Association of small, dense LDL-cholesterol concentration and lipoprotein particle characteristics with coronary heart disease: A systematic review and meta-analysis

Liou, Lathan; Kaptoge, Stephen

doi:10.1371/journal.pone.0241993

Cited by 84 publications

(50 citation statements)

References 64 publications

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“…While a recent systematic review and meta-analysis found that both small dense LDL particles and concentration were associated with risk of CAD across 21 studies representing >30 000 subjects, there was substantial heterogeneity across studies, and observational findings more broadly may be limited by residual environmental confounding. 39 In contrast, 2 recent observational studies have suggested that remnant cholesterol is more strongly predictive of ASCVD events than other lipoprotein-related traits. 40 , 41 The prioritization of L.LDL.P does not preclude the possibility that small LDL or remnant particles also cause ASCVD.…”

Section: Discussionmentioning

confidence: 97%

Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

et al. 2021

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Background: Lipoprotein-related traits have been consistently identified as risk factors for atherosclerotic cardiovascular disease, largely on the basis of studies of coronary artery disease (CAD). The relative contributions of specific lipoproteins to risk of peripheral artery disease (PAD) have not been well-defined. We leveraged large-scale genetic association data to investigate effects of circulating lipoprotein-related traits on PAD risk. Methods: Genome-wide association study summary statistics for circulating lipoprotein-related traits were used in the MR Bayesian model averaging framework to prioritize the most likely causal major lipoprotein and subfraction risk factors for PAD and CAD. MR was used to estimate the effect of ApoB-lowering on PAD risk using gene regions proxying lipid-lowering drug targets. Genes relevant to prioritized lipoprotein subfractions were identified using transcriptome-wide association studies. Results: ApoB was identified as the most likely causal lipoprotein-related risk factor for both PAD (marginal inclusion probability [MIP] 0.86, p = 0.003) and CAD (MIP 0.92, p = 0.005). Genetic proxies for ApoB (apolipoprotein B)-lowering medications were associated with reduced risk of both PAD (OR 0.87 per 1 standard deviation decrease in ApoB, 95% CI 0.84 to 0.91, p = 9 x 10 -10 ) and CAD (OR 0.66, 95% CI 0.63 to 0.69, p = 4 x 10 -73 ), with a stronger predicted effect of ApoB-lowering on CAD (ratio of effects 3.09, 95% CI 2.29 to 4.60, p < 1 × 10 -6 ). Extra-small-VLDL particle concentration (XS.VLDL.P) was identified as the most likely subfraction associated with PAD risk (MIP 0.91, p = 2.3 x 10 -4 ), while large-LDL particle concentration (L.LDL.P) was the most likely subfraction associated with CAD risk (MIP 0.95, p = 0.011). Genes associated with XS.VLDL.P and L.LDL.P included canonical ApoB-pathway components, although gene-specific effects were variable. Lipoprotein(a) was associated with increased risk of PAD, independent of ApoB (OR 1.04, 95% CI 1.03 to 1.04, 95% CI 1.0 x 10 -33 ). Conclusions: ApoB was prioritized as the major lipoprotein fraction causally responsible for both PAD and CAD risk. However, ApoB-lowering drug targets and ApoB-containing lipoprotein subfractions had diverse associations with ASCVD, and distinct subfraction-associated genes suggest possible differences in the role of lipoproteins in the pathogenesis of PAD and CAD.

