Elevated Remnant Cholesterol Research Articles

Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity

The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.

The role of remnant cholesterol in patients with ST-segment elevation myocardial infarction.

Remnant cholesterol (RC) is the cholesterol content within triglyceride-rich lipoproteins. It promotes atherosclerotic cardiovascular disease beyond LDL cholesterol (LDL-C). The prognostic role of RC in patients with ST-segment elevation myocardial infarction (STEMI) is unknown. We aimed to estimate RC-related risk beyond LDL-C in patients with STEMI. A total of 6602 consecutive patients with STEMI treated with primary percutaneous coronary intervention (PCI) from 1999 to 2016 were included. Remnant cholesterol was calculated as total cholesterol minus LDL-C minus HDL cholesterol. Adjusted Cox models were used to estimate the association between continuous RC levels and all-cause mortality, cardiovascular death, ischaemic stroke, and recurrent myocardial infarction (MI) at long-term (median follow-up of 6.0 years). Besides, discordance analyses were applied to examine the risk of the discordantly high RC (RC percentile rank minus LDL-C percentile rank > 10 units) compared with the discordantly low RC (LDL-C percentile rank minus RC percentile rank > 10 units). The concordance was defined as the percentile rank difference between RC and LDL-C ≤ 10 units. The median age of patients was 63 years [interquartile range (IQR) 54-72] and 74.8% were men. There were 2441, 1651, and 2510 patients in the discordantly low RC group, concordant group, and discordantly high RC group, respectively. All outcomes in the discordantly high RC group were higher than the other groups, and the event rate of all-cause mortality in this group was 31.87%. In the unadjusted analysis, the discordantly high RC was associated with increased all-cause mortality [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.63-2.04] and increased cardiovascular death (HR 1.79, 95% CI 1.55-2.06) compared with the discordantly low RC. In an adjusted model, RC was associated with higher all-cause mortality (HR 1.14, 95% CI 1.07-1.22). The discordantly high RC was associated with increased all-cause mortality (adjusted HR 1.55, 95% CI 1.37-1.75) and increased cardiovascular death (adjusted HR 1.47, 95% CI 1.25-1.72) compared with the discordantly low RC. There were no associations between RC and ischaemic stroke or recurrent MI. In patients with STEMI treated with primary PCI, elevated RC levels beyond LDL-C and discordantly high RC were independently associated with increased all-cause mortality.

Association between remnant cholesterol and insulin resistance levels in patients with metabolic-associated fatty liver disease

The relationship between remnant cholesterol (RC) and homeostasis model assessment-insulin resistance (HOMA-IR) in the context of metabolic-associated fatty liver disease (MAFLD) remains an area of ambiguity. This investigation was designed to elucidate the potential association between RC and HOMA-IR in a cohort of American adults diagnosed with MAFLD. Data from 5533 participants were procured from the 2017–2018 US National Health and Nutrition Examination (NHANES) databases. A weighted linear regression model was employed to analyze the association between RC and HOMA-IR in the context of MAFLD. Preliminary analysis revealed that 44.67% of the participants were diagnosed with MAFLD, with a higher prevalence observed in individuals aged 50–64 years (31.84%, p < 0.0001) and in males compared to females (53.48% vs. 46.52%, p < 0.0001). A positive correlation was identified between RC and HOMA-IR in MAFLD patients. The threshold effect analysis model indicated a breakpoint at RC = 30 mg/dl, with a more pronounced positive correlation when RC < 30 mg/dl (β = 0.17, p < 0.001). Receiver operating characteristic analysis further demonstrated that among all lipid parameters, RC exhibited the largest area under the curve. The study findings suggest a positive correlation between RC and HOMA-IR in MAFLD patients, indicating that elevated RC may serve as an independent risk factor for MAFLD.

Elevated remnant cholesterol and non-HDL cholesterol concentrations from real-world laboratory results: a cross-sectional study in Southeast Asians.

