Residual Cholesterol Research Articles

Clinical outcomes according to residual cholesterol and inflammatory risk in patients undergoing PCI

Abstract Background Elevated concentrations of low-density lipoprotein cholesterol (LDL-c) and low grade vascular inflammation, commonly quantified using high-sensitivity C-reactive protein (hsCRP), have been demonstrated to be causal in the development of atherosclerotic disease. Whilst recent large-scale trials have investigated the relative impact of LDL-c and inflammation on cardiovascular outcomes, there is a scarcity of data in real-world patients undergoing percutaneous coronary intervention (PCI). Purpose To investigate the relative drivers of residual risk in patients with established statin treatment undergoing PCI in a contemporary large-scale cohort. Methods From January 2012 to February 2020 patients undergoing PCI at a tertiary center were included for current analysis. Patients were categorized into 4 subgroups according to different combinations of LDL-c and hsCRP concentrations at baseline: no residual cholesterol or inflammatory risk (LDL-c <70 mg/dL + hsCRP <2 mg/L), residual cholesterol risk (LDL-c ≥70 mg/dL + hsCRP <2 mg/L), residual inflammatory risk (LDL-c <70 mg/dL + hsCRP ≥2 mg/L), and combined residual cholesterol and inflammatory risk (LDL-c ≥70 mg/dL + hsCRP ≥2 mg/L). Individuals who presented with acute myocardial infarction, neoplastic disease and hsCRP concentrations >10 mg/l were excluded. The outcome of interest was major adverse cardiac events (MACE - composite of all-cause mortality, myocardial infarction, or stroke). A univariable cox regression model was calculated. Results Overall, 10,845 patients were included. In total, 3,210 patients displayed neither cholesterol nor inflammatory risk and 3,059 individuals had elevated cholesterol risk only. In 1,839 patients an inflammatory risk was noted, whilst 2,737 patients presented with combined cholesterol and inflammatory risk. Kaplan-Meier curves for 1-year follow-up are displayed in Figure 1. Patients with residual inflammatory risk had the highest event rate of the composite endpoint (5.2%), followed by patients with combined residual risk (3.5%), individuals with residual cholesterol risk (2.3%) and persons with neither cholesterol nor inflammatory risk (2.4%; p<0.0001 for log rank test across all groups). An association with MACE was solely documented for patients with residual inflammatory risk (HR: 2.09, 95% CI: 1.52 - 2.88; p<.001), and also borderline significant for combined cholesterol and inflammatory risk (HR: 1.41, 95% CI: 1.03 - 1.95; p=0.034), whilst this was not the case for patients with elevated cholesterol risk only (see Figure 2). Conclusion In a contemporary real-world cohort of statin treated patients undergoing PCI, inflammation irrespective of LDL-c concentrations was the driver for adverse cardiovascular outcomes. This data might be helpful to further define target populations for both intensified lipid-lowering as well as anti-inflammatory treatment approaches.

Exposure to elevated cholesterol results in a non-reversible epigenetic and metabolic shift in macrophages associated with increased residual inflammatory risk

Abstract Almost all patients with or at high risk of atherosclerosis are treated with statin therapy. However, there remains a high burden of cardiovascular risk in these patients. Indeed, it is now clear that residual inflammatory risk is a stronger predictor of cardiovascular events, cardiovascular death, and all-cause death than residual cholesterol risk (as measured by low-density lipoprotein cholesterol). Therefore, in this study we sought to better understand the origin of inflammatory residual risk associated with previous exposure to high cholesterol. Tissue resident macrophages and bone marrow derived macrophages (BMDM) from mice which have been exposed to high cholesterol display an augmented polarisation profile. BMDM’s generated ex vivo are grown under standard condition so any effects come from in vivo exposure to high cholesterol. BMDMs from high cholesterol mice display a heighten M1 and blunted M2-like phenotype. Metabolomic analysis of M(IL-4) macrophages reveal they have breaks in the TCA cycle resulting in reduced capacity to utilise OxPhos which is needed for full M(IL-4) polarisation. Macrophages from chimeric mice generated by bone marrow transfer of high cholesterol bone marrow into irradiated normo-cholesterol mice retain the same phenotype as macrophages from high-cholesterol mice. Critically we demonstrate that there are genome wide irreversible epigenetic changes in bone marrow cells and tissue resident macrophages as a result of exposure to high cholesterol. Mice from a high cholesterol background have an increased number of total HSC (lin-ckit+sca1+) within the bone marrow, however, there is a decreased in the total number of long term (LT)-HSC; critically, this phenotype is not reversible when lipids levels are normalised using monoclonal antibody therapy against PCSK9. This is coupled with an irreversible myeloid skewing in the bone marrow immune cell composition. Newly recruited macrophages within the adipose also retain a heighten M1 and blunted M2-like phenotype despite lipid normalisation conferring a negative systemic metabolic phenotype. Critically, these data show that cholesterol induces long term epigenetic and metabolic changes to HSC and macrophages, which may account for residual inflammatory risk.

