JAMDA 14 (2013) 853e854
JAMDA journal homepage: www.jamda.com
Editorial
Statins and the Nursing Home John E. Morley MB, BCh a, *, Gerald Mahon MD b a b
Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, St. Louis, MO Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, MO
In this issue of the Journal, we published yet another article showing that high cholesterol has little relationship to mortality.1 This is in contrast to the well-established data demonstrating a clear correlation of low total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to increasing mortality.2 The correlation to low total cholesterol to mortality is almost certainly related to it being caused by weight loss (under nutrition) and an increase in cytokines both of which are associated with increased mortality.3e10 Frailty represents another important cause of poor outcomes in older persons.11e15 Frailty is associated with low cholesterol.16 Thus, cholesterol represents a classical example of reverse epidemiology in older persons.17 The wrinkle introduced in the article by Jacobs et al1 is that in the very old (85e90 years of age), statins resulted in a decreased mortality, and there was a strong trend in older persons. The authors point out that their study was observational and noninterventional; nevertheless, this finding deserves to be taken seriously. A major caveat is that this study began in 1990 when the majority of older persons were unlikely to receive statins. Thus, it could have been that those who received statins were a special group who had a high atherosclerotic burden and a recent myocardial infarction or stroke. This would be in keeping with the finding that persons 80e97 years of age with angiographically proven atherosclerosis had a 50% relative risk reduction in total mortality when given a statin.18 Alternatively, statins could have a noncholesterol associated action, as was suggested by the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluation Rosuvastatin (JUPITER) trial.19 Statins have antioxidant and anti-inflammatory effects among others that could explain these outcomes. In deciding whether or not to give statins to older nursing home residents, the side-effects of statins need to be taken under consideration. Statins are clearly associated with myositis.20 Statin use may increase risk of falls based upon 1 observational study.21 Another review article suggests that elderly females are more prone to statin myopathy than men.22 Thus, statins may be an important cause of morbidity in nursing homes.23e26 Sarcopenia has increased risk of morbidity or mortality in the elderly.27e31 There probably is an increased risk of falls in elderly patients with sarcopenia who take
statins.27 Persons with low vitamin D levels are also at particular risk for statin-induced myositis.32e34 Thus, any persons on statins should have creatine kinase and aldolase measured, and if they are falling, statins should be withdrawn. While statin use in middle-aged persons may reduce the risk of dementia, it would seem that in older persons they have no effect or may aggravate the cognitive decline.35e39 Padala et al40 found a worsening of cognition in persons on statins, using a prospective withdrawal and rechallenge pilot study. It has been suggested that if statins impair cognition, this may be less likely if hydrophilic rather than lipophilic statins were used. Polypharmacy has been clearly established to be a major hazard in older persons.41e48 Thus, the addition of a statin requires the discerning physician to make a decision that it will be more likely to improve the person’s outcome than do harm. The Assessment for Survival and Cardiovascular Events (AURORA) study in hemodialysis patients found no significant effects of rosuvastatin.49 This trial, with persons who are generally frail, could be considered a proxy for nursing home residents and thus would weigh against the use of statins in nursing homes. Peterson et al50 recently pointed out that no randomized controlled trial has demonstrated an effect of lowering cholesterol on total mortality in persons over 80 years of age. Available studies in persons 75 years or older give conflicting data, but in general, failed to show a decrease in mortality. Based on the available data, we would suggest that the discerning physician may limit statin use in the majority of nursing home residents to those who have had a recent myocardial infarction or stroke, though even for these individuals, there may be no difference in allcause mortality.51 As was stressed by the International Association of Gerontology and Geriatrics/World Health Organization white paper on nursing homes, there is an urgent need for randomized controlled trials in nursing home residents.52 Only 31.8% of patients who had a cardiac hospitalization and then were discharged to a nursing home received a statin.53 In another study, 30% of nursing home residents in Spain received statins.54 In another study in the USA, 87% of persons with coronary artery disease were receiving statins.55 These data strongly highlight the need for a randomized controlled study of statins in nursing homes.
