Increased Risk Of Atherosclerosis Research Articles

Investigating the Relationship Between Cigarettes and Hookah Smoking with Coronary Artery Disease

Background: Cardiovascular disease (CVD) is recognized as a leading global cause of mortality, with tobacco use being one of the established risk factors responsible for 29% of related deaths. Although tobacco smoking, particularly through hookah, is increasing globally, limited data are available to evaluate its impact on CVD. This study aimed to investigate the relationship between cigarette and hookah smoking and coronary artery disease (CAD). Objectives: This study evaluated the relationship between cigarette and hookah smoking and coronary artery involvement based on coronary angiography findings. Methods: In this hospital-based cross-sectional study, 256 patients were included, with 128 patients in the CAD group (showing at least 50% stenosis in the left main artery or over 70% stenosis in other coronary arteries) and 128 patients in the normal angiography group. We assessed their smoking status, categorizing participants as current smokers, ex-smokers, or never-smokers. To ensure the collection of accurate and reliable data, we conducted face-to-face interviews, observations, and administered a questionnaire and medical checklist. Results: Based on multivariable logistic regression models, after adjusting for additional risk factors, individuals who smoked exhibited an approximately eight-fold higher likelihood of developing CAD compared to non-smokers. Additionally, hookah users showed a five-fold increase in CAD risk compared to non-hookah users (P = 0.001). Conclusions: Cigarette and hookah smoking are significantly associated with CAD, with cigarette smoking showing a comparatively stronger association with CAD than hookah use when considering other risk factors.

Abstract 4137682: Genome wide association study for residualized apolipoprotein B elucidates its role in coronary artery disease risk

Background: Recent studies have shown apolipoprotein B (ApoB), the principle atherogenic lipoproteins, to have greater predictive ability for coronary artery disease (CAD) risk over standard lipid parameters. Moreover, discordantly high ApoB relative to Low-density lipoprotein cholesterol (LDLC) has repeatedly been associated with increased CAD risk. Aim: Given the strong genetic effects of ApoB and LDLC, we sought to characterize the discordance between ApoB and LDLC by genetics to obtain mechanistic insights into this emerging risk factor. Method: We derived residualized-ApoB regressing ApoB on LDLC in European-like populations (N = 383,500) in the UK Biobank. Using residualized-ApoB as an outcome, we explored clinical associations and conducted genome wide association study (GWAS). Result: Residualized-ApoB only modestly correlated with ApoB and LDLC (Spearman’s rho = 0.248 and -0.0079 respectively). We observed increased residualized-ApoB in males and individuals with lipid lowering therapy. Increased residualized-ApoB was associated with increased risk for CAD [Odds Ratio; 1.25 (95% Confidence interval 1.23-1.27)] independent from LDLC, ApoB, and Triglycerides. By GWAS, we observed significant heritability for residualized-ApoB [h 2 = 12.3 (SE 0.012)] and 195 significantly associated genetic loci ( P < 5 × 10 -8 ). Only 59 of these lead variants were associated with ApoB or LDLC. We also found different effects in ApoB-related loci. For example, ApoB-increasing alleles at APOB (rs533617) and APOE (rs7412) loci increased residualized-ApoB but ApoB-increasing alleles at ABCG8 (rs4245791) and HAPLN4-TM6SF2 (rs150641967) loci decreased residualized-ApoB. Conclusions: Exploiting genetics, we determined significant heritability of residualized-ApoB which was partially correlated with ApoB/LDLC. We identified distinct effects of genetic variants on residualized-ApoB. Our results provide the clues for further precise understanding of regulatory mechanisms between ApoB and LDLC.

Abstract 4128377: Association between Mean Platelet Volume (MPV) and coronary artery disease: An analysis of NHANEs 2017-2020