Trends and Prospects of Low-Density Lipoprotein Cholesterol in Stroke: A Bibliometric Analysis.

Management of low-density lipoprotein cholesterol (LDL-C) in stroke is a crucial component of cardiovascular disease care. Recent years have seen substantial progress in understanding and managing LDL-C in the context of stroke. This study utilized bibliometric methods to analyze and synthesize trends in this area over the past decade, incorporating 2,841 publications from the Web of Science database. The analyses included trend topic analysis, co-authorship analysis, and co-citation analysis. The findings indicate that research had predominantly concentrated on epidemiological studies related to pharmacological management strategies. Future research is expected to continue exploring lipid-lowering therapies, including both established treatments like statins and newer drugs such as proprotein convertase subtilisin-kexin type 9 inhibitors. Assessing residual cholesterol and employing Mendelian randomization techniques may become potential research hotspots. The New England Journal of Medicine is the most globally influential journal, while Circulation holds the most influence within the field, and Atherosclerosis ranks as the most prolific. International collaboration in this research area was strong between the USA and England, followed by the USA and China. However, collaboration between productive institutions in the USA and China remains limited, highlighting the need to strengthen partnerships between these institutions to further advance the field.

Residual inflammatory risk predicts long-term outcomes following stenting for symptomatic intracranial atherosclerotic stenosis

Background and purposeResidual inflammatory risk (RIR) can predict the unfavourable outcomes in patients with minor ischaemic stroke. However, the impact of preprocedural RIR on long-term outcomes in patients with symptomatic...

Associations of Urinary Heavy Metal Mixtures with High Remnant Cholesterol among US Adults: Evidence from the National Health and Nutrition Examination Survey (1998-2018).

The main objective of our study is to explore the associations between combined exposure to urinary heavy metals and high remnant cholesterol (HRC), a known cardiovascular risk factor. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, we conducted a cross-sectional analysis of 5690 participants, assessing urinary concentrations of ten heavy metals. Ten heavy metals in urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Fasting residual cholesterol ≥0.8 mmol/L was defined as HRC (using blood samples). Statistical analyses included weighted multivariable logistic regression, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) to evaluate the associations of heavy metal exposure with HRC. Stratified analyses based on individual characteristics were also conducted. Multivariable logistic regression found that the four metals (OR Q4 vs. Q1: 1.33, 95% CI: 1.01-1.75 for barium (Ba); OR Q4 vs. Q1: 1.50, 95% CI: 1.16-1.94 for cadmium (Cd); OR Q4 vs. Q1: 1.52, 95% CI: 1.15-2.01 for mercury (Hg); OR Q4 vs. Q1: 1.35, 95% CI: 1.06-1.73 for lead (Pb)) were positively correlated with the elevated risk of HRC after adjusting for covariates. In addition, all three mixed models, including WQS (OR: 1.25; 95% CI: 1.07-1.46), qgcomp (OR: 1.17; 95% CI: 1.03-1.34), and BKMR, consistently showed a significant positive correlation between co-exposure to heavy metal mixtures and HRC, with Ba and Cd being the main contributors within the mixture. These associations were more pronounced in younger adults (20 to 59 years), males, and those with a higher body mass index status (≥25 kg/m2). Our findings reveal a significant relationship between exposure to the mixture of heavy metals and HRC among US adults, with Ba and Cd being the major contributors to the mixture's overall effect. Public health efforts aimed at reducing heavy metal exposure can help prevent HRC and, in turn, cardiovascular disease.

