High triglyceride levels alter the correlation of apolipoprotein B with low- and non-high-density lipoprotein cholesterol mostly in individuals with diabetes or metabolic syndrome

doi:10.1016/j.atherosclerosis.2016.02.001

Atherosclerosis

Volume 247, April 2016, Pages 58-63

https://doi.org/10.1016/j.atherosclerosis.2016.02.001 Get rights and content

Highlights

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We assessed the correlations of ApoB with LDL and non-HDL in dyslipidemic subjects.
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Subjects were divided according to the presence of diabetes/metabolic syndrome and TG levels.
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No difference was found in subjects with low TG levels, regardless of the presence of diabetes/metabolic syndrome.
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High TG levels reduced the correlation of ApoB with LDL and non-HDL in both groups.
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More profound reductions were noticed in subjects with diabetes/metabolic syndrome.

Abstract

Objective

To assess the correlation of Apolipoprotein B (Apo-B) with low-density (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) in untreated individuals attending a lipid clinic.

Methods

This was a retrospective study conducted in Greece and including 1000 dyslipidemic subjects. We included individuals not taking lipid-lowering therapy at baseline visit and divided them in 2 groups: subjects diagnosed with diabetes or fulfilling the criteria of metabolic syndrome (MetS) and hyperlipidemic subjects without diabetes or MetS. The correlations (r²) of Apo-B with LDL-C and non-HDL-C were assessed in these 2 groups. Further analyses were performed according to the baseline triglyceride (TG) levels (<and ≥200 mg/dL).

Results

From 821 eligible subjects, 51% were diagnosed with diabetes or MetS. The correlations between Apo-B and LDL-C or non-HDL-C were similar for the individuals with TG < 200 mg/dL. Specifically, Apo-B was significantly correlated with LDL-C (r² = 0.755, p < 0.01, for those with diabetes or MetS; r² = 0.848, p < 0.01, for non-diabetic and no MetS hyperlipidemic subjects). The corresponding correlations between Apo-B and non-HDL-C for the 2 groups were 0.743 and 0.838, respectively (p < 0.01). Although these correlations remained significant for the individuals with high TG levels (≥200 mg/dL), the correlation factor was markedly decreased mostly in those with diabetes or MetS (r² = 0.600, p < 0.01, for the correlation between Apo-B and LDL-C; r² = 0.604, p < 0.01, for the correlation between Apo-B and non-HDL-C); in contrast, the corresponding correlations were stronger in the non-diabetic and no MetS hyperlipidemic individuals (r² = 0.710 and 0.714, respectively, p < 0.01).

Conclusion

Apo-B correlation with both LDL-C and non-HDL-C is reduced in individuals with high TG levels and in particular for those with diabetes or MetS.

Introduction

The reduction of low-density lipoprotein cholesterol (LDL-C) has been the primary target for cardiovascular (CV) disease protection [1]. Currently applicable European guidelines also recommend non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (Apo-B) as alternative targets for the management of dyslipidemias in individuals with metabolic syndrome (MetS), diabetes, high triglyceride (TG) levels or chronic kidney disease [1]. LDL-C is a measure of cholesterol contained in the major atherogenic lipoprotein, whereas non-HDL-C represents the sum of the mass of cholesterol and cholesterol ester in all atherogenic lipoproteins [chylomicrons, very-low-density lipoprotein (VLDL) and their remnants, LDL and lipoprotein (a)] with Apo-B as their major apolipoprotein constituent [2], [3]. Individuals with diabetes, MetS or hypertriglyceridemia exhibit a characteristic pattern of abnormalities in serum lipids, known as “atherogenic dyslipidemia”, which consists of high concentrations of triglyceride-rich lipoproteins (TRLs), small-dense LDL and low levels of high-density lipoprotein cholesterol (HDL-C) [4], [5]. Non-HDL-C and Apo-B levels are proposed to be measured in such individuals as alternative targets, since they both denote all these atherogenic particles; instead, LDL-C represents only the mass of cholesterol within the LDL particles [3], [6]. Several meta-analyses have shown that Apo-B and non-HDL-C are better markers for monitoring CV risk reduction in statin-treated individuals [7], [8]. To date there are limited data on the relation of Apo-B with LDL-C or non-HDL-C in the conditions where atherogenic dyslipidemia is evident, such as MetS and diabetes, despite their continuously growing prevalence [9]. Few studies have found that Apo-B is highly correlated with non-HDL-C, while high TG levels modify the correlation of Apo-B with non-HDL-C and mostly with LDL-C in untreated individuals [10], [11], [12].

