Comparisons of Apolipoprotein B Levels Estimated by Immunoassay, Nuclear Magnetic Resonance, Vertical Auto Profile, and Non-High-Density Lipoprotein Cholesterol in Subjects With Hypertriglyceridemia (SAFARI Trial)
Center for Human Nutrition, Departments of Internal Medicine and Clinical Nutrition, University of Texas Southwestern Medical Center, and Metabolic Unit, Veterans Affairs Medical Center, Dallas, Texas, USA.
Low-density lipoprotein (LDL) cholesterol and triglyceride-rich lipoproteins constitute non-high-density lipoprotein (non-HDL) cholesterol. These are atherogenic lipoproteins and non-HDL cholesterol is a secondary target of treatment beyond LDL cholesterol in patients with hypertriglyceridemia. Some investigators favor total apolipoprotein B over non-HDL cholesterol as the secondary target of treatment. This is based on publications suggesting that total apolipoprotein B is more predictive of cardiovascular events than non-HDL cholesterol. Several methods are available for estimating total apolipoprotein B. This study compared total apolipoprotein estimated by immunonephelometric assay (INA), vertical auto profile (VAP), nuclear magnetic resonance (NMR), and non-HDL cholesterol levels in patients with hypertriglyceridemia from the previously reported Simvastatin plus Fenofibrate for Combined Hyperlipidemia (SAFARI) trial. Total apolipoprotein B levels were found to be highest by INA, intermediate by NMR and non-HDL cholesterol, and lowest by VAP. Concordance for non-HDL cholesterol levels among the INA, VAP, and NMR methods was better than that for total apolipoprotein B levels; the correlation between non-HDL cholesterol and apolipoprotein B by INA was strongest (0.929). In patients with a low triglyceride/HDL cholesterol ratio (<3.5), total apolipoprotein B determined by INA was higher than that estimated from non-HDL cholesterol levels, whereas in patients with a high triglyceride/HDL C ratio (≥3.5), apolipoprotein B predicted using non-HDL cholesterol was in better agreement with INA-determined apolipoprotein B levels. Similar trends were observed with VAP using equations specific for LDL particle size. In conclusion, more work is needed to improve agreement of apolipoprotein B measurements among methods employed clinically. Non-HDL cholesterol is also useful to predict total apolipoprotein B and some improvement may be attained by taking into account the ratio of triglyceride/HDL cholesterol as a measurement of LDL particle size.
"Combined with its good reproducibility, TGL/HDL ratio may well be a clinically useful screening tool for this purpose. Interestingly, TGL/HDL ratio has been found in other studies to be an effective tool for predicting gestational diabetes , cardiovascular risk in patients with familial hypercholestrolemia , atherogenic apolipoprotein B levels  and as a surrogate marker in the mechanistic pathway through which pioglitazone possibly delays coronary atheroma progression in diabetic patients . "
[Show abstract][Hide abstract] ABSTRACT: Intentional weight loss, by reducing insulin resistance, results in both better glycemic control and decreased need for anti-diabetic medications. However, not everyone who is successful with weight loss is able to reduce anti-diabetic medication use. In this retrospective cohort study, we assessed the predictive accuracy of baseline triglyceride (TGL)/HDL ratio, a marker of insulin resistance, to screen patients for success in reducing anti-diabetic medication use with weight loss.
Case records of 121 overweight and obese attendees at two outpatient weight management centers were analyzed. The weight loss intervention consisted of a calorie-restricted diet (~1000Kcal/day deficit), a behavior modification plan, and a plan for increasing physical activity.
Mean period of follow-up was 12.5 ± 3.5 months. By study exit, mean weight loss and mean HbA1c% reduction were 15.4 ± 5.5 kgs and 0.5 ± 0.2% respectively. 81 (67%) in the study cohort achieved at least 1 dose reduction of any anti-diabetic medication. Tests for predictive accuracy of baseline TGL/HDL ratio ≤ 3 to determine success with dose reductions of anti-diabetic medications showed a sensitivity, specificity, positive predictive value, negative predictive value, area under the curve, likelihood ratio (LR) + and LR-of 81, 83, 90, 70, 78, 4.8 and 0.2, respectively. Reproducibility of TGL/HDL ratio was acceptable.
TGL/HDL ratio shows promise as an effective screening tool to determine success with dose reductions of anti-diabetic medications. The results of our study may inform the conduct of a systematic review using data from prior weight loss trials.
PLoS ONE 07/2013; 8(7):e69285. DOI:10.1371/journal.pone.0069285 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Some practitioners use advanced lipoprotein analysis with the goal of better predicting risk and individualizing lifestyle and drug therapy for cardiovascular prevention. Unfortunately, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle number and size, other lipoprotein subfractionation, apolipoproteins B and A, and lipoprotein(a) have not yet met current standards for biomarker evaluation, and it remains to be determined whether these tests incrementally add to cardiovascular risk predicted by traditional risk factors. More importantly, it has yet to be determined whether treatment strategies guided by, or targeting, these measures improve cardiovascular outcomes. Drug therapies known to alter advanced lipoprotein analysis parameters, specifically niacin and fenofibrate, have not been shown to additionally reduce cardiovascular risk in recent randomized trials of high-risk patients treated with statin therapy. These findings suggest advanced lipoprotein analysis-guided strategies may not further reduce cardiovascular events and could lead to increased adverse effects and costs; this approach needs further research to establish its role in individualizing therapies for cardiovascular prevention. In contrast, a large body of evidence supports focusing on LDL cholesterol reduction and intensification of statin therapy to reduce cardiovascular risk.
Journal of the American College of Cardiology 12/2012; 60(25):2607-15. DOI:10.1016/j.jacc.2012.04.067 · 16.50 Impact Factor
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