The relationship between NLR, LDL-C/HDL-C, NHR and coronary artery disease
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SUBMITTER: Yuan S
PROVIDER: S-EPMC11236180 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundHigh LDL-cholesterol (LDL-C) is a well-known risk factor for coronary artery disease (CAD). PCSK9, HMGCR, NPC1L1, ACLY, and LDLR gene have been reported as lipid lowering drug genes related to LDL-C lowering. However relevant Asian studies were rare.MethodsWe examined the causality between LDL-c drug target genes and CAD using Korean and Japanese data using the two sample Mendelian Randomization (MR) method. We conducted two-sample MR analysis of LDL-c lowering drug target genes (7 Single-nucleotide polymorphisms (SNP) in PCSK9, 6 SNPs in HMGCR, 5 SNPs in NPC1L1, 9 SNPs in ACLY, 3 SNPs in LDLR) and CAD. We used summary statistics data from the Korean Genome Epidemiology Study (KOGES) for LDL-C data, and Biobank of Japan (BBJ) for CAD data.ResultsFor every 10 mg/dl decrease in LDL-C determined by four significant SNPs in the PCSK9 gene, the risk of CAD decreased by approximately 20% (OR = 0.80, 95% CI: 0.75-0.86). The risk of CAD decreased by 10% for every 10 mg/dl decrease in LDL-C due to the six significant SNPs in the HMGCR gene (OR = 0.90, 95% CI: 0.86-0.94). Due to the two significant SNPs in the gene LDLR, the risk of CAD decreased by approximately 26% for every 10 mg/dl decrease in LDL-C (OR = 0.74, 95% CI: 0.66-0.82). The combined effect on CAD showed the largest effect size for the PCSK9 gene and LDLR gene, and the reduced CAD risk induced by these two genes together was OR = 0.78 (95%CI, 0.74-0.83). Finally, the combined effect of all three genes (PCSK9, HMGCR, and LDLR) was OR = 0.85 (95%CI, 0.79-0.91).ConclusionLDL-C reduction estimated by SNPs in LDL-C lowering drug target genes significantly reduced the risk of CAD. We found the potential of using of proxy research design for clinical trials using LDL-C lowering drugs.
| S-EPMC11905656 | biostudies-literature
Project description:BackgroundThe increase of low-density lipoprotein cholesterol (LDL-C) is widely accepted as an important factor in the occurrence of atherosclerosis. In recent years, the guidelines have recommended non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for lipid-lowering therapy. But even as research on the relationship between LDL-C/HDL-C and atherosclerosis increases, it is still undetermined which index is most closely related to the severity of acute ST-segment elevation myocardial infarction (STEMI).Methods901 patients who received coronary angiography due to chest pain were selected. Among them, 772 patients with STEMI represented the test group, and 129 patients with basically normal coronary angiography represented the control group. Researchers measured fasting blood lipids and other indicators after admission, and determined the severity of coronary artery disease using the Gensini score.ResultsLDL-C/HDL-C and non-HDL-C indexes were statistically different between the two patient groups. In the test group, total cholesterol (TC), triglycerides (TG), LDL-C, high density lipoprotein cholesterol (HDL-C), non-HDL-C, arteriosclerosis index (AI), and LDL-C/HDL-C all correlated with the patients' Gensini score. After applying the stepwise method of multiple linear regression analysis (R2 = 0.423, β = 0.518, p < 0.05), LDL-C/HDL-C had the most correlation with the patient's Gensini score. ROC curve analysis suggested that LDL-C/HDL-C can predict whether patients with chest pain are STEMI (AUC: 0.880, 95% Cl: 0.847-0.912, p < 0.05). When cutoff value is 2.15, sensitivity is 0.845, and specificity is 0.202, LDL-C/HDL-C is an effective indicator for predicting whether patients with chest pain have STEMI.ConclusionCompared to ratios of non-HDL-C and LDL-C, the LDL-C/HDL-C ratio in patients with STEMI is more correlated with the severity of coronary artery disease. It can better evaluate the severity of coronary artery disease and better predict whether patients with chest pain are STEMI.