Residual inflammatory risk and vulnerable plaque in the carotid artery in patients with ischemic stroke.

Inflammation is a central driver of atherogenesis and eventual plaque rupture. This study aimed to evaluate the association between residual inflammatory risk (RIR) and vulnerable plaques in the carotid artery in patients with ischemic stroke. Patients with acute ischemic stroke were enrolled from January 2021 to July 2022. They were divided into four groups: RIR only (LDL-C <2.6 mmol/L and hsCRP ≥2 mg/L), residual cholesterol risk (RCR) only (LDL-C ≥2.6 mmol/L and hsCRP <2 mg/L), both risk or residual cholesterol and inflammatory risk (RCIR) (LDL-C ≥2.6 mmol/L and hsCRP ≥2 mg/L), and neither risk (LDL-C <2.6 mmol/L and hsCRP <2 mg/L). Vulnerable plaques were determined if it had a low attenuated plaque CT value of <35 Hounsfield Units (HU) and a remodeling index of >1.1, which indicated a positive remodeling. Out of the 468 enrolled patients, 157 (33.5%) were detected to have vulnerable plaques. The proportion of patients with neither risk, RIR, RCR, and RCIR were 32.9%, 28.6%, 18.8%, and 19.7%, respectively. Patients with vulnerable plaques exhibited a higher prevalence of hyperlipidemia (P = 0.026), higher proportion of RIR (P = 0.015), a higher ratio of stroke subtypes of large artery atherosclerosis (P = 0.012), and high leukocyte counts (P < 0.001). The logistic regression analysis detected that RIR was associated with vulnerable plaques after adjusted for major confounding factors (OR 1.98, 95% CI 1.13-3.45, P = 0.016), especially in the large artery atherosclerosis subtype (OR 2.71, 95% CI 1.08-6.77, P = 0.034). In patients with ischemic stroke, RIR is associated with the vulnerability of carotid plaques, especially for those with the large artery atherosclerosis subtype. Therefore, further studies investigating the interventions to modulate inflammation in these patients may be warranted.

Prevention of Atherosclerotic Cardiovascular Disease in Rheumatoid Arthritis: Persistent Low-grade In-flammation May be an Impediment Needing Attention

Objective: To determine the status of ‘residual inflammatory risk’ (RIR) and ‘residual cholesterol risk’ (RCR) in patients with Rheumatoid Arthritis (RA) in remission with the aim of estimating their atheroscle-rotic cardiovascular disease (ASCVD) risk. Methods: The study included patients with RA in remission during their last two clinic visits on treatment with disease- mod-ifying anti-rheumatic drugs (DMARDs). Using the QRISK-3 calculator, participants were stratified into four risk categories for ASCVD: ‘Very high’, ‘High’, ‘Moderate’, and ‘Low’. Patients were prescribed lipid-lowering drugs targeting low-density lipoprotein cholesterol (LDL-C) levels to &lt;50 mg/dl, &lt;70 mg/dl, &lt;100 mg/dl or &lt;130 mg/dl, respectively. Those with a history of ASCVD before or during the follow-up period was excluded from the study. Multimorbidity were also recorded in all the patients. Results: The study included 130 patients with RA in remission. The results showed that despite being in remission and taking treatment for lipid control, 81 (62%) and 91 (70%) patients still had ‘RIR’ and ‘RCR’, respectively. Hypertension, hypothyroidism, type-2 diabetes mellitus and obesity were the common multimorbidity. Conclusions: Persistent RIR in 62% of patients despite being in remission, could possibly be due to the current ‘liberal’ definition of RA permitting hs-CRP level up to &lt;10 mg/l, which is five-fold higher than the recommended &lt;2 mg/l for ASCVD prevention. Hence it may be necessary to revise the definition of ‘remission’ in RA factoring in the suggested lower level of hs-CRP. Additionally, rheumatologists might need to be more vigilant in lipid management with appropriate patient education regarding RCR.

