The role of remnant cholesterol beyond low-density lipoprotein cholesterol in diabetes mellitus

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: June 27, 2022

Abstract Background Previous research has linked elevated low-density lipoprotein cholesterol (LDL-C) and remnant (RC) with diabetes mellitus (DM). The present study aims to estimate the RC-related DM risk beyond LDL-C, investigate extent which association of RC is mediated via insulin resistance inflammation. Methods We enrolled 7308 individuals without previous history into from China Health Nutrition Survey. Fasting was calculated as total minus LDL-C high-density cholesterol. Subjects were divided four groups according their (100 mg/dL) (24 levels evaluate role vs. on DM. A logistic regression analysis then employed relationships between discordant/concordant mediation undertaken identify potential mediators. Results Of all participants, a 625 (8.55%) patients newly diagnosed Compared high LDL-C/low group, low LDL-C/high group more common in patients. After multivariate adjustment, associated Moreover, manifested 4.04-fold (95% CI 2.93–5.56) 1.61-fold 1.21–2.15) higher DM, relative those RC. subgroup indicated that likely be related females. Similar results also shown when sensitivity analyses performed different clinical cut-points LDL-C. Insulin inflammation partially Conclusions Our findings provided evidence for associations may pro-inflammatory state. In addition, women are susceptible exposure-related

Language: Английский

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Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study

European Heart Journal, Journal Year: 2023, Volume and Issue: 44(39), P. 4186 - 4195

Published: June 26, 2023

The strength of the relationship triglyceride-rich lipoproteins (TRL) with risk coronary heart disease (CHD) compared low-density lipoprotein (LDL) is yet to be resolved.

Language: Английский

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Non-HDL-cholesterol in dyslipidemia: Review of the state-of-the-art literature and outlook

Atherosclerosis, Journal Year: 2023, Volume and Issue: 383, P. 117312 - 117312

Published: Sept. 30, 2023

Dyslipidemia refers to unhealthy changes in blood lipid composition and is a risk factor for atherosclerotic cardiovascular diseases (ASCVD). Usually, low-density lipoprotein-cholesterol (LDL-C) the primary goal dyslipidemia management. However, non-high-density lipoprotein cholesterol (non-HDL-C) has gained attention as an alternative, reliable goal. It encompasses all plasma lipoproteins like LDL, triglyceride-rich (TRL), TRL-remnants, [Lp(a)] except high-density (HDL). In addition LDL-C, several other constituents of non-HDL-C have been reported be atherogenic, aiding pathophysiology atherosclerosis. They are acknowledged contributors residual ASCVD that exists patients on statin therapy with controlled LDL-C levels. Therefore, now considered independent or predictor CVD. The popularity attributed its ease estimation non-dependency fasting status. also better at predicting therapy, and/or those obesity, diabetes, metabolic disorders. addition, large follow-up studies individuals higher baseline younger age (<45 years) were more prone adverse CVD events older age, suggesting predictive ability over long term. Consequently, recommended secondary management by most international guidelines. Intriguingly, geographical patterns recent epidemiological showed remarkably high attributable mortality high-risk countries. This review highlights role pathogenesis prognosis. need country-specific approach community/population level discussed. Overall, can become co-primary

Language: Английский

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Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(10), P. 913 - 925

Published: May 29, 2024

Angiopoietin-like 3 (ANGPTL3) inhibits lipoprotein and endothelial lipases hepatic uptake of triglyceride-rich remnants.

Language: Английский

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Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(10), P. 899 - 912

Published: May 28, 2024

Persons with mixed hyperlipidemia are at risk for atherosclerotic cardiovascular disease due to an elevated non-high-density lipoprotein (HDL) cholesterol level, which is driven by remnant in triglyceride-rich lipoproteins. The metabolism and clearance of lipoproteins down-regulated through apolipoprotein C3 (APOC3)-mediated inhibition lipase.

Language: Английский

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Independent Causal Effect of Remnant Cholesterol on Atherosclerotic Cardiovascular Outcomes: A Mendelian Randomization Study

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2023, Volume and Issue: 43(9)

Published: July 13, 2023

Observational studies suggested that residual risk of cardiovascular events after LDL (low-density lipoprotein) cholesterol lowering may be linked to remnant (RC). We conducted a large-scale Mendelian randomization study investigate the causal role RC predict coronary artery disease (CAD), myocardial infarction (MI), and stroke risk.We extracted single-nucleotide polymorphisms for from genome-wide association databases. estimated genetic with outcomes CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-Wide Replication Meta-Analysis Plus Coronary Genetics), Metastroke consortium, as well GLGC (Global Lipids Genetics Consortium). Genetic variants were used instruments, thereby minimizing confounding reverse causation biases observational studies.By leveraging data combined sample 958 434 participants, we found evidence significant effect on CAD (odds ratio [OR], 1.51 per SD unit increase in [95% CI, 1.42-1.60]; P=5.3×10-5), MI (OR, 1.57 1.21-2.05]; P=9.5×10-4), 1.23 1.12-1.35]; P=3.72×10-6). There was no pleiotropy. The remained consistent accounting effects RC-associated cholesterol: OR, 1.49 (95% 1.37-1.61) 1.80 1.70-19.1) without meaningful indirect exerted these via mediator.This showed robust between outcomes. is independent cholesterol. Early screening along long-term inhibition should focus future therapeutic interventions.

