January 6th, 2010
Lp(a): Risk and Relevance
L. David Hillis, MD
Clarke et al. provide convincing evidence that plasma Lp(a) lipoprotein is causally related to coronary artery disease. What’s needed next? First, we need to assess whether knowledge of Lp(a) lipoprotein concentrations improves predictive discrimination over more traditional risk factors. Second, we need an intervention that selectively lowers plasma Lp(a) lipoprotein concentrations and a randomized clinical trial to assess its efficacy. Of currently FDA-approved medications, niacin is the only agent that effectively lowers plasma Lp(a) lipoprotein concentrations. Is it time for a randomized trial of niacin in patients with elevated plasma Lp(a) lipoprotein concentrations?
2 Responses to “Lp(a): Risk and Relevance”
NEJM Journal Watch — Recent Cardiology Articles- To Lower Stroke Risk in Patients Undergoing Atrial Fibrillation Ablation, Is a Device or a Medication Better?
- Intensive vs. Standard Blood Pressure Lowering in Patients with Diabetes
- Anticoagulation in Patients with Cancer-Associated Pulmonary Embolism: How Long is Long Enough?
- Spironolactone Use After Percutaneous Intervention for Acute Myocardial Infarction
- CRISPR/Cas9 Gene Editing for Transthyretin Cardiomyopathy
INTERHEART?
Is it necessary to put this study and potential niacin therapy into context with the INTERHEART study published in the Lancet (McQueen et al, Lancet 2008:372: 224-33). Just to recap, in this paper, with > 12000 patients with acute MI and >14000 controls, ApoB/ApoA1 ratio was determined to be a better predictor of recurrence of MI than cholesterol ratios. Could one argue that rather than simply studying Apo levels, perhaps a niacin study could be directed at treating and altering ApoB/ApoA1 ratios? Admittedly, the above study did not compare lipoprotein levels directly against cholesterol, therefore I am curious about it’s applicability.
ApoB concentrations provide information regarding all atherogenic particles (Lp(a), LDL, VLDL, and IDL), and ApoA1 has several beneficial effects (i.e., it guides reverse cholesterol transport; it has antioxidant and anti-inflammatory activities; and it increases nitric oxide production). Not surprisingly, as John points out, the ApoB/ApoA ratio is a better predictor of CV benefits than cholesterol ratios (any combination of total, HDL, or LDL). A large trial of niacin would tell us if it is efficacious and, if so, whether the effects were related to changes in particular lipoproteins (i.e., Lp(A) or ApoB/ApoA1 ratios).