Cumulative residual cholesterol predicts the risk of cardiovascular disease in the general population aged 45 years and older

BackgroundNumerous studies have affirmed a robust correlation between residual cholesterol (RC) and the occurrence of cardiovascular disease (CVD). However, the current body of literature fails to adequately address the link between alterations in RC and the occurrence of CVD. Existing studies have focused mainly on individual RC values. Hence, the primary objective of this study is to elucidate the association between the cumulative RC (Cum-RC) and the morbidity of CVD.MethodsThe changes in RC were categorized into a high-level fast-growth group (Class 1) and a low-level slow-growth group (Class 2) by K-means cluster analysis. To investigate the relationship between combined exposure to multiple lipids and CVD risk, a weighted quantile sum (WQS) regression analysis was employed. This analysis involved the calculation of weights for total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), which were used to effectively elucidate the RC.ResultsAmong the cohort of 5,372 research participants, a considerable proportion of 45.94% consisted of males, with a median age of 58. In the three years of follow-up, 669 participants (12.45%) had CVD. Logistic regression analysis revealed that Class 2 individuals had a significantly reduced risk of developing CVD compared to Class 1. The probability of having CVD increased by 13% for every 1-unit increase in the Cum-RC according to the analysis of continuous variables. The restricted cubic spline (RCS) analysis showed that Cum-RC and CVD risk were linearly related (P for nonlinearity = 0.679). The WQS regression results showed a nonsignificant trend toward an association between the WQS index and CVD incidence but an overall positive trend, with the greatest contribution from TC (weight = 0.652), followed by LDL (weight = 0.348).ConclusionCum-RC was positively and strongly related to CVD risk, suggesting that in addition to focusing on traditional lipid markers, early intervention in patients with increased RC may further reduce the incidence of CVD.

Diagnostic Value of Echocardiography Combined with Residual Cholesterol for Asymptomatic Myocardial Ischaemia in Coronary Artery Disease.

This study aimed to investigate the diagnostic value of combined echocardiography and residual cholesterol in asymptomatic myocardial ischaemia. One hundred and fifty-seven patients were seen at Hefei BOE Hospital from 2019 to 2022. The patients were divided into two groups, the observation group (n=90, confirmed asymptomatic myocardial ischaemia) and the control group (n=67, negative diagnosis), based on coronary angiography. The observation group had significantly higher residual cholesterol levels (p=0.001). A combined approach of echocardiography and serum residual cholesterol values showed statistically higher accuracy (p<0.05), with ROC curve analysis supporting the superiority of this method [AUC 0.788 (0.711-0.865), Yoden index 0.576]. It also demonstrated higher sensitivity (88.9%) and specificity (68.7%). The study concluded that combined echocardiography and serum residual cholesterol testing offer superior diagnostic efficacy and practicality for asymptomatic myocardial ischaemia, recommending it for the clinical use. Key Words: Echocardiography, Residual cholesterol, Asymptomatic myocardial ischaemia, Diagnosis.

Association between nontraditional lipid parameters and the risk of type 2 diabetes and prediabetes in patients with nonalcoholic fatty liver disease: from the national health and nutrition examination survey 2017-2020.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder strongly linked to type 2 diabetes mellitus (T2DM). Understanding the predictive value of lipid parameters in identifying abnormal glucose metabolism in NAFLD patients is crucial for early intervention. This study analyzed data from the National Health and Nutrition Examination Survey(NHANES) database (2017-2020) involving 1066 NAFLD patients. Participants were categorized into three groups: T2DM (n=414), prediabetes mellitus (pre-DM) (n=507), and normoglycemia (NG) (n=145). Traditional lipid parameters [triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)] and nontraditional lipid parameters [atherogenic index of plasma (AIP), residual cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C)] were evaluated for their association with T2DM and pre-DM. Elevated TG levels were significantly associated with an increased risk of T2DM and pre-DM, whereas high HDL-C demonstrated a protective effect. Among nontraditional lipid parameters, increased AIP and RC were most strongly associated with T2DM risk, while high non-HDL-C was best associated with the development of pre-DM. Stratified analyses revealed that these associations were stronger in younger, non-obese, smoking, and female NAFLD patients. Nontraditional lipid parameters, particularly AIP and RC, show superior predictive value over traditional lipid parameters in identifying abnormal glucose metabolism in NAFLD patients. Incorporating these novel biomarkers into clinical practice could enhance early detection and prevention strategies for T2DM and pre-DM in this high-risk population.