Language: Английский

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Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry

European Heart Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Background and Aims Overweight obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence individuals with heterozygous familial hypercholesterolaemia (HeFH) whether they confer additional of ASCVD independent LDL cholesterol (LDL-C) remains unclear. Methods Cross-sectional analysis was conducted 35 540 patients HeFH across 50 countries, EAS FH Studies Collaboration registry. Prevalence World Health Organization–defined body mass index categories investigated adults (n = 29 265) children/adolescents 6275); association prevalent ASCVD. Results Globally, 52% 27% children were overweight or obese, highest noted Northern Africa/Western Asia. A higher overweight/obesity found non-high-income vs. high-income countries. Median age at diagnosis 9 years older than normal weight adults. Obesity associated a more atherogenic lipid profile lipid-lowering medication. coronary artery increased progressively both Compared weight, odds (odds ratio 9.28, 95% confidence interval 1.77–48.77, adjusted age, sex, lipids, medication) stroke 2.35, 2.10–2.63 1.65, 1.27–2.14, respectively), less consistently peripheral disease. Adjusting diabetes, hypertension smoking modestly attenuated associations. Conclusions common contribute to from childhood, LDL-C Sustained management is needed reduce HeFH.

Language: Английский

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Remnant cholesterol and the risk of cardiovascular disease in type 2 diabetes: a nationwide longitudinal cohort study

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: Nov. 2, 2022

Abstract Background Elevated remnant cholesterol (remnant-C) is considered a risk factor for cardiovascular disease (CVD); however, whether this notion applies to the East Asian population with type 2 diabetes (T2D) has not been established. This study investigated association between remnant-C concentrations and of CVD in Korean patients T2D. Methods By using National Health Insurance Service database, 1,956,452 T2D without atherosclerotic who underwent regular health checks 2009 2012 were included. Cox regression analyses conducted assess incident comprising myocardial infarction (MI) ischemic stroke. Results In total, 50,120 (2.56%) cases MI 73,231 (3.74%) strokes occurred during median follow-up 8.1 years. The adjusted hazard ratios stroke highest quartile 1.281 (95% confidence interval [CIs], 1.249–1.314) 1.22 (1.195–1.247) stroke, compared those lowest quartiles. results similar, based on stratified analysis by age, sex, use statin or fibrate, levels other cholesterol. increased was profound had longer duration. A concentration ≥ 30 mg/dL differentiated at higher CVD, lower concentrations, regardless LDL-C target ≤ 100 mg/dL. Conclusion T2D, associated independent level conventional factors. Our finding confirmed evidence causal role as residual

Language: Английский

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Remnant Cholesterol Variability and Incident Ischemic Stroke in the General Population

Stroke, Journal Year: 2022, Volume and Issue: 53(6), P. 1934 - 1941

Published: May 11, 2022

Background: Studies have demonstrated that remnant cholesterol is correlated with the risk of ischemic stroke. However, it unknown whether visit-to-visit variability in concentration affects We sought to examine role subsequent development stroke general population. Methods: performed a post hoc analysis including eligible participants from Kailuan Study cohort who underwent 3 health examinations and were free atrial fibrillation, myocardial infarction, stroke, cancer, or known lipid-medication use 2006 2010. Participants followed up until end 2017. Variability was quantified as independent mean, average real variability, SD. Multivariate using Fine Gray competing model estimate subhazard ratios assuming death risk. Results: The final study comprised 38 556 participants. After median follow-up 7.0 years, 1058 individuals newly diagnosed adjusting for age (time scale), sex, smoking status, alcohol consumption, physical activity, hypertension, diabetes, family history cardiovascular disease, body mass index, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density triglycerides, mean highest quartile (quartile 4) associated an increased compared lowest 1), (subhazard ratio, 1.27 [95% CI, 1.06–1.53]). For each 1-SD increase by 9% 1.09 1.03–1.16]). association also significant SD indices variability. Conclusions: Greater higher

Language: Английский

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Remnant Cholesterol Predicts Long-term Mortality of Patients With Metabolic Dysfunction–associated Fatty Liver Disease

The Journal of Clinical Endocrinology & Metabolism, Journal Year: 2022, Volume and Issue: 107(8), P. e3295 - e3303

Published: May 6, 2022

Abstract Context Elevated serum remnant cholesterol independently predicts risks of cardiovascular diseases. However, the association between and metabolic dysfunction–associated fatty liver disease (MAFLD) remains unclear. Objective This study aimed to explore with MAFLD its long-term mortality. Methods We extracted data from NHANES III, 1988 to1994 linked mortality until December 31, 2015. The was analyzed by multivariable logistic regression. Cox proportional hazards regression performed assess whether elevated increased all-cause cause-specific mortalities in patients. Results At baseline, 28.6% (1474/5156) participants had MAFLD. In regression, fourth quartile associated an risk compared first (odds ratio [OR]: 1.714; 95% CI, 1.586-1.971; P &lt; .001). normal levels triglycerides, low-density lipoprotein high-density cholesterol, relationship remained significant (OR: 1.346; 1.248-1.761; During a median follow-up 307 months, patients were higher (hazard [HR]: 2.183; 1.825-2.407; .001), as well (HR: 2.346; 2.046-2.885; .001) cancer-related 2.366; 1.864-2.932; quartile. Conclusion Remnant predicted all-cause, cardiovascular,

Language: Английский

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