Mary NHaan, University of Michigan, Epidemiology, 109 S Observatory St, rm 5174mnhaan@umich.edu
Caryn Cramer, Jack Kalbfleisch, Ken Langa, Sandro Galea
Submitted September 11, 2008
The Goldstein et al. letter highlights the importance of considering adverse effects from overly effective lipid lowering drugs.
Some studies have found a decline in cholesterol levels in older populations associated with adverse outcomes. Interpretation of decline is not straightforward. Curb et al. [6] found a u-shaped association between coronary heart disease outcomes and concluded that LDL-lowering drugs could still be used in older populations with the caveat that statins have the potential to lower LDL-C too far. Reasons for declines of cholesterol in old age may be multivariate (e.g., weight loss, reduction in muscle mass) and may be unrelated to statin use. LDL declines may be markers of prodromal changes accompanied by cognitive decline.
Baseline LDL-C levels in our population were higher in non-statin vs. statin users: 123 vs. 112 mg/dl respectively (p=0.0002). Total cholesterol was 212 vs. 204, p=0.016). LDL in statin users declined over time more rapidly than in non-statin users. We found that higher LDL-C over time is associated with higher mortality rates (Cox model =HR: 1.89 for a LDL-C SD of 34.5, p=0.02) which may indicate a direct effect of LDL-C or the residual association of LDL with heart disease. Change in LDL-C over time is not associated with dementia/CIND incidence. LDL-C does modify the effect of statin use on dementia/CIND. A one SD decrease in LDL-C (34.5 mg/dl) is associated with an approximately 54% increase in the benefit associated with statin use. (HR for statin use: 0.29, p=0.04 for interaction between LDL and statins).
Our results confirm that those who are taking statins over time may experience lower rates of cognitive impairment and dementia related to the reduction in LDL-C. This result does not support a treatment recommendation.
We would enthusiastically support a primary prevention trial that could examine the effects of lowering lipids on the development of incident dementia and AD. However, a primary prevention trial should be preceded by a better understanding of the mechanisms by which statins may confer this benefit and should include arms for both behavioral and various drug treatments.
Reference
6. Curb JD, Abbott RD, Rodriguez BL et al. Prospective association between low and high total and low-density lipoprotein cholesterol and coronary heart disease in elderly men. J Am Geriatr Soc 2004;52:1975-1980.
Disclosure: Caryn Cramer was employed by Pfizer Corporation during completion of her doctoral degree during which time this study was conducted. Pfizer did not provide any material support for this study, and did not participate in the design, conduct, management, analysis, interpretation, review, or approval of the study or the manuscript. The other authors have reported no disclosures.
The Goldstein et al. letter highlights the importance of considering adverse effects from overly effective lipid lowering drugs.
Some studies have found a decline in cholesterol levels in older populations associated with adverse outcomes. Interpretation of decline is not straightforward. Curb et al. [6] found a u-shaped association between coronary heart disease outcomes and concluded that LDL-lowering drugs could still be used in older populations with the caveat that statins have the potential to lower LDL-C too far. Reasons for declines of cholesterol in old age may be multivariate (e.g., weight loss, reduction in muscle mass) and may be unrelated to statin use. LDL declines may be markers of prodromal changes accompanied by cognitive decline.
Baseline LDL-C levels in our population were higher in non-statin vs. statin users: 123 vs. 112 mg/dl respectively (p=0.0002). Total cholesterol was 212 vs. 204, p=0.016). LDL in statin users declined over time more rapidly than in non-statin users. We found that higher LDL-C over time is associated with higher mortality rates (Cox model =HR: 1.89 for a LDL-C SD of 34.5, p=0.02) which may indicate a direct effect of LDL-C or the residual association of LDL with heart disease. Change in LDL-C over time is not associated with dementia/CIND incidence. LDL-C does modify the effect of statin use on dementia/CIND. A one SD decrease in LDL-C (34.5 mg/dl) is associated with an approximately 54% increase in the benefit associated with statin use. (HR for statin use: 0.29, p=0.04 for interaction between LDL and statins).
Our results confirm that those who are taking statins over time may experience lower rates of cognitive impairment and dementia related to the reduction in LDL-C. This result does not support a treatment recommendation.
We would enthusiastically support a primary prevention trial that could examine the effects of lowering lipids on the development of incident dementia and AD. However, a primary prevention trial should be preceded by a better understanding of the mechanisms by which statins may confer this benefit and should include arms for both behavioral and various drug treatments.
Reference
6. Curb JD, Abbott RD, Rodriguez BL et al. Prospective association between low and high total and low-density lipoprotein cholesterol and coronary heart disease in elderly men. J Am Geriatr Soc 2004;52:1975-1980.
Disclosure: Caryn Cramer was employed by Pfizer Corporation during completion of her doctoral degree during which time this study was conducted. Pfizer did not provide any material support for this study, and did not participate in the design, conduct, management, analysis, interpretation, review, or approval of the study or the manuscript. The other authors have reported no disclosures.