Association between length of daily siesta and brachial-ankle pulse wave velocity (baPWV): a community-based cross sectional study in North China.

To date, many studies have showna link between siesta andcardiovascular events. Little is known regarding the connection between siesta and brachial-ankle pulse wave velocity (baPWV) levels, even though baPWV can determinethe degree ofatherosclerosis and vascular stiffness. Thus, we examined the relationship between siestatime and baPWV in a cross-sectional study. Interviews, physical examinations, lab testing, and electron beam computed tomography were all part of the baseline evaluation forparticipants aged older than 35. Baseline data were compared for 3different siesta habits: irregular or no siestas, daily short siestas (1h or less), and daily long siestas (> 1h). Utilizing logistic regression models and multivariate linear regression, the link between siestatime and baPWV was determined. Among all 6566participants, the different siesta groups had a significant difference of the degrees of AS (P < 0.001). The same outcome was true for both males (P < 0.001) and females (P < 0.001). Numerous cardiovascular risk variables and markers of subclinical atherosclerosis were positively correlated with daily extended siestas. Results from thefully adjusted model showed that long siestas (> 60min, OR = 1.18, 95%CI: 1.06-1.31, P = 0.002) were linked to a more severe level of the baPWV. For age or gender stratification, we found significant differences between non-siesta and > 60min siesta groups. Multiple linear regression analysis revealed a positive connection between siesta duration and baPWV (β = 0.197, P = 0.038). An elevated risk of atherosclerosis was shown to accompany prolonged siestas. These results need to be followed up on with prospective studies and additional lab work.

Lipid phosphate phosphatase 3 maintains NO-mediated flow-mediated dilatation in human adipose resistance arterioles.

Microvascular dysfunction predicts adverse cardiovascular events despite absence of large vessel disease. A shift in the mediator of flow-mediated dilatation (FMD) from nitric oxide (NO) to mitochondrial-derived hydrogen peroxide (H2 O2 ) occurs in arterioles from patients with coronary artery disease (CAD). The underlying mechanisms governing this shift are not completely defined. Lipid phosphate phosphatase 3 (LPP3) is a transmembrane protein that dephosphorylates lysophosphatidic acid, a bioactive lipid, causing a receptor-mediated increase in reactive oxygen species. A single nucleotide loss-of-function polymorphism in the gene coding for LPP3 (rs17114036) is associated with elevated risk for CAD, independent of traditional risk factors. LPP3 is suppressed by miR-92a, which is elevated in the circulation of patients with CAD. Repression of LPP3 increases vascular inflammation and atherosclerosis in animal models. We investigated the role of LPP3 and miR-92a as a mechanism for microvascular dysfunction in CAD. We hypothesized that modulation of LPP3 is critically involved in the disease-associated shift in mediator of FMD. LPP3 protein expression was reduced in left ventricle tissue from CAD relative to non-CAD patients (P=0.004), with mRNA expression unchanged (P=0.96). Reducing LPP3 expression (non-CAD) caused a shift from NO to H2 O2 (% maximal dilatation: Control 78.1±11.4% vs. Peg-Cat 30.0±11.2%; P<0.0001). miR-92a is elevated in CAD arterioles (fold change: 1.9±0.01 P=0.04), while inhibition of miR-92a restored NO-mediated FMD (CAD), and enhancing miR-92a expression (non-CAD) elicited H2 O2 -mediated dilatation (P<0.0001). Our data suggests LPP3 is crucial in the disease-associated switch in the mediator of FMD. KEY POINTS: Lipid phosphate phosphatase 3 (LPP3) expression is reduced in heart tissuepatients with coronary artery disease (CAD). Loss of LPP3 in CAD is associated with an increase in the LPP3 inhibitor, miR-92a. Inhibition of LPP3 in the microvasculature of healthy patients mimics the CAD flow-mediated dilatation (FMD) phenotype. Inhibition of miR-92a restores nitric oxide-mediated FMD in the microvasculature of CAD patients.

