Cholesterol Lowering Drugs for the Elderly, a Very Bad Idea

by Jeffrey Dach MD

A Flawed and Corrupted Study

A 2008 publication by Jonathon Afilalo in the Journal of the American College of Cardiology concludes that," Statins reduce all-cause mortality in elderly patients and the magnitude of this effect is substantially larger than had been previously estimated. "  

Statistics Manipulated

This 2008 metanalysis by Afilalo is a statistical sleight of hand that gives the results opposite to reality.  Their conclusion is directly opposite to multiple previous studies.  Also, this published study had no Disclosure Statement, another warning sign of bias from authors receiving compensation from drug companies.

Lowering Cholesterol in the Elderly is a BAD IDEA

Contrary to the above flawed 2008 metanalysis, it is a very bad idea to lower the cholesterol levels in the elderly with statin drugs. An excellent article on the topic appeared on the Junk Food Science Blog.

Here's the evidence:

1) the Honolulu Heart Study published in Lancet 2001, showed that patients with the lowest cholesterol had the highest mortality.  The authors concluded,"These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations  in elderly people."

2) Krumholz from Yale published his study in JAMA 1994 looking at elevated cholesterol to see if it was associated with increased all-cause mortality or heart disease.  He reported that elevated cholesterol was NOT a risk factor for mortality or heart disease.  He said,"our findings do not support the hypothesis that hypercholesterolemia or low HDL-C are important risk factors for all-cause mortality, coronary heart disease mortality, or hospitalization for myocardial infarction or unstable angina in this cohort of persons older than 70 years."

3) Beatrice Golomb MD in Geriatric Times 2004, reports that in the elderly, higher cholesterol is linked with improved survival.

She says, "While patients at high risk for cardiovascular disease receive mortality benefit from statins in studies predominating in middle-aged men (Scandinavian Simvastatin Survival Study Group, 1994), no trend toward survival benefit is seen in elderly patients at high risk for cardiovascular disease (Shepherd et al., 2002).   A less favorable risk-benefit profile may particularly hold for patients older than 85, in whom benefits may be more attenuated and risks more amplified (Weverling-Rijnsburger et al., 1997). In fact, in this older group, higher cholesterol has been linked observationally to improved survival."

Adverse Side Effects

Adverse side effects from statin drugs are devastating with cognitive impairment, dementia, neuropathy, and muscle damage.

New Cholesterol Guidelines are Wrong

In September 2004 numerous prestigious doctors petitioned the FDA with a letter asking that the cholesterol guidelines be re-evaluated.  They had been set lower by a corrupt committee of doctors receiving money from the drug companies. 

Update Feb 21, 2010  Here are additional studies and references why lowering the cholesterol in the elderly leads to increased mortality:

1a) Forette Lancet 1989: Mortality was lowest at serum cholesterol 7.0 mmol/l (271), Mortality was 5.2 times higher at a cholesterol of 155 compared to mortality at cholesterol of 271.

2a) Weverling, Lancet 1997 , In people older than 85 years, high total cholesterol concentrations are associated with longevity owing to lower mortality from cancer and infection.

3a) Kelleher J Womens Health 2004,  Low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases.  This applied to men, across the entire age range, and in women from the age of 50 onward only.

references (1a 2a 3a)

1a) http://www.ncbi.nlm.nih.gov/pubmed/2564950
Lancet. 1989 Apr 22;1(8643):868-70.

Cholesterol as risk factor for mortality in elderly women.

Forette B, Tortrat D, Wolmark Y. Centre Claude Bernard de Gérontologie, Hôpital Sainte Périne, Paris, France.

92 women aged 60 years and over (mean 82.2, SD 8.6) living in a nursing home and free from overt cancer were followed-up for 5 years. 53 died during this period; necropsy revealed cancer in only 1 patient. Serum total cholesterol at entry ranged from 4.0 to 8.8 mmol/l (mean 6.3, SD 1.1). Cox's proportional hazards analysis showed a J-shaped relation between serum cholesterol and mortality.

Mortality was lowest at serum cholesterol 7.0 mmol/l (271), 5.2 times higher than the minimum at serum cholesterol 4.0 mmol/l (155), and only 1.8 times higher when cholesterol concentration was 8.8 mmol/l (340). This relation held true irrespective of age, even when blood pressure, body weight, history of myocardial infarction, creatinine clearance, and plasma proteins were taken into account. The relation between low cholesterol values and increased mortality was independent of the incidence of cancer. conversion factor (multiply by 38.67)

2a) http://www.ncbi.nlm.nih.gov/pubmed/9343498
Total cholesterol and risk of mortality in the oldest old.Lancet. 1997 Oct 18;350(9085):1119-23.

Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG.
Department of General Internal Medicine, Leiden University Medical Center, The Netherlands.

BACKGROUND: The impact of total serum cholesterol as a risk factor for cardiovascular disease decreases with age, which casts doubt on the necessity for cholesterol-lowering therapy in the elderly. We assessed the influence of total cholesterol concentrations on specific and all-cause mortality in people aged 85 years and over.

METHODS: In 724 participants (median age 89 years), total cholesterol concentrations were measured and mortality risks calculated over 10 years of follow-up. Three categories of total cholesterol concentrations were defined: < 5.0 mmol/L (194), 5.0-6.4 mmol/L, and > or = 6.5 mmol/L (251). In a subgroup of 137 participants, total cholesterol was measured again after 5 years of follow-up. Mortality risks for the three categories of total cholesterol concentrations were estimated with a Cox proportional-hazards model, adjusted for age, sex, and cardiovascular risk factors. The primary causes of death were coded according to the International Classification of Diseases (ICD-9).

FINDINGS: During 10 years of follow-up from Dec 1, 1986, to Oct 1, 1996, a total of 642 participants died. Each 1 mmol/L increase in total cholesterol (39) corresponded to a 15% decrease in mortality (risk ratio 0.85 [95% CI 0.79-0.91]). This risk estimate was similar in the subgroup of participants who had stable cholesterol concentrations over a 5-year period. The main cause of death was cardiovascular disease with a similar mortality risk in the three total cholesterol categories. Mortality from cancer and infection was significantly lower among the participants in the highest total cholesterol category than in the other categories, which largely explained the lower all-cause mortality in this category.

INTERPRETATION: In people older than 85 years, high total cholesterol concentrations are associated with longevity owing to lower mortality from cancer and infection. The effects of cholesterol-lowering therapy have yet to be assessed.

3a) http://www.ncbi.nlm.nih.gov/pubmed/15006277

J Womens Health (Larchmt). 2004 Jan-Feb;13(1):41-53.

Why Eve is not Adam: prospective follow-up in 149,650 women and men of cholesterol and other risk factors related to cardiovascular and all-cause mortality. by Ulmer H, Kelleher C, Diem G, Concin H. Institute of Biostatistics and Documentation, Leopold Franzens University of Innsbruck, Innsbruck, Austria.

PURPOSE: To assess the impact of sex-specific patterns in cholesterol levels on all-cause and cardiovascular mortality in the Vorarlberg Health Monitoring and Promotion Programme (VHM&PP).

METHODS : In this study, 67413 men and 82237 women (aged 20-95 years) underwent 454448 standardized examinations, which included measures of blood pressure, height, weight, and fasting samples for cholesterol, triglycerides, gamma-glutamyl transferase (GGT), and glucose in the 15-year period 1985-1999. Relations between these variables and risk of death were analyzed using two approaches of multivariate analyses (Cox proportional hazard and GEE models).

RESULTS: Patterns of cholesterol levels showed marked differences between men and women in relation to age and cause of death. The role of high cholesterol in predicting death from coronary heart disease could be confirmed in men of all ages and in women under the age of 50.

In men, across the entire age range, although of borderline significance under the age of 50, and in women from the age of 50 onward only, low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases. Triglycerides > 200 mg/dl had an effect in women 65 years and older but not in men.

CONCLUSIONS: This large-scale population-based study clearly demonstrates the contrasting patterns of cholesterol level in relation to risk, particularly among those less well studied previously, that is, women of all ages and younger people of both sexes. For the first time, we demonstrate that the low cholesterol effect occurs even among younger respondents, contradicting the previous assessments among cohorts of older people that this is a proxy or marker for frailty occurring with age.

To read more about cholesterol and the elderly, see  Drugs that Don't Work and Natural Therapies that Do, a book by David Brownstein MD. Chapter 2 covers Cholesterol Lowering Drugs.

Left image: book cover courtesy of David Brownstein MD.