Background: Recent data showed that mean platelet volume (MPV) is linked to mortality after myocardial infarction and restenosis following coronary angioplasty. However, its association with coronary artery disease (CAD) remains unclear. Therefore, we aim to investigate the association between MPV and CAD using a nationwide database. Methods: We analyzed retrospective cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020, including participants aged 18 years and older. The data on MPV were classified into three groups: below the 10th percentile (P10), between the 10th and 90th percentiles (P10 to P90), and above the 90th percentile (P90). Univariable and multivariable logistic regression models were utilized to identify the association between MPV and CAD. Results: A total of 12,156 patients with MPV results were identified. Their mean age was 37 ± 24 years, with females constituting 51.0% of the population. The racial distribution was primarily White at 33.8%, Black at 25.7%, Mexican American at 13.2%, Asian at 10.7%, and other races at 16.6%. The participants were categorized into three MPV groups: below P10 (11.2%), P10 to P90 (77.3%), and above P90 (11.5%), with median MPV values of 6.8, 8, and 9.7 fL, respectively. In a univariable analysis using participants with MPV in the P10 to P90 as a reference, those with MPV above the 90th percentile had a significantly higher risk of CAD, with an OR of 1.39 (P90-MPV: 95% CI 1.05, 1.83; P=0.021). No significant association was found between participants with MPV below the 10th percentile and risk of CAD (P10-MPV: OR 0.91, 95% CI 0.59, 1.41; P=0.684). After adjusting for age, gender, smoking status, blood pressure (SBP >130 vs <130 mmHg), type 2 diabetes, urine albumin creatinine levels, serum creatinine, heart failure, and stroke history, the association between those with MPV above P90 and increased CAD risk remained significant (P90-MPV aOR 1.65; 95% CI 1.16, 2.34; P=0.005). Gender and race did not modify this effect. Conclusion: Our findings indicate that high MPV (above the 90th percentile) is positively associated with the risk of CAD in the general population. Further longitudinal cohort studies are necessary to explore this relationship and its clinical implications thoroughly.

ApoE Receptor-2 R952Q Variant in Macrophages Elevates Soluble LRP1 to Potentiate Hyperlipidemia and Accelerate Atherosclerosis in Mice.

apoER2 (apolipoprotein E receptor-2) is a transmembrane receptor in the low-density lipoprotein receptor (LDLR) family with unique tissue expression. A single-nucleotide polymorphism that encodes the R952Q sequence variant has been associated with elevated plasma cholesterol levels and increased myocardial infarction risk in humans. The objective of this study was to delineate the mechanism underlying the association between the apoER2 R952Q variant and increased atherosclerosis risk. An apoER2 R952Q mouse model was generated using a CRISPR/Cas9 strategy, intercrossed with LDLR knockout mice, followed by feeding a Western-type high-fat high-cholesterol diet for 16 weeks. Atherosclerosis was investigated by immunohistology. Plasma lipids and lipid distributions among the various lipoprotein classes were analyzed by colorimetric assay. Tissue-specific effects of the R952Q sequence variant on atherosclerosis were analyzed by bone marrow transplant studies. sLRP1 (soluble low-density lipoprotein receptor-related protein 1) was measured in plasma and conditioned media from bone marrow-derived macrophages by ELISA and GST-RAP (glutathione S-transferase-receptor-associated protein) pull-down, respectively. P38 MAPK (mitogen-activated protein kinase) phosphorylation in VLDL (very-low-density lipoprotein)-treated macrophages was determined by Western blot analysis. Consistent with observations in humans with this sequence variant, the apoER2 R952Q mutation exacerbated diet-induced hypercholesterolemia, via impediment of plasma triglyceride-rich lipoprotein clearance, to accelerate atherosclerosis in Western diet-fed LDLR knockout mice. Reciprocal bone marrow transplant experiments revealed that the apoER2 R952Q mutation in bone marrow-derived cells instead of non-bone marrow-derived cells was responsible for the increase in hypercholesterolemia and atherosclerosis. Additional data showed that the apoER2 R952Q mutation in macrophages promotes VLDL-induced LRP1 (low-density lipoprotein receptor-related protein 1) shedding in a p38 MAPK-dependent manner. The apoER2 R952Q mouse model recapitulates characteristics observed in human disease. The underlying mechanism is that the apoER2 R952Q mutation in macrophages exacerbates VLDL-stimulated sLRP1 production in a p38 MAPK-dependent manner, resulting in its competition with cell surface LRP1 to impede triglyceride-rich lipoprotein clearance, thereby resulting in increased hypercholesterolemia and accelerated atherosclerosis.

Causal Links Between Renal Function and Cardiac Structure, Function, and Disease Risk.