Evaluating the use of novel atherogenicity indices and insulin resistance surrogate markers in predicting the risk of coronary artery disease: a case‒control investigation with comparison to traditional biomarkers

BackgroundDue to the contribution of coronary artery disease (CAD) to serious cardiovascular events, determining biomarkers that could robustly predict its risk would be of utmost importance. Thus, this research was designed to assess the value of traditional cardio-metabolic indices, and more novel atherogenicity indices and insulin resistance surrogate markers in the identification of individuals at risk of CAD.MethodsA case‒control survey was conducted, in which 3085 individuals were enrolled. Their clinical and biochemical data were gathered at baseline. The investigated indices included the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), lipoprotein combine index (LCI), cholesterol index (CHOLINDEX), Castelli’s risk indices-I, II (CRI-I, CRI-II), and metabolic score for insulin resistance (METS − IR). To examine the relationship between these variables and CAD risk, multiple regression analyses adjusted for potential confounders were conducted.ResultsOverall, 774 angiographically confirmed CAD patients (mean age = 54 years) were compared with 3085 controls (mean age = 51 years). Higher triglyceride, total cholesterol and fasting blood sugar levels and lower HDL-C levels were related to an elevated risk of CAD (P-for-trend < 0.001), while the direct association between increased serum LDL-C concentrations and a greater risk of CAD only became apparent when excluding those with diabetes, and statin users. Among novel indices, greater values of the majority of these markers, including AIP, CRI-I, and -II, CHOLINDEX, LCI, and TyG-index, in comparison to the lower values, significantly elevated CAD risk (P-for-trend < 0.001).ConclusionAccording to the current findings, novel atherogenicity indices and insulin resistance surrogate markers, in particular, AIP, CRI-I and II, CHOLINDEX, LCI, and TyG-index, may be useful in predicting CAD risk.

New Trends and Therapies for Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is associated with an elevated risk of atherosclerosis. The finding of monogenic defects indicates higher atherosclerotic risk in comparison with hypercholesterolemia of other etiologies. However, in heterozygous FH, cardiovascular risk is heterogeneous and depends not only on high cholesterol levels but also on the presence of other biomarkers and genes. The development of atherosclerosis risk scores specific for heterozygous FH and the use of subclinical coronary atherosclerosis imaging help with identifying higher-risk individuals who may benefit from further cholesterol lowering with PCSK9 inhibitors. There is no question about the extreme high risk in homozygous FH, and intensive LDL-cholesterol-lowering therapy must be started as soon as possible. These patients have gained life free of events in comparison with the past, but a high atherosclerosis residual risk persists. Furthermore, there is also the issue of aortic and supra-aortic valve disease development. Newer therapies such as inhibitors of microsomal transfer protein and angiopoietin-like protein 3 have opened the possibility of LDL-cholesterol normalization in homozygous FH and may provide an alternative to lipoprotein apheresis for these patients. Gene-based therapies may provide more definite solutions for lowering high LDL cholesterol and consequent atherosclerosis risk for people with FH.

Antiplatelet Effects of PCSK9 Inhibitors in Primary Hypercholesterolemia.

Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel group of hypolipidemic drugs that are recommended particularly for high-risk hypercholesterolemia patients, including those with primary hypercholesterolemia (PH), where lifelong exposure to high low-density lipoprotein (LDL) cholesterol levels results in an elevated risk of atherosclerosis at an early age. The onset and progression of atherosclerosis is significantly influenced by activated platelets. Oxidized LDL influences platelet activation by interacting with their surface receptors and remodeling the composition of their cell membrane. This results in platelet aggregation, endothelial cell activation, promotion of inflammation and oxidative stress, and acceleration of lipid accumulation in atherosclerotic plaques. PCSK9 inhibitors reduce platelet activation by both significantly lowering LDL levels and reducing the LDL receptor-mediated activation of platelets by PCSK9. They also work synergistically with other hypolipidemic and antithrombotic drugs, including statins, ezetimibe, acetylsalicylic acid, clopidogrel, and ticagrelor, which enhances their antiplatelet and LDL-lowering effects. In this review, we summarize the currently available evidence on platelet hyperreactivity in PH, the effects of PCSK9 inhibitors on platelets, and their synergism with other drugs used in PH therapy.

Alteration of type I interferon response is associated with subclinical atherosclerosis in virologically suppressed HIV-1-infected male patients.