Using XGBoost for Predicting In-Stent Restenosis Post-DES Implantation: Role of Lymphocyte-to-Monocyte Ratio and Residual Cholesterol.

This study aims to investigate their correlation and predictive utility for in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI). We collected medical records of 668 patients who underwent PCI treatment from January 2022 to December 2022. Based on follow-up results (ISR defined as luminal narrowing ≥ 50% on angiography), all participants were divided into ISR and non-ISR groups. The XGBoost machine learning (ML) model was employed to identify the optimal predictive variables from a set of 31 variables. Discriminatory ability was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), while calibration and performance of the prediction models were assessed using the Hosmer-Lemeshow (HL) test and calibration plots. Clinical utility of each model was evaluated using decision curve analysis (DCA). In the XGBoost importance ranking of predictive factors, LMR and RC ranked first and fourth, respectively. The AUC of the entire XGBoost ML model was 0.8098, whereas the model using traditional stepwise backward regression, comprising five predictive factors, had an AUC of 0.706. The XGBoost model showed superior predictive performance with a higher AUC, indicating better discrimination and predictive accuracy for ISR compared to traditional methods. LMR and RC are identified as cost-effective and reliable biomarkers for predicting ISR risk in ACS patients following drug-eluting stent (DES) implantation. LMR and RC represent cost-effective and reliable biomarkers for predicting ISR risk in ACS patients following drug-eluting stent implantation. Enhances the accuracy and clinical utility of ISR prediction models, offering clinicians a robust tool for risk stratification and personalized patient management.

Relationship between residual cholesterol and cognitive performance: a study based on NHANES.

Age-related cognitive impairment impacts a significant portion of the elderly population. Remnant cholesterol (RC) has attracted increased attention in relation to cardiovascular disease, diabetes, hypertension, and fatty liver disease. Nevertheless, its role in cognitive function is still enigmatic, prompting our exploration into the potential associations between them. A total of 1,331 participants from the NHANES (2011-2014) database, all aged over 60, were included in this investigation. Cognitive function was assessed using four widely applied tests, including the Consortium to Establish a Registry for Alzheimer's Disease Word Learning (CERAD-WL), CERAD Delayed Recall (CERAD-DR), Animal Fluency Test (AFT), as well as Digit Symbol Substitution test (DSST). Z-score is calculated by scores from the above four tests. The association between RC, total cholesterol (TC) to RC and cognitive performance was assessed by logistic regression analyses. In addition, restricted cubic spline (RCS) regression was performed to assess non-linearity between RC and cognitive function. Subgroup analysis was performed to evaluate the robustness of the results in populations with relevant covariate variables. Those with Z-scores below the 25% quartile are defined as having cognitive impairment, totaling 498 individuals. Observationally, higher RC levels and a lower TC/RC were associated with an increased risk of cognitive impairment. After adjusting for confounding factors, the impact of RC levels on cognitive performance quartiles was consistent across various subgroups, except in individuals with trouble sleeping, no/unknown alcohol use, and no hypertension. Americans with high RC levels and trouble sleeping are more likely to develop cognitive impairment, with an odds ratio of 2.33 (95% CI: 1.18-4.59). This study suggests that higher RC levels and lower levels of TC/RC are associated with an increased likelihood of cognitive impairment, suggesting that RC can serve as a novel and convenient indicator for predicting the risk of cognitive impairment in the US population.