Chronic kidney disease (CKD) increases the risk of adverse cardiovascular outcomes. However, the causal relationships between renal function and cardiovascular diseases (CVD) remain incompletely understood. This study aimed to determine the causal relationships between genetic susceptibility to impaired renal function and the risk of CVD endpoints, as well as cardiac structure and function detectable by cardiac magnetic resonance imaging (CMR). Bidirectional Mendelian randomization (MR) analyses were conducted using summary-level data from genome-wide association studies. The exposures were blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and CKD. The outcomes included atrial fibrillation, coronary artery disease (CAD), myocardial infarction, heart failure, stroke, and various CMR parameters. Sensitivity analyses, multivariable MR adjusting for cardiometabolic traits, and replication in the FinnGen cohort were performed. Elevated BUN levels (OR 1.505; 95% CI 1.077 to 2.103; P = 0.017) were causally associated with increased CAD risk, but this relationship was attenuated after adjusting for cardiometabolic traits. Increased UACR was causally linked to higher risks of CAD (OR 1.260; 95% CI 1.042 to 1.523; P = 0.017), myocardial infarction (OR 1.424; 95% CI 1.137 to 1.783; P = 0.002), and stroke (OR 1.182; 95% CI 1.012 to 1.379; P = 0.035), with the association for stroke remaining significant after multivariable adjustment. Reduced eGFR was causally related to decreases in ascending aorta diameter, proximal pulmonary artery diameter, right atrial size, left ventricular stroke volume, and right ventricular volumes, even after accounting for potential confounders. CKD was causally associated with a reduced pulmonary artery-to-aorta ratio and proximal pulmonary artery diameter. This comprehensive MR study establishes causal roles of genetic susceptibility to impaired renal function influencing cardiovascular outcomes and cardiac structure.

Methionine synthetase A2756G and Cystathionine-β-synthase 844ins68 polymorphisms and coronary artery disease: a meta-analysis

Objective: Methionine synthetase (MS) A2756G and Cystathionine-β-synthase (CBS) 844ins68 gene polymorphisms were indicated to be associated with increased coronary artery disease (CAD) risk. Nevertheless, because the results of each experiment are different, there is no consensus till now. This meta-analysis aimed to clarify the relationship between MS gene A2756G and CBS gene 844ins68 polymorphisms and CAD.Methods: 11,555 participants from 24 individual studies, 2162 participants from 6 individual studies were included in the MS gene A2756G and CBS 844ins68 gene polymorphisms meta-analysis respectively. To determine whether MS gene A2756G or CBS gene 844ins68 polymorphism was associated with CAD risk, a random or fixed-effect genetic model was adopted using pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs).Results:MS gene A2756G polymorphism was significantly associated with CAD under recessive (OR: 1.400, 95% CI: 1.119-1.751, P=0.003) and homozygous genetic models (OR: 1.360, 95% CI: 1.084-1.706, P=0.008). In the African subgroup, the association was significant under the allelic, recessive, dominant, heterozygous, homozygous and additive (P<0.05) genetic models. In the Asian subgroup, the association was significant under the allelic, recessive and homozygous genetic models (P<0.05). No significant association was found between CBS 844ins68 gene polymorphism and CAD under all of the genetic models (P>0.05).Conclusions:MS gene A2756G polymorphism was significantly associated with increased CAD risk, especially in the African and Asian population. The G allele carriers of MS gene A2756G polymorphism were more susceptible to be suffered from CAD disease than others.

Relationship of EDNRA rs6842241 and MRAS rs9818870 polymorphic variants with predisposition to coronary artery disease and their effect on the lipid-lowering effect of rosuvastatin

Aim. To study the effect of EDNRA rs6842241 and MRAS rs9818870 polymorphic variants on the lipid-lowering effect of rosuvastatin in patients with coronary artery disease (CAD), and to determine the role of these loci in the development of CAD among Central Russia residents.Material and methods. The pharmacogenetic study involved 116 patients with class II-III stable angina. Patients received rosuvastatin with dose titration to achieve target low-density lipoprotein cholesterol (LDL-C) levels. The genetic and epidemiological study included DNA samples of 1960 Central Russia residents (1261 patients with CAD and 699 healthy individuals). Genotyping of polymorphic variants was performed on a MassARRAY-4 genomic mass spectrometer. Associations of polymorphisms with lipid changes for 1, 6 and 12 months of follow-up were calculated using linear regression analysis adjusted for sex, age, body mass index and rosuvastatin dose; associations with CAD risk — using logistic regression analysis adjusted for sex and age. The statistical significance of associations was calculated using the permutation test.Results. Carriage of the AA and CA genotypes of EDNRA rs6842241 variant was associated with a weakening of the rosuvastatin lipid-lowering effect in relation to total cholesterol (β=0,075, p=0,001) and LDL-C (β=0,145, p=0,017) at the end of the first month and 12 months of therapy (β=0,049, p=0,013 and β=0,072, p=0,040, respectively). Carriage of the AA genotype of EDNRA rs6842241 variant was associated with an increased CAD risk (odds ratio 5,36; 95% confidence interval 1,62-17,71, p=0,004). MRAS rs9818870 variant was not associated with rosuvastatin pharmacogenetics or with the CAD risk. Both polymorphic variants were not associated with lipid levels outside of lipid-lowering therapy, as well as with the triglyceride changes. High-density lipoprotein cholesterol levels during the entire follow-up period changed insignificantly.Conclusion. The EDNRA rs6842241 variant is associated with both a weakening of the lipid-lowering effect of rosuvastatin in CAD and an increased risk of its development in the population.