Given human immunodeficiency virus‐1 (HIV‐1)‐infected patients have alterations in the type I interferon (IFN‐I) pathway and are also at elevated risk of atherosclerosis, we evaluated IFN‐I response and subclinical cardiovascular disease (CVD) association in HIV‐1‐infected patients. Transcript levels of IFN‐α/β and IFN‐stimulated gene 56 (ISG56) were evaluated by RT/real‐time PCR in peripheral blood mononuclear cells collected from asymptomatic HIV‐1‐positive male patients at high risk of developing CVD (n = 34) and healthy subjects (n = 21). Stenosis degree (≥ or <50%), calcium volume score, calcium Agatston score, and myocardial extracellular volume were examined by coronary computerized tomography scan. Carotid intima‐media thickness (cIMT), Framingham risk score, atherosclerotic cardiovascular disease (ASCVD) score, and risk score developed by data collection on adverse effects of anti‐HIV drugs (D:A:D) were also measured. Increased IFN‐α, IFN‐β, and ISG56 levels were observed in all HIV‐1‐infected males compared to healthy controls (p < .001 for all genes analyzed). HIV‐1‐infected patients with a stenosis degree ≥50% showed a higher Framingham risk score (p = .019), which was correlated with IFN‐β and ISG56 levels. HIV‐1‐infected males with enhanced IFN‐I levels and stenosis displayed a higher ASCVD calculated risk (p = .011) and D:A:D score (p = .004). Also, there was a trend toward higher IFN‐α and ISG56 mRNA levels in HIV‐1‐positive patients with an increased cIMT (p > .05). Dysregulation of IFN‐I response might participate in the pathogenesis of HIV‐1‐associated CVD.

Oral Administration of Succinoglycan Riclin Improves Diet-Induced Hypercholesterolemia in Mice.

Epidemiological studies have demonstrated that hypercholesterolemia is associated with an elevated risk of atherosclerosis and cardiovascular diseases. In addition to the available cholesterol-lowering drugs, nutritionally balanced diets containing functional foods have attracted much interest as potential candidates to improve hypercholesterolemia. In the study, we demonstrated that dietary succinoglycan riclin effectively alleviated diet-induced hypercholesterolemia. Compared with the high-cholesterol-diet (HCD) group, the high-riclin group significantly decreased levels of the serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and hepatic cholesterol (34, 40, and 51%, respectively), consequently improving hepatic steatosis and reducing proinflammatory cytokine expressions. 1H nuclear magnetic resonance (NMR)-based lipidomics and metabolomics analyses revealed that the riclin group partially reversed metabolic profile changes induced by the HCD, approaching that of the normal diet (ND) group. Riclin has no direct effects on cholesterol metabolism-related gene expression among the three HCD model groups. Basically, riclin increased the solution viscosity and interfered in the process of bile acid-cholesterol emulsification, decreasing cholesterol digestion and promoting cholesterol and bile acid excretion in the feces. These results suggested potential therapeutic utility of succinoglycan riclin as a food additive for people suffering from hypercholesterolemia and related diseases.

Acyl-CoA: cholesterol acyltransferases-2 gene polymorphism is associated with increased susceptibility to coronary artery disease in Uygur population in Xinjiang, China.

Background: Acyl-CoA: cholesterol acyltransferases (ACAT) is the only enzyme that catalyzes the synthesis of cholesterol esters (CE) from free cholesterol and long-chain fatty acyl-CoA and plays a critical role in cellular cholesterol homeostasis. In the present study, our primary objective was to explore whether the single-nucleotide polymorphisms (SNPs) in ACAT-2 gene were associated with coronary artery disease (CAD) in Uygur subjects, in Xinjiang, China.Methods: We designed a case–control study including 516 CAD patients and 318 age- and sex-matched control subjects. Using the improved multiplex ligation detection reaction (iMLDR) method, we genotyped two SNPs (rs28765985 and rs7308390) of ACAT-2 gene in all subjects.Results: We found that the genotypes, the dominant model (CC + CT vs TT) and over-dominant model (CT vs CC + TT) of rs28765985 were significantly different between CAD patients and the controls (P=0.027, P=0.012 and P=0.035, respectively). The rs28765985 C allele was associated with a significantly elevated CAD risk [CC/CT vs TT: odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.02–2.16, P=0.04] after adjustment for confounders. The TC and LDL-C levels were significantly higher in rs28765985 CC/CT genotypes than that in TT genotypes (P<0.05).Conclusions: Rs28765985 of ACAT-2 gene are associated with CAD in Uygur subjects. Subjects with CC/CT genotype or C allele of rs28765985 were associated with an increased risk of CAD.