The authors declare no conflicts of interest. * Address correspondence to John E. Morley, MB, BCh, Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, 1402 S Grand Blvd, M238, St. Louis, MO 63104. E-mail address: [email protected] (J.E. Morley).
References 1. Jacobs JM, Cohen A, Ein-Mor E, Stessman J. Cholesterol, statins, and longevity from age 70 to 90 years. J Am Med Dir Assoc 2013;14:883e888. 2. Morley JE. The cholesterol conundrum. JAGS 2011;59:1955e1956.
1525-8610/$ - see front matter Copyright Ó 2013 - American Medical Directors Association, Inc. http://dx.doi.org/10.1016/j.jamda.2013.09.016
854
Editorial / JAMDA 14 (2013) 853e854
3. Argiles JM, Anker SD, Evans WJ, et al. Consensus on cachexia definitions. J Am Med Dir Assoc 2010;11:229e230. 4. Rolland Y, Perrin A, Gardette V, et al. Screening older people at risk of malnutrition or malnourished using the Simplified Nutritional Appetite Questionnaire (SNAQ): A comparison with the Mini-Nutritional Assessment (MNA) tool. J Am Med Dir Assoc 2012;13:31e34. 5. Bell CL, Tamura BK, Masaki KH, Amella EJ. Prevalence and measures of nutritional compromise among nursing home patients: Weight loss, low body mass index, malnutrition, and feeding dependency, a systematic review of the literature. J Am Med Dir Assoc 2013;14:94e100. 6. Farkas J, von Haehling S, Kalantar-Zadeh K, et al. Cachexia as a major public health problem: Frequent, costly, and deadly. J Cachexia Sarcopenia Muscle 2013;4:173e178. 7. Morley JE. Undernutrition: A major problem in nursing homes. J Am Med Dir Assoc 2011;12:243e246. 8. Tamura BK, Bell CL, Masaki KH, Amella EJ. Factors associated with weight loss, low BMI, and malnutrition among nursing home patients: A systematic review of the literature. J Am Med Dir Assoc 2013;14:649e655. 9. Soenen S, Chapman IM. Body weight, anorexia, and under nutrition in older people. J Am Med Dir Assoc 2013;14:642e648. 10. Morley JE. Weight loss in older persons: New therapeutic approaches. Curr Pharm Des 2007;13:3637e3647. 11. Morley JE, Vellas B, van Kan GA, et al. Frailty consensus: A call to action. J Am Med Dir Assoc 2013;14:392e397. 12. Le Reste JY, Nabbe P, Manceau B, et al. The European General Practice Research Network presents a comprehensive definition of multimorbidity in family medicine and long term care, following a systematic review of relevant literature. J Am Med Dir Assoc 2013;14:319e325. 13. Morley JE. Frailty, falls, and fractures. J Am Med Dir Assoc 2013;14:149e151. 14. Hoogendijk EO, van Hout HP. Investigating measurement properties of the Groningen Frailty Indicator: A more systematic approach is needed. J Am Med Dir Assoc 2012;13:757. 15. Peters LL, Boter H, Buskens E, Slaets JP. Measurement properties of the Groningen Frailty Indicator in home-dwelling and institutionalized elderly people. J Am Med Dir Assoc 2012;13:546e551. 16. Ranieri P, Rozzini R, Franzoni S, et al. Serum cholesterol levels as a measure of frailty in elderly patients. Exp Aging Res 1998;24:169e179. 17. Kalantar-Zadeh K, Horwich TB, Oreopoulos A, et al. Risk factor paradox in wasting diseases. Curr Opin Clin Nutr Metab Care 2007;10:433e442. 18. Allen Maycock CA, Muhlestein JB, Horne BD, et al. Statin therapy is associated with reduced mortality across all age groups of individuals with significant coronary disease, including very elderly patients. J Am Coll Cardiol 2002;40: 1777e1785. 19. Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195e2207. 20. Goldstein MR, Mascitelli L, Pezzetta F. Statin therapy, muscle function and vitamin D. Q J Med; 2009:890e891. 21. Scott D, Blizzard L, Fell J, Jones G. Statin therapy, muscle function and falls risk in community-dwelling older adults. Q J Med 2009;102:625e633. 22. Bhardwaj S, Selvarajah S, Schneider EB. Muscular effects of statins in the elderly female: A review. Clin Intervent Aging 2013;8:47e59. 23. Saliba D, Jones M, Streim J, et al. Overview of significant changes in the Minimum Data Set for nursing homes version 3.0. J Am Med Dir Assoc 2012;13: 595e601. 