Genetic Polymorphisms and Genetic Risk Scores Contribute to the Risk of Coronary Artery Disease (CAD) in a North Indian Population.

Coronary artery disease (CAD) is the leading cause of death in India. Many genetic polymorphisms play a role in regulating oxidative stress, blood pressure and lipid metabolism, contributing to the pathophysiology of CAD. This study examined the association between ten polymorphisms and CAD in the Jat Sikh population from Northern India, also considering polygenic risk scores. This study included 177 CAD cases and 175 healthy controls. The genetic information of GSTM1 (rs366631), GSTT1 (rs17856199), ACE (rs4646994), AGT M235T (rs699), AGT T174M (rs4762), AGTR1 A1166C (rs5186), APOA5 (rs3135506), APOC3 (rs5128), APOE (rs7412) and APOE (rs429358) and clinical information was collated. Statistical analyses were performed using SPSS version 27.0 and SNPstats. Significant independent associations were found for GST*M1, GST*T1, ACE, AGT M235T, AGT T174M, AGTR1 A1166C and APOA5 polymorphisms and CAD risk (all p < 0.05). The AGT CT haplotype was significantly associated with a higher CAD risk, even after controlling for covariates (adjusted OR = 3.93, 95% CI [2.39-6.48], p < 0.0001). The APOA5/C3 CC haplotype was also significantly associated with CAD (adjusted OR = 1.86, 95% CI [1.14-3.03], p < 0.05). A higher polygenic risk score was associated with increased CAD risk (adjusted OR = 1.98, 95% CI [1.68-2.34], p < 0.001). Seven polymorphisms were independently associated with an increase in the risk of CAD in this North Indian population. A considerable risk association of AGT, APOA5/C3 haplotypes and higher genetic risk scores is documented, which may have implications for clinical and public health applications.

Investigating the Added Value of Beck's Depression Inventory in Atherosclerosis Prediction: Lessons from Paracelsus 10,000.

Background: Depression is the most common mental illness worldwide and generates an enormous health and economic burden. Furthermore, it is known to be associated with an elevated risk of arteriosclerotic cardiovascular diseases (ASCVD), particularly stroke. However, it is not a factor reflected in many ASCVD risk models, including SCORE2. Thus, we analysed the relationship between depression, ASCVD and SCORE2 in our cohort. Methods: We analysed 9350 subjects from the Paracelsus 10,000 cohort, who underwent both a carotid artery ultrasound and completed a Beck Depression Inventory (BDI) screening. Patients were categorised binomially based on the BDI score. Atherosclerotic carotid plaque or absence was dichotomised for logistic regression modelling. Odds ratios and adjusted relative risks were calculated using Stata. Results: Subjects with an elevated BDI (≥14) had higher odds for carotid plaques compared to subjects with normal BDI, especially after adjusting for classical risk factors included in SCORE2 (1.21; 95%CI 1.03-1.43, p = 0.023). The adjusted relative risk for plaques was also increased (1.09; 95%CI 1.01-1.18, p = 0.021). Subgroup analysis showed an increased odds of plaques with increases in depressive symptoms, particularly in women and patients ≤55 yrs. Conclusions: In our cohort, the BDI score is associated with subclinical atherosclerosis beyond classical risk factors. Thus, depression might be an independent risk factor which may improve risk stratification if considered in ASCVD risk prediction models, such as SCORE2. Furthermore, reminding clinicians to take mental health into consideration to identify individuals at increased atherosclerosis risk may provide added opportunities to address measures which can reduce the risk of ASCVD.