Pilot Study of Novel Intermittent Fasting Effects on Metabolomic and Trimethylamine N-oxide Changes During 24-hour Water-Only Fasting in the FEELGOOD Trial.

Intermittent fasting (IF) has been connected with health benefits such as weight loss, lower risk of coronary artery disease (CAD) and diabetes, increased longevity, and improved quality of life. However, the mechanisms of these IF benefits in humans require further investigation. This study sought to elucidate some of these mechanisms through secondary analyses of the Fasting and ExprEssion of Longevity Genes during fOOD abstinence (FEELGOOD) trial, in which apparently healthy participants were randomized in a Latin square design to a 24-h water-only fast and a 24-h ad libitum fed day. Two pathways were investigated, with trimethylamine N-oxide (TMAO) levels measured due to their association with elevated risk of CAD, along with conductance of a broad panel of metabolic analytes. Measurements were made at baseline, at the end of the fasting day, and at the end of the fed day. A fasting mean of 14.3 ng in TMAO was found versus the baseline mean of 27.1 ng with p = 0.019, although TMAO levels returned to baseline on refeeding. Further, acute alterations in levels of proline, tyrosine, galactitol, and urea plasma levels were observed along with changes in 24 other metabolites during the fasting period. These acute changes reveal short-term mechanisms which, with consistent repeated episodes of IF, may lead to improved health and reduced risk of CAD and diabetes.

Genomic Risk Stratification Predicts All-Cause Mortality After Cardiac Catheterization.

Coronary artery disease (CAD) is influenced by genetic variation and traditional risk factors. Polygenic risk scores (PRS), which can be ascertained before the development of traditional risk factors, have been shown to identify individuals at elevated risk of CAD. Here, we demonstrate that a genome-wide PRS for CAD predicts all-cause mortality after accounting for not only traditional cardiovascular risk factors but also angiographic CAD itself. Individuals who underwent coronary angiography and were enrolled in an institutional biobank were included; those with prior myocardial infarction or heart transplant were excluded. Using a pruning-and-thresholding approach, a genome-wide PRS comprised of 139 239 variants was calculated for 1503 participants who underwent coronary angiography and genotyping. Individuals were categorized into high PRS (hiPRS) and low-PRS control groups using the maximally selected rank statistic. Stratified analysis based on angiographic findings was also performed. The primary outcome was all-cause mortality following the index coronary angiogram. Individuals with hiPRS were younger than controls (66 years versus 69 years; P=2.1×10-5) but did not differ by sex, body mass index, or traditional risk-factor profiles. Individuals with hiPRS were at significantly increased risk of all-cause mortality after cardiac catheterization, adjusting for traditional risk factors and angiographic extent of CAD (hazard ratio, 1.6; 95% CI, 1.2-2.2; P=0.004). The strongest increase in risk of all-cause mortality conferred by hiPRS was seen among individuals without angiographic CAD (hazard ratio, 2.4; 95% CI, 1.1-5.5; P=0.04). In the overall cohort, adding hiPRS to traditional risk assessment improved prediction of 5-year all-cause mortality (area under the receiver-operating curve 0.70; 95% CI, 0.66-0.75 versus 0.66; 95% CI, 0.61-0.70; P=0.001). A genome-wide PRS improves risk stratification when added to traditional risk factors and coronary angiography. Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality.

Risk of Coronary Artery Disease in Patients With Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis

BackgroundThe association between chronic inflammation and the accelerated development of atherosclerosis is well recognized. However, it remains controversial as to whether the risk of coronary artery disease (CAD) is elevated in patients with systemic lupus erythematosus (SLE). The objective of this meta-analysis was to obtain a better estimate of the risk of CAD in patients with SLE. MethodsAn English-restricted literature review was conducted according to PRISMA guidelines using key databases, surveying all articles published through October 31, 2017. Specific search terms included “SLE” and “coronary artery disease” as well as appropriate MeSH terms. The Newcastle-Ottawa scale was used for quality assessment. ResultsNine studies were identified and included in this meta-analysis. The pooled risk ratio of CAD in patients with SLE was 3.39 (95% CI: 2.15–5.35). The statistical heterogeneity of this meta-analysis was high, with an I2 value of 79.5%. An elevated risk of CAD was consistently observed in both female and male SLE patients (pooled risk ratio: 3.27 [95% CI: 2.01–5.30] and 3.16 [95% CI: 2.02–4.94], respectively). ConclusionsSLE patients are at significantly higher risk of developing CAD. However, as relatively few studies were available for incorporation into this meta-analysis, there is a clear need for further studies with larger sample sizes that better parse gender-related differences in CAD susceptibility among SLE patients. Future work to standardize cardiovascular risk factor identification and monitoring in SLE patients is also needed.