Triglyceride-rich remnant lipoproteins (TRLs) are considered atherogenic due to the presence of remnant cholesterol, which is transported by apolipoprotein B. In clinical practice, the concentration of TRLs can be estimated by calculating remnant cholesterol or non-HDL cholesterol levels. This study aims to investigate the proportion of patients who have low LDL cholesterol (LDL-C) concentration but elevated remnant cholesterol concentration, stratified by the presence of hypertriglyceridaemia and ethnicity, using real-world hospital data. Our secondary aim is to investigate the proportion of patients with elevated non-HDL cholesterol levels using guideline-recommended goals. A 2-year retrospective study was conducted at a single centre, analyzing lipid blood tests of all patients, including directly measured LDL-C. Fasting for blood tests was not mandatory. The study included a total of 21,605 consecutive patients with plasma lipid profiles analyzed in our hospital laboratory. The median age was 61 years. In patients with ASCVD (n = 14,704), 23.7% had an LDL-C level of <1.8 mmol/L, 11.3% had elevated remnant cholesterol concentrations at ≥0.65 mmol/L, and 48.8% were at the non-high-density lipoprotein cholesterol (non-HDL-C) goal (<2.6 mmol/L). Among patients diagnosed with atherosclerotic cardiovascular disease (ASCVD) with LDL-C levels of <1.8 mmol/L (n = 3,484), only 11.9% had high levels of remnant cholesterol, but 96% of the ASCVD patients also achieved the recommended non-HDL-C target of <2.6 mmol/L. When the LDL-C level was <1.8 mmol/L, the mean concentration of remnant cholesterol was 0.214 mmol/L when the triglyceride level was <1.7 mmol/L (n = 3,380), vs. 0.70 mmol/L when the triglyceride level was elevated (n = 724), p < 0.001. Among patients with a triglyceride level of ≥1.7 mmol/L and an LDL-C level of <.8 mmol/L, there were 254 patients with elevated remnant cholesterol concentration and 71 patients with suboptimal non-HDL levels. Malays had a higher mean remnant cholesterol concentration compared with both Chinese and Indians across all LDL-C levels, particularly in the presence of hypertriglyceridaemia. An elevated remnant cholesterol concentration of >0.65 mmol/L was present in 11% of all patients. The current guideline-recommended non-HDL-C goal, which uses a 0.8 mmol/L estimate of remnant cholesterol concentration, was achieved in >92% of patients, suggesting that it is unlikely to be clinically useful for the majority of our patient population except where there is concomitant hypertriglyceridaemia. Further studies are needed to establish the appropriate non-HDL-C goal or calculated remnant cholesterol concentration, paired with the LDL-C goal or otherwise, in a Southeast Asian population.

Remnant cholesterol and risk of incident hypertension: a population-based prospective cohort study.

Remnant cholesterol (RC) has been associated with atherosclerotic cardiovascular disease, but its relationship with hypertension remains unclear. This prospective cohort study aimed to investigate the association between RC and subsequent hypertension risk. Data from the UK Biobank, comprising 295,062 participants initially free of hypertension, were analyzed. Cox proportional hazards regression assessed the association between RC quartiles and hypertension risk. Discordance analysis evaluated the risk of hypertension in discordant/concordant groups of RC and low-density lipoprotein cholesterol (LDL-C) using the difference in percentile units (>10 units). Restricted cubic spline curves were used to model the relationship between RC and hypertension risk. The mean ± SD age of participants was 55.1 ± 8.1 years, with 40.6% being men and 94.7% White. During a median follow-up of 12.8 years, 39,038 participants developed hypertension. Comparing extreme quartiles of RC, the hazard ratio (HR) for incident hypertension was 1.20 (95% CI: 1.17-1.24). After adjusting for traditional risk factors, each 1 mmol/L increase in RC levels was associated with a 27% higher risk of incident hypertension (HR: 1.27; 95% CI: 1.23-1.31). The discordant group with high RC/low LDL-C exhibited a higher risk of incident hypertension compared to the concordant group (HR: 1.06; 95% CI: 1.03-1.09). Spline curves further demonstrated a positive association between RC and the risk of incident hypertension. We concluded that elevated RC emerged as an independent risk factor of incident hypertension, extending beyond traditional risk factors. Monitoring RC levels and implementing interventions to lower RC may have potential benefits in preventing hypertension.

Effects of elevated remnant cholesterol on outcomes of acute ischemic stroke patients receiving mechanical thrombectomy.