LDLR variant classification for improved cardiovascular risk prediction in familial hypercholesterolemia

Background and aimsFamilial hypercholesterolemia (FH) is a genetic disorder marked by high LDL cholesterol and an increased premature coronary artery disease (CAD) risk. Current dichotomous classification of LDL receptor gene (LDLR) variants may inadequately capture patient variability in LDL cholesterol levels and CAD risk. This study assessed a novel approach for determining LDLR variant severity using variant-specific LDL cholesterol percentiles. MethodsParticipants of the Dutch FH cascade screening program were screened for 456 LDLR variants. For each LDLR variant carrier, a sex- and age-specific LDL cholesterol percentile was derived from the LDL cholesterol level measured at study entry, i.e. generally from the blood drawn for DNA analysis. These percentiles were used to calculate the mean LDL cholesterol percentile for each variant. Based on the variant-specific LDL cholesterol percentiles, carriers were grouped into the following LDL cholesterol strata: <75th, 75th-88th, 88th-92nd, 92nd-96.5th, 96.5th-98th, and ≥98th percentile. Additionally, variants were categorized into class 1 (LDLR deficient) and non-class 1 (often LDLR defective) variants. CAD risk between carriers in the different LDL cholesterol strata and non-carriers was compared using a Cox proportional hazard model. ResultsOut of 35,067 participants, 12,485 (36 %) LDLR variant carriers (mean age 38.0 ± 20.0 years, 47.7 % male) were identified. Carriers had a 5-fold higher CAD risk compared with non-carriers. Hazard ratios for CAD increased gradually from 2.2 (95%CI 0.97–5.0) to 12.0 (95%CI 5.5–24.8) across the LDL cholesterol strata. A 7.3-fold and 3.9-fold increased CAD risk was observed in carriers of class 1 and non-class 1 LDLR variants, respectively. ConclusionsThis study presents a refined approach for classifying LDLR variants based on their impact on LDL cholesterol levels, allowing for more precise, genotype-specific CAD risk estimation in FH patients compared with traditional methods.

Evaluation of Polygenic Risk Scores for Prediction of Coronary Artery Disease in a Greek Case-Control Study.

Coronary artery disease (CAD) stands as the most predominant type of cardiovascular disease (CVD). Polygenic risk scores (PRSs) have become essential tools for quantifying genetic susceptibility, and researchers endeavor to improve their predictive precision. The aim of the present work is to assess the performance and the relative contribution of PRSs developed for CVD or CAD within a Greek population. The sample under study comprised 924 Greek individuals (390 cases with CAD and 534 controls) from the THISEAS study. Nine PRSs drawn from the PGS catalog were replicated and tested for CAD risk prediction. PRSs computations were performed in the R language, and snpStats was used to process genotypic data. Descriptive characteristics of the study were analyzed using the statistical software IBM SPSS Statistics v21.0. The effectiveness of each PRS was assessed using the PRS R2 metric provided by PRSice2. Among nine PRSs, PGS000747 greatly increased the predictive value of primary CAD risk factors by 21.6% (p-value = 2.63 × 10-25). PGS000012 was associated with a modest increase in CAD risk by 2.2% (p-value = 9.58 × 10-4). The remarkable risk discrimination capability of PGS000747 stands out as the most noteworthy outcome of our study.

Lifestyle factors, genetic susceptibility to obesity and their interactions on coronary artery disease risk: A cohort study in the UK Biobank

ObjectiveWe aimed to evaluate potential modifying effects of genetic susceptibility to obesity on the association of lifestyle factors with coronary artery disease (CAD) risk. MethodsA total of 328,606 participants (54% women) were included using data from the UK Biobank. We evaluated the risk of developing CAD associated with obesity-related polygenic scores (PGSs) and healthy lifestyle scores (HLSs). HLSs were constructed using six lifestyle factors. Obesity PGSs were created using genetic variants identified by genome-wide association studies, including 941 variants for body mass index (BMI) and 457 for waist-to-hip ratio (WHR). Both HLSs and PGSs were categorized into three groups. ResultsDuring a 9-year median follow-up, 14,541 participants developed CAD. An unhealthy lifestyle was significantly associated with an increased CAD risk (hazard ratio [HR] = 2.24, 95% confidence interval [CI] = 2.09–2.40). High BMI and WHR PGSs were each significantly associated with an increased CAD risk (HRBMI = 1.23, 1.17–1.29; HRWHR = 1.15, 1.09–1.21). Lifestyle factors explained 41% (95% CI = 38%–45%) of CAD, while genetic variants for BMI explained only 10% (7%–14%). Risks of CAD were increased with poorer HLS independent of obesity-related PGSs. Individuals with the most unhealthy lifestyle and highest BMI PGS had the highest risk of CAD risk (HR = 2.59, 95% CI = 2.26–2.97), compared with participants with the healthiest lifestyle and lowest BMI PGS. ConclusionsWhile the observational nature of the study precludes the establishment of causality, our study provides supports for a causal association between obesity and CAD risk and the importance of lifestyle modification in the prevention of CAD.