The aim of the present study was to assess the correlation of Apo-B with LDL-C and non-HDL-C in untreated hyperlipidemic individuals including those with diabetes or MetS, according to their baseline TG levels.

Section snippets

Methods

This was a retrospective (from 1999 to 2013) observational study as previously described [13], [14]. Briefly, dyslipidemic adults with a follow-up greater than 3 years in the Outpatient Lipid Clinic of the University Hospital of Ioannina in Greece were included. A complete assessment of their serum lipid profile along with CV risk factors and concomitant treatment was available. The study protocol was approved by the institutional Ethics committee.

Demographic characteristics as well as various

Results

Eight hundred twenty one subjects were finally eligible for inclusion in the study following the exclusion of those already on lipid-lowering therapy. Among them, 10% were diagnosed with diabetes and 41% fulfilled the criteria of MetS. Baseline study participants' characteristics are described in Table 1. Briefly, those with diabetes or MetS were older and had higher levels of waist circumference, BMI, glucose, HOMA-IR, HbA1c, BP, and lower HDL-C, Apo-A-I, Lp(a) levels compared with the rest of

Discussion

Our results demonstrated a similar correlation of Apo-B either with LDL-C or non-HDL-C. We also found that Apo-B correlation with LDL-C or non-HDL-C decreased if TG levels were greater than 200 mg/dL, and this reduction was more evident in individuals with diabetes or MetS.

LDL-C, which has long been the cornerstone of hyperlipidemia diagnosis as well as the treatment target, represents the mass of cholesterol within the major lipoprotein particle [1], [3]. On the other hand, non-HDL-C

Conclusion

Apo-B correlation with both LDL-C and non-HDL-C is reduced in individuals with high TG levels and mostly in those with diabetes or MetS.

Conflicts of interest

None.

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Cited by (20)

A More Atherogenic Lipoprotein Status Is Present in Adults With Type 2 Diabetes Mellitus Than in Those Without With Equivalent Degrees of Hypertriglyceridemia
2022, Canadian Journal of Diabetes
Citation Excerpt :
To our knowledge, there has only been 1 previous study on the association between non-HDLC and apoB with respect to TG and T2DM (26). Barkas et al (26) reported a lower correlation between non-HDLC and apoB in a smaller sample of 83 patients with T2DM who were analyzed together with 336 patients with metabolic syndrome. Most of these patients had NTG, with only 29 patients with T2DM, and 36 patients with metabolic syndrome who had TG levels between 2.3 and 4.5 mmol/L.
The impact of type 2 diabetes (T2DM) on biomarkers denoting lipoprotein compositional status was studied in mild and moderate hypertriglyceridemia (HTG). Diabetic dyslipidemia pathophysiology could contribute to differences in lipoprotein compositional status, which could be reflected in the preferred cardiovascular disease risk prediction markers in HTG: non–high-density lipoprotein cholesterol (non-HDLC) and apolipoprotein B (apoB).
A total of 2,775 fasting lipid profiles from a tertiary care lipid clinic were analyzed as 2 subgroups (with and without T2DM), stratified by triglyceride (TG) levels: normotriglyceridemia (TG 0.01 to 1.7 mmol/L), mild HTG (TG 1.71 to 5 mmol/L) and moderate HTG (TG 5.01 to 10 mmol/L). The mean non-HDLC:apoB ratio in each TG stratum and subgroup was analyzed. We also used linear regression to assess the correlation between non-HDLC and apoB.
The mean non-HDLC:apoB ratio was increased in both subgroups in patients with mild and moderate HTG, compared to those with normotriglyceridemia. In moderate HTG, the mean non-HDLC:apoB ratio in the subgroup with T2DM was significantly lower than the subgroup without T2DM. In mild and moderate HTG, the subgroup with T2DM had a stronger correlation between non-HDLC and apoB than did the subgroup without T2DM.
In mild and moderate HTG, adults with T2DM exhibit lipid profiles that represent a different and more atherogenic lipoprotein compositional status, when compared with adults without T2DM. For the same severity of HTG, the lipoprotein compositional status in diabetic dyslipidemia suggests that there is increased abundance of smaller non-HDL particles and their remnants, which are highly atherogenic.
Les répercussions du diabète de type 2 (DT2) sur les biomarqueurs indiquant la composition des lipoprotéines ont fait l’objet de l’étude sur l’hypertriglycéridémie (HTG) légère et modérée. La physiopathologie de la dyslipidémie du diabète pourrait contribuer aux différences dans la composition des lipoprotéines, qui pourraient se refléter dans les marqueurs de prédiction privilégiés du risque de maladies cardiovasculaires lors d’HTG : le cholestérol non à lipoprotéines de haute densité (non-HDLC) et l’apolipoprotéine B (apoB).
Un total de 2775 bilans lipidiques à jeun d’une clinique des lipides d’un hôpital de soins tertiaires ont fait l’objet d’une analyse en 2 sous-groupes (atteints ou non du DT2), d’une stratification en fonction des concentrations en triglycérides (TG) : normotriglycéridémie (TG de 0,01 à 1,7 mmol/L), HTG légère (TG de 1,71 à 5 mmol/L) et HTG modérée (TG de 5,01 à 10 mmol/L). La moyenne du ratio non-HDLC:apoB de chaque strate de TG et sous-groupe a fait l’objet d’une analyse. Nous avons également utilisé la régression linéaire pour évaluer la corrélation entre le non-HDLC et l’apoB.
La moyenne du ratio non-HDLC:apoB a augmenté dans les 2 sous-groupes de patients qui avaient une HTG légère ou modérée, et par rapport à ceux qui avaient une normotriglycéridémie. Lors d’HTG modérée, la moyenne du ratio non-HDLC:apoB du sous-groupe atteint du DT2 était significativement plus basse que celle du sous-groupe non atteint du DT2. Lors d’HTG légère ou modérée, le sous-groupe atteint du DT2 montrait une corrélation plus forte du non-HDLC et d’apoB que le sous-groupe non atteint du DT2.
Lors d’HTG légère et modérée, les adultes atteints du DT2 montrent des bilans lipidiques qui représentent une composition différente et plus athérogène des lipoprotéines lorsqu’on les compare aux adultes non atteints du DT2. Lors d’HTG de même gravité, la composition des lipoprotéines dans la dyslipidémie diabétique indique qu’il y a une augmentation des plus petites particules de non-HDL et de leurs résidus, qui sont hautement athérogènes.
Atherogenic dyslipidemia increases the risk of incident diabetes in statin-treated patients with impaired fasting glucose or obesity
2019, Journal of Cardiology
Citation Excerpt :
The diagnosis of impaired fasting glucose (IFG) was defined by a baseline fasting plasma glucose concentration 100–125 mg/dL (5.5–6.9 mmol/L) [13]. Based on the results of a previous study of ours showing that the amount of TG-rich lipoproteins and small dense low-density lipoproteins was greater in case of TG ≥200 mg/dL (2.3 mmol/L) in our study participants [14], the diagnosis of MixDys was made in case of baseline TG ≥200 mg/dL (2.3 mmol/L) and HDL-C <50 mg/dL (1.3 mmol/L) or <40 mg/dL (1 mmol/L) for the female and male subjects, respectively. Overweight/obesity was defined in case of BMI ≥25 kg/m2.
To investigate which metabolic factors increase the risk of incident diabetes (T2D) in statin-treated patients.
A retrospective study conducted in Greece including 1241 consecutive individuals with dyslipidemia attending a lipid clinic for ≥3 years. After defining associations with incident T2D, we assessed the risk of new-onset T2D based on the presence of impaired fasting glucose (IFG), atherogenic dyslipidemia, and overweight/obesity.
After excluding 166 patients with baseline T2D and 193 subjects taking lipid-lowering therapy at the baseline visit, 882 participants were included in the study. Eleven percent (n = 94) developed T2D during their follow-up (median 6 years; IQR: 4–10). Baseline patients’ age (OR: 1.05; 95% CI: 1.02–1.08, p < 0.01), family history of diabetes (OR: 3.58; 95% CI: 1.86–6.91, p < 0.01), IFG (OR: 6.56; 95% CI: 3.53–12.12, p < 0.01), overweight/obesity (OR: 2.65; 95% CI: 1.39–5.05, p < 0.01), atherogenic dyslipidemia (OR: 3.27; 95% CI: 1.50–7.15, p < 0.01), and treatment with high-intensity statins (OR: 3.51; 95% CI: 1.89–6.51, p < 0.01) were independently associated with increased risk of T2D in statin-treated patients. Among the IFG subjects, atherogenic dyslipidemia (OR: 3.44; 95% CI: 1.31–9.04, p = 0.01) and overweight/obesity (OR: 2.54; 95% CI: 1.14–5.66, p < 0.05) independently increased the risk of T2D. Among the overweight/obese ones, atherogenic dyslipidemia independently increased the risk of T2D (adjusted OR: 5.60; 95% CI: 2.19–14.30, p < 0.01).
Atherogenic dyslipidemia appears to be an independent risk factor for new-onset T2D in statin-treated patients, while IFG, overweight/obesity and family history of diabetes remain risk factors for new-onset T2D in this group.
Cholesterol efflux capacity of large, small and total HDL particles is unaltered by atorvastatin in patients with type 2 diabetes
2018, Atherosclerosis
Research on the biologic activities of HDL, such as cholesterol efflux capacity and HDL composition, has allowed the understanding of the effect of interventions directed to improve cardiovascular risk. Previously, statin therapy has shown conflicting results about its effects on cholesterol efflux capacity of HDL; the underlying mechanisms are unclear but studies with positive effects are associated with an increase of HDL-cholesterol levels. We investigated if 10 weeks of atorvastatin therapy changes HDL efflux capacity and the chemical composition of its subpopulations.
In a before-after design basis, HDL-cholesterol levels, chemical composition and cholesterol efflux capacity from HDL subpopulations isolated by isophynic ultracentrifugation were assessed in plasma samples from 60 patients with type 2 diabetes mellito (T2DM) at baseline and after 10 weeks of treatment with 20 mg atorvastatin. Cholesterol efflux was measured from human THP-1 cells using large, light HDL2b and small, dense 3c subpopulations as well as total HDL as acceptors. Changes of cholesterol efflux and chemical composition of HDL after treatment were analyzed. Correlations among variables potentially involved in cholesterol efflux were evaluated.
A significant decrease of 4% in HDL-cholesterol levels was observed from 47 (42–54) to 45 (39–56) mg/dL, p = 0.02. Cholesterol efflux from total-HDL and HDL2b and 3c subfractions was maintained unchanged after treatment. The total mass of HDL remained unaffected, except for the HDL3a subpopulation accounted for by a significant increase in total protein content. No significant correlations for variables previously known to be associated with cholesterol efflux were found in our study.
Short therapy of 10 weeks with 20 mg of atorvastatin does not modify the cholesterol efflux capacity neither the total mass of HDL2b, HDL3c and total HDL. The discrepancy with previous reports may be due to the selective effects among different classes of statins or differences in the approaches to measure cellular cholesterol efflux.
The CHADS<inf>2</inf> and CHA<inf>2</inf>DS<inf>2</inf>-VASc scores predict atrial fibrillation in dyslipidemic individuals: Role of incorporating low high-density lipoprotein cholesterol levels
2017, International Journal of Cardiology
Citation Excerpt :
In addition, we investigated whether CHADS2 and CHA2DS2-VASc scores have utility in predicting AF among these individuals and assess the additional predictive value of low HDL-C levels. This was a retrospective (from 1999 to 2015) observational study as previously described [17–20]. Briefly, dyslipidemic adults followed-up for ≥ 3 years in the Outpatient Lipid Clinic of the University Hospital of Ioannina in Greece were included.
