Dr. Ron’s Research Review – February 19, 2020

©

This week’s research review focuses on Apolipoprotein B

Apolipoprotein B-100 (also called apolipoprotein B or apo B) is involved in the metabolism of lipids and is the main protein constituent of lipoproteins such as very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL, the "bad cholesterol").
Cholesterol-rich, apolipoprotein B (apoB)-containing lipoproteins are now widely accepted as the most important causal agents of atherosclerotic cardiovascular disease. (Shapiro and Fazio, 2017)
Apo B concentrations, which reflect the number of small, dense LDL particles in plasma, are a significant predictor of cardiometabolic risk among adults with a high prevalence of metabolic syndrome, independent of waist circumference and CRP. (Onat et al., 2007)

Niacin

Niacin reduces LDL-C, ApoB and non-HDL-C, with or without concurrent statin treatment. (Brinton et al., 2016)
A study examined the effects of extended-release niacin/laropiprant (ERN/LRPT) on the relationships between apoB:LDL-C and apoB:non-HDL-C in patients with type 2 diabetes mellitus.
Type 2 diabetes mellitus (T2DM) patients (n = 796) had LDL-C ≥1.55 and <2.97 mmol/L and TG <5.65 mmol/L following a 4-week, lipid-modifying run-in (~78 % taking statins). ApoB:LDL-C and apoB:non-HDL-C correlations were assessed after randomized (4:3), double-blind ERN/LRPT or placebo for 12 weeks. Pearson correlation coefficients between apoB:LDL-C and apoB:non-HDL-C were computed and simple linear regression models were fitted for apoB:LDL-C and apoB:non-HDL-C at baseline and Week 12, and the correlations between measured apoB and measured vs predicted values of LDL-C and non-HDL-C were studied.
LDL-C and especially non-HDL-C were well correlated with apoB at baseline, and treatment with ERN/LRPT increased these correlations, especially between LDL-C and apoB. Despite the tighter correlations, many patients who achieved non-HDL-C goal, and especially LDL-C goal, remained above apoB goal. There was a trend towards greater increases in these correlations in the higher plasma triglycerides (TG) subgroup, non-significant possibly due to the small number of subjects.
Extended-release niacin/laropiprant treatment increased association of apoB with LDL-C and non-HDL-C in patients with T2DM. Lowering LDL-C, non-HDL-C and apoB with niacin has the potential to reduce coronary risk in patients with T2DM. (Brinton et al., 2016)

Omega 3 Fatty Acids

Omega 3 fatty acids added to standard treatment with fluvastatin may provide an additional benefit on postprandial atherogenic particles. (Valdivielso et al., 2009)
A study published in Cardiovascular Diabetology described the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day. The Hospital Virgen de la Victoria and University of Malaga, Spain conducted the study.
Patients with type 2 diabetes and mixed hyperlipidemia were recruited. Fasting lipid profile was taken when patients were treated with diet, diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids. The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA.
The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides, VLDL triglycerides and the triglyceride/HDL cholesterol ratio, and an increase in HDL cholesterol (P < 0.05). Fluvastatin induced a reduction of 26% in B100 (P < 0.05) and 14% in B48 (NS). However, the addition of omega 3 fatty acids enhanced this reduction to 32% in B100 (NS) and up to 36% in B48 (P < 0.05).
These preliminary findings therefore suggest an additional benefit on postprandial atherogenic particles when omega 3 fatty acids are added to standard treatment with fluvastatin. (Valdivielso et al., 2009)

Walnuts

Daily consumption walnuts significantly reduced non-HDL-cholesterol and apolipoprotein-B, which may explain in part the epidemiological observation that regular walnut consumption decreases CHD risk. (Wu et al., 2014)
A study published in Metabolism assessed the effect of walnuts on lipid and glucose metabolism, adipokines, inflammation and endothelial function in healthy Caucasian men and postmenopausal women ≥50years old. The University of Munich Medical Center, Germany conducted the study.
Forty subjects (mean±SEM: age 60±1years, BMI 24.9±0.6kg/m(2); 30 females) were included in a controlled, cross-over study and randomized to receive first a walnut-enriched (43g/d) and then a Western-type (control) diet or vice-versa, with each lasting 8weeks and separated by a 2-week wash-out. At the beginning and end of each diet phase, measurements of fasting values, a mixed meal test and an assessment of postprandial endothelial function (determination of microcirculation by peripheral artery tonometry) were conducted. Area under the curve (AUC), incremental AUC (iAUC) and treatment×time interaction (shape of the curve) were evaluated for postprandial triglycerides, VLDL-triglycerides, chylomicron-triglycerides, glucose and insulin.
Compared with the control diet, the walnut diet significantly reduced non-HDL-cholesterol (walnut vs. control: -10±3 vs. -3±2mg/dL; p=0.025) and apolipoprotein-B (-5.0±1.3 vs. -0.2±1.1mg/dL; p=0.009) after adjusting for age, gender, BMI and diet sequence. Total cholesterol showed a trend toward reduction (p=0.073). Fasting VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glucose, insulin, HOMA-IR, and HbA1c did not change significantly. Similarly, fasting adipokines, C-reactive protein, biomarkers of endothelial dysfunction, postprandial lipid and glucose metabolism and endothelial function were unaffected.
Daily consumption of 43g of walnuts for 8weeks significantly reduced non-HDL-cholesterol and apolipoprotein-B, which may explain in part the epidemiological observation that regular walnut consumption decreases CHD risk. (Wu et al., 2014)

