Non-HDL-C and Apo B

• Apo B levels, which represent the total number of atherogenic lipoprotein particles, better correlate with CAD (coronary artery disease) than LDL-C, in treated as well  as untreated patients.¹ Similarly, non-HDL-C, which represents the cholesterol contained in all atherogenic lipoproteins has also been demonstrated to best LDL-C in predicting CAD.¹ Thus, both Apo B and non-HDL-C provides a better risk estimation compared with LDL-C, particularly in people with high TG (triglycerides), metabolic syndrome, diabetes, or chronic kidney disease.^{2, 3}

• Recent studies show that VLDL-C is as much or more atherogenic than LDL-C. The combined risk from LDL-C and VLDL-C is best assessed by calculating non-HDL-C, which is obtained by simply subtracting HDL-C from the TC.⁴

• Non–HDL-C has been shown to be a strong predictor of severity of coronary atherosclerosis and CVD (cardiovascular disease) events particularly in people who have elevations in both TC and TG. In patients with LDL-C <100 mg/dL, those with non-HDL-C >130 mg/dL have an 84% increased risk of CVD.^{5, 6}

• Non-HDL-C is the second lipid target of therapy after LDL-C in people with high TG and has well defined cut points that are set 30 mg/dl higher than LDL-C targets in every CAD risk category.⁴ A meta-analysis of 30 lipid lowering trials (mostly statins) showed a 1:1 relationship between non-HDL-C lowering  and CAD risk reduction; ⁷ A 40 mg/dL lower non-HDL-C achieved with lipid-optimizing therapy confers a 35-40% reduction in CAD risk.⁴

• TG levels were not independently associated with CAD risk, once adjusted for non-HDL-C levels  in the ERFC( Emerging Risk  Factors Collaboration) involving  more than 300,000 individuals.^{8, 9} In ERFC the predictive value of Apo B (1.58) and non-HDL-C were nearly identical (1.59) in people without treatment but non-HDL-C was superior among those receiving treatment.^{9, 10}

 

Table 118A. Comparison of non-HDL-C ApoB and  LDL-C and suggested treatment goals 11
	LDL-C	Non-HDL-C	Apo B
Primary target	Yes	No	No
Secondary target	NA	Yes	No
Established cut points	Yes	Yes	No*
Superiority in risk prediction, especially in people with high TG, metabolic syndrome, diabetes, or CKD	NA	Yes	Yes
Assessment in non-fasting state	No	Yes	Yes
Additional cost	No	No	Substantial
Additional delay in getting results	No	No	Yes
Treatment goal  in patients with CAD or diabetic patients with one or more major additional risk factors	<70 mg/dl	<100 mg/dl	<80 mg/dl
Treatment goal  in high-risk patients without CAD or diabetes but 2 or more major CAD risk factors; or diabetic patients  without other major CAD risk factors**	<100 mg/dl	<130 mg/dl	<90 mg/dl
NA not applicable. * Only one consensus recommendation has been published**Other CAD risk factors include family history of premature CAD, smoking or high blood pressure

• Among patients with cardiometabolic risk, treatment to levels of LDL-C < 100 mg/dl, non-HDL-C < 130 mg/dl, and Apo B < 90 mg/dl has been recommended for those individuals at high risk for CVD. For people with highest risk, the treatment goals are LDL-C < 70 mg/dl, non HDL-C < 100 mg/dl, and Apo-B< 80 mg/dl is suggested. (Table 118A).^{2, 11}

• Although both  non-HDL-C and Apo B perform better than LDL-C in CVD risk prediction, non-HDL-C has several practical advantages that allow its wider use.⁸ The cost of Apo B is several times higher than non-HDL-C, which does not require any additional expenditure or delay in getting results.⁸

• Although both offer the practical benefits of accuracy independent of TG level and prandial state, non-HDL-C proves to be the better marker of choice at this time, given established cutpoints with safe and achievable goals, no additional cost, and quick time to result with an easy mathematical calculation.⁸

• Given its ease of use non-HDL-C can be immediately implemented as realistic primary target of lipid management rather than ordering another expensive test and learning to Apo B goals that are at marked variance with the non-HDL-C goals, especially in those treated with intensive statin therapy.^{1, 8}

Sources

1.Milani RV, Lavie CJ. Another step forward in refining risk stratification moving past low-density lipoprotein cholesterol. J Am Coll Cardiol. Jul 26 2011;58(5):464-466.

2. Catapano AL, Reiner Z, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis. Jul 2011;217 Suppl 1:1-44.

3. Robinson JG, Wang S, Smith BJ, Jacobson TA. Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. J Am Coll Cardiol. Jan 27 2009;53(4):316-322.

4. Enas E.A., Hancy Chennikkara Pazhoor MD, Arun Kuruvila MBBS, Krishnaswami Vijayaraghavan MD F. Intensive Statin Therapy for Indians:Part I Benefits. Indian Heart J 2011; 63: 211-227.

5. Renault BJ, Rana JS. Beyond low-Density Lipoprotein Cholesterol. JAAC. 2010;55:35-41.

6. Lewington S, Whitlock G, Clarke R, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. Dec 1 2007;370(9602):1829-1839.

7. Robinson J, Wang S, Smith BJ, Jacobson TA. Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. J Am Coll Cardiol. Jan 27 2009;53(4):316-322.

8. 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. Jul 26 2011;58(5):457-463.

9. Di Angelantonio E, Sarwar N, Perry P, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. Nov 11 2009;302(18):1993-2000.

10. Jiang R, Schulze MB, Li T, et al. Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes. Diabetes Care. Aug 2004;27(8):1991-1997.

11. Brunzell JD, Davidson M, Furberg CD, et al. Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J Am Coll Cardiol. Apr 15 2008;51(15):1512-1524.