Large cohort studies provided evidence that elevated remnant cholesterol (RC) was an important risk factor for ischemic stroke. However, the association between high RC and clinical outcomes in acute ischemic stroke (AIS) individuals was still undetermined. This retrospective study enrolled 165 AIS patients undergoing mechanical thrombectomy in one tertiary stroke center. We divided patients into two groups based on the median of their RC levels (0.49 mmol/L). The modified Rankin Scale (mRS) was used to evaluate the primary outcome 90 days after the onset of symptoms. The mRS scores ≤ 2 and ≤ 1 at 90 days were deemed as favorable and excellent outcomes, respectively. In the overall AIS patients undergoing mechanical thrombectomy, there was no obvious distinction between the high and low RC group at 90-day favorable outcome (41.0% vs. 47.1%, P = 0.431) or excellent outcome (23.1% vs. 31.0%, P = 0.252). In the subgroup analysis stratified by stroke etiology, non-large artery atherosclerosis (non-LAA) stroke patients yielded with less favorable or excellent prognosis in the high RC group (26.8% vs. 46.8%, adjusted OR = 0.31, 95%CI: 0.11-0.85, P = 0.023; or 12.2% vs. 29.0%, adjusted OR = 0.18, 95%CI: 0.04-0.80, P = 0.024, respectively.). Post hoc power analyses indicated that the power was sufficient for favorable outcome (80.38%) and excellent outcome (88.72%) in non-LAA stroke patients. Additionally, RC can enhance the risk prediction value of a poor outcome (mRS scores 3-6) based on traditional risk indicators (including age, initial NIHSS score, operative duration, and neutrophil-to-lymphocyte ratio) for non-LAA stroke patients (AUC = 0.86, 95%CI: 0.79-0.94, P < 0.001). In AIS patients undergoing mechanical thrombectomy, elevated RC was independently related to poor outcome for non-LAA stroke patients, but not to short-term prognosis of LAA stroke patients.

Remnant cholesterol and all-cause mortality risk: findings from the National Health and Nutrition Examination Survey, 2003-2015.

Cholesterol carried in triglyceride-rich lipoproteins, also called remnant cholesterol, is increasingly acknowledged as an important causal risk factor for atherosclerosis. Elevated remnant cholesterol, marked by elevated plasma triglycerides, is associated causally with an increased risk of atherosclerotic cardiovascular disease. However, the association with all-cause mortality and cause-specific mortality is inconclusive. This study aimed to test the hypothesis that remnant cholesterol levels and plasma triglycerides are associated with increased all-cause mortality and mortality from cardiovascular disease, cancer, and other causes. Using a contemporary population-based cohort, 7,962 individuals from the National Health and Nutrition Examination Survey (NHANES) aged over 40 years at baseline in 2003-2015 were included. During up to 109.2 (± 1.44) months of follow-up, 1,323 individuals died: 385 individuals died from cardiovascular disease, 290 from cancer, 80 from cerebrovascular disease, and 568 from other causes. Compared with the middle tertile remnant cholesterol level, multivariable-adjusted mortality hazard ratios were 1.20 (95% confidence interval 1.02-1.40) for all-cause mortality. For the highest tertile remnant cholesterol level, multivariable-adjusted mortality hazard ratios were 1.21 (95% confidence interval 1.05,1.40). Our conclusions remained stable in subgroup analyses. Exploratory analysis of the cause of death subcategories showed corresponding hazard ratios of 1.25 (1.13-1.38) for Non-cardiovascular and Non-cerebrovascular Death for lower remnant cholesterol individuals, 1.47 (1.01-2.15) for cancer death for lower remnant cholesterol (RC) individuals, and 1.80 (1.36-2.38) for cancer death for higher RC individuals. RC levels were associated with U-shaped all-cause mortality. RC was associated with mortality from non-cardiovascular, non-cerebrovascular, and cancer, but not from cardiovascular causes. This novel finding should be confirmed in other cohorts.

Remnant cholesterol and risk of premature mortality: an analysis from a nationwide prospective cohort study.

