More Evidence for Lowering LDL to Below 70

October 04, 2011

October 4, 2011 (Gwangju, South Korea)New data from an observational study has suggested that further benefit may be achieved by giving statins to high-risk patients who already have very low LDL levels [1].

While the data can be viewed only as hypothesis generating, it has fueled the idea that LDL levels of 70 mg/dL, the currently recommended target, may not be the lowest point for benefit.

Commenting on the study for heartwire , Dr John LaRosa (SUNY Downstate Medical Center, Brooklyn, NY), said: "I liked this study. It is very intriguing. Although observational studies like this can never conclude anything definite, this study implies that we have not yet identified an LDL level below which there is no further reduction in risk. I think this is worth trying to do."

In the study, published in the October 11, 2011 issue of the Journal of the American College of Cardiology, a team led by Dr Ki Hong Lee (Chonnam National University Hospital, Gwangju, South Korea), analyzed data from a registry of MI patients. They compared outcomes among 1054 patients with LDL levels below 70 mg/dL at the time of their MI as to whether they were discharged on a statin or not.

Results showed that the rate of major adverse cardiac events at one year was significantly lower in those patients who were taking a statin, with the benefit mainly driven by the reduction of cardiac death and coronary revascularization.

Risk of Major Cardiac Events in MI Patients With Low LDL Taking a Statin vs Those Not Taking a Statin

Outcome HR (95% CI) p
Death/recurrent MI/target vessel revascularization/CABG* 0.56 (0.34–0.89) 0.015
Cardiac death 0.47 (0.23–0.93) 0.031
Coronary revascularization 0.45 (0.24–0.85) 0.013

*Primary end point

Noting that previous data on lowering LDL to below 70 have been inconsistent, the researchers say the present study adds evidence in favor of such an idea in high-risk patients.

Other lipid experts asked to comment on the study for heartwire were also generally impressed by these data, although all pointed out the need to confirm such observations in a randomized trial.

Dr Christie Ballantyne (Baylor College of Medicine, Houston, TX) said: "I think we have to always have great caution in the evaluation of observational studies. However, there are substantial data that statins have benefit in patients who have a high risk for atherothrombotic events even if they have a low level of LDL from randomized trials, and many clinicians have already adopted the practice of placing any patient with ACS on a statin regardless of the LDL level. This study is one more piece of evidence to support the pragmatic approach to have all patients with ACS on a statin at the time of discharge."

Dr Michael Miller (University of Maryland Medical School, Baltimore) added, "This is an interesting study that is not inconsistent with the post hoc data from the PROVE-IT TIMI 22 trial, which showed reduced CV risk with on-treatment LDL <60 mg/dL compared with LDL >80 mg/dL" [2].

Supportive of Pleiotropic Effects

Dr Roger Blumenthal (Johns Hopkins University, Baltimore, MD) suggested the study supported the pleiotropic effects of statins and the idea that the ideal LDL-C is probably closer to 50 than to 70 mg/dL. "We have known for a long time that statins improve vascular endothelial function, reduce vascular inflammation, stabilize plaques, attenuate prothrombotic tendencies, and favorably influence myocardial protection and remodeling. Usually patients with very low LDL-C levels are older and often have other important comorbidities, such as diabetes mellitus and hypertension. Even though the calculated LDL is low, their [apolipoprotein B] apoB or non-HDL cholesterol is likely relatively high. Thus, patients with very low LDL-C levels might benefit nearly as much from statin therapy as patients with higher LDL-C levels," he told heartwire .

LaRosa, who wrote an editorial [3] accompanying Lee's study, expanded on his views to heartwire : "I used to be skeptical about the idea of trying to achieve very low cholesterol levels, but now I am more accommodating. As cholesterol levels are coming down, we are seeing much lower rates of bypass surgery and elective angioplasty. I think elective angioplasty will eventually disappear altogether."

Chimpanzees eat very little fat. They have LDL levels in the range of 40 to 70, and they don't get atherosclerosis.

He noted that levels of LDL below 70 are on a par with those of nonhuman primates who don't develop atherosclerosis, adding that, like these primates, humans were designed to be vegetarians. "Our dental anatomy suggests that we are not meant to be meat eaters. Animals that eat meat have sharp tearing teeth, while we have flatter teeth more similar to vegetarian animals. I believe humans are not anatomically or metabolically designed to be meat eaters, and because we do consume animal fat that's why we get atherosclerosis. Chimpanzees don't eat meat; they eat very little fat. They have LDL levels in the range of 40 to 70, and they don't get atherosclerosis. Maybe we wouldn't get atherosclerosis either if we had levels this low."

On the flaws of the current study, LaRosa points out that cholesterol levels were measured just once--around the time of MI--and that might not be a reliable measure, as it is known that LDL levels fall temporarily with stress. "Also, they didn't measure LDL levels at follow-up. The only thing we know is that those patients who took statins did better. But this study is not meant to be definitive. It is just suggesting a hypothesis, which to me seems entirely reasonable. "

Randomized Study Needed

He is keen for a study to be done to look at this issue further. "We haven't previously thought it was realistic to try to get LDL down below 70. But maybe now there is enough evidence that this might be a worthwhile strategy." He added that a trial investigating this would also address concerns about the possible dangers of very low cholesterol, which he says "have really never been answered satisfactorily."

Miller added that the ongoing IMPROVE-IT study that is evaluating whether lowering LDL to less than 50 mg/dL is clinically superior to 70 mg/dL post-ACS, although he pointed out that the comparator is ezetimibe added to statin therapy.