24. Whitney J, Close JC, Jackson SH, Lord SR. Understanding risk of falls in people with cognitive impairment living in residential care. J Am Med Dir Assoc 2012; 13:535e540. 25. Morley JE, Rolland Y, Tolson D, Vellas B. Increasing awareness of the factors producing falls: The mini falls assessment. J Am Med Dir Assoc 2012;13:87e90. 26. Morley JE. Falls and fractures. J Am Med Dir Assoc 2007;8:276e278. 27. Scott D, Blizzard L, Fell J, Jones G. The epidemiology of sarcopenia in community living older adults: What role does lifestyle play? J Cachexia Sarcopenia Muscle 2011;2:125e134. 28. Cesari M, Vellas B. Sarcopenia: A novel clinical condition or still a matter for research? J Am Med Dir Assoc 2012;13:766e767. 29. Landi F, Liperoti R, Fusco D, et al. Sarcopenia and mortality among older nursing home residents. J Am Med Dir Assoc 2012;13:121e126. 30. Morley JE, Abbatecola AM, Argiles JM, et al. Sarcopenia with limited mobility: An international consensus. J Am Med Dir Assoc 2011;12:403e409.
31. Fielding RA, Vellas B, Evans WJ, et al. Sarcopenia: An undiagnosed condition in older adults. Current consensus definition: Prevalence, etiology, and consequences. International Working Group on Sarcopenia. J Am Med Dir Assoc 2011;12:249e256. 32. Ahmed W, Khan N, Glueck CJ, et al. Low serum 25 (OH) vitamin D levels (
JAMDA journal homepage: www.jamda.com
Editorial
Statins and the Nursing Home John E. Morley MB, BCh a, *, Gerald Mahon MD b a b
Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, St. Louis, MO Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, MO
In this issue of the Journal, we published yet another article showing that high cholesterol has little relationship to mortality.1 This is in contrast to the well-established data demonstrating a clear correlation of low total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to increasing mortality.2 The correlation to low total cholesterol to mortality is almost certainly related to it being caused by weight loss (under nutrition) and an increase in cytokines both of which are associated with increased mortality.3e10 Frailty represents another important cause of poor outcomes in older persons.11e15 Frailty is associated with low cholesterol.16 Thus, cholesterol represents a classical example of reverse epidemiology in older persons.17 The wrinkle introduced in the article by Jacobs et al1 is that in the very old (85e90 years of age), statins resulted in a decreased mortality, and there was a strong trend in older persons. The authors point out that their study was observational and noninterventional; nevertheless, this finding deserves to be taken seriously. A major caveat is that this study began in 1990 when the majority of older persons were unlikely to receive statins. Thus, it could have been that those who received statins were a special group who had a high atherosclerotic burden and a recent myocardial infarction or stroke. This would be in keeping with the finding that persons 80e97 years of age with angiographically proven atherosclerosis had a 50% relative risk reduction in total mortality when given a statin.18 Alternatively, statins could have a noncholesterol associated action, as was suggested by the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluation Rosuvastatin (JUPITER) trial.19 Statins have antioxidant and anti-inflammatory effects among others that could explain these outcomes. In deciding whether or not to give statins to older nursing home residents, the side-effects of statins need to be taken under consideration. Statins are clearly associated with myositis.20 Statin use may increase risk of falls based upon 1 observational study.21 Another review article suggests that elderly females are more prone to statin myopathy than men.22 Thus, statins may be an important cause of morbidity in nursing homes.23e26 Sarcopenia has increased risk of morbidity or mortality in the elderly.27e31 There probably is an increased risk of falls in elderly patients with sarcopenia who take