BIOMARKERS OF CARDIOVASCULAR COMPLICATIONS ASSOCIATED WITH COVID-19 DISEASE

The coronavirus disease (COVID-19), which caused a global pandemic in the world, is now becoming an endemic, seasonal disease. Therefore, the search for new biomarkers to predict the course of the disease and its outcomes remains extremely important. It has been found that COVID-19 affects not only the respiratory system but also other organs and systems of the body. In particular, the target of the SARS-CoV-2 virus is the cardiovascular system. Because the severity of COVID-19 disease is highly variable, laboratory biomarkers can provide important prognostic information already at the emergency stage, especially in patients with atypical manifestations. It has been demonstrated that viral infections, and in particular COVID-19, can cause changes in the host's lipid profile. Changes in the processes of intracellular cholesterol biosynthesis and its transport in the bloodstream of patients with COVID-19 have been reported. Thus, in patients suffering from COVID-19, significantly reduced levels of total іукгь cholesterol (C), HDL, and LDL cholesterol, and an increased ratio of triglycerides/C have been recorded. Patients with COVID-19 are characterized by an increased content of residual (remnant) cholesterol, which is defined as cholesterol present in residual lipoproteins rich in triglycerides and, as shown by the results of genetic, observational, and clinical studies, is associated with the development of atherosclerosis and overall mortality. Several peptide cardiac biomarkers have become other predictors of cardiovascular prognosis in patients with COVID-19: highly sensitive cardiac troponin – successfully used in clinical practice as a marker of myocyte damage for diagnosis and prognostic assessment of acute coronary syndrome; N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of myocardial stretch; peptide ST2 – a marker of remodeling of myocardial extracellular matrix, which prevents fibrosis, cardiac hypertrophy and apoptosis; copeptin is a biomarker of neurohumoral activation. The review provides a concise analysis of currently known cardiac biomarkers in COVID-19 and their prognostic significance.

The analysis of serum lipids profile in Guillain-Barre syndrome.

Guillain-Barre syndrome (GBS) is an immune-mediated inflammatory peripheral neuropathy. This study aimed to conduct a systematic analysis of the serum lipids profile in GBS. We measured the serum lipids profile in 85 GBS patients and compared it with that of 85 healthy controls matched for age and sex. Additionally, we analyzed the correlation between lipids and the severity, subtypes, precursor infections, clinical outcomes, clinical symptoms, immunotherapy, and other laboratory markers of GBS. Compared to the healthy controls, GBS exhibited significantly elevated levels of Apolipoprotein B (APOB), Apolipoprotein C2 (APOC2), Apolipoprotein C3 (APOC3), Apolipoprotein E (APOE), triglycerides (TG), and residual cholesterol (RC). Conversely, Apolipoprotein A1 (APOA1), Apolipoprotein A2 (APOA2), and high-density lipoprotein (HDL) were substantially lower in GBS. Severe GBS displayed noticeably higher levels of APOC3 and total cholesterol (TC) compared to those with mild disease. Regarding different clinical outcomes, readmitted GBS demonstrated higher RC expression than those who were not readmitted. Moreover, GBS who tested positive for neuro-virus antibody IGG in cerebrospinal fluid (CSF) exhibited heightened expression of APOC3 in comparison to those who tested negative. GBS with cranial nerve damage showed significantly reduced expression of HDL and APOA1 than those without such damage. Additionally, GBS experiencing limb pain demonstrated markedly decreased HDL expression. Patients showed a significant reduction in TC after intravenous immunoglobulin therapy. We observed a significant positive correlation between lipids and inflammatory markers, including TNF-α, IL-1β, erythrocyte sedimentation rate (ESR), white blood cells, monocytes, and neutrophils in GBS. Notably, APOA1 exhibited a negative correlation with ESR. Furthermore, our findings suggest a potential association between lipids and the immune status of GBS. The research demonstrated a strong connection between lipids and the severity, subtypes, clinical outcomes, precursor infections, clinical symptoms, immunotherapy, inflammation, and immune status of GBS. This implies that a low-fat diet or the use of lipid-lowering medications may potentially serve as an approach for managing GBS, offering a fresh viewpoint for clinical treatment of this condition.

