What Should We Measure to Calculate CV Risk — LDL, Non-HDL, or Apo B?

Every flow has its ebb. – Anon

The persistence of cardiovascular (CV) events in more than 1 in 3 US adults despite a decrease in the prevalence of elevated LDL cholesterol (LDL-C) underscores the need to optimize cardiovascular (CV) risk stratification.1 The comparative performance of the three foremost lipid markers – LDL-C, apolipoprotein B (apoB), and non-HDL cholesterol (non-HDL-C) – has been an area of ongoing debate. A beneficial biomarker for cardiovascular risk stratification is one that enables robust prognostic information while providing an accurate therapeutic target. A central concept of enhanced risk stratification is grounded in effective risk reclassification by means of improved discriminative ability beyond the current gold standard.2 Cumulative evidence to date demonstrates that both non-HDL-C and apoB meet this criterion for both prognostic and therapeutic targets when compared to LDL-C.3 This is partially because they account for an atherogenic spectrum more relevant to the increasingly diabetic and obese US population.1,3

In clinical practice, effective risk stratification is most impactful in the highest CV risk patients as this group, when aggressively managed, has the potential for the greatest absolute risk reduction of future events with lipid-lowering therapy. Given that secondary prevention patients are largely on statin therapy favors biomarkers that provide accurate on-treatment prognostic information – namely non-HDL-C and apoB. Importantly, both of these markers also provide improved discriminative ability in primary prevention patients.3 Evidence directly comparing the performance of these two markers, however, continues to accumulate in a contending fashion with resultant reluctance to implement new and proven tools on the part of physicians.3-5

Although apoB may demonstrate a more sound pathophysiologic representation of atherosclerotic risk, it is unlikely to be ready for implementation in clinical practice for a number of reasons. Currently, specific treatment targets remain controversial, available therapies provide only limited reduction, there is an increased test cost, and the particle-centric conceptual framework is less well understood by most primary care physicians.3 Despite competitive performance of both markers, non-HDL-C remains the better marker at this time given that there is no associated additional cost, and no additional new tests need to be ordered. It is easy to calculate, and remains within a familiar lipid-centric framework with targets relevant to LDL-C goals – all benefits not shared by apoB.3 At this time, we advocate that physicians use non-HDL-C in tandem with LDL-C to maximize a cost-effective approach to cardiovascular risk assessment and treatment.

  1. Roger VL, Go AS, Lloyd-Jones DM, et al. Executive summary: Heart disease and stroke statistics--2012 update: A report from the american heart association.Circulation 2012;125:188-197.
  2. Cook NR. Statistical evaluation of prognostic versus diagnostic models: Beyond the ROC curve. Clin Chem 2008;54:17-23.
  3. Ramjee V, Sperling LS, Jacobson TA. Non-high-density lipoprotein cholesterol versus apolipoprotein B in cardiovascular risk stratification: Do the math. J Am Coll Cardiol 2011;58:457-463.
  4. Boekholdt SM, Arsenault BJ, Mora S, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: A meta-analysis. JAMA 2012;307:1302-1309.
  5. Martin SS, Metkus TS, Horne A, et al. Waiting for the national cholesterol education program adult treatment panel IV guidelines, and in the meantime, some challenges and recommendations. Am J Cardiol 2012;110:307-313.

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