To explore the relationship between remnant cholesterol (RC) and the risk of premature mortality as well as life expectancy in the general population. We included a total of 428 804 participants from the UK Biobank for analyses. Equivalent population percentiles approach based on the low-density lipoprotein cholesterol cut-off points was performed to categorize participants into three RC groups: low (with a mean RC of 0.34mmol/L), moderate (0.53mmol/L), and high (1.02mmol/L). We used multivariable Cox proportional hazards models to evaluate the relationship between RC groups and the risk of premature mortality (defined as death before age 75 years). Life table methods were used to estimate life expectancy by RC groups. During a median follow-up of 12.1 years (Q1-Q3 11.0-13.0), there were 23 693 all-cause premature deaths documented, with an incidence of 4.83 events per 1000 person-years [95% confidence interval (CI): 4.77-4.89]. Compared with the low RC group, the moderate RC group was associated with a 9% increased risk of all-cause premature mortality [hazard ratio (HR) = 1.09, 95% CI: 1.05-1.14], while the high RC group had an 11% higher risk (HR=1.11, 95% CI: 1.07-1.16). At the age of 50 years, high RC group was associated with an average 2.2 lower years of life expectancy for females, and an average 0.1 lower years of life expectancy for males when compared with their counterparts in the low RC group. Elevated RC was significantly related to an increased risk of premature mortality and a reduced life expectancy. Premature death in the general population would benefit from measurement to aid risk stratification and proactive management of RC to improve cardiovascular risk prevention efforts.

Effects of remnant cholesterol on the efficacy of genotype-guided dual antiplatelet in CYP2C19 loss-of -function carriers with minor stroke or transient ischaemic attack: a post-hoc analysis of the CHANCE-2 trial

The atherogenicity of remnant cholesterol (RC), a contributor to residual risk of cardiovascular events, has been underlined by recent guidelines. We aimed to evaluate the relationship between RC levels and the efficacy and safety of genotype-guided dual antiplatelet therapy in the CHANCE-2 trial. This post-hoc study used data from the CHANCE-2 trial, which was a randomised, double-blind, placebo-controlled trial of 6412 patients (aged >40 years) enrolled from 202 hospitals in China, between Sept 23, 2019, and March 22, 2021, who carried CYP2C19 loss-of-function alleles and had either an acute minor stroke or high-risk transient ischaemic attack (TIA), and could start treatment within 24h of symptom onset. Participants received either (1:1) ticagrelor plus aspirin (control) or clopidogrel plus aspirin (intervention) and the effect of reducing the 3-month risk of any new stroke was assessed (ischemic or haemorrhagic, primary outcome). From the CHANCE-2 study population, we enrolled 5890 patients with complete data on RC. The cutoff point of RC for distinguishing patients with greater benefit from ticagrelor-aspirin versus clopidogrel-aspirin was determined with subpopulation treatment effect pattern plot. The primary efficacy and safety outcome was recurrent stroke and severe or moderate bleeding within 90 days, respectively. CHANCE-2 is registered with ClinicalTrials.gov, NCT04078737. The cutoff to define elevated RC was 0.91mmol/L. Ticagrelor-aspirin versus clopidogrel-aspirin was associated with a reduced risk of recurrent stroke in patients with non-elevated RC levels (122 [5.3%] versus 179 [7.8%]; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.54-0.85), but this benefit was absent in those with elevated RC levels (58 [8.4%] versus 48 [7.3%]; HR, 1.10; 95% CI, 0.73-1.65; P-interaction=0.03). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin on recurrent stroke decreased as RC levels increased. The rates of severe or moderate bleeding between treatment groups were similar across RC categories (0.3% versus 0.3%, P-interaction=0.95). Our post-hoc findings suggest that RC could be a potential biomarker to discriminate patients who received more benefits from ticagrelor-aspirin versus clopidogrel-aspirin therapy in CYP2C19 loss-of-function carriers with minor stroke or TIA. These findings need to be validated in an independent study. The National Key Research and Development Program of China, Beijing Natural Science Foundation Haidian original innovation joint fund, Fund for Young Talents of Beijing Medical Management Center, the high-level public health talents, Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University; and Salubris.