Orange Juice

Orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet. (Aptekmann and Cesar, 2013)
A study published in Lipids in Health and Disease investigated the whether long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels. The Department of Food and Nutrition, Univ Estadual Paulista, Araraquara, Brazil conducted the study.
The sample consisted of 103 men (18-66 y) and 26 women (18-65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice.
Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (-11%, p <0.001), LDL-cholesterol (-18%, p < 0.001), apolipoprotein B (apo B) (-12%, p < 0.01) and LDL/HDL ratio (-12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (-5%, p <0.02), LDL-cholesterol (-12%, p <0.03), apolipoprotein B (-12%, p <0.01) and LDL/HDL ratio (-16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers.
Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet. (Aptekmann and Cesar, 2013)

Dr. Ron

 


Articles

 

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects.
            (Aptekmann and Cesar, 2013)  Download
BACKGROUND:  This study investigated the hypothesis that long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels. METHODS:  The sample consisted of 103 men (18-66 y) and 26 women (18-65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice. RESULTS:  Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (-11%, p <0.001), LDL-cholesterol (-18%, p < 0.001), apolipoprotein B (apo B) (-12%, p < 0.01) and LDL/HDL ratio (-12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (-5%, p <0.02), LDL-cholesterol (-12%, p <0.03), apolipoprotein B (-12%, p <0.01) and LDL/HDL ratio (-16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers. CONCLUSION:  Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet.

Effects of extended-release niacin/laropiprant on correlations between apolipoprotein B, LDL-cholesterol and non-HDL-cholesterol in patients with type 2 diabetes.
            (Brinton et al., 2016)  Download
BACKGROUND:  LDL-C, non-HDL-C and ApoB levels are inter-correlated and all predict risk of atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes mellitus (T2DM) and/or high TG. These levels are lowered by extended-release niacin (ERN), and changes in the ratios of these levels may affect ASCVD risk. This analysis examined the effects of extended-release niacin/laropiprant (ERN/LRPT) on the relationships between apoB:LDL-C and apoB:non-HDL-C in patients with T2DM. METHODS:  T2DM patients (n = 796) had LDL-C ≥1.55 and <2.97 mmol/L and TG <5.65 mmol/L following a 4-week, lipid-modifying run-in (~78 % taking statins). ApoB:LDL-C and apoB:non-HDL-C correlations were assessed after randomized (4:3), double-blind ERN/LRPT or placebo for 12 weeks. Pearson correlation coefficients between apoB:LDL-C and apoB:non-HDL-C were computed and simple linear regression models were fitted for apoB:LDL-C and apoB:non-HDL-C at baseline and Week 12, and the correlations between measured apoB and measured vs predicted values of LDL-C and non-HDL-C were studied. RESULTS:  LDL-C and especially non-HDL-C were well correlated with apoB at baseline, and treatment with ERN/LRPT increased these correlations, especially between LDL-C and apoB. Despite the tighter correlations, many patients who achieved non-HDL-C goal, and especially LDL-C goal, remained above apoB goal. There was a trend towards greater increases in these correlations in the higher TG subgroup, non-significant possibly due to the small number of subjects. CONCLUSIONS:  ERN/LRPT treatment increased association of apoB with LDL-C and non-HDL-C in patients with T2DM. Lowering LDL-C, non-HDL-C and apoB with niacin has the potential to reduce coronary risk in patients with T2DM.

