NMR Cases for Physicians

Which of the following therapeutic options would be appropriate?

A) No changes needed

B) TLC measures (no TFA, ▼SFA, ▼dietary cholesterol, plant stanol, fiber supplement)

C) TLC measures (weight loss, daily exercise, ▼high-GI carbs, ▲marine ω-3 PUFA, ▲ω-9 MUFA, ▼ω-6 PUFA + above)

D) ▲Lipitor to 40-80 mg qd

E) Change Lipitor to Crestor 20-40 mg qd

F) Add Zetia 10 mg qd

G) Change Lipitor to Vytorin 10/20-80 mg qd

H) Add Tricor 145 mg qd

I) Add Niaspan 500-2000 mg qd

J) Add Omacor 2-4 caps qd

This individual is at very high future CV risk (T2DM+CHD) and would have LDL-C goal(s) of < 100 mg/dL (some would say < 70 mg/dL) and thus total LDL-P goal(s) of < 1000 nmol/L (versus < 700 nmol/L). His LDL-C is at goal but his total LDL-P is not. This patient’s elevated total LDL-P is made up primarily of large LDL particles [total LDL-P to small LDL-P ratio ≥ 2] so what is required is further up-regulation of ApoB/E receptors. A) not appropriate; B) appropriate and might work if patient not already doing this; C) extra TLC measures all good ideas but unlikely to further reduce patient’s elevated large LDL-P; D) might work but probably not; E) might work; F) appropriate; G) appropriate; H) might work but probably not; I) might work but probably not; and J) probably not appropriate.

Which of the following therapeutic options would be appropriate?



A) No changes needed

B) TLC measures (no TFA, ▼SFA, ▼dietary cholesterol, plant stanol, fiber supplement)

C) TLC measures (weight loss, daily exercise, ▼high-GI carbs, ▲marine ω-3 PUFA, ▲ω-9 MUFA, ▼ω-6 PUFA + above)

D) ▲Pravachol to 80 mg qd

E) Change Pravachol to Crestor 10-40 mg qd

F) Add Zetia 10 mg qd

G) Change Pravachol to Vytorin 10/10-80 mg qd

H) Add Tricor 145 mg qd

I) Add Niaspan 500-2000 mg qd

J) Add Omacor 2-4 caps qd

This individual is at moderate increased future CV risk and would have LDL-C goal of < 130 mg/dL (some would say < 100 mg/dL) and thus total LDL-P goal of < 1300 nmol/L (versus < 1000 nmol/L). Her LDL-C is at goal but her total LDL-P is not. This patient’s elevated total LDL-P is made up primarily of small LDL particles [total LDL-P to small LDL-P ratio < 2] so what is required is increasing LDL particle size to make them recognizable by ApoB/E receptors. A) not appropriate; B) not appropriate (although all good ideas); C) appropriate and might work if patient not already doing this; D) not appropriate; E) might work but probably not; F) not appropriate; G) might work but probably not; H) appropriate; I) appropriate; and J) might work but probably not (since TG < 200 mg/dL).

Which of the following therapeutic options would be appropriate?



A) No changes needed

B) TLC measures (no TFA, ▼SFA, ▼dietary cholesterol, plant stanol, fiber supplement)

C) TLC measures (weight loss, daily exercise, ▼high-GI carbs, ▲marine ω-3 PUFA, ▲ω-9 MUFA, ▼ω-6 PUFA + above)

D) ▲Zocor to 40-80 mg qd

E) Change Zocor to Crestor 10-40 mg qd

F) Change Zocor to Vytorin 10/10-80 mg qd

G) Add Tricor 145 mg qd

H) Add Niaspan 500-2000 mg qd

I) Add Omacor 2-4 caps qd



This individual is at moderate increased future CV risk and would have LDL-C goal of < 130 mg/dL (some would say < 100 mg/dL) and thus total LDL-P goal of < 1300 nmol/L (versus < 1000 nmol/L). Her total LDL-P is at goal but her LDL-C is not. We know that elevated LDL-C is predictive of increased future CV risk ONLY when it coexists with elevated total LDL-P. This patient’s total LDL-P is made up primarily of large LDL particles [total LDL-P to small LDL-P ratio ≥ 2] so IF we wanted to lower LDL-C (by lowering total LDL-P) what would be required is further up-regulation of ApoB/E receptors. A) appropriate (although MUST mention in chart decision made with patient to NOT treat elevated LDL-C based on appropriate total LDL-P) ; B) appropriate if patient not already doing this; C) extra TLC measures unlikely to further reduce patient’s large LDL-P; D) might work but probably not; E) might work; F) appropriate; G) might work but probably not; H) might work but probably not; and I) not appropriate

Which of the following therapeutic options would be appropriate?