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Jeffrey Dach MD
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Links and References

http://junkfoodscience.blogspot.com/2008/01/reading-evidence-closely-statins-for.html
Reading the evidence closely — statins for seniors

http://www.mdconsult.com/das/citation/body/103436352-2/jorg=journal&source=MI&sp=9963308&sid=0/N/9963308/1.html
Total cholesterol and risk of mortality in the oldest old. - Weverling-Rijnsburger AW -
Lancet - 1 CT-1997; 350(9085): 1119-23 (From NIH/NLM MEDLINE)

INTERPRETATION: In people older than 85 years, high total cholesterol concentrations are associated with longevity owing to lower mortality from cancer and infection. The effects of cholesterol-lowering therapy have yet to be assessed.

http://www.ncbi.nlm.nih.gov/pubmed/11502313
Lancet. 2001 Aug 4;358(9279):351-5.
Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD.
Clinical Epidemiology and Geriatrics Division, Department of Medicine, John A Bums School of Medicine, University of Hawaii at Manoa, 1356 Lusitana Street, 7th Floor, Honolulu, HI 96813-2427, USA. schatzi@hawaii.edu

BACKGROUND: A generally held belief is that cholesterol concentrations should be kept low to lessen the risk of cardiovascular disease. However, studies of the relation between serum cholesterol and all-cause mortality in elderly people have shown contrasting results. To investigate these discrepancies, we did a longitudinal assessment of changes in both lipid and serum cholesterol concentrations over 20 years, and compared them with mortality. METHODS: Lipid and serum cholesterol concentrations were measured in 3572 Japanese/American men (aged 71-93 years) as part of the Honolulu Heart Program. We compared changes in these concentrations over 20 years with all-cause mortality using three different Cox proportional hazards models. FINDINGS: Mean cholesterol fell significantly with increasing age. Age-adjusted mortality rates were 68.3, 48.9, 41.1, and 43.3 for the first to fourth quartiles of cholesterol concentrations, respectively. Relative risks for mortality were 0.72 (95% CI 0.60-0.87), 0.60 (0.49-0.74), and 0.65 (0.53-0.80), in the second, third, and fourth quartiles, respectively, with quartile 1 as reference. A Cox proportional hazard model assessed changes in cholesterol concentrations between examinations three and four. Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1.64, 95% CI 1.13-2.36). INTERPRETATION: We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4.65 mmol/L) in elderly people.

http://www.ncbi.nlm.nih.gov/pubmed/7772105
JAMA. 1994 Nov 2;272(17):1335-40
Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. Krumholz HM, Seeman TE, Merrill SS, Mendes de Leon CF, Vaccarino V, Silverman DI, Tsukahara R, Ostfeld AM, Berkman LF.  Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8017.

OBJECTIVES--To determine whether elevated serum cholesterol level is associated with all-cause mortality, mortality from coronary heart disease, or hospitalization for acute myocardial infarction and unstable angina in persons older than 70 years. Also, to evaluate the association between low levels of high-density lipoprotein cholesterol (HDL-C) and elevated ratio of serum cholesterol to HDL-C with these outcomes. DESIGN--Prospective, community-based cohort study with yearly interviews. PARTICIPANTS--A total of 997 subjects who were interviewed in 1988 as part of the New Haven, Conn, cohort of the Established Population for the Epidemiologic Study of the Elderly (EPESE) and consented to have blood drawn. MAIN OUTCOME MEASURES--The risk factor-adjusted odds ratios of the 4-year incidence of all-cause mortality, mortality from coronary heart disease, and hospitalization for myocardial infarction or unstable angina were calculated for the following: subjects with total serum cholesterol levels greater than or equal to 6.20 mmol/L (> or = 240 mg/dL) compared with subjects with cholesterol levels less than 5.20 mmol/L (< 200 mg/dL); subjects in the lowest tertile of HDL-C level compared with those in the highest tertile; and subjects in the highest tertile of the ratio of total serum cholesterol to HDL-C level compared with those in the lowest tertile. RESULTS--Elevated total serum cholesterol level, low HDL-C, and high total serum cholesterol to HDL-C ratio were not associated with a significantly higher rate of all-cause mortality, coronary heart disease mortality, or hospitalization for myocardial infarction or unstable angina after adjustment for cardiovascular risk factors. The risk factor-adjusted odds ratio for all-cause mortality was 0.99 (95% confidence interval [CI], 0.56 to 2.69) for the group who had cholesterol levels greater than or equal to 6.20 mmol/L (> or = 240 mg/dL) compared with the group that had levels less than 5.20 mmol/L (< 200 mg/dL); 1.00 (95% CI, 0.59 to 1.70) for the group in the lowest tertile of HDL-C compared with those in the highest tertile; and 1.03 (95% CK, 0.62 to 1.71) for subjects in the highest tertile of the ratio of total serum cholesterol to HDL-C compared with those in the lowest tertile. CONCLUSIONS--Our findings do not support the hypothesis that hypercholesterolemia or low HDL-C are important risk factors for all-cause mortality, coronary heart disease mortality, or hospitalization for myocardial infarction or unstable angina in this cohort of persons older than 70 years.