statins.27 Persons with low vitamin D levels are also at particular risk for statin-induced myositis.32e34 Thus, any persons on statins should have creatine kinase and aldolase measured, and if they are falling, statins should be withdrawn. While statin use in middle-aged persons may reduce the risk of dementia, it would seem that in older persons they have no effect or may aggravate the cognitive decline.35e39 Padala et al40 found a worsening of cognition in persons on statins, using a prospective withdrawal and rechallenge pilot study. It has been suggested that if statins impair cognition, this may be less likely if hydrophilic rather than lipophilic statins were used. Polypharmacy has been clearly established to be a major hazard in older persons.41e48 Thus, the addition of a statin requires the discerning physician to make a decision that it will be more likely to improve the person’s outcome than do harm. The Assessment for Survival and Cardiovascular Events (AURORA) study in hemodialysis patients found no significant effects of rosuvastatin.49 This trial, with persons who are generally frail, could be considered a proxy for nursing home residents and thus would weigh against the use of statins in nursing homes. Peterson et al50 recently pointed out that no randomized controlled trial has demonstrated an effect of lowering cholesterol on total mortality in persons over 80 years of age. Available studies in persons 75 years or older give conflicting data, but in general, failed to show a decrease in mortality. Based on the available data, we would suggest that the discerning physician may limit statin use in the majority of nursing home residents to those who have had a recent myocardial infarction or stroke, though even for these individuals, there may be no difference in allcause mortality.51 As was stressed by the International Association of Gerontology and Geriatrics/World Health Organization white paper on nursing homes, there is an urgent need for randomized controlled trials in nursing home residents.52 Only 31.8% of patients who had a cardiac hospitalization and then were discharged to a nursing home received a statin.53 In another study, 30% of nursing home residents in Spain received statins.54 In another study in the USA, 87% of persons with coronary artery disease were receiving statins.55 These data strongly highlight the need for a randomized controlled study of statins in nursing homes.
The authors declare no conflicts of interest. * Address correspondence to John E. Morley, MB, BCh, Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, 1402 S Grand Blvd, M238, St. Louis, MO 63104. E-mail address: [email protected] (J.E. Morley).
References 1. Jacobs JM, Cohen A, Ein-Mor E, Stessman J. Cholesterol, statins, and longevity from age 70 to 90 years. J Am Med Dir Assoc 2013;14:883e888. 2. Morley JE. The cholesterol conundrum. JAGS 2011;59:1955e1956.
1525-8610/$ - see front matter Copyright Ó 2013 - American Medical Directors Association, Inc. http://dx.doi.org/10.1016/j.jamda.2013.09.016
854
Editorial / JAMDA 14 (2013) 853e854
3. Argiles JM, Anker SD, Evans WJ, et al. Consensus on cachexia definitions. J Am Med Dir Assoc 2010;11:229e230. 4. Rolland Y, Perrin A, Gardette V, et al. Screening older people at risk of malnutrition or malnourished using the Simplified Nutritional Appetite Questionnaire (SNAQ): A comparison with the Mini-Nutritional Assessment (MNA) tool. J Am Med Dir Assoc 2012;13:31e34. 5. Bell CL, Tamura BK, Masaki KH, Amella EJ. Prevalence and measures of nutritional compromise among nursing home patients: Weight loss, low body mass index, malnutrition, and feeding dependency, a systematic review of the literature. J Am Med Dir Assoc 2013;14:94e100. 6. Farkas J, von Haehling S, Kalantar-Zadeh K, et al. Cachexia as a major public health problem: Frequent, costly, and deadly. J Cachexia Sarcopenia Muscle 2013;4:173e178. 