October, 2012

VOL 3 ISSUE 1

CHRONICLES IN CHOLESTEROL
An Insiders Guide to State of The Art Cardiovascular Prevention Laboratory Testing Available From Everest Clinical Laboratories
The primary lipoprotein in LDL and other atherogenic particles is Apo B. There are two isoforms of Apo B: B-100, which is associated with very LDL, intermediate DL, LDL particles, and B-48 which is associated with chylomicrons. ApoB lipoproteins are essential in the formation LDL cholesterol and there is a 1:1 ratio between ApoB particles and atherogenic particles, making them currently the most accurate assessments of the atherogenicity of a patients lipid profile. For example, although a normal LDL-C cholesterol measurement might be found, an LDL subclass pattern with large and buoyant particles could have a normal Apo B level, whereas small, dense particles would result in an elevated Apo B level. Apo A1 is the primary lipoprotein in HDL cholesterol. HDL particles may have multiple ApoA1 lipoproteins with the above 1:1 ratio not being as predictive in assessing HDL functionality. ApoA1, however may more accurately reflect the reverse cholesterol flux of HDL functionality, rather than measurement of absolute HDL amount. One measure that is increasingly being used to express the appropriate balance of forward and reverse cholesterol balance is the Apo B:Apo A-1 ratio. This ratio reflects the balance between atheregenic forward cholesterol transportation and antiatherogenic reverse cholesterol transportation. Is this a valid measure in assessing the patients cardiovascular and cerebrovascular risk? Does it provide more information than a standard lipid profile? Yes, In one study, researchers in the Netherlands found that an Apo B:Apo A-1 ratio greater than 1.37 provided predictive power for major adverse cardiovascular events. Furthermore, there seems to be ethnic differences in this measurement that exceed the observed racial differences seen in standard lipid profiles. Researchers observed statistically significant differences in the ApoB:ApoA-1 between European Americans and African Americans, further supporting the evidence that race and ethnicity play a role in CVD risk.

In This Issue: ApoB:ApoA-1 Ratio This ratio reflects the balance between atheregenic forward cholesterol transportation and antiatherogenic reverse cholesterol transportation. ApoB:ApoA-1 ratios seem to be the most important predictor of CVD risk in patients with metabolic syndrome

Different ethnic and racial groups have vastly different ApoB:ApoA-1 ratios

October, 2012

VOL 3 ISSUE 1

ApoB:ApoA-1 ratios seem to be the most important predictor of CVD risk in patients with metabolic syndrome. Often these patients have normal standard lipid profiles. Similarly, obese children have been shown to have markedly abnormal ratios in the setting of normal standard lipid profiles. In these studies, the ratio was the most important predictor, not the individual ApoB and ApoA1 values. The alteration in overall plasma lipids amongst those with a high ApoB:ApoA-1 ratio is largely accounted for by differences in insulin resistance. With higher fasting plasma glucose and fasting plasma insulin levels, patients are at risk for diabetes or developing the metabolic syndrome. ApoB:ApoA-1 can uniquely be used to assess cardiovascular risk in these patients. Multivariate analysis of other ratios such as Total Cholesterol:HDL or LDL:HDL do not show similar predictive value for CVD prediction. Importantly at similar ApoB levels, an increase of LDL-C was associated with decreased CVD risk, indicating that LDL-c measurement becomes less predictive when there is larger LDL particle size and thus decreased risk. Apo B level appears less predictive of CVD risk in patients with hypertriglyceridemia. Lifestyle interventions to improve Apo A1 and B are similar to those for increasing HDL and lowering LDL, respectively. The INTERHEART Study, looked at more than 27,000 people in 52 countries on six continents. In this study, the highest apoB:apoA1 ratios were seen in South Asians, Arabs and Persians, and Latin Americans for men and women separately and combined. The lowest ratios were in the Chinese and black African populations. Thus cholesterol balance, determined by the ApoB:ApoA-1 ratio has repeatedly shown to be a better marker than lipids, lipoproteins and lipid ratios for the prediction of CVD risk.

ApoB:ApoA-1 ratios offers improvement in reclassifying CVD risk at 10 years compared to traditional lipid parameters and other calculated ratios.

By Spencer Kroll MD PhD National Lipid Association Board Certified Board of Directors, Northeast Lipid Association