| S-EPMC9288699 | biostudies-literature
Project description:Atrial fibrillation (AF) is more prevalent in individuals with chronic kidney disease (CKD) compared to the general population. While a potential inverse correlation between lipid levels and AF has been proposed, it remains unclear if this relationship applies to CKD patients. This study examined the connection between the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) and the likelihood of AF in CKD patients. Data was gathered from 21,091 consecutive CKD patients between 2006 and December 31, 2015. We examined the link between the LDL-C/HDL-C ratio and AF in CKD patients through binary logistic regression, as well as various sensitivity and subgroup analyses. The dataset that backs up these analyses is available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230189 . Of the 21,091 CKD patients, 211 (1.00%) were diagnosed with AF. The cohort, predominantly male (79.93%), had a mean age of 60.89 ± 10.05 years. The mean LDL-C/HDL-C ratio was 1.39 ± 0.35. After adjusting for covariates, a significant inverse association was observed between the LDL-C/HDL-C ratio and the incidence of AF in CKD patients (OR = 0.422, 95% CI 0.273-0.652, P = 0.00010). The robustness of these findings was confirmed through sensitivity analysis. Subgroup analysis revealed a strong correlation between the LDL-C/HDL-C ratio and incident AF in patients without hypertension (HR = 0.26, 95% CI 0.15-0.45). Conversely, this association was absent in hypertensive patients (HR = 1.09, 95% CI 0.54-2.17). Our research shows an independent inverse correlation between the LDL-C/HDL-C ratio and the risk of AF in CKD patients. It is advised to refrain from excessively aggressive reduction of LDL levels in CKD patients, as this could elevate the risk of developing AF.
| S-EPMC11291658 | biostudies-literature
Project description:BackgroundHDL is endowed with several metabolic, vascular, and immunoinflammatory protective functions. Among them, a key property is to promote reverse cholesterol transport from cells back to the liver. The aim of this study was to estimate the association of scavenger receptor class B type I (SR-BI)- and ATP binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux (the two major routes for cholesterol efflux to HDL) with the presence, extent, and severity of coronary artery disease (CAD), vascular wall remodelling processes, coronary plaque characteristics, and the incidence of myocardial infarction in the different subgroups of patients from the CAPIRE study.MethodsPatients (n = 525) from the CAPIRE study were divided into two groups: low-risk factors (RF), with 0-1 RF (n = 263), and multiple-RF, with ≥2 RFs; within each group, subjects were classified as no-CAD or CAD based on the segment involvement score (SIS) evaluated by coronary computed tomography angiography (SIS = 0 and SIS > 5, respectively). SR-BI- and ABCA1-mediated cholesterol efflux were measured using the plasma of all patients.ResultsSR-BI-mediated cholesterol efflux was significantly reduced in patients with CAD in both the low-RF and multiple-RF groups, whereas ABCA1-mediated cholesterol efflux was similar among all groups. In CAD patients, multivariable analysis showed that SR-BI-mediated cholesterol efflux <25th percentile predicted cardiovascular outcome (odds ratio 4.1; 95% CI: 1.3-13.7; p = .019), whereas ABCA-1-mediated cholesterol efflux and HDL-C levels significantly did not. Despite this finding, reduced SR-BI-mediated cholesterol efflux was not associated with changes in high-risk plaque features or changes in the prevalence of elevated total, non-calcified, and low-attenuation plaque volume.ConclusionSR-BI-mediated cholesterol efflux capacity is lower in patients with diffuse coronary atherosclerosis. In addition, a lower SR-BI-mediated cholesterol efflux capacity is associated with the worst clinical outcomes in patients with CAD, independently of atherosclerotic plaque features. Key MessagesIncreased cholesterol efflux capacity, an estimate of HDL function, is associated with a reduced CVD risk, regardless of HDL-C levels.HDL-C levels are significantly lower in patients with CAD.Lower SR-BI-mediated cholesterol efflux capacity is observed in patients with diffuse coronary atherosclerosis and is associated with the worst clinical outcomes in patients with CAD, independently of atherosclerotic plaque features.
| S-EPMC9090377 | biostudies-literature
Project description:Coronary artery disease (CAD) is the principal cause of death in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to investigate whether NAFLD is causally involved in the pathogenesis of CAD. For this, previously reported NAFLD susceptibility genes were clustered and tested for an association with CAD in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis plus the Coronary Artery Disease Genetics (CARDIoGRAMplusC4D) Consortium data set. The role of plasma lipids as a potential mediator was explored by using data from the Global Lipids Genetics Consortium. Statistical analyses revealed that the combination of 12 NAFLD genes was not associated with CAD in 60,801 CAD cases and 123,504 controls (odds ratio [OR] per NAFLD risk allele, 1.0; 95% confidence interval [CI], 0.99-1.00). In a subsequent sensitivity analysis, a positive relationship was observed after exclusion of gene variants that are implicated in NAFLD through impaired very low-density lipoprotein secretion (i.e., microsomal triglyceride transfer protein [MTTP], patatin-like phospholipase domain containing 3 [PNPLA3], phosphatidylethanolamine N-methyltransferase [PEMT], and transmembrane 6 superfamily member 2 [TM6SF2]) (OR, 1.01; 95% CI, 1.00-1.02). Clustering of the excluded genes showed a significant negative relationship with CAD (OR, 0.97; 95% CI, 0.96-0.99). A substantial proportion of the observed heterogeneity between the individual NAFLD genes in relation to CAD could be explained by plasma lipids, as reflected by a strong relationship between plasma lipids and CAD risk conferred by the NAFLD susceptibility genes (r = 0.76; P = 0.004 for low-density lipoprotein cholesterol). Conclusion: NAFLD susceptibility genes do not cause CAD per se. The relationship between these genes and CAD appears to depend to a large extent on plasma lipids. These observations strongly suggest taking plasma lipids into account when designing a new drug to target NAFLD.
