Author + information
- Carl J. Lavie, MD, FACC* ( and )
- Richard V. Milani, MD, FACC
- ↵*Cardiac Rehabilitation, Exercise Laboratories, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121-2483
We read with interest the excellent and thought-provoking recent report in the June 2, 2004, issue of JACCby O'Keefe et al. (1) suggesting that the optimal low-density lipoprotein (LDL) is 50 to 70 mg/dl. We agree with most of the points in their paper, particularly regarding the fact that lower levels of LDL may be optimal, and we have already routinely implemented getting LDL levels at least under 80 mg/dl (and often in the range of 50 to 70 mg/dl) in patients following acute coronary syndrome (ACS), as based on the Thrombolysis In Myocardial Infarction (TIMI)-22 trial (2), and generally are more aggressive than the national goals for patients with stable atherosclerosis; however, caution is needed before routinely recommending levels of LDL of 50 to 70 mg/dl. Although it is hard to argue with the investigators' dietary and life-style recommendations (1,3), the use of pharmacologic intervention to achieve these therapeutic targets may be premature. It is hoped that the ongoing intensity trials (TNT, SEARCH, IDEAL, A2Z) will not only provide further insight into this area but also provide information on cost-effectiveness of this approach. In addition, the investigators note that only one-third of vascular patients are currently reaching the more liberal LDL goal of <100 mg/dl, not to mention the fact that most vascular patients also have low levels of high-density lipoprotein (HDL) cholesterol and many have elevated levels of non-HDL cholesterol, both of which may need additional treatment (4,5).
The researchers also listed several “unintended” benefits of LDL lowering, one of which was reduction in dementia (1,6). However, current published data are quite conflicting with regards to the effects of statins on cognitive function and memory loss. Early examination of hospital databases revealed a possible connection between statin use and subsequent development of dementia, where use of lovastatin or pravastatin was associated with a lower prevalence of Alzheimer's disease (7). Another report from the United Kingdom, using a nested case-control study of patients aged 50 years and older, described an adjusted relative risk of developing dementia among patients receiving statin therapy of 0.29 (95% confidence interval, 0.13 to 0.63; p = 0.002) (8). However, two recent large prospective studies have further assessed this. The Heart Protection Study (HPS) was the first prospective statin study to evaluate cognitive impairment as an outcome of the trial (9). In HPS, no significant differences were found in cognitive function or diagnosis of dementia between treatment groups during this 5-year study with simvastatin. The PROSPER study also specifically and prospectively addressed cognitive function, including dementia, in its study population of patients aged 70 to 82 years (average 75 years) who demonstrated no evidence of cognitive dysfunction at study entry, and found no effect of pravastatin treatment on this domain during a 3-year trial (10). Based on these two large-scale prospectively designed investigations, we can conclude that statin therapy does not appear to have any beneficial or adverse effect on cognitive function assessed over a 3 to 5-year period. Conceivably, a longer follow-up time may be needed to detect a significant impact on dementia (11).
Most recently, because of the considerable attention given to this topic by the lay media, many patients have been concerned about statins actually causing memory loss and cognitive impairment. Although this idea is mostly based on isolated case reports without causality being established (12,13), the media attention given to this topic has led to numerous phone calls to physicians' offices as well as some patients stopping their statins. Although these reports raise the possibility that statins, in rare cases, may be associated with cognitive impairment, this is not supported by data in over 30,000 patients in the two large-scale prospective studies (9,10).
Further studies are needed before routinely adjusting therapeutic targets for LDL in patients without ACS especially to targeted LDL levels between 50 to 70 mg/dl, and long-term studies are still required to better assess the clinical impact of statins on cognitive function.
- American College of Cardiology Foundation
- O'Keefe J.H.,
- Cordain L.,
- Harris W.H.,
- Moe R.M.,
- Vogel R.
- Gotto A.M.,
- Brinton E.A.
- Toth P.P.
- ↵MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002;360:7–22.