Dose-Response Associations of Lipid Traits With Coronary Artery Disease and Mortality

Apolipoprotein B (apoB), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) are associated with coronary artery disease (CAD). However, trial evidence for the association of intensive LDL-C lowering and TG lowering with mortality is less definitive. To investigate the associations of apoB, LDL-C, and TG with CAD and mortality, both overall and by sex and age, and to characterize the shapes of these associations. This genetic association study used linear and nonlinear mendelian randomization (MR) to analyze a population-based cohort of individuals of European ancestry from the UK Biobank, which recruited participants from 2006 to 2010 with follow-up information updated until September 2021. Data analysis occurred from December 2022 to November 2023. Genetically predicted apoB, LDL-C, and TG. The primary outcomes were CAD, all-cause mortality, and cause-specific mortality. Genetic associations with CAD were calculated using logistic regression, associations with all-cause mortality using Cox proportional hazards regression, and associations with cause-specific mortality using cause-specific Cox proportional hazards regression with censoring for other causes of mortality. This study included 347 797 participants (mean [SD] age, 57.2 [8.0] years; 188 330 female [54.1%]). There were 23 818 people who developed CAD and 23 848 people who died. Genetically predicted apoB was positively associated with risk of CAD (odds ratio [OR], 1.65 per SD increase; 95% CI 1.57-1.73), all-cause mortality (hazard ratio [HR], 1.11; 95% CI, 1.06-1.16), and cardiovascular mortality (HR, 1.36; 95% CI, 1.24-1.50), with some evidence for larger associations in male participants than female participants. Findings were similar for LDL-C. Genetically predicted TG was positively associated with CAD (OR, 1.60; 95% CI 1.52-1.69), all-cause mortality (HR, 1.08; 95% CI, 1.03-1.13), and cardiovascular mortality (HR, 1.21; 95% CI, 1.09-1.34); however, sensitivity analyses suggested evidence of pleiotropy. The association of genetically predicted TG with CAD persisted but it was no longer associated with mortality outcomes after controlling for apoB. Nonlinear MR suggested that all these associations were monotonically increasing across the whole observed distribution of each lipid trait, with no diminution at low lipid levels. Such patterns were observed irrespective of sex or age. In this genetic association study, apoB (or, equivalently, LDL-C) was associated with increased CAD risk, all-cause mortality, and cardiovascular mortality, all in a dose-dependent way. TG may increase CAD risk independent of apoB, although the possible presence of pleiotropy is a limitation. These insights highlight the importance of apoB (or, equivalently, LDL-C) lowering for reducing cardiovascular morbidity and mortality across its whole distribution.

Association of flavonoid intake with coronary artery disease risk in the older population based on the National Health and Nutrition Examination Survey.

We investigated the association between flavonoid intake and coronary artery disease (CAD) risk in older adults. Data were extracted from the National Health and Nutrition Examination Survey (age ≥ 70 years; 2007-2010 and 2017-2018; n = 2 417). The total flavonoid and flavonoid subclass intake was calculated using validated food frequency questionnaires. The association between flavonoid intake and CAD risk was examined using generalized linear models with restricted cubic spline models. After multivariate adjustment, anthocyanin intake was positively associated with CAD risk; no significant associations were observed between other flavonoid subcategories and endpoint outcomes. Anthocyanins exhibited a non-linear association with CAD risk, and threshold effect analysis showed an inflection point of 15.8 mg/day for anthocyanins. Per unit increase in anthocyanins, the odds of CAD on the left of the inflection point decreased by 2%, while the odds on the right increased by 35.8%. Excessive flavonoid intake may increase CAD risk in the older population.