| S-EPMC6442707 | biostudies-literature
Project description:Background and aimsThere is an ongoing debate on whether NAFLD is an active contributor or an innocent bystander in the pathogenesis of coronary artery disease (CAD). The aim of the present study was to assess the causal relationship between NAFLD and CAD.Approach and resultsWe performed two-sample Mendelian randomization (MR) analyses using summary-level data to assess the association between genetically predicted NAFLD (i.e., chronically elevated serum alanine aminotransferase levels [cALT], imaging-based and biopsy-confirmed NAFLD) and risk of CAD. Analyses were repeated after exclusion of NAFLD susceptibility genes that are associated with impaired VLDL secretion.Inverse-variance weighted MR analyses showed a statistically significant association between genetically predicted cALT and risk of CAD (OR: 1.116, 95% CI: 1.039, 1.199), but not for the other NAFLD-related traits (OR: 1.046, 95% CI: 0.764, 1.433 and OR: 1.014, 95% CI: 0.968, 1.062 for imaging-based and biopsy-confirmed NAFLD, respectively). MR-Egger regression revealed a statistically significant intercept, indicative of directional pleiotropy, for all traits. Repeat analyses after exclusion of genes associated with impaired VLDL secretion showed consistent associations between genetically predicted NAFLD and CAD for all traits (i.e., cALT [OR: 1.203, 95% CI: 1.113, 1.300]), imaging-based (OR: 2.149, 95% CI: 1.276, 3.620) and biopsy-confirmed NAFLD (OR: 1.113, 95% CI: 1.041, 1.189), which persisted when more stringent biopsy-confirmed NAFLD criteria were used (OR: 1.154, 95% CI: 1.043, 1.278) or when more stringent MR methods were applied. MR-Egger regression did not show a statistically significant intercept.ConclusionThe two-sample MR analyses showed a robust association between genetically predicted NAFLD and CAD after exclusion of genetic variants that are implicated in impaired VLDL secretion.
| S-EPMC9970021 | biostudies-literature
Project description:BackgroundPrevious studies have reported conflicting results about the association of vitamin D (VD) level with coronary artery disease (CAD). We aimed to study the association of VD with atherosclerotic CAD in Egyptian individuals.ResultsWe prospectively enrolled 188 consecutive CAD patients with a median age of 55(50-62) years; 151(80.3%) were male. All patients were diagnosed by cardiac catheterization and were compared with 131 healthy controls. VD levels were measured in serum samples of all participants. Compared to controls, CAD patients had a significantly lower median VD level, 14.65 (9.25-21.45) versus 42.0 (32.0-53.0) ng/mL, p < 0.001. VD was correlated with the number of diseased coronary arteries and lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, p < 0.001 for each). By multivariate analyses, VD was an independent predictor of CAD [OR 1.22 (95% CI 1.07-1.4), p = 0.003, optimal cut-off value 30 ng/mL (AUC 0.92, sensitivity 81% and specificity 81.4%), p < 0.001], and the number of diseased coronary arteries, p < 0.001, especially three-vessel disease [OR 0.83 (95% CI 0.72-0.95), p = 0.008].ConclusionsWe have shown that low VD should be considered a non-traditional risk factor for CAD in Egyptian individuals. Low VD was correlated with coronary atherosclerosis, especially in patients with multivessel effects.