To investigate the value of CHADS₂ and CHA₂DS₂-VASc scores in predicting atrial fibrillation (AF) among dyslipidemic individuals and assess the additional value of incorporating low levels of high-density lipoprotein cholesterol (HDL-C).
This observational study included 1241 individuals attending a lipid clinic. Models including clinical and laboratory parameters were constructed to test the predictive value of CHADS₂ and CHA₂DS₂-VASc scores as well as low HDL-C levels for incident AF. Low HDL-C levels were defined as < 40 and < 50 mg/dL for male and female subjects, respectively.
After excluding 18 patients with AF at baseline, 1223 subjects were followed-up for a median period of 6 years (IQR: 4–10), and 34 (2.8%) developed AF. Baseline CHADS₂ (OR: 1.71; 95% CI: 1.28–2.29, p < 0.001) and CHA₂DS₂-VASc scores (OR: 1.56; 95% CI: 1.26–1.92, p < 0.001) as well as low HDL-C levels (OR: 3.79; 95% CI: 1.85–7.75, p < 0.001) were significantly associated with new-onset AF. ROC curve analyses showed that both CHADS₂ and CHA₂DS₂-VASc scores were significant predictors for new-onset AF (C-Statistic: CHADS₂ 0.679, p < 0.001; CHA₂DS₂-VASc 0.698, p < 0.001). Higher CHADS₂ scores were associated with reduced event-free survival from AF (log-rank = 10.62, p = 0.001) with differences potentiated if stratified by CHA₂DS₂-VASc score (log-rank = 22.29, p < 0.001). After incorporating low HDL-C levels, both scores achieved slightly higher C-Statistic for AF prediction (0.690 and 0.707, respectively, p < 0.001).
CHADS₂ and CHA₂DS₂-VASc scores predict new AF in dyslipidemic patients. Risk prediction improved modestly when low HDL-C levels were included.
An evidence-based analysis of the National Lipid Association recommendations concerning non-HDL-C and apoB
2016, Journal of Clinical Lipidology
Citation Excerpt :
This is a substantial portion of the population. Moreover, discordance will be even greater in high cardiovascular risk groups such as individuals with diabetes and patients with the metabolic syndrome in whom correlation between non-HDL-C and apoB is much lower.50 The Framingham Heart Study demonstrated that elevated non-HDL-C at age 55 years, particularly if the finding was present on previous examinations, is associated with high intermediate term risk even in those whose 10-year risk threshold was <7.5%.51
The National Lipid Association (NLA) selected non-HDL-C as its prime index of the cardiovascular risk associated with the apoB lipoproteins. ApoB was recommended only as an optional secondary target after low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol (HDL-C) targets were achieved.
The aims of this analysis were to determine whether (1) all relevant uses of apoB were considered by the NLA; (2) all the relevant evidence was considered by the NLA panel; and (3) all the evidence that was considered was interpreted correctly.
(1) The utility of apoB in the diagnosis of the atherogenic dyslipoproteinemias was not considered. (2) All the relevant observational studies were not identified, and some that were cited were incorrectly interpreted. In particular, an equal hazard ratio for two markers in a group does not mean they will predict risk equally in individuals within the group in whom they are discordant. This matters because discordance analysis consistently demonstrates apoB and LDL particle number are more accurate measures of cardiovascular risk than LDL-C/non-HDL-C. (3) The target levels of apoB selected by the NLA are too high relative to the levels selected for LDL-C and non-HDL-C.
The review of the evidence by the NLA was incomplete. More complete examination of the evidence indicates that apoB is a more accurate marker of cardiovascular risk than non-HDL-C and that the practice of lipidology would be improved by inclusion of apoB along with lipoprotein lipids in routine clinical care.
Association of apolipoproteins and lipoprotein(a) with metabolic syndrome: a systematic review and meta-analysis
2023, Lipids in Health and Disease

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High triglyceride levels alter the correlation of apolipoprotein B with low- and non-high-density lipoprotein cholesterol mostly in individuals with diabetes or metabolic syndrome

Highlights

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Conclusion

Conflicts of interest

Atherosclerosis

Atherosclerosis

J. Am. Coll. Cardiol.

Metab. Clin. Exp.

Atherosclerosis

Am. J. Cardiol.

J. Clin. Lipidol.

J. Am. Coll. Cardiol.

J. Am. Coll. Cardiol.

Am. J. Cardiol.

Am. J. Cardiol.

Am. J. Cardiol.

ESC/EAS Guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS)

Eur. Heart J.