Association of genetic polymorphisms in vascular endothelial growth factor with susceptibility to coronary artery disease: a meta\u2013analysis

BackgroundSingle nucleotide polymorphisms (SNPs) located in the vascular endothelial growth factor (VEGF) gene may be correlated with the susceptibility to coronary artery disease (CAD) – although results have been controversial. The aim of this meta–analysis is to clarify the effects of VEGF –2578A/C (rs699947), −1154G/A (rs1570360), +405C/G (rs2010963), and + 936C/T (rs3025039) polymorphisms on CAD risk.MethodsPooled odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated to estimate the strength of the association between VEGF gene polymorphisms and CAD risk. Fixed- or random-effects model was used depending on the heterogeneity between studies.ResultsIn total, 13 eligible articles containing 29 studies were analysed. The pooled analysis indicated that the VEGF gene polymorphisms of rs699947, rs2010963, and rs3025039 were associated with an increased risk of CAD, whereas no significant associations were observed with the rs1570360 polymorphism. A subgroup analysis stratified by ethnicity revealed that the rs699947 and rs3025039 polymorphisms were associated with CAD risk in Asian populations. In addition, stratification by control source indicated an increased risk of CAD susceptibility with the rs699947 polymorphism for population–based studies of reduced heterogeneity.ConclusionsIn summary, we concluded that the VEGF gene polymorphisms rs699947, rs2010963, and rs3025039 are correlated with an elevated CAD risk.

Interactions between ALDH2 rs671 polymorphism and lifestyle behaviors on coronary artery disease risk in a Chinese Han population with dyslipidemia: A guide to targeted heart health management

BackgroundBoth aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism and lifestyle behaviors are involved in coronary artery disease (CAD), while the interaction between them is currently unknown.MethodsA nested case-control study was conducted in 161 patients with CAD and 495 controls in dyslipidemia population in Yinzhou District, Ningbo, Zhejiang Province, China, in August 2013. Anthropometric data and blood samples were collected, demographic characteristics and lifestyle behaviors information were obtained by a face-to-face interview, dietary intake was assessed by a food frequency questionnaire, and genomic DNA was genotyped.ResultsCarriers with increasing number of A alleles had an elevated CAD risk compared with G allele carriers (adjusted OR = 1.483, 95% CI = 1.114–1.974). Carriers of rs671 A/G and A/A genotypes had a higher CAD risk than carriers of G/G genotype (adjusted OR = 1.492, 95% CI = 1.036–2.148). Similarly, individuals with rs671 A/A genotype had a higher CAD risk than individuals with A/G and G/G genotypes (adjusted OR = 2.161, 95% CI = 1.139–4.101). We found a borderline additive interaction between regular fried food intake and A/A and A/G genotypes, and a significantly additive interaction between sedentary/light physical activity and A/A and A/G genotypes.ConclusionsIndividuals with A/A or A/G genotypes of rs671 have a higher CAD risk, if they lack physical activity and take fried food regularly, than individuals with G/G genotypes. These findings can help to provide a guide to targeted heart health management.

Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians

Background: Coronary artery disease (CAD) is a complex metabolic disorder in which lifestyle and genetic factors are known to play key roles in pathogenesis. The paraoxonase 1 (PON1) enzyme has a defensive effect against CAD progression, as it safeguards low-density lipoproteins (LDLs) from oxidative modifications. The most extensively studied genetic variants in the PON1 gene are Q192R and L55M, which have been related with LDL antioxidative activity and risk of CAD. Objective: The present case-control study intended to examine the Q192R and L55M polymorphisms and their association with the risk of CAD patients in north Indians. Methods: A total of 872 subjects (412 CAD patients and 460 controls) were recruited from north India. The PON1 gene was amplified and genotypes were studies using PCR-RFLP. χ² analysis was performed to compare genotype/allele frequencies in patients and controls. Results: The present study indicated abdominal obesity, elevated body mass index, and dyslipidemia with increased levels of total cholesterol and triglycerides as well as reduced high-density lipoprotein cholesterol in CAD subjects compared to healthy controls (p < 0.05). Logistic regression analysis of the data revealed an association of the RR genotype of the Q192R polymorphism with an about 2-fold elevated risk of CAD (OR = 2.23, 95% CI = 1.47–3.37, p = 0.0001). Contrariwise, the L55M polymorphism did not show significant association with CAD (OR = 1.81, 95% CI = 0.66–4.95, p = 0.326). Conclusions: The Q192R polymorphism in the PON1 gene may be a susceptibility gene associated with increased risk of CAD in an Asian Indian population.

ACAT-1 gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a case-control study.

Several studies suggest an important role of Acyl-CoA: cholesterol acyltransferase-1(ACAT-1) in the development of atherosclerosis. The aim of present study was to investigate whether there exists a possible correlation between genetic variations in ACAT-1 genes and coronary artery disease (CAD) risk. Four polymorphisms (rs1044925, rs11545566, rs12121758 and rs10913733) were finally selected and genotyped in 750 CAD patients and 580 health controls, using the improved multiplex ligation detection reaction (iMLDR) method. We found that the rs11545566 G allele was associated with a significantly elevated CAD risk [GG vs. AA: adjusted odds ratio (AOR) = 1.62, 95% confidence interval (CI) = 1.13-2.32, P = 0.008; GA/GG vs. AA: AOR = 1.67, 95% CI = 1.22-2.29, P = 0.001]. The rs10913733 G allele was also associated with a significantly elevated CAD risk (GG vs. TT: AOR = 1.57, 95% CI = 1.08-2.28, P = 0.018; GT/GG vs. TT: AOR = 1.39, 95% CI = 1.07-1.79, P = 0.013). Multivariate linear regression analysis showed that the rs11545566 polymorphism was independently associated with the Gensini scores (P = 0.005). The Gensini score of subjects in the variant GG genotype group and the GG/GA genotype group were higher than the score of subjects in the AA genotype group (32.49 ± 26.60 and 31.26 ± 26.96 vs. 23.45 ± 21.64; P = 0.001 and 0.002, respectively). Our results demonstrate that ACAT-1 rs1154556 and rs10913733 polymorphism are novel genetic factors in the development of CAD. Rs11545566 was also associated with the severity of CAD.

Type 2 Diabetes in Young Females Results in Increased Serum Amyloid A and Changes to Features of High Density Lipoproteins in Both HDL2 and HDL3.

Persons with type 2 diabetes mellitus (T2DM) have an elevated risk of atherosclerosis. High-density lipoproteins (HDL) normally protect against cardiovascular disease (CVD), but this may be attenuated by serum amyloid A (SAA). In a case-control study of young females, blood samples were compared between subjects with T2DM (n = 42) and individuals without T2DM (n = 42). SAA and apolipoprotein AI (apoAI) concentrations, paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP), and lecithin-cholesterol acyltransferase (LCAT) activities were measured in the serum and/or HDL2 and HDL3 subfractions. SAA concentrations were higher in T2DM compared to controls: serum (30 mg/L (17, 68) versus 15 mg/L (7, 36); p = 0.002), HDL2 (1.0 mg/L (0.6, 2.2) versus 0.4 mg/L (0.2, 0.7); p < 0.001), and HDL3, (13 mg/L (8, 29) versus 6 mg/L (3, 13); p < 0.001). Serum-PON-1 activity was lower in T2DM compared to that in controls (38,245 U/L (7025) versus 41,109 U/L (5690); p = 0.043). CETP activity was higher in T2DM versus controls in HDL2 (232.6 μmol/L (14.1) versus 217.1 μmol/L (25.1); p = 0.001) and HDL3 (279.5 μmol/L (17.7) versus 245.2 μmol/L (41.2); p < 0.001). These results suggest that individuals with T2DM have increased SAA-related inflammation and dysfunctional HDL features. SAA may prove to be a useful biomarker in T2DM given its association with elevated CVD risk.