Serum apolipoprotein B predicts dyslipidemia, metabolic syndrome and, in women, hypertension and diabetes, independent of markers of central obesity and inflammation.
            (Onat et al., 2007)  Download
OBJECTIVES:  To investigate the role of serum apolipoprotein (apo) B levels in predicting metabolic syndrome (MS), hypertension, atherogenic dyslipidemia and type II diabetes. METHODS:  Prospective evaluation of 1125 men and 1223 women, aged 28-74 years, participating in the survey 1997/1998 who had serum apo B determinations and were followed-up for a mean 5.9 years. Tertiles of apo B were formed by cut points by 120 and 95 mg/dl. MS was defined by modified ATPIII criteria. RESULTS:  Apo B values exhibited no significant difference among sexes. Low-density lipoprotein (LDL)-cholesterol and triglycerides were their leading determinants on linear regression analysis. By logistic regression analyses, the top versus bottom apo B tertile predicted significantly newly developing MS in both sexes separately with two-fold relative risks (RRs) (P<0.02) and the development of high triglyceride/low high-density lipoprotein-cholesterol dyslipidemia with nearly threefold RRs (P=0.001), after adjustment for waist circumference, C-reactive protein (CRP), physical activity grade and family income category. Development of hypertension was predicted only in women by the apo B top tertile (fully adjusted RR 1.71 [95% CI 1.001; 2.92]), while the significance of the prediction regarding age-adjusted diabetes in women (RR 1.86 [95% CI 1.04; 3.36]) attenuated after adjustment for the stated confounding factors. CONCLUSIONS:  Apo B concentrations, which reflect the number of small, dense LDL particles in plasma, are a significant predictor of cardiometabolic risk among adults with a high prevalence of MS, independent of waist circumference and CRP.


 

Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease.
            (Shapiro and Fazio, 2017)  Download
Cholesterol-rich, apolipoprotein B (apoB)-containing lipoproteins are now widely accepted as the most important causal agents of atherosclerotic cardiovascular disease. Multiple unequivocal and orthogonal lines of evidence all converge on low-density lipoprotein and related particles as being the principal actors in the genesis of atherosclerosis. Here, we review the fundamental role of atherogenic apoB-containing lipoproteins in cardiovascular disease and several other humoral and parietal factors that are required to initiate and maintain arterial degeneration. The biology of foam cells and their interactions with high-density lipoproteins, including cholesterol efflux, are also briefly reviewed.

Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: a randomized controlled cross-over clinical trial.
            (Wu et al., 2014)  Download
BACKGROUND:  Walnut consumption is associated with reduced risk of coronary heart disease (CHD). OBJECTIVE:  We assessed the effect of walnuts on lipid and glucose metabolism, adipokines, inflammation and endothelial function in healthy Caucasian men and postmenopausal women ≥50years old. DESIGN:  Forty subjects (mean±SEM: age 60±1years, BMI 24.9±0.6kg/m(2); 30 females) were included in a controlled, cross-over study and randomized to receive first a walnut-enriched (43g/d) and then a Western-type (control) diet or vice-versa, with each lasting 8weeks and separated by a 2-week wash-out. At the beginning and end of each diet phase, measurements of fasting values, a mixed meal test and an assessment of postprandial endothelial function (determination of microcirculation by peripheral artery tonometry) were conducted. Area under the curve (AUC), incremental AUC (iAUC) and treatment×time interaction (shape of the curve) were evaluated for postprandial triglycerides, VLDL-triglycerides, chylomicron-triglycerides, glucose and insulin. RESULTS:  Compared with the control diet, the walnut diet significantly reduced non-HDL-cholesterol (walnut vs. control: -10±3 vs. -3±2mg/dL; p=0.025) and apolipoprotein-B (-5.0±1.3 vs. -0.2±1.1mg/dL; p=0.009) after adjusting for age, gender, BMI and diet sequence. Total cholesterol showed a trend toward reduction (p=0.073). Fasting VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glucose, insulin, HOMA-IR, and HbA1c did not change significantly. Similarly, fasting adipokines, C-reactive protein, biomarkers of endothelial dysfunction, postprandial lipid and glucose metabolism and endothelial function were unaffected. CONCLUSION:  Daily consumption of 43g of walnuts for 8weeks significantly reduced non-HDL-cholesterol and apolipoprotein-B, which may explain in part the epidemiological observation that regular walnut consumption decreases CHD risk.


 

References

Aptekmann, NP and TB Cesar (2013), ‘Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects.’, Lipids Health Dis, 12 119. PubMed: 23919812
Brinton, EA, et al. (2016), ‘Effects of extended-release niacin/laropiprant on correlations between apolipoprotein B, LDL-cholesterol and non-HDL-cholesterol in patients with type 2 diabetes.’, Lipids Health Dis, 15 (1), 116. PubMed: 27405296
Onat, A, et al. (2007), ‘Serum apolipoprotein B predicts dyslipidemia, metabolic syndrome and, in women, hypertension and diabetes, independent of markers of central obesity and inflammation.’, Int J Obes (Lond), 31 (7), 1119-25. PubMed: 17299378
Shapiro, MD and S Fazio (2017), ‘Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease.’, F1000Res, 6 134. PubMed: 28299190
Wu, L, et al. (2014), ‘Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: a randomized controlled cross-over clinical trial.’, Metabolism, 63 (3), 382-91. PubMed: 24360749