Dataset Information

The LDL Apolipoprotein B-to-LDL Cholesterol Ratio: Association with Cardiovascular Mortality and a Biomarker of Small, Dense LDLs.

ABSTRACT:

Background and objective

Small, dense low-density lipoproteins (LDLs) are considered more atherogenic than normal size LDLs. However, the measurement of small, dense LDLs requires sophisticated laboratory methods, such as ultracentrifugation, gradient gel electrophoresis, or nuclear magnetic resonance. We aimed to analyze whether the LDL apolipoprotein B (LDLapoB)-to-LDL cholesterol (LDLC) ratio is associated with cardiovascular mortality and whether this ratio represents a biomarker for small, dense LDLs.

Methods

LDLC and LDLapoB were measured (beta-quantification) and calculated (according to Friedewald and Baca, respectively) for 3291 participants of the LURIC Study, with a median (inter-quartile range) follow-up for cardiovascular mortality of 9.9 (8.7-10.7) years. An independent replication cohort included 1660 participants. Associations of the LDLapoB/LDLC ratio with LDL subclass particle concentrations (ultracentrifugation) were tested for 282 participants.

Results

In the LURIC Study, the mean (standard deviation) LDLC and LDLapoB concentrations were 117 (34) and 85 (22) mg/dL, respectively; 621 cardiovascular deaths occurred. Elevated LDLapoB/LDLC (calculated and measured) ratios were significantly and independently associated with increased cardiovascular mortality in the entire cohort (fourth vs. first quartile: hazard ratio (95% confidence interval) = 2.07 (1.53-2.79)) and in statin-naïve patients. The association between calculated LDLapoB/LDLC ratio and cardiovascular mortality was replicated in an independent cohort. High LDLapoB/LDLC ratios were associated with higher LDL5 and LDL6 concentrations (both p < 0.001), but not with concentrations of larger LDLs.

Conclusions

Elevated measured and calculated LDLapoB/LDLC ratios are associated with increased cardiovascular mortality. Use of LDLapoB/LDLC ratios allows estimation of the atherogenic risk conferred by small, dense LDLs.

SUBMITTER: Silbernagel G

PROVIDER: S-EPMC9220033 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

The LDL Apolipoprotein B-to-LDL Cholesterol Ratio: Association with Cardiovascular Mortality and a Biomarker of Small, Dense LDLs.

Silbernagel Günther G Scharnagl Hubert H Saely Christoph H CH Reinthaler Markus M Rief Martin M Kleber Marcus E ME Larcher Barbara B Chapman John J Schaefer Juergen R JR Drexel Heinz H März Winfried W

Biomedicines 20220602 6

Background and Objective: Small, dense low-density lipoproteins (LDLs) are considered more atherogenic than normal size LDLs. However, the measurement of small, dense LDLs requires sophisticated laboratory methods, such as ultracentrifugation, gradient gel electrophoresis, or nuclear magnetic resonance. We aimed to analyze whether the LDL apolipoprotein B (LDLapoB)-to-LDL cholesterol (LDLC) ratio is associated with cardiovascular mortality and whether this ratio represents a biomarker for small, ...[more]

PMID: 35740324

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Project description:BackgroundElevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populations are mostly limited to coronary heart disease.ObjectivesThe purpose of this study was to prospectively evaluate whether triglyceride-rich lipoprotein cholesterol (TRL-C) and small-dense low-density lipoprotein cholesterol (sdLDL-C) concentrations associate with composite and individual incident cardiovascular disease (CVD) outcomes including myocardial infarction (MI), ischemic stroke (IS), and peripheral artery disease (PAD).MethodsIn a prospective case-cohort study within the Women's Health Study, TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens of case subjects (n = 480) and the reference subcohort (n = 496). Risk associations were evaluated for total CVD (MI, IS, PAD, and CVD death), coronary and cerebrovascular disease (MI, IS, CVD death), and individual outcomes (MI, IS, and PAD). Models were adjusted for traditional risk factors, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein.ResultsThe risk of both composite outcomes significantly increased across quartiles of TRL-C and sdLDL-C. TRL-C was significantly associated with MI and PAD (MI hazard ratio [HR]Q4: 3.05 [95% confidence interval (CI): 1.46 to 6.39]; ptrend = 0.002; PAD HRQ4: 2.58 [95% CI: 1.18 to 5.63]; ptrend = 0.019), whereas sdLDL-C was significantly associated with MI alone (HRQ4: 3.71 [95% CI: 1.59 to 8.63]; ptrend < 0.001). Both markers weakly associated with IS. Association patterns were similar for continuous exposures and, for TRL-C, among subjects with low atherogenic particle concentrations (apolipoprotein B <100 mg/dl).ConclusionsTRL-C strongly associates with future MI and PAD events, whereas sdLDL-C strongly associates with MI alone. These findings signal that the cholesterol content of TRLs and sdLDL influence atherogenesis independently of low-density lipoprotein cholesterol, and high sensitivity C-reactive protein, with potentially different potency across vascular beds. (Women's Health Study; NCT00000479).

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Project description:AimsThe total cholesterol (TC)/high-density lipoprotein (HDL) cholesterol ratio may carry additional information not available in more commonly used single cholesterol measures. Analysis of discordance between lipid parameters might help assess the impact of such additional information on the risk of atherosclerotic cardiovascular disease. We aimed to investigate the role of the TC/HDL-cholesterol ratio in determining atherosclerotic cardiovascular disease risk when discordant with low-density lipoprotein (LDL) cholesterol and non-HDL-cholesterol.MethodsWe studied 14,403 Atherosclerosis Risk in Communities (ARIC) study participants who were free of atherosclerotic cardiovascular disease at baseline. TC/HDL-cholesterol discordance with LDL-cholesterol (estimated by the novel Martin/Hopkins method) and non-HDL-cholesterol was assessed at five visits and determined by being at or above the median for each lipid parameter. We constructed Cox proportional hazard models to estimate the risk for incident atherosclerotic cardiovascular disease events associated with each lipid concordance/discordance category using a time-varying approach.ResultsMean age of participants was 54.1 years, 56% women and 25% black. There were 2634 atherosclerotic cardiovascular disease events over a median (interquartile range) follow-up of 24.2 (16.0-25.4) years. Among individuals with LDL-cholesterol and non-HDL-cholesterol less than the median, 26% and 21% had discordant TC/HDL-cholesterol at or above the median, respectively. These individuals had a 24% (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.09, 1.41) and 29% (HR 1.29, 95% CI 1.13, 1.46) greater risk of incident atherosclerotic cardiovascular disease, respectively, compared to those with TC/HDL-cholesterol less than the median after multivariable adjustment. In individuals with diabetes with LDL-cholesterol or non-HDL-cholesterol less than the median, discordant TC/HDL-cholesterol at or above the median was more prevalent at 48% and 38%, respectively.ConclusionClinically significant discordance exists between TC/HDL-cholesterol, available from the standard lipid profile, and the routinely used non-HDL-cholesterol and LDL-cholesterol. Such discordance may help inform atherosclerotic cardiovascular disease risk management, particularly in individuals with diabetes in whom discordance is more common.

Dataset Information

The LDL Apolipoprotein B-to-LDL Cholesterol Ratio: Association with Cardiovascular Mortality and a Biomarker of Small, Dense LDLs.

Background and objective

Methods

Results

Conclusions

Publications

The LDL Apolipoprotein B-to-LDL Cholesterol Ratio: Association with Cardiovascular Mortality and a Biomarker of Small, Dense LDLs.

Similar Datasets

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