Abstract 16545: Effect of Residual Risk of Inflammation and Lipoprotein(a) on Adverse Cardiovascular Outcomes in Optimally Treated Patients According to Glucose Tolerance Status

Introduction: Currently, risks of residual inflammation and residual lipoprotein(a) [Lp(a)] remains in patients with coronary artery disease (CAD) even after lipid-lowering therapy. Hypothesis: This study aims to investigate the association between dual residual risk of inflammation and Lp(a) and adverse cardiovascular events in a large, multicenter cohort with CAD, which has not been investigated. Methods: A total of 3,546 patients with CAD were consecutively enrolled. Based on the Lp(a) and hypersensitive C-reactive protein levels, patients were divided into those with no residual risk, residual Lp(a) risk (RLR), residual inflammatory risk (RIR), and residual cholesterol and inflammatory risk (RLIR). All patients were followed for the major adverse cardiovascular events (MACEs), including all cause mortality, non-fatal myocardial infarction, and non-fatal stroke. Multivariable Cox proportional hazard model was conducted to determine hazard ratio (HR) of MACEs for RIR, RCR, and RCIR with different glucose tolerance status. Results: Over an average of 2.01 years follow-up, 326 MACEs were recorded. Multivariate Cox analysis showed that higher RIR were significantly related to an increased risk of MACEs, while elevated RLR were associated with a slightly but non-significantly increased MACEs risk. Moreover, when participants were subgrouped according to RLR, RIR and glucose tolerance status together, High RLR+High RIR+Diabetes group had significantly higher risk of MACEs [hazard ratio (HR) 2.93, 95% confidence interval (CI) 1.71-5.02] compared with the reference group (Low RLR+Low RIR+Non-diabetes). Conclusions: The combination of RLR, RIR and glucose tolerance status potentiated the adverse effect on MACEs among statin-treated patients with CAD, suggesting that multiple residual risk factors assessment may be a better strategy to improve stratification in very-high risk population.

Abstract 12263: Inflammation and Cholesterol as Predictors of Cardiovascular Events and Risk Reduction With Bempedoic Acid Among Statin Intolerant Patients: An Analysis of the CLEAR Outcomes Trial

Introduction: Among contemporary statin-treated patients, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is a stronger predictor of future cardiovascular (CV) events and all-cause mortality than residual cholesterol risk assessed by low density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients is unknown but has implications for the choice of preventive therapies including bempedoic acid, an agent that reduces both LDLC and hsCRP. Methods: In the multi-national CLEAR-Outcomes trial, 13,970 statin-intolerant patients were randomly allocated 1:1 to 180 mg oral bempedoic acid daily or matching placebo and followed for incident myocardial infarction (MI), stroke, coronary revascularization, CV death, and all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse CV events after adjustment for traditional risk factors and treatment (bempedoic acid vs. placebo). Results: Baseline hsCRP was significantly associated with incident composite endpoint of MI, stroke, coronary revascularization, and CV death (highest vs lowest hsCRP quartile, HR=1.43, 95% CI 1.24-1.65), CV mortality (HR=2.00, 95% CI 1.53-2.61), and all-cause mortality (HR=2.21, 95% CI 1.79-2.73). By contrast, the relationship of baseline LDLC quartile (highest vs. lowest) to future CV events was smaller for the composite endpoint (HR=1.19, 95% CI 1.04-1.37) and neutral for CV mortality (HR 0.90, 95% CI 0.70-1.17) and all-cause mortality (HR 0.95, 95% CI 0.78-1.16) such that risks were high for those with elevated hsCRP irrespective of LDLC level. Compared to placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months and demonstrated similar efficacy in reducing major adverse CV events across all levels of hsCRP and LDLC. Interpretation: Among contemporary statin-intolerant patients, inflammation assessed by hsCRP was a stronger predictor of risk for future CV events and death than was hyperlipidemia assessed by LDLC. Compared to placebo, bempedoic acid had similar efficacy for reducing CV risk across hsCRP and LDLC strata.

Association of exposures to serum terpenes with the prevalence of dyslipidemia: a population-based analysis.