Elevated remnant cholesterol in atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study

Abstract Background Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population; the association in individuals with diabetes is not known. Purpose We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of peripheral artery disease, myocardial infarction, ischemic stroke, and any ASCVD in individuals with diabetes. Methods We studied 4,569 individuals with diabetes and 102,674 individuals without diabetes from the Copenhagen General Population Study (2003-2015). In those with diabetes, during up to 15 years of follow-up, 236 were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischemic stroke, and 498 with any ASCVD in national Danish health registries. Remnant cholesterol was calculated from a standard lipid-profile as total cholesterol minus HDL cholesterol minus LDL cholesterol. Results Individuals with diabetes had higher levels of remnant cholesterol, but lower levels of LDL cholesterol, compared to individuals without diabetes (Figure 1). Statin use could explain the lower levels of LDL cholesterol but did not associate with levels of remnant cholesterol. Multivariable adjusted hazard ratios (95% confidence interval) per doubling of remnant cholesterol and LDL cholesterol were 1.8 (1.2-2.5) and 0.9 (0.6-1.2) for peripheral artery disease, 1.8 (1.3-2.6) and 1.0 (0.7-1.4) for myocardial infarction, 1.6 (1.1-2.3) and 1.1 (0.8-1.6) for ischemic stroke, and 1.7 (1.4-2.2) and 0.9 (0.7-1.1) for any ASCVD, respectively. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischemic stroke, and 1.6-fold for any ASCVD. Elevated remnant cholesterol explained 14% (95% confidence interval: 6-23%) of excess risk of PAD; corresponding numbers were 26% (10-41%) for myocardial infarction, 34% (5-64%) for ischemic stroke, and 24% (12-36%) for any ASCVD (Figure 2). LDL cholesterol was lower in individuals with diabetes than in individuals without diabetes and could therefore not explain excess risk. Conclusions Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes and explained 24% of their excess risk of ASCVD. Clinical trials should determine if remnant cholesterol lowering can prevent ASCVD in individuals with diabetes.

Atherogenic lipid profile in patients with acute coronary syndrome

Abstract Background Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients with acute coronary syndrome (ACS). Objective To evaluate the control status of atherogenic lipid profile among ACS patients within 12 months after discharge. Methods We retrospectively analyzed the data from the multi-center iHeart program. Twenty tertiary hospitals in China were included. Natural language processing technique was used to extract real-world data from electronic health records (EHRs). Patients with a diagnosis of ACS from January 2014 to December 2021 during index hospitalization and having at least one medical record after discharge within 12 months were enrolled. Measurements of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non–high-density lipoprotein cholesterol (non-HDL-C), triglycerides (TGs), apolipoprotein B (ApoB), lipoprotein (a) (Lp[a]) at baseline and follow-up were collected and analyzed. Remnant cholesterol (RC) was calculated as TC minus HDL-C minus LDL-C. The treatment goal of LDL-C was defined as &amp;lt;1.8 mmol/L according to the guideline. An even lower LDL-C goal of &amp;lt;1.4 mmol/L was recommended in specific patients at extremely high risk with concomitant diabetes or ischemic cerebral vascular diseases. Results Among the 3956 patients, the mean age was 72 (12) years, and 64.8% were men. Diabetes was common (22.7%). There were 1612 (40.7%) patients with unstable angina, 391(9.9%) patients with non-ST-elevation myocardial infarction, 1146 (29.0%) patients with ST-elevation myocardial infarction, and 807 (20.4%) patients with undetermined ACS category. At baseline, the mean values for TC, LDL-C, HDL-C, non-HDL-C, ApoB, and RC were 4.61 (1.26) mmol/L, 2.83 (0.98) mmol/L, 1.12 (0.30) mmol/L, 3.38 (0.75) mmol/L, 96 (34) mg/dL, and 0.65 (0.56) mmol/L, respectively. The median values for TGs and Lp(a) were 1.44 mmol/L [1.06, 2.00] and 27.22 mg/dL [12.34, 39.2], respectively. The rate of lipid-lowering treatment was 94.8% (statins 93.1%, PCSK9 inhibitors 0.4%). The levels of TC, TGs, LDL-C, HDL-C, non-HDL-C, and ApoB were significantly decreased (P &amp;lt; 0.001) within 12 months. Median Lp(a) was 19.52 mg/dL [8.73, 39.08] (P = 0.117). Mean RC was 0.69 (1.10) mmol/L (P &amp;lt; 0.001). Overall, the proportion of patients achieving the LDL-C level of &amp;lt;1.8 mmol/L at baseline increased from 13.42% to 36.6% during follow-up. In patients with concomitant diabetes or ischemic cerebral vascular diseases, the rate of LDL-C &amp;lt;1.4 mmol/L was 17.79% and 17.52%, respectively. Conclusion Only 1/3 of patients had LDL-C &amp;lt;1.8mmol/L within 12 months after ACS. Despite the high treatment rate of statins, Lp(a) level had no change beyond the reduction in LDL-C. Elevated remnant cholesterol may be a critical contributor to residual risk. Novel therapeutics targeting the whole atherogenic lipid profile will be warranted to improve cardiovascular outcomes.LDL-C control rate within 12 months