Association of air pollution exposure and increased coronary artery disease risk: the modifying effect of genetic susceptibility

BackgroundBoth genetic factors and air pollution are risk factors for coronary artery disease (CAD), but their combined effects on CAD are uncertain. The study aimed to comprehensively investigate their separate, combined and interaction effects on the onset of CAD.MethodsWe utilized data from the UK Biobank with a recruitment of 487,507 participants who were free of CAD at baseline from 2006 to 2010. We explored the separate, combined effect or interaction association among genetic factors, air pollution and CAD with the polygenic risk score (PRS) and Cox proportional hazard models.ResultsThe hazard ratios (HRs) [95% confidence interval (CI)] of CAD for 10-µg/m3 increases in PM2.5, NO2 and NOx concentrations were 1.25 (1.09, 1.44), 1.03 (1.01, 1.05) and 1.01 (1.00, 1.02), respectively. Participants with high PRS and air pollution exposure had a higher risk of CAD than those with the low genetic risk and low air pollution exposure, and the HRs (95% CI) of CAD in the PM2.5, PM10, NO2 and NOx high joint exposure groups were 1.56 (1.48, 1.64), 1.55(1.48, 1.63), 1.57 (1.49, 1.65), and 1.57 (1.49, 1.65), respectively. Air pollution and genetic factors exerted significant additive effects on the development of CAD (relative excess risk due to the interaction [RERI]: 0.12 (0.05, 0.19) for PM2.5, 0.17 (0.10, 0.24) for PM10, 0.14 (0.07, 0.21) for NO2, and 0.17 (0.10, 0.24) for NOx; attributable proportion due to the interaction [AP]: 0.09 (0.04, 0.14) for PM2.5, 0.12 (0.07, 0.18) for PM10, 0.11 (0.06, 0.16) for NO2, and 0.13 (0.08, 0.18) for NOx).ConclusionExposure to air pollution was significantly related to an increased CAD risk, which could be further strengthened by CAD gene susceptibility. Additionally, there were positive additive interactions between genetic factors and air pollution on the onset of CAD. This can provide a more comprehensive, precise and individualized scientific basis for the risk assessment, prevention and control of CAD.

Factors associated with secondary coronary artery disease in rheumatoid arthritis patients: A systematic review and meta-analysis based on observational studies.

The main objective of this systematic review was to investigate the factors influencing the development of coronary artery disease (CAD) in patients with rheumatoid arthritis (RA). PubMed, Embase, Web of Science, Wan Fang Date, CBM, CNKI, and VIP databases were systematically searched to select the relevant literature. The quality of the incorporated studies was assessed with reference to the Newcastle-Ottawa Scale. Stata16 was adopted to summarise the odds ratios, risk ratios, hazard ratios, and 95% confidence intervals for meta-analysis. A total of 29 studies were included in this analysis, wherein the average age of RA patients was 50.5-81years and the proportion of women was 44.4%-92%. The present meta-analysis suggested that increased CAD risk in RA patients was associated with age, male gender, smoking, glucocorticoids, Health Assessment Questionnaire scores, hyperlipidaemia, hypertension, diabetes, and C-reactive protein concentration. The present systematic review revealed the influencing factors of secondary CAD in RA patients, some of which could reduce the risk of secondary CAD through effective interventions, such as smoking cessation, exercise, and medications. However, the effects of age, RA severity, and different medication subgroups on CAD risk stratification warrant further investigation.

Does gestational diabetes mellitus increase the risk of cardiovascular disease? A Mendelian randomization study.

In recent years, epidemiological studies have revealed the relationship between gestational diabetes mellitus (GDM) and cardiovascular disease (CVD). In this study, we utilized Mendelian randomization (MR) to investigate the potential causal impact of GDM on cardiovascular disease for the first time. We retrieved summary statistics from published genome-wide association studies. MR was first performed using significant SNPs extracted from the eighth data release of the FinnGen study. Next, a replication analysis for coronary artery disease (CAD) was conducted in another European ancestry population to validate our findings. Finally, mediation analysis was carried out to assess potential mediation effects. Our data analysis revealed that genetically predicted GDM was significantly associated with increased CAD risk (OR 1.10, 95% CI 1.02-1.18, p 0.006). Replication analysis confirmed a significant genetic association between GDM and CAD (OR 1.07, 95% CI 1.02-1.12, p 0.003) in another European ancestry population. Mediation analysis indicated no significant mediation effect by type 2 diabetes mellitus (T2DM)on the GDM-CAD relationship (mediation effect β [95% CI]: 0.005 [-0.003, -0.017]). Women with a prior history of GDM face an elevated risk of future CAD. This increased risk of CAD cannot be solely attributed to the subsequent onset of diabetes. Regular CAD risk assessment and primary prevention strategies are of paramount importance for women with a history of GDM.