A) No therapy needed

B) TLC measures (no TFA, ▼SFA, ▼dietary cholesterol, plant stanol, fiber supplement)

C) TLC measures (weight loss, daily exercise, ▼high-GI carbs, ▲marine ω-3 PUFA, ▲ω-9 MUFA, ▼ω-6 PUFA + above)

D) Begin Statin 10-80 mg qd

E) Begin Zetia 10 mg qd

F) Begin Statin as above + Zetia as above

G) Begin Tricor 145 mg qd

H) Begin Statin as above + Tricor as above

I) Begin Zetia as above + Tricor as above

J) Begin Niaspan 500-2000 mg qd

K) Begin Statin as above + Niaspan as above

L) Begin Zetia as above + Niaspan as above

M) Begin Omacor 2-4 caps qd

N) Begin Statin as above + Omacor as above

O) Begin Zetia as above + Omacor as above

This individual is at moderate increased future CV risk and would have LDL-C goal of < 130 mg/dL (some would say < 100 mg/dL) and thus total LDL-P goal of < 1300 nmol/L (versus < 1000 nmol/L). His LDL-C is at goal but his total LDL-P is not. This patient’s elevated total LDL-P is made up primarily of small LDL particles [total LDL-P to small LDL-P ratio < 2] so what is required is up-regulating ApoB/E receptors AND increasing LDL particle size to make them recognizable by those ApoB/E receptors. A) not appropriate; B) not appropriate (although all good ideas); C) appropriate and might work if patient not already doing this; D) might work but probably not; E) might work but probably not; F) might work but probably not; G) might work but probably not; H) appropriate; I) appropriate: J) might work but probably not; K) appropriate; L) appropriate; M) not appropriate; N) appropriate; O) might work but probably not (since TG < 200 mg/dL).

5. Describe the LDL particle effects of the major lipoprotein-modifying drug classes (Statins, CAI, BAS, Niacin, Fibrates, Glitazones, Fish oils)?

Statins (see Image below): A) decrease intra-hepatic FC levels (by inhibiting cholesterol synthesis); B) decease intra-hepatic CE levels; C) decrease production of small VLDL particles; D) decrease bloodstream levels of large LDL particles; E) up-regulate ApoB/E receptors to clear primarily large LDL particles from the bloodstream; F) increase conversion of large VLDL particles into small VLDL particles (by indirect PPARα effect); G) block conversion of large LDL particles into small LDL particles (by inhibiting HL and CETP); and H) decrease bloodstream levels of small LDL particles. Statins do, however, (I) seem to increase cholesterol absorption within the proximal small bowel enterocyte (by up-regulating NPC1L1 and down-regulating ABCG5/G8).

CAI (see Image below): A) inhibit cholesterol absorption within the proximal small bowel enterocyte; B) decease intra-hepatic FC levels; C) decrease intra-hepatic CE levels; D) decrease production of small VLDL particles; E) decrease bloodstream levels of primarily large LDL particles; and F) up-regulate ApoB/E receptors to clear primarily large LDL particles from the bloodstream.

BAS (see Image below): A) block the re-absorption of bile acids in the distal small bowel; B) decease intra-hepatic FC levels; C) decrease intra-hepatic CE levels; D) decrease production of small VLDL particles; E) decrease bloodstream levels of primarily large LDL particles; and F) up-regulate ApoB/E receptors to clear primarily large LDL particles from the bloodstream. BAS do, however: G) increase intra-hepatic TG production; H) increase the production of large VLDL particles; and I) modestly increase bloodstream levels of small LDL particles.

Niacin (see Image below): A) inhibits HSL in visceral adipose tissue and thus decreases serum FFA levels; B) block DGAT2 and reduces hepatic TG levels; C) reduces synthesis of primarily large VLDL particles; D) decreases bloodstream levels of primarily small LDL particles; E) inhibits HL to block conversion of large LDL particles into small LDL particles; and F) promotes LPL to increase the conversion of large VLDL particles into small VLDL particles.

Fibrates (see Image below), via PPARα-induced β-oxidation of FFA within the hepatocyte, lower FFA (A) levels, block DGAT2 and inhibit TG (B) production, leading to decreased production of primairly large VLDL (C) and thus primarily small LDL (D) particles. Fibrates also up-regulate LPL production, decrease ApoC-III production and increase ApoA-V production, all of which enhance the conversion of large VLDL into small VLDL particles (E).

Glitazones (see Image below) function similar to fibrates but are probably at least four times less potent overall in their effects.

Fish oils usually decrease hepatic TG synthesis, thus reducing the production of large VLDL particles (note that rarely in certain individuals they may actually increase TG production since, as a type of FFA, they can serve as substrate for TG production). They work primarily by increasing the proteolysis of large VLDL particles just prior to their secretion (clue being TG level > 200 mg/dL). Fish oils may induce LPL and decrease ApoC-III to promote clearance of large VLDL particles from the bloodstream. They thus usually decrease bloodstream levels of small LDL particles but may increase bloodstream levels of large LDL particles.