Role of HDL Cholesterol in Residual Risk for CAD
Role of HDL Cholesterol in Residual Risk for CAD
Abstract & Commentary
By Michael H. Crawford, MD
Source: Ridker PM, et al. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: An analysis from the JUPITER trial. Lancet. 2010;376:333-339.
Despite impressive reductions in cardiovascular risk in primary and secondary prevention trails with statin therapy, risk does not reach zero. A low HDL could explain at least some of this residual risk, but current data are inconsistent. Thus, the JUPITER trial database was analyzed to answer this question. JUPITER was a randomized trial of 20 mg of rosuvastatin vs. placebo in more than 17,000 apparently healthy individuals with LDL cholesterol levels < 130 mg/dL, but who had an elevated high sensitivity (hs) CRP (> 2 mg/L). JUPITER showed a 20% reduction in mortality after less than two years follow-up and a 44% reduction in cardiovascular events. Average LDL was 55 mg/dL in the statin group. For this analysis, the subjects were divided into quartiles of HDL, and an association with the primary end-point of first non-fatal myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death was sought. As compared to placebo, for all quartiles of HDL, rosuvastatin significantly reduced the primary endpoint to a similar extent as the main trial. Rosuvastatin also increased HDL by 4% on average. In the placebo group, cardiovascular events increased inversely with the HDL level. The highest HDL quartile patients (> 55 mg/dL) had a 46% lower event rate. In the rosuvastatin group, this difference in events across the HDL quartiles was abolished. Factors shown to be associated with residual cardiovascular risk in the statin-treated patients were age, male sex, and smoking status. The authors concluded that HDL is a useful component of initial cardiovascular risk assessment, but HDL does not predict residual risk in those treated with a potent statin who achieve low LDL levels.
Commentary
This analysis of the large JUPITER trial database addresses an important and vexing clinical issue: the patient with low HDL values. In the specific case of this study, it is the patient with a presumed need for primary prevention treatment because of a high hsCRP value, but relatively normal LDL values, who is put on a statin and achieves impressive reductions in LDL. In such a patient, this study shows that the HDL level does not predict future events. This result dampens enthusiasm for attacking the low HDL, especially since there are few agents available to raise HDL and trials with new HDL raising agents have been disappointing. So can we breathe a sigh of relief and ignore HDL values in those with good LDL lowering on statins?
To be precise, these data only apply to apparently healthy non-diabetics with relatively normal LDL values, but a raised hsCRP value. How many such patients exist in a general population is debatable, but I have heard estimates of as low as 4%. This also presupposes that we measure hsCRP in everyone with a relatively normal LDL to find these people. This approach has not been uniformly embraced by public health leaders. Is there evidence that this data can be applied more widely? Four secondary prevention trials of high-dose statin therapy have shown the same lack of prediction of future events by HDL levels. So at least for secondary prevention, potent statin treatment to a low LDL may be enough. Of course, neither this trial nor any others were designed primarily to answer the question of the value of raising HDL when LDL is low.
At this point, it might be prudent to try to raise HDL by encouraging exercise and trying available therapies such as niacin, especially in those with diabetes, metabolic syndrome, and others at higher risk than the patients in this study. However, pushing HDL-raising therapy in the lower-risk patient who achieves a low LDL on therapy would have little evidence-based support at this time.
Despite impressive reductions in cardiovascular risk in primary and secondary prevention trails with statin therapy, risk does not reach zero.Subscribe Now for Access
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