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ORIGINAL ARTICLE
Year : 2019  |  Volume : 22  |  Issue : 3  |  Page : 355-360

Defining apolipoprotein B treatment targets


1 Department of Chemical Pathology, University College Hospital, Ibadan, Nigeria
2 Department of Chemical Pathology, College of Medicine, University of Ibadan, Oyo, Nigeria

Date of Acceptance13-Dec-2018
Date of Web Publication6-Mar-2019

Correspondence Address:
Dr. G O Ayoade
Department Chemical Pathology, University College Hospital, Ibadan, Oyo
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_348_17

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   Abstract 


Background: Apolipoprotein B (apo B) has been widely reported to be a better predictor of cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). This is the reason apo B treatment target values based on the equivalence to LDL-C values in healthy population has been advocated using percentiles from population studies. The aim of this study was to determine the apo B values equivalent to currently used medical decision targets for LDL-C concentration in a population of healthy Nigerians and examine for any demographic influence. Materials and Methods: A total of 252 apparently healthy individuals (89 males, 163 females), between the ages of 30 and 65 years were selected from core health workers (medical and nursing staffs) of University College Hospital Ibadan between December 2015 and May 2016. Serum lipids and apo B were measured using enzymatic and immunoturbidimetry method, respectively. Results: The mean apo B of the study population were 94 and 98 mg/dL in men and women, respectively. Mean apo B concentration was significantly higher in the female participants in the age groups above 55 years. LDL-C concentrations of 100, 130, 160, and 190 mg/dL corresponded to the 15th, 55th, 87th, and 95th percentile, respectively. The corresponding apo B concentrations were 73 mg/dL (15th percentile), 95 mg/dL (55th percentile), 124 mg/dL (87th percentile), and 145 mg/dL (95th percentile). The group of participants with LDL-C of <130 mg/dL and the group with equivalent apo B of <95 mg/dL has the same clinical and biochemical characteristics in both men and women. Conclusion: This study has defined apo B targets that may potentially be used to guide the initiation of therapy in persons with dyslipidemia. It has also demonstrated the population level relationship that exists between apo B and LDL-cholesterol and has shown the gender and age-related influence of apo B distribution in the population.

Keywords: Apolipoprotein B, low density lipoprotein cholesterol, treatment targets


How to cite this article:
Ayoade G O, Kuti M A. Defining apolipoprotein B treatment targets. Niger J Clin Pract 2019;22:355-60

How to cite this URL:
Ayoade G O, Kuti M A. Defining apolipoprotein B treatment targets. Niger J Clin Pract [serial online] 2019 [cited 2019 Mar 25];22:355-60. Available from: http://www.njcponline.com/text.asp?2019/22/3/355/253452




   Introduction Top


Over the past 2 decades, randomized clinical trials have provided evidence establishing the association between low density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD).[1],[2],[3] Increased LDL-C predicts risk of CVD. Several recent studies have suggested that apolipoprotein B (apo B) may be a better predictor than LDL-C.[4],[5],[6] Apolipoprotein B was a stronger predictor of death from acute myocardial infarction than LDL-C as demonstrated in the apolipoprotein-related mortality risk study with similar findings also reported in the INTERHEART study which showed that apo B had the highest odds ratio of any single measure for the prediction of risk of coronary heart disease and was superior to LDL-C and nonhigh density lipoprotein cholesterol (non-HDL-C) in all ethnic groups.[4],[7] The 4S study (Scandinavian Simvastatin Survival Study), LIPID (Long-term intervention with Pravastatin in Ischemic Disease), and ThROMBOstudy all concluded that apo B is a significant predictor of recurrent cardiovascular events independent of LDL-C or non-HDL-C.[8],[9],[10] As a result of the above, recent guidelines have recommended the reduction in apo B levels as a target for therapy among patients considered to be at high risk of developing CVD.[11],[12],[13] These will require the definition of medical decision cut-points (MDC-P) for apo B that can be used to guide therapy. The adoption, by someauthorities, of MDC-P derived from a review of data from clinical trials has been criticized.[14] This is because the derivation of such MDC-P was not the original intention of those trials.[14] Some experts have therefore suggested that the MDC-P for apo B should be derived such that they are equivalent to MDC-Ps that are currently in use for LDL-C in terms of population percentiles.[15] They suggest that while there is likely to have been a shift in the distribution of lipids and lipoproteins over time so that what was once the 20th percentile is now the 30th percentile, the equivalence between a given percentile of apo B and LDL-C is unlikely to shift significantly. They further argue that although the relative risk associated with a given concentration of apo B or LDL-C may vary somewhat with race, the relationship between apo B and LDL-C with CVD risk is strong for all racial groups. Other authors have criticized this approach indicating that the use of such equivalent values in their population will result in the adoption of apo B targets that are so low that they may be unachievable with two or three lipid lowering agents.[16] Their population of study was mainly white and excluded persons with plasma triglycerides exceeding 400 mg/dL in other to calculate LDL-C using the Friedewald formula.