7. Morley JE. Undernutrition: A major problem in nursing homes. J Am Med Dir Assoc 2011;12:243e246. 8. Tamura BK, Bell CL, Masaki KH, Amella EJ. Factors associated with weight loss, low BMI, and malnutrition among nursing home patients: A systematic review of the literature. J Am Med Dir Assoc 2013;14:649e655. 9. Soenen S, Chapman IM. Body weight, anorexia, and under nutrition in older people. J Am Med Dir Assoc 2013;14:642e648. 10. Morley JE. Weight loss in older persons: New therapeutic approaches. Curr Pharm Des 2007;13:3637e3647. 11. Morley JE, Vellas B, van Kan GA, et al. Frailty consensus: A call to action. J Am Med Dir Assoc 2013;14:392e397. 12. Le Reste JY, Nabbe P, Manceau B, et al. The European General Practice Research Network presents a comprehensive definition of multimorbidity in family medicine and long term care, following a systematic review of relevant literature. J Am Med Dir Assoc 2013;14:319e325. 13. Morley JE. Frailty, falls, and fractures. J Am Med Dir Assoc 2013;14:149e151. 14. Hoogendijk EO, van Hout HP. Investigating measurement properties of the Groningen Frailty Indicator: A more systematic approach is needed. J Am Med Dir Assoc 2012;13:757. 15. Peters LL, Boter H, Buskens E, Slaets JP. Measurement properties of the Groningen Frailty Indicator in home-dwelling and institutionalized elderly people. J Am Med Dir Assoc 2012;13:546e551. 16. Ranieri P, Rozzini R, Franzoni S, et al. Serum cholesterol levels as a measure of frailty in elderly patients. Exp Aging Res 1998;24:169e179. 17. Kalantar-Zadeh K, Horwich TB, Oreopoulos A, et al. Risk factor paradox in wasting diseases. Curr Opin Clin Nutr Metab Care 2007;10:433e442. 18. Allen Maycock CA, Muhlestein JB, Horne BD, et al. Statin therapy is associated with reduced mortality across all age groups of individuals with significant coronary disease, including very elderly patients. J Am Coll Cardiol 2002;40: 1777e1785. 19. Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195e2207. 20. Goldstein MR, Mascitelli L, Pezzetta F. Statin therapy, muscle function and vitamin D. Q J Med; 2009:890e891. 21. Scott D, Blizzard L, Fell J, Jones G. Statin therapy, muscle function and falls risk in community-dwelling older adults. Q J Med 2009;102:625e633. 22. Bhardwaj S, Selvarajah S, Schneider EB. Muscular effects of statins in the elderly female: A review. Clin Intervent Aging 2013;8:47e59. 23. Saliba D, Jones M, Streim J, et al. Overview of significant changes in the Minimum Data Set for nursing homes version 3.0. J Am Med Dir Assoc 2012;13: 595e601. 24. Whitney J, Close JC, Jackson SH, Lord SR. Understanding risk of falls in people with cognitive impairment living in residential care. J Am Med Dir Assoc 2012; 13:535e540. 25. Morley JE, Rolland Y, Tolson D, Vellas B. Increasing awareness of the factors producing falls: The mini falls assessment. J Am Med Dir Assoc 2012;13:87e90. 26. Morley JE. Falls and fractures. J Am Med Dir Assoc 2007;8:276e278. 27. Scott D, Blizzard L, Fell J, Jones G. The epidemiology of sarcopenia in community living older adults: What role does lifestyle play? J Cachexia Sarcopenia Muscle 2011;2:125e134. 28. Cesari M, Vellas B. Sarcopenia: A novel clinical condition or still a matter for research? J Am Med Dir Assoc 2012;13:766e767. 29. Landi F, Liperoti R, Fusco D, et al. Sarcopenia and mortality among older nursing home residents. J Am Med Dir Assoc 2012;13:121e126. 30. Morley JE, Abbatecola AM, Argiles JM, et al. Sarcopenia with limited mobility: An international consensus. J Am Med Dir Assoc 2011;12:403e409.
31. Fielding RA, Vellas B, Evans WJ, et al. Sarcopenia: An undiagnosed condition in older adults. Current consensus definition: Prevalence, etiology, and consequences. International Working Group on Sarcopenia. J Am Med Dir Assoc 2011;12:249e256. 32. Ahmed W, Khan N, Glueck CJ, et al. Low serum 25 (OH) vitamin D levels (