Abstract 16738: Impact of Remnant Cholesterol Level on Long-Term Outcomes in Patients With Multivessel Disease Undergoing Coronary Artery Bypass Grafting

Introduction: The remnant cholesterol (RC) is being increasingly documented as an important risk factors of coronary artery disease. Thus far, the impact of RC level on the long-term outcomes of patients with multivessel coronary artery disease (MVD) undergoing coronary artery bypass graft (CABG) has not been investigated. Hypothesis: Elevated RC level is associated with increased risk of MACCEs in patients with MVD undergoing CABG. Methods: All patients who were diagnosed with multivessel coronary artery disease and undergoing CABG between 2011 and 2020 were considered for enrollment. RC was calculated as total cholesterol minus HDL-C minus LDL-C. Patients were categorized by RC thresholds and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs) was examined according to the RC level at one-year post-CABG. Results: A total of 2,072 patients (60.8 ± 8.3 years; 83.5% men) were included in this study. Patients was divided into four groups: RC &lt; 0.5 mmol /L, RC of 0.5-0.99 mmol/L, RC of 1.0-1.49, mmol/L, and RC ≥ 1.5 mmol/L. During a median follow-up of 4.2 years after the 1-year assessment, 25.0% of the patients had occurrences of MACCEs. The multivariable adjusted hazard ratios (95% CI) for MACCEs, cardiac death, nonfatal myocardial infarction, re-revascularization, cardiac rehospitalization (admission because of angina or heart failure) and nonfatal stroke, were respectively 2.49 (1.99-3.12), 2.20 (1.18-3.86), 3.18 (2.16-5.84), 3.02 (2.12-4.34), 1.93 (1.42-2.87), and 1.37 (0.83-2.27) in patients with RC ≥ 1.50 mmol/L, compared with patients with 1-year RC &lt; 0.5 mmol/L. The 1-year RC level was significantly associated with MACCEs, with the lowest risk of MACCEs reflected in the patients with RC &lt; 0.5 mmol/L. Conclusions : In patients with MVD undergoing CABG, the RC level at one-year after CABG were independently associated with long-term outcomes.

Remnant Cholesterol in Young Adulthood Is Associated With Left Ventricular Remodeling and Dysfunction in Middle Age: The CARDIA Study.

Recent studies have shown that remnant cholesterol (RC) is associated with incident heart failure; however, its association with left ventricular (LV) structure and function is unclear. We aimed to evaluate the association between RC levels in young adulthood and LV structure and function in middle age. We included 3321 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) at baseline. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus calculated low-density lipoprotein cholesterol, and the RC trajectories that followed a similar pattern of change over time were identified using the latent class growth mixture model. LV structure and function were assessed using echocardiography at CARDIA study year 25. Multivariable linear regression models were performed to assess the associations of both baseline and trajectories of RC levels with LV structure and function. Among 3321 participants, the mean age was 24.99±3.62 years: 1450 (43.90%) were male, and 1561 (47.00%) were Black. After multivariate adjustment, higher baseline RC (per SD in log-transformed) was associated with higher LV mass index (β=1.29; P=0.004), worse global longitudinal strain (β=0.19; P<0.001), worse global circumferential strain (β=0.16; P=0.014), lower septal e' (β=-0.26; P<0.001), lower lateral e' (β=-0.18; P=0.003), and higher E/e' (β=0.15; P=0.003). Three RC trajectories were identified during follow-up: low increasing (42.4%), moderate increasing (45.5%), and high increasing (12.1%). Similarly, compared with the low-increasing group, the high-increasing RC trajectory group was related to higher LV mass index, worse global longitudinal strain, lower septal e', lower lateral e', and higher E/e'. Elevated RC levels in young adulthood were related to adverse LV structural and functional alterations in midlife. Long-term trajectories of RC levels during young adulthood help identify individuals at a higher risk for adverse LV remodeling and dysfunction. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005130.