This study sought to examine hitherto unresearched relationships between serum terpenes and the prevalence of dyslipidemia. Serum terpenes such as limonene, α-pinene, and β-pinene from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were used as independent variables in this cross-sectional study. Continuous lipid variables included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), residual cholesterol (RC), and apolipoprotein B (Apo B). Binary lipid variables (elevated TC, ≥5.18 mmol/L; lowered HDL-C, <1.04 mmol/L in men, and <1.30 mmol/L in women; elevated non-HDL-C, ≥4.2 mmol/L; elevated TG, ≥1.7 mmol/L; elevated LDL-C, ≥3.37 mmol/L; elevated RC, ≥1.0 mmol/L; and elevated Apo B, ≥1.3 g/L) suggest dyslipidemia. The relationships between the mixture of serum terpenes with lipid variables were investigated using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). The study for TC, HDL-C, and non-HDL-C included a total of 1,528 people, whereas the analysis for TG, LDL-C, RC, and Apo B comprised 714 participants. The mean age of the overall participants was 47.69 years, and 48.77% were male. We found that tertiles of serum terpene were positively associated with binary (elevated TC, non-HDL-C, TG, LDL-C, RC, Apo B, and lowered HDL-C) and continuous (TC, non-HDL-C, TG, LDL-C, RC, and Apo B, but not HDL-C) serum lipid variables. WQS regression and BKMR analysis revealed that the mixture of serum terpenes was linked with the prevalence of dyslipidemia. According to our data, the prevalence of dyslipidemia was correlated with serum concentrations of three terpenes both separately and collectively.

Remnant cholesterol has an important impact on increased carotid intima-media thickness in non-diabetic individuals

To investigate the correlation the correlation between residual cholesterol (RC) and increased carotid intima-media thickness(cIMT) in non-diabetic individuals. This study included 1786 non-diabetic individuals who underwent carotid ultrasound. RC was calculated based on total cholesterol (TC), LDL-C, and high density lipoprotein cholesterol (HDL-C). The subjects were divided into the cIMT thickening group (cIMT ≥ 0.1 cm) and non-thickening group (cIMT < 0.1 cm) groups based on cIMT, binary logistic regression with different models and receiver operating characteristic (ROC) curves were adopted to evaluate the predictive ability of RC in cIMT. Of the research participants , their median age was 55 (49–51) years, 1121 (63%) were male, and 209 (12%) had hypertension, and people in the cIMT thickening group (925) were more likely to be older and male than those in the non-thickening group (843). Across the different RC subgroups, there was an increasing trend in maximum cIMT (P < 0.001) as RC levels increased within quartiles. RC was found to be an independent risk predictor for cIMT thickening (all P < in models 1–3); and this result persisted in the LDL-C normal subgroup (P = 0.002). The results suggested that RC was an independent predictor of cIMT thickening in non-diabetic individuals and had a strong atherogenic effect.

Inflammation and cholesterol at the crossroads of vascular risk

Although the role of inflammation in atherosclerosis is established, whether this relationship remains important after lowering low-density lipoprotein cholesterol (LDL-C) is still unclear. Recently in The Lancet, Ridker etal. demonstrated that residual inflammatory risk was a stronger predictor of fatal and non-fatal events compared to residual cholesterol risk, supporting the concept of inflammation testing to guide vascular risk reduction.

HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins

BackgroundTo investigate the association of HMGCR and NPC1L1 gene polymorphisms with residual cholesterol risk (RCR) in patients with premature triple-vessel disease (PTVD).MethodsThree SNPs within HMGCR including rs12916, rs2303151, and rs4629571, and four SNPs within NPC1L1 including rs11763759, rs4720470, rs2072183, and rs2073547 were genotyped. RCR was defined as achieved low-density lipoprotein cholesterol (LDL-C) concentrations after statins higher than 1.8 mmol/L (70 mg/dL).ResultsFinally, a total of 609 PTVD patients treated with moderate-intensity statins were included who were divided into two groups: non-RCR group (n = 88) and RCR group (n = 521) according to LDL-C concentrations. Multivariate logistic regression showed the homozygotes for the minor allele of rs12916 within HMGCR gene (CC) were associated with a 2.08 times higher risk of RCR in recessive model [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.16–3.75]. In codominant model, the individuals homozygous for the minor allele of rs12916 (CC) were associated with a 2.26 times higher risk of RCR (OR: 2.26, 95% CI: 1.16–4.43) while the heterozygous individuals (CT) were not, compared with the individuals homozygous for the major allele of rs12916 (TT). There was no significant association between the SNPs within NPC1L1 gene and RCR in various models.ConclusionsWe first reported that the variant homozygous CC of rs12916 within HMGCR gene may incur a significantly higher risk of RCR in PTVD patients treated with statins, providing new insights into early individualized guidance of precise lipid-lowering treatment.