Abstract 17580: "Healthy Smile for a Healthy Heart": A National Study on the Correlation Between Periodontal Diseases and Coronary Artery Disease

Introduction: Chronic inflammatory periodontal disease (CIPD) is a common disease of the supporting tissues of the teeth that manifest as swelling, bleeding, pain, and clinical attachment loss (CAL) upon periodontal examination. CIPD has been associated with a chronic inflammatory state, also a known risk factor for coronary artery disease (CAD). Hypothesis: There is a possible correlation between CIPD and CAD. Methods: We utilized the 2013-2014 National Health and Nutrition Examination Survey database. We included participants aged 30 years and above who reported having gum disease and had undergone a periodontal examination. CAL measured in millimeters, was reported at six different locations around 28 teeth. To obtain national estimates, we conducted complex survey sample analyses, accounting for weights, clustering, and strata. Furthermore, we adjusted for well-known CAD risk factors in multivariate analyses. Results: Our study included 184,010,722 participants; 7.3% had CAD (n=13,461,796), and 17.1% reported CIPD (n=31,425,382). Baseline Characteristics are presented in Table 1. The unadjusted rate of CAD was higher in patients with CIPD than those without CIPD [10.3% (n=3,238,995) vs 6.7% (n=10,222,801), p=0.018]. Similarly, average CAL was higher in patients with CAD (2.04 vs 1.62 mm, p&lt;0.001). After adjusting for confounders listed in Table 1, CIPD was a significant predictor of CAD (OR 1.744, 95% CI 1.088-2.796, p=0.012). The average CAL of all the teeth also predicted CAD (OR 1.195, 95% CI 1.025-1.394, p=0.026). Conclusions: Our data suggest that patients with reported CIPD had a 1.7 times higher risk of developing CAD. Similarly, each 1 mm increase in CAL leads to a 20% increased CAD risk (OR 1.2). Further prospective studies are needed to confirm these findings and to explore whether treatment of CIPD mitigates the increased CAD risk. These findings underscore the significance of optimizing dental health in patients with CAD.

Abstract 18381: Long-Term Coronary Artery Disease Risk in Female Adults With Surgically-Induced Menopause : A Systematic Review

Introduction: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in female adults. Prior studies have suggested an association between surgically-induced menopause (SIM) and long-term CAD risk. Yet, the pathophysiology and clinical significance of this relationship remains unclear. As SIM causes a premature cessation of potentially cardioprotective hormones, this review aimed to further investigate if SIM is a risk factor for CAD. Methods: SCOPUS, Web of Science, Cochrane Library, OVID/Embase, SciELO, and LILACS were searched from inception to April 2023 for observational studies reporting the effects of hysterectomy, oophorectomy, and/or salpingectomy prior to age fifty on long-term CAD risk. Results: Among 3056 identified records, nineteen studies were included with a combination of benign and malignant surgical indications. The studies reported on coronary heart disease (n=6), CAD (n=4), ischemic heart disease (n=3), and myocardial infarction (n=7). Sixteen articles with an average of 106,433 participants per study demonstrated a significantly increased risk of CAD following SIM (Table 1). In particular, hysterectomy with or without bilateral oophorectomy, and bilateral oophorectomy alone were found to have the most profound influence. Unilateral oophorectomy or hysterectomy with salpingo-oophorectomy did not appear to increase CAD risk. Average follow-up duration after SIM ranged from six to twenty-four years. Five studies adjusted for post-menopausal hormone replacement therapy use. Conclusions: SIM may elevate long-term CAD risk following hysterectomy and/or bilateral oophorectomy. Given that the majority of SIM are performed pre- or peri-menopausal for benign indications, understanding the associated cardiovascular risks is vital for informed decision-making, early detection, and prevention.

Circulating fatty acids, genetic risk, and incident coronary artery disease: A prospective, longitudinal cohort study.

The role of fatty acids (FAs) in primary prevention of coronary artery disease (CAD) is highly debated, and the modification effect by genetic risk profiles remains unclear. Here, we report the prospective associations of circulating FAs and genetic predisposition with CAD development in 101,367 U.K. Biobank participants. A total of 3719 CAD cases occurred during a mean follow-up of 11.5 years. Plasma monounsaturated FAs (MUFAs) were positively associated with risk of CAD, whereas the risk was significantly lower with higher n-3 polyunsaturated FAs (PUFAs) and more reductions in risk were detected among TT carriers of rs174547. Furthermore, increased plasma saturated FAs (SFAs) and linoleic acid were related to a significant increase in CAD risk among participants with high genetic risk (genetic risk score > 90%). These findings suggest that individuals with high genetic risk need to reduce plasma SFAs levels for CAD prevention. Supplementation of n-3 PUFAs for CAD prevention may consider individuals' genetic makeup.