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Section: Discussionmentioning

confidence: 97%

Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

et al. 2021

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“…Lipoprotein a has also been shown as an independent risk factor for cardiovascular diseases [ 2 ]. Among LDL particles, small dense LDL and oxidized LDL have been reported to be the most important contributors to the development of atherosclerotic cardiovascular disease (ASCVD) [ 3 , 4 ]. Earlier studies have shown that controlling LDL-C is a cornerstone in the prevention and treatment of ASCVD [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Factors Associated with Medication Non-Adherence in Patients with Dyslipidemia

et al. 2021

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Lack of medication adherence among patients with dyslipidemia negatively affects health-related outcomes. This study aims to evaluate medication adherence; we also aim to investigate the predictors of non-adherence among patients with dyslipidemia in Jordan. Medication adherence was evaluated in a total of 228 dyslipidemia patients. The Beliefs about Medicines Questionnaire was also used to assess patients’ beliefs about medications. The majority of the current study participants (73.2%) reported non-adherence to the prescribed medications. There were significant negative associations between medication adherence and concerns of prescription drug use (B = −0.41, p-value < 0.01), duration of dyslipidemia (B = −0.22, p-value < 0.01), and the number of medications (B = −0.64, p-value < 0.01). Positive associations were found between medication adherence and the necessity of prescription drug use (B = 0.43, p-value < 0.01), taking statin and fibrate (B = 2.04, p-value < 0.01), and moderate-intensity statin (B = 2.34, p-value < 0.01). As for patients’ beliefs about medications, the item “My medicine to lower my cholesterol disrupted my life” had the highest mean (3.50 ± 0.99). This study revealed a low adherence rate to medication among patients with dyslipidemia. It also demonstrates modifiable factors such as beliefs regarding perceived risk, medication harms, treatment duration, and the number of medications associated with poor adherence in patients with dyslipidemia.

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“…As suggested previously, sdLDL particles are associated with increased TG and apolipoprotein B levels (associated with LDL-C), and decreased HDL-C and apolipoprotein A1 levels (associated with HDL-C) [ 36 ]. Additionally, the sdLDL subclass is considered to be more atherogenic, and therefore, a significant risk factor for CVD [ 12 – 23 ]. On the other hand, sdLDL particles may not be an independent risk factor for CVD after other risk factors have been considered, such as total cholesterol, LDL particle number, and LDL-C, HDL-C, and TG concentrations, according to certain studies [ 24 , 34 , 115 – 119 ].…”

Section: Discussionmentioning

confidence: 99%

“…There are larger, more buoyant LDL particles and smaller, denser LDL particles. These smaller, denser LDL particles are considered to be more atherogenic, and therefore, a significant risk factor for CVD and cardiovascular events [ 12 – 23 ]. LDL subclasses may be characterized by densities and diameters [ 11 , 24 – 27 ], as presented in Table 1 .…”

Section: Introductionmentioning

confidence: 99%

The effects of fat consumption on low-density lipoprotein particle size in healthy individuals: a narrative review

Froyen

2021

Lipids Health Dis

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Cardiovascular disease (CVD) is the number one contributor to death in the United States and worldwide. A risk factor for CVD is high serum low-density lipoprotein cholesterol (LDL-C) concentrations; however, LDL particles exist in a variety of sizes that may differentially affect the progression of CVD. The small, dense LDL particles, compared to the large, buoyant LDL subclass, are considered to be more atherogenic. It has been suggested that replacing saturated fatty acids with monounsaturated and polyunsaturated fatty acids decreases the risk for CVD. However, certain studies are not in agreement with this recommendation, as saturated fatty acid intake did not increase the risk for CVD, cardiovascular events, and/or mortality. Furthermore, consumption of saturated fat has been demonstrated to increase large, buoyant LDL particles, which may explain, in part, for the differing outcomes regarding fat consumption on CVD risk. Therefore, the objective was to review intervention trials that explored the effects of fat consumption on LDL particle size in healthy individuals. PubMed and Web of Science were utilized during the search process for journal articles. The results of this review provided evidence that fat consumption increases large, buoyant LDL and/or decreases small, dense LDL particles, and therefore, influences CVD risk.

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Association of small, dense LDL-cholesterol concentration and lipoprotein particle characteristics with coronary heart disease: A systematic review and meta-analysis

Cited by 84 publications

References 64 publications

Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

Factors Associated with Medication Non-Adherence in Patients with Dyslipidemia

The effects of fat consumption on low-density lipoprotein particle size in healthy individuals: a narrative review

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