Elevated remnant cholesterol and atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study

Aims/hypothesisElevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. This association is not well studied in individuals with diabetes, who are often included in clinical trials of remnant cholesterol-lowering therapy. We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of ASCVD in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol.MethodsWe included 4569 white Danish individuals with diabetes (58% statin users) nested within the Copenhagen General Population Study (2003–2015). The ASCVDs peripheral artery disease, myocardial infarction and ischaemic stroke were extracted from national Danish health registries without losses to follow-up. Remnant cholesterol was calculated from a standard lipid profile.ResultsDuring up to 15 years of follow-up, 236 individuals were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischaemic stroke and 498 with any ASCVD. Multivariable adjusted HR (95% CI) per doubling of remnant cholesterol was 1.6 (1.1, 2.3; p=0.01) for peripheral artery disease, 1.8 (1.2, 2.5; p=0.002) for myocardial infarction, 1.5 (1.0, 2.1; p=0.04) for ischaemic stroke, and 1.6 (1.2, 2.0; p=0.0003) for any ASCVD. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischaemic stroke and 1.6-fold for any ASCVD. Excess risk explained by elevated remnant cholesterol and low-grade inflammation was 14% and 8% for peripheral artery disease, 26% and 16% for myocardial infarction, 34% and 34% for ischaemic stroke, and 24% and 18% for any ASCVD, respectively. LDL-cholesterol did not explain excess risk, as it was not higher in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol.Conclusions/interpretationElevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes. Remnant cholesterol and low-grade inflammation explained substantial excess risk of ASCVD conferred by diabetes. Whether remnant cholesterol should be used as a treatment target remains to be determined in randomised controlled trials.Graphical

Elevated remnant cholesterol in atherosclerotic cardiovascular disease in diabetes: A population-based prospective cohort study

Elevated remnant cholesterol in atherosclerotic cardiovascular disease in diabetes: A population-based prospective cohort study

Dual elevated remnant cholesterol and C-reactive protein in myocardial infarction, atherosclerotic cardiovascular disease, and mortality

Dual elevated remnant cholesterol and C-reactive protein in myocardial infarction, atherosclerotic cardiovascular disease, and mortality

Association between remnant cholesterol and progression of bioprosthetic valve degeneration.

Remnant cholesterol (RC) seems associated with native aortic stenosis. Bioprosthetic valve degeneration may share similar lipid-mediated pathways with aortic stenosis. We aimed to investigate the association of RC with the progression of bioprosthetic aortic valve degeneration and ensuing clinical outcomes. We enrolled 203 patients with a median of 7.0 years (interquartile range: 5.1-9.2) after surgical aortic valve replacement. RC concentration was dichotomized by the top RC tertile (23.7 mg/dL). At 3-year follow-up, 121 patients underwent follow-up visit for the assessment of annualized change in aortic valve calcium density (AVCd). RC levels showed a curvilinear relationship with an annualized progression rate of AVCd, with increased progression rates when RC >23.7 mg/dL (P = 0.008). There were 99 deaths and 46 aortic valve re-interventions in 133 patients during a median clinical follow-up of 8.8 (8.7-9.6) years. RC >23.7 mg/dL was independently associated with mortality or re-intervention (hazard ratio: 1.98; 95% confidence interval: 1.31-2.99; P = 0.001). Elevated RC is independently associated with faster progression of bioprosthetic valve degeneration and increased risk of all-cause mortality or aortic valve re-intervention.

Relationship between remnant cholesterol and risk of heart failure in participants with diabetes mellitus.

Evidence about the association between calculated remnant cholesterol (RC) and risk of heart failure (HF) in participants with diabetes mellitus (DM) remains sparse and limited. We included a total of 22 230 participants with DM from the UK Biobank for analyses. Participants were categorized into three groups based on their baseline RC measures: low (with a mean RC of 0.41mmol/L), moderate (0.66mmol/L), and high (1.04mmol/L). Cox proportional hazards models were used to evaluate the relationship between RC groups and HF risk. We performed discordance analysis to evaluate whether RC was associated with HF risk independently of low-density lipoprotein cholesterol (LDL-C). During a mean follow-up period of 11.5 years, there were a total of 2232 HF events observed. The moderate RC group was significantly related with a 15% increased risk of HF when compared with low RC group (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.01-1.32), while the high RC group with a 23% higher HF risk (HR=1.23, 95% CI: 1.05-1.43). There was significant relationship between RC as a continuous measure and the increased HF risk (P<0.01). The association between RC and risk of HF was stronger in participants with HbA1c level ≥ 53mmol/mol when compared with HbA1c < 53mmol/mol (P for interaction=0.02). Results from discordance analyses showed that RC was significantly related to HF risk independent of LDL-C measures. Elevated RC was significantly associated with risk of HF in patients with DM. Moreover, RC was significantly related to HF risk independent of LDL-C measures. These findings may highlight the importance of RC management to HF risk in patients with DM.

Dual elevated remnant cholesterol and C-reactive protein in myocardial infarction, atherosclerotic cardiovascular disease, and mortality

Background and aimsElevated remnant cholesterol and low-grade inflammation each cause atherosclerotic cardiovascular disease (ASCVD); however, it is unknown whether joint elevation of both factors confers the highest risk. We tested the hypothesis that dual elevated remnant cholesterol and low-grade inflammation marked by elevated C-reactive protein is associated with the highest risk of myocardial infarction, ASCVD, and all-cause mortality. MethodsThe Copenhagen General Population Study randomly recruited white Danish individuals aged 20–100 years in 2003–2015 and followed them for a median 9.5 years. ASCVD was cardiovascular mortality, myocardial infarction, stroke, and coronary revascularization. ResultsIn 103,221 individuals, we observed 2,454 (2.4%) myocardial infarctions, 5,437 (5.3%) ASCVD events, and 10,521 (10.2%) deaths. The hazard ratios increased with each of stepwise higher remnant cholesterol and stepwise higher C-reactive protein. In individuals with the highest tertile of both remnant cholesterol and C-reactive protein compared to individuals with the lowest tertile of both, the multivariable adjusted hazard ratios were 2.2 (95%CI:1.9–2.7) for myocardial infarction, 1.9 (1.7–2.2) for ASCVD, and 1.4 (1.3–1.5) for all-cause mortality. Corresponding values for only the highest tertile of remnant cholesterol were 1.6 (1.5–1.8), 1.4 (1.3–1.5), and 1.1 (1.0–1.1), and those for only the highest tertile of C-reactive protein were 1.7 (1.5–1.8), 1.6 (1.5–1.7), and 1.3 (1.3–1.4), respectively. There was no statistical evidence for interaction between elevated remnant cholesterol and elevated C-reactive protein on risk of myocardial infarction (p = 0.10), ASCVD (p = 0.40), or all-cause mortality (p = 0.74). ConclusionsDual elevated remnant cholesterol and C-reactive protein confers the highest risk of myocardial infarction, ASCVD, and all-cause mortality, that is, compared to either of these two factors individually.

Remnant Cholesterol Is Associated With Gestational Diabetes Mellitus: A Cohort Study.

The association between remnant cholesterol (RC) and gestational diabetes mellitus (GDM) risk is unclear. This study investigated the association between RC and GDM. We used data from the Tongji Maternal and Child Health Cohort, a prospective cohort study in China. Fasting lipid concentrations were measured around 16 weeks' gestation. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. GDM was diagnosed by a 75-g oral glucose tolerance test at 24 to 28 weeks' gestation. Log-Poisson regression models were performed to estimate relative risks (RRs) of GDM across quartiles of RC levels and triglyceride (TG) levels after adjustment for potential confounders. TG and RC were mutually adjusted. Among 2528 women, 256 (10.1%) developed GDM. The adjusted RRs (95% CIs) for GDM across increasing quartiles of RC were 1.00 (reference), 1.35 (0.91, 1.99), 1.68 (1.16, 2.45), and 1.73 (1.19, 2.50), respectively. Compared to pregnant women without 3 risk indicators (TG <2.08 mmol/L, RC <0.40 mmol/L, and pre-BMI <24.0 kg/m2), the risk of GDM was elevated in those with normal pre-BMI but high RC (aRR: 1.54; 95% CI: 1.08, 2.19) or high TG (aRR: 2.15; 95% CI: 1.33, 3.49). For those with all 3 risk indicators, the risk of GDM was the highest (aRR: 4.80; 95% CI: 3.20, 7.18). Elevated RC levels were associated with the increased risk of GDM and independent of traditional risk factors. Pregnant women with high pre-BMI, high TG, and high RC were at greatly increased risk of GDM.