| S-EPMC10635996 | biostudies-literature
Project description:BackgroundLower low-density lipoprotein cholesterol (LDL-C) is significantly associated with improved prognosis in patients with coronary artery disease (CAD). However, LDL-C reduction does not decrease all-cause mortality among CAD patients when renal function impairs. The association between low baseline LDL-C (< 1.8 mmol/L) and mortality is unknown among patients with CAD and advanced kidney disease (AKD). The current study aimed to evaluate prognostic value of low baseline LDL-C level for all-cause death in these patients.MethodsIn this observational study, 803 CAD patients complicated with AKD (eGFR < 30 mL/min/1.73 m2) were enrolled between January 2008 to December 2018. Patients were divided into two groups (LDL-C < 1.8 mmol/L, n = 138; LDL-C ≥ 1.8 mmol/L, n = 665). We used Kaplan-Meier methods and Cox regression analyses to assess the association between baseline low LDL-C levels and long-term all-cause mortality.ResultsAmong 803 participants (mean age 67.4 years; 68.5% male), there were 315 incidents of all-cause death during a median follow-up of 2.7 years. Kaplan-Meier analysis showed that low LDL-C levels were associated with worse prognosis. After adjusting for full 24 confounders (e.g., age, diabetes, heart failure, and dialysis, etc.), multivariate Cox regression analysis revealed that lower LDL-C level (< 1.8 mmol/L) was significantly associated with higher risk of all-cause death (adjusted HR, 1.38; 95% CI, 1.01-1.89).ConclusionsOur data demonstrated that among patients with CAD and AKD, a lower baseline LDL-C level (< 1.8 mmol/L) did not present a higher survival rate but was related to a worse prognosis, suggesting a cautiousness of too low LDL-C levels among patients with CAD and AKD.
| S-EPMC8101096 | biostudies-literature
Project description:Whilst a correlation has been established between wide left main coronary artery bifurcation [left anterior descending-left circumflex (LAD-LCx)] angle (>80°) and the development of coronary artery disease (CAD), this retrospective, causal-comparative pilot study aimed to explore whether a relationship exists between right coronary artery (RCA)-aorta angle and CAD. Thirty normal cases were identified via radiology reports and selected as the control group with coronary computed tomography angiography (CCTA) scans performed on a 320-slice computed tomography (CT) scanner. Thirty CAD cases were selected with invasive coronary angiography performed to confirm the degree of stenosis, and CCTA performed on dual source and 320-slice CT scanners. An independent sample t-test was used to compare the differences in coronary angles between the normal and CAD group, and analysis of variance (ANOVA) was used to assess for significant differences between coronary angles in normal and CAD subgroups. Coronary angle measurements were conducted by two independent assessors with high intraclass correlation (r=0.971–0.998, P<0.001). RCA-aorta angle measurements were significantly larger in the normal group [87.47°, 95% confidence interval (CI): 79.31° to 95.78°] compared to the CAD group (76.82°, 95% CI: 67.82° to 85.61°, P=0.05). No significant difference was found between RCA-aorta angle and degree of coronary stenosis (P=0.75). This study suggests a relationship between narrow RCA-aorta angle and CAD.
| S-EPMC10006145 | biostudies-literature
Project description:This study aimed to determine the size and distribution of LDL and HDL particles in North African acute coronary syndrome (ACS) patients and to compare the level of small dense LDL (sdLDL) to other markers used in cardiovascular risk prediction.MethodsA total of 205 ACS patients and 100 healthy control subjects were enrolled. LDL particle size and LDL and HDL subclass distributions were measured using Quantimetric Lipoprint® linear polyacrylamide gel electrophoresis. Lipid ratios (total cholesterol, LDL cholesterol, non-HDL cholesterol, and HDL cholesterol) were determined to calculate the atherogenic index of plasma (AIP), the atherogenic coefficient (AC), Castelli's Risk-I (CR-I), and Castelli's Risk-II (CR-II). Receiver operating characteristic (ROC) curve analyses and area under the curve (AUC) were used to assess the predictive value of sdLDL as a marker for cardiovascular disease.ResultsThe ACS patients, compared to the healthy control subjects, displayed an alteration of LDL particle distribution, with a significant increase in sdLDL serum concentrations (0.303 ± 0.478 mmol/L vs. 0.0225 ± 0.043 mmol/L, respectively, p < 0.001). The sdLDL levels had a high discrimination accuracy [AUC = 0.847 ± 0.0353 (95% CI 0.778 to 0.916, p < 0.0001)]. The best predictive cutoff value of ACS determined with the maximum Youden index (J) [(sensitivity + specificity) - 1 = 0.60] was 0.038 mmol/L. A Spearman correlation analysis showed that sdLDL levels were moderately but significantly and positively correlated with AC and CR-I (r = 0.37, p < 0.001) and weakly but significantly correlated with PAI and CR-II; r = 0.32 (p < 0.001) and r = 0.30 (p < 0.008), respectively. The subclass distribution of HDL particles from ACS patients was also altered, with a decrease in large HDL particles and an increase in small HDL particles compared to HDL from healthy control subjects.ConclusionDue to their high atherogenicity, sdLDL levels could be used as a valuable marker for the prediction cardiovascular events.
| S-EPMC10135780 | biostudies-literature