http://www.cmellc.com/geriatrictimes/g040618.html
Statin Adverse Effects: Implications for the Elderly
by Beatrice A. Golomb, M.D., Ph.D. Geriatric Times  May/June 2004  Vol. V  Issue 3

Discussion  Observational studies show that as age increases within the elderly age range, high cholesterol flattens then reverses as a risk factor for mortality (Weverling-Rijnsburger et al., 1997). Although it remains to be fully clarified whether these findings have relevance to cholesterol-lowering treatment, the exclusive major randomized trial of statins conducted in the elderly does nothing to dispel a possible causal association, as it did not show benefit of statins to survival. The impact was completely neutral on mortality despite selecting for an elderly population at only moderately older age and selecting for particularly high risk of heart disease--the elderly group in whom greater benefits and lower risks would be expected (Shepherd et al., 2002). There are reasons for concern that still older people--those elderly not selecting for high cardiac risk and those who are frailer than clinical trials generally select--might fare less well. Caution should be exercised in provision of statins as with all treatments in elderly patients. Any time a patient develops a new problem or worsening of an existing problem, the medication list should be reviewed and a possible contribution by medications should be considered. This principle is by no means confined to statins. It is particularly true in elderly patients who may be on many medications with interacting effects, and in whom ability to withstand adverse drug reactions may be attenuated.

http://cspinet.org/new/pdf/finalnihltr.pdf
PETITION TO THE NATIONAL INSTITUTES OF HEALTH SEEKING AN INDEPENDENT REVIEW PANEL TO RE-EVALUATE THE NATIONAL CHOLESTEROL EDUCATION PROGRAM GUIDELINES September 23, 2004

http://www.thincs.org/unpublic.ArchIntMed.htm
Letter to Archives of Internal Medicine, submitted on July 20, 2002
Exaggerated benefit of statin treatment in the elderly?    by Uffe Ravnskov, MD, PhD Joel M. Kauffman; PhD, Peter H. Langsjoen, M.D., Kilmer S. McCully, M.D., Paul J. Rosch, 
  
 
http://content.onlinejacc.org/cgi/content/short/51/1/37
 J Am Coll Cardiol, 2008; 51:37-45, doi:10.1016/j.jacc.2007.06.063

CLINICAL RESEARCH: LIPIDS AND ATHEROSCLEROSIS
Statins for Secondary Prevention in Elderly Patients. A Hierarchical Bayesian Meta-Analysis A Hierarchical Bayesian Meta-Analysis, Jonathan Afilalo, MD et al.

Objectives: This study was designed to determine whether statins reduce all-cause mortality in elderly patients with coronary heart disease.

Background: Statins continue to be underutilized in elderly patients because evidence has not consistently shown that they reduce mortality.

Methods: We searched 5 electronic databases, the Internet, and conference proceedings to identify relevant trials. In addition, we obtained unpublished data for the elderly patient subgroups from 4 trials and for the secondary prevention subgroup from the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) trial. Inclusion criteria were randomized allocation to statin or placebo, documented coronary heart disease, 50 elderly patients (defined as age 65 years), and 6 months of follow-up. Data were analyzed with hierarchical Bayesian modeling.

Results: We included 9 trials encompassing 19,569 patients with an age range of 65 to 82 years. Pooled rates of all-cause mortality were 15.6% with statins and 18.7% with placebo. We estimated a relative risk reduction of 22% over 5 years (relative risk [RR] 0.78; 95% credible interval [CI] 0.65 to 0.89). Furthermore, statins reduced coronary heart disease mortality by 30% (RR 0.70; 95% CI 0.53 to 0.83), nonfatal myocardial infarction by 26% (RR 0.74; 95% CI 0.60 to 0.89), need for revascularization by 30% (RR 0.70; 95% CI 0.53 to 0.83), and stroke by 25% (RR 0.75; 95% CI 0.56 to 0.94). The posterior median estimate of the number needed to treat to save 1 life was 28 (95% CI 15 to 56).

Conclusions: Statins reduce all-cause mortality in elderly patients and the magnitude of this effect is substantially larger than had been previously estimated.

But this published study had no Disclosure Statement, which is highly unusual for published studies.

http://www.nytimes.com/2008/01/29/health/29well.html?_r=1&oref=slogin
Great Drug, but Does It Prolong Life? New York Times By TARA PARKER-POPE  Published: January 29, 2008