The present study aims to determine the apo B values equivalent to currently used MDC-P targets for LDL-C concentrations in a population of healthy Nigerians and also examine for any demographic influence on apo B and LDL-C concentrations. The implication of such derived targets on apo B guided therapy for dyslipidaemia will be discussed.


   Materials and Methods Top


Ethics statement

Ethical approval granted by University of Ibadan/University College Hospital (UI/UCH) Health Research Ethics Committee with assigned number: UI/EC/15/0049. Written informed consent was obtained from each participant before data collection.

Study design and participants

This was a cross-sectional study carried out over a period of 6 months between December 2015 and May 2016 among health care workers in University College Hospital (UCH), Ibadan. A total of 252 apparently healthy adults between the ages of 30 and 65 years were recruited. The health care workers were specifically recruited for this study as they were more likely to be aware of their medical history. Subjects with history of cardiovascular diseases, diabetes, renal diseases, and those on lipid lowering drugs were excluded from the study.

Sample collection and storage

Fasting blood samples were collected for total cholesterol (TC), triglycerides (TG), HDL-C, and apo B into ethylene diamine tetra acetic acid (EDTA) bottles and fasting plasma glucose (FPG) into fluoride oxalate bottles. Plasma was separated by centrifugation and stored at -20 until laboratory analysis.

Laboratory analysis

Plasma apo B was assayed using immunoturbidimetry technique on Landwind automated chemistry analyzer platform (Landwind C 100 plus) from Shenzen Landwind Industry Co. China. TC, TG and HDL-C were assayed using the enzymatic methods also on Landwind automated chemistry analyzer. LDL-C was calculated using the Frieldewald's equation.

Data analysis

Continuous data were presented as mean (SD), while proportions were presented as number (percent). All continuous variables are presented as mean (SD). Comparisons of means were performed using the Student's t test while proportions were compared using the chi squared test. Differences among age groups were assessed by analysis of variance with a post hoc least significance difference test. Analysis was done using IBM Statistical Package for Social Sciences (SPSS) version 20. A P value of <0.05 was considered statistically significant.


   Results Top


[Table 1] shows demographic, clinical, and biochemical characteristics of the study participants. Female participants had a significantly higher body mass index (BMI) and HDL-C than the male participants.
Table 1: Demographic, clinical, and biochemical characteristics of study subjects

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[Table 2] shows the mean apo B concentrations of the age groups of the participants by gender. Mean apo B concentrations was significantly higher in the female participants in the age groups above 55 years. The means of apo B for the age groups within each gender was significantly different for the female participants [F (6, 155) = 2.47, P = 0.027] but was not significant for the males [F (6, 81) = 0.905, P = 0.496) or the entire population [F (6, 243) = 1.93, P = 0.077]. Post hoc comparisons using the least significance difference test indicated that the mean score for the age group 30-34 years was significantly different from other age groups; 40-44 years (P = 0.048), 45-49 years (P = 0.037), 55-59 years (P = 0.004) and >60 years (P = 0.004). The mean score of the 35-39 years age group was also significantly different from the age groups 55-59 years (P = 0.019) and >60 years (P = 0.019). Comparison for other age groups was not significant.
Table 2: Mean Apo B concentrations by age group and gender

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LDL- C concentrations of 100, 130, 160, and 190 mg/dL corresponded to the 15th, 55th, 87th and 95th percentile, respectively. The corresponding apo B concentrations were 73 mg/dL (15th percentile), 95 mg/dL (55th percentile), 124 mg/dL (87th percentile), and 145 mg/dL (95th percentile). [Table 3] compares the clinical characteristics of participants with LDL-C <130 mg/dL to those whose apo B concentrations were <95 mg/dL. [Table 4] however compares participants whose LDL-C >130 mg/dL to those whose apo B concentrations were >95 mg/dL. There is strong association between LDL-C and apo B, as LDL-C is the only determinants of plasma apo B levels in both men and women as indicated by linear regression analyses [Table 5].
Table 3: Characteristics of subjects with LDL <130 mg/dL and those with apo B<95 mg/dL (mean±2SD)

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Table 4: Characteristics of subjects with LDL ≥130 mg/dL and those with Apo B ≥95 mg/dL (mean±2SD)

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Table 5: Linear regression analysis of LDC-C and Apo B

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   Discussion Top


By using percentiles that are equivalent to the currently recommended LDL-C therapeutic target concentrations, the corresponding concentration of apo B among our study participants was 73 mg/dL for LDL-C of 100 mg/dL; 95 mg/dL for LDL-C of 130 mg/dL, 124 mg/dL for LDL-C of 160 mg/dL and 145 mg/dL for LDL-C of 190 mg/dL. The clinical utility of the equivalence of these concentrations of apo B and LDL-C was demonstrated by the near identical characteristics of the subjects who were defined by using either apo B of 95 mg/dL or the corresponding LDL-C concentration of 130 mg/dL. This would suggest that the relationship between apo B and LDL-C is strong not only at the individual level but also at a community level.

Using data from the Framingham Offspring Study, Contois et al. determined apo B medical decision values of 78 and 97 mg/dL as population percentile equivalent values for LDL-C concentrations of 100 and 130 mg/dL, respectively.[15],[17] These values are very similar to the result obtained in our study population. The results of our study are therefore also similarly subject to the criticism of prescribing apo B targets of 73 mg/dL that were difficult to achieve in the EXPLORER (Examination of Potential Lipid Modifying Effects of Rosuvastatin in Combination With Ezetimibe versus Rosuvastatin) trials despite the use of the highest dose of the most potent statins.[18] However, given the perspective included in the updated guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease, these concentrations should rather be used as a guide to make decisions on when to initiate statin therapy and not as treatment targets.[19],[20] The values we define here may therefore potentially guide the initiation of therapy based on apo B concentration as the most recent guideline management of dyslipidaemia by American association of clinical endocrinology recommend optimal apo B value of 80 mg/dL, consistent with the result of our study [21]

Among our participants apo B concentrations were subject to gender- and age-related influences. Female participants below the age of 55 years had lower apo B values than the male participants although the difference is not statistically significant. The females after the age of 55 years had significantly higher apo B values compared to male participants. Our findings are somewhat different from those reported by Schaefer et al. and Contois et al. who were using data from the 3rd and 4th cycle of the Framingham Offspring Study, respectively.[17],[20] Among their population, they observed significantly higher apo B values in males who were below 60 years. Their observed significant difference was however lost above the age of 60 years with the females participant having higher values than the males. Our findings and those from the two Framingham reports may be explained by the changes in estrogen levels that occur in the postmenopausal period. It has been suggested that estrogen may be involved in the clearance of apo B particles. Hormone replacement therapy has been shown to reduce apo B levels by over 10% in postmenopausal women.[22] This is also supported by our findings that women younger than 35 years of age had significantly lower apo B levels compared to those older than 40 years, with the difference becoming most pronounced in women older than 55 years. This age-related difference was not observed among our male participants.

In conclusion, we have demonstrated the population level relationship that exists between apo B and LDL-cholesterol. We further defined apo B targets that may potentially be used to guide the initiation of therapy in persons with dyslipidemia. Finally, we have demonstrated gender and age-related influences of apo B distribution in the population, especially among women.


   Conclusion Top


Apo B treatments targets which has the potential clinical usefullness in assessment of dyslipidemic patient has been defined in this population. The relationship between apo B and LDL-C has been established and tahlsiso r aegpeo rat nadls goe snhdoewr sa ftfheactt sa gthee a anpdo g Be nddisetrr iibnufltuioenn.ce apo B distribution in this poulation.

Financial support and sponsorship

Nil

Conflict of interest

There are